Final Comment 

Response Document for 

the Second List of 

Chemicals and 

Substances for Tier 1 

Screening Under the 

Endocrine Disruptor 

Screening Program

(Categorized Public 

Comments)
Office of Water (4607M)

February 2013

http://water.epa.gov/drink/
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page i

Contents

1. INTRODUCTION AND OVERVIEW................................................................................................ 1

2. COMMENTS AND EPA RESPONSES BY COMMENT CODE ........................................................ 12

EPA Comment Code: 1000 General Comments..................................................................... 12

EPA Comment Code: 1010 General Comments Agreeing with EPA .................................... 22

EPA Comment Code: 1020 Continue Use of Qualifying Language ...................................... 25

EPA Comment Code: 1030 General Comments Disagreeing with EPA................................ 42

EPA Comment Code: 1035 Animal Testing........................................................................... 44

EPA Comment Code: 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2 ......................................................................................... 50

EPA Comment Code: 1050 Evaluation Criteria Review........................................................ 80

EPA Comment Code: 1060 SDWA 1457............................................................................. 151

EPA Comment Code: 1065 EPA's Authority to Require Testing ........................................ 172

EPA Comment Code: 1070 Increase Transparency.............................................................. 186

EPA Comment Code: 1075 Request for Formal Response .................................................. 191

EPA Comment Code: 2005 Pesticides as a Group ............................................................... 204

EPA Comment Code: 2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays..................................................................................... 209

EPA Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations.................................... 216

EPA Comment Code: 2030 Contaminants Unlikely to Persist in Drinking Water .............. 241

EPA Comment Code: 2040 Naturally Occurring Contaminants.......................................... 276

EPA Comment Code: 2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints ....................................................... 288

EPA Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like Effect. 319

EPA Comment Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements ............................................ 371

EPA Comment Code: 2090 Contaminants with MCLG of Zero.......................................... 399

EPA Comment Code: 2100 Pesticide Registration Review Issues....................................... 406

EPA Comment Code: 4000 Chemicals Currently Not Included on the EDSP List.............. 415

EPA Comment Code: 5000 Comments Related to a Deadline Extension............................ 424

List of Exhibits

EXHIBIT 1: EDSP CONTAMINANTS AND ASSOCIATED EPA COMMENT CODES .......................... 2

EXHIBIT 2: ORGANIZATIONS AND INDIVIDUALS COMMENTING ON THE SECOND EDSP LIST.. 10
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Comment Response Document

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1. Introduction and Overview

Background

The Endocrine Disruptor Screening Program (EDSP) was established in 1998 in response to a 

Congressional mandate in the Federal Food, Drug, and Cosmetic Act (FFDCA), which directed the U.S. 

Environmental Protection Agency (EPA or the agency) “to develop a screening program . . . to 

determine whether certain substances may have an effect in humans that is similar to an effect produced 

by a naturally occurring estrogen, or such other endocrine effect as [EPA] may designate.” If a substance 

is found to have an effect, EPA is directed to take action to ensure protection of public health.

In general, EPA intends to use the data collected under the EDSP, along with other information, to 

determine if a pesticide chemical, or other substances, may pose a risk to human health or the 

environment due to disruption of the endocrine system. The determination that a chemical does or is not 

likely to have the potential to interact with the endocrine system will be made on a weight of evidence 

basis taking into account data from the Tier 1 assays and/or other scientifically relevant information. 

Chemicals that go through Tier 1 screening and are found to have the potential to interact with the 

estrogen, androgen, or thyroid hormone systems will proceed to the next stage of EDSP where EPA will 

determine which, if any, of the Tier 2 assays are necessary based on the available data. Tier 2 assays are 

designed to identify any adverse endocrine-related effects caused by the substance, and establish a 

quantitative relationship between the dose and that endocrine effect. Further information regarding the 

EDSP and requirements for Tier 1 and Tier 2 assays can be found on the agency’s EDSP Web site, at 

http://www.epa.gov/endo. 

For inclusion on the second EDSP list, EPA considered chemicals contained on the Office of Water 

(OW) and Office of Pesticide Programs (OPP) priority lists. EPA identified candidate chemicals that are 

either contaminants regulated with a national primary drinking water regulation (NPDWR) or are 

unregulated contaminants that are listed on the third Contaminant Candidate List (CCL 3). Next, EPA 

identified candidate chemicals from OPP based on pesticides that were scheduled for Registration 

Review during fiscal years 2007 and 2008. Consolidating the lists of OW and OPP chemicals resulted in 

over 200 chemicals. EPA pared down this initial second EDSP list by excluding any chemical that fell 

into one or more of the following categories: (i) biological agent and naturally occurring chemicals; (ii) 

chemicals for which the manufacturer, importer or registrant cannot be clearly identified; (iii) chemicals 

already included on the first EDSP list, because EDSP orders have already been issued for these 

chemicals; (iv) chemicals that are hormones with confirmed endocrine effects; (v) chemicals not likely 

to be biologically active or which are incompatible with testing assays for various reasons due to one or 

more of their physiochemical properties; and (vi) pesticides that are scheduled for registration review 

after FY 2008. 

The second list of chemicals for Tier 1 Screening for the EDSP was published on November 17, 2010 

(75 FR 70248). There were approximately 134 chemicals on the second ESDP list. The final list 

includes 109 chemicals and is being published simultaneously with this comment response document

(USEPA, 2012b).

In the Federal Register notice, EPA requested information by public comment that may inform the 

exclusion or inclusion of chemicals on the second EDSP list. This document presents the comments 

received and responses from EPA. Approximately 59 public submissions (in the form of letters, e-mails, 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 2

and/or postings to www.regulations.gov) were received by EPA. All original public submissions can be 

found in their respective docket locations at www.regulations.gov, under Docket ID EPA–HQ–OW–

2009–0477.

EPA’s Categorization of Public Comments and Document Organization

EPA has divided the public comments received into a list of numerically ordered topics (referred to as 

“EPA Comment Codes”). To organize and track public submissions, EPA assigned a document 

identification (ID) number. These “document IDs” were assigned to give each public submission a 

unique identifier.

EPA has read each public submission and, where appropriate, subdivided the comments into “comment 

sections,” or distinct issue areas, based on topical breaks within the submission. EPA grouped these 

comment sections (hereinafter referred to as “comments”) and assigned it a part number. Comments that 

were similar in topic were then grouped together into a corresponding EPA Comment Code. Each EPA 

Comment Code was assigned a four digit reference number. 

Comments and Responses by Comment Code – Section 2

Section 2 presents the public comments and EPA’s responses. These are organized first by EPA 

Comment Code, (i.e., the topical subsections within Section 2); then within each Comment Code, 

comments are organized numerically by EPA Document ID. Readers can first find the comment code for 

topics they are interested in, and then find responses to specific individual comments. The commenters’

name and organization are also given for each comment. Any comment can be read as it appears within 

the commenter’s original letter, e-mail, or posting by searching on the associated Document ID on 

www.regulations.gov (see explanation of Document IDs in the introduction to this section, “EPA’s 

Categorization of Public Comments and Document Organization”). The Document ID can also be used

to find additional information, such as tables or figures, which may be included within the context of 

comments or attachments in the commenter’s original submission.

Many contaminant-specific comments were submitted related to contaminant properties and/or data that 

commenters considered to be reasons for exclusion from the EDSP List 2. These comments were 

categorized into the broader EPA Comment Codes that relate to programmatic criteria (e.g., 2040 

Naturally Occurring Contaminants). Exhibit 1, below, provides a list of contaminants and the EPA 

Comment Code sections where responses can be found. 

Exhibit 1: EDSP Contaminants and Associated EPA Comment Codes

Contaminant EPA Comment Codes

1,1,1-Trichloroethane 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

1,1,2-Trichloroethane 1060 SDWA 1457

1065 EPA's Authority to Require Testing

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2090 Contaminants with MCLG of Zero
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5000 Comments Related to a Deadline Extension

1,1-Dichloroethylene 1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2090 Contaminants with MCLG of Zero

1,2,4-Trichlorobenzene 1050 Evaluation Criteria Review

1,2-Dibromo-3-chloropropane(DBCP) 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

1,2-Dichloroethane 1060 SDWA 1457

1065 EPA's Authority to Require Testing

2070 Contaminants Not Expected to Produce Estrogen-like 

Effect

2080 Contaminants with Low or No Comprehensive 

Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements

2090 Contaminants with MCLG of Zero

5000 Comments Related to a Deadline Extension

1,2-Dichloropropane 1035 Animal Testing

1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

1-Butanol 1050 Evaluation Criteria Review

1060 SDWA 1457

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2,4,5-TP 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

4,4′-Methylenedianiline (MDA) 1050 Evaluation Criteria Review

1060 SDWA 1457

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Acetaldehyde 1000 General Comments

1050 Evaluation Criteria Review

1065 EPA's Authority to Require Testing

1075 Request for Formal Response

2030 Contaminants Unlikely to Persist in Drinking Water

2040 Naturally Occurring Contaminants

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Acetochlor 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

1060 SDWA 1457

2005 Pesticides as a Group

2070 Contaminants Not Expected to Produce Estrogen-like Effect
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Comment Response Document

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2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2100 Pesticide Registration Review Issues

Acetochlor ethane sulfonic acid (ESA) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Acetochlor oxanilic acid (OA) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Acrolein 1065 EPA’s Authority to Require Testing

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Acrylamide 1050 Evaluation Criteria Review

1060 SDWA 1457

2040 Naturally Occurring Contaminants

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2090 Contaminants with MCLG of Zero

Alachlor 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

1060 SDWA 1457

2005 Pesticides as a Group

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2100 Pesticide Registration Review Issues

Alachlor ethane sulfonic acid (ESA) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Alachlor oxanilic acid (OA) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Benzene 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Benzo(a)pyrene (PAHs) 1050 Evaluation Criteria Review

Benzyl chloride 1050 Evaluation Criteria Review
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1060 SDWA 1457

2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays

2030 Contaminants Unlikely to Persist in Drinking Water

Carbon tetrachloride 1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2090 Contaminants with MCLG of Zero

Chlordane 1050 Evaluation Criteria Review

1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2090 Contaminants with MCLG of Zero

Chlorobenzene 1050 Evaluation Criteria Review

Clomazone 2070 Contaminants Not Expected to Produce Estrogen-like Effect

2100 Pesticide Registration Review Issues

Cumene hydroperoxide (CHP) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays

2030 Contaminants Unlikely to Persist in Drinking Water

Dalapon 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Di(2-ethylhexyl)adipate 1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Dichloromethane 1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2090 Contaminants with MCLG of Zero

Dimethipin 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Dinoseb 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Endrin 1050 Evaluation Criteria Review

1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2090 Contaminants with MCLG of Zero

Epichlorohydrin (ECH) 1035 Animal Testing
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2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Erythromycin 1035 Animal Testing

1065 EPA's Authority to Require Testing

1075 Request for Formal Response

Ethylbenzene 1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Ethylene dibromide 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Ethylene glycol 1035 Animal Testing

1050 Evaluation Criteria Review

2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Ethylene thiourea (ETU) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2005 Pesticides as a Group

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2100 Pesticide Registration Review Issues

Fenamiphos 2005 Pesticides as a Group

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Fenarimol 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Fenoxaprop-p-ethyl 2005 Pesticides as a Group

Fenoxycarb 1050 Evaluation Criteria Review

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Flumetsulam 1020 Continue Use of Qualifying Language

1035 Animal Testing

1050 Evaluation Criteria Review

1065 EPA's Authority to Require Testing

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2100 Pesticide Registration Review Issues

Fosetyl-Al (Aliette) 2005 Pesticides as a Group

HCFC-22 1060 SDWA 1457

2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Heptachlor 1050 Evaluation Criteria Review

1060 SDWA 1457
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2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2090 Contaminants with MCLG of Zero

Heptachlor epoxide 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Hexachlorocyclopentadiene 1050 Evaluation Criteria Review

1060 SDWA 1457

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Hydrazine 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

1050 Evaluation Criteria Review

2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Isoxaben 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2030 Contaminants Unlikely to Persist in Drinking Water 

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Lindane 1050 Evaluation Criteria Review

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Methanol 1050 Evaluation Criteria Review

1075 Request for Formal Response

2030 Contaminants Unlikely to Persist in Drinking Water

2040 Naturally Occurring Contaminants

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Methoxychlor 1050 Evaluation Criteria Review

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption

or Other Reproductive Developmental Endpoints

Methyl tert-butyl ether 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2030 Contaminants Unlikely to Persist in Drinking Water

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Molinate 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Nitrobenzene 1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Nitroglycerin 1035 Animal Testing

1065 EPA's Authority to Require Testing

1075 Request for Formal Response
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2070 Contaminants Not Expected to Produce Estrogen-like Effect

o-Dichlorobenzene 1050 Evaluation Criteria Review

o-Toluidine 1050 Evaluation Criteria Review

Oxirane, methyl- (propylene oxide or PO) 1035 Animal Testing

2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays

2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Oxyfluorfen 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2100 Pesticide Registration Review Issues

p-Dichlorobenzene 1050 Evaluation Criteria Review

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Perchlorate 1000 General Comments

1020 Continue Use of Qualifying Language

1050 Evaluation Criteria Review

1065 EPA's Authority to Require Testing

2040 Naturally Occurring Contaminants

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

2070 Contaminants Not Expected to Produce Estrogen-like Effect

4000 Chemicals Currently Not Included on the EDSP List

Perfluorooctanoic acid (PFOA) 1050 Evaluation Criteria Review

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Picloram 1050 Evaluation Criteria Review

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

2100 Pesticide Registration Review Issues

Polychlorinated biphenyls (PCBs) 1065 EPA's Authority to Require Testing

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Propetamphos 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Pyridate 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

2070 Contaminants Not Expected to Produce Estrogen-like Effect

Quinoline 1035 Animal Testing

1065 EPA's Authority to Require Testing

1075 Request for Formal Response

RDX 2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Sodium tetrathiocarbonate 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations
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Styrene 2030 Contaminants Unlikely to Persist in Drinking Water

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Sulfosate 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Temephos 2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

Tetrachloroethylene 1060 SDWA 1457

2090 Contaminants with MCLG of Zero

Toluene diisocyanate 1060 SDWA 1457

2030 Contaminants Unlikely to Persist in Drinking Water

Toxaphene 1050 Evaluation Criteria Review

2020 Contaminants No Longer Manufactured or Imported, or Used in 

the US, also Includes Pesticides with Cancelled Registrations

trans-1,2-Dichloroethylene 2070 Contaminants Not Expected to Produce Estrogen-like Effect

2080 Contaminants with Low or No Comprehensive Occurrence Data 

and Therefore Do Not Meet SDWA 1457 Requirements

Trichloroethylene (TCE) 1060 SDWA 1457

2070 Contaminants Not Expected to Produce Estrogen-like Effect

2090 Contaminants with MCLG of Zero

Triethylamine 2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays

2030 Contaminants Unlikely to Persist in Drinking Water

Triphenyltin hydroxide (TPTH) 1040 Complete List 1- Evaluate Tier 1 Screening Results before 

Proceeding with EDSP List 2

2030 Contaminants Unlikely to Persist in Drinking Water

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Vinclozolin 1050 Evaluation Criteria Review

2060 Chemicals with Toxicity Data Indicating Endocrine Disruption 

or Other Reproductive Developmental Endpoints

Cross-Referencing of Responses

In many cases, several commenters addressed the same or similar issues. For these comments, EPA has 

cross-referenced responses to avoid redundancy and to ensure consistency. Responses are crossreferenced by providing the pertinent EPA Document ID and part number, along with the EPA 

Comment Code where the comment is located. As noted above, Section 2 is organized first by EPA 

Comment Code (the subsections within the chapter), then numerically by EPA Document ID.

Response to Comment Code

Many comments received by EPA addressed similar topics and were thus grouped under the same EPA 

Comment Code. In several of these cases, the same response was appropriate for multiple comments, 

and EPA developed a “General Response” section which appears at the beginning of each EPA 

Comment Code section, where applicable. Responses to individual comments may point the reader to 

the appropriate Response to Comment Code.

Who Submitted Comments

EPA received 59 public submissions with the majority of comments coming from the industry, or 

consultants writing on behalf of the industry. Two comments were from drinking water organizations.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 10

Exhibit 2 presents the Document ID, Commenter Name, and Organizations for the 59 comments 

received.

Exhibit 2: Organizations and Individuals Commenting on the Second EDSP List

Document ID Commenter Name Organization

EPA-HQ-OPPT-2009-0477-0006 Wendelyn Jones CropLife America

EPA-HQ-OPPT-2009-0477-0007 Richard A.Becker on behalf 

of Michael P. Walls

American Chemistry Council

EPA-HQ-OPPT-2009-0477-0008 Catherine Willett People for the Ethical Treatment of Animals

EPA-HQ-OPPT-2009-0477-0010 Peter E. Voytek The HAP Task Force (HAP) 

EPA-HQ-OPPT-2009-0477-0011 Marcy I. Banton LyondellBasell Industries

EPA-HQ-OPPT-2009-0477-0012 Sushma Bhatia et al. San Francisco REACH Team

EPA-HQ-OPPT-2009-0477-0013 Gail Charnley HealthRisk Strategies

EPA-HQ-OPPT-2009-0477-0014 John J. Jachetta Dow AgroSciences LLC

EPA-HQ-OPPT-2009-0477-0015 Cindy Loy Dow AgroSciences LLC

EPA-HQ-OPPT-2009-0477-0016 Terry Medley E.I. du Pont de Nemours and Company

EPA-HQ-OPPT-2009-0477-0018 P. J. Snyder Shell Downstream Inc., U.S.

EPA-HQ-OPPT-2009-0477-0019 Catherine Willett People for the Ethical Treatment of Animals 

(PETA), et al.

EPA-HQ-OPPT-2009-0477-0020 Nneka T. Breaux Dow AgroSciences LLC

EPA-HQ-OPPT-2009-0477-0021 Linda G. Ferguson American Pacific Corporation

EPA-HQ-OPPT-2009-0477-0022 Marie R. Martinko Society of the Plastics Industry, Inc.

EPA-HQ-OPPT-2009-0477-0023 Patricia Kablach Casano General Electric Company

EPA-HQ-OPPT-2009-0477-0024 Gregory A. Dolan Methanol Institute

EPA-HQ-OPPT-2009-0477-0025 Howard J. Feldman American Petroleum Institute

EPA-HQ-OPPT-2009-0477-0026 Nneka T. Breaux Dow AgroSciences LLC

EPA-HQ-OPPT-2009-0477-0027 Leslie Berry American Chemistry Council Oxo Process 

Panel

EPA-HQ-OPPT-2009-0477-0028 Thomas W. Curtis American Water Works Association

EPA-HQ-OPPT-2009-0477-0029 Richard A. Becker American Chemistry Council

EPA-HQ-OPPT-2009-0477-0030 James C. Lamb Hercules, a wholly owned subsidiary of 

Ashland, Inc.

EPA-HQ-OPPT-2009-0477-0031 Francis X. Sherman AkzoNobel

EPA-HQ-OPPT-2009-0477-0032 Paul H. Dugard Honeywell International, Inc., and Mexichem 

Fluor, Inc.

EPA-HQ-OPPT-2009-0477-0033 Rebecca J. Bernstein Arkema Inc.

EPA-HQ-OPPT-2009-0477-0034 Peter E. Voytek HAP Task Force

EPA-HQ-OPPT-2009-0477-0035 Sahar Osman-Sypher American Chemistry Council

EPA-HQ-OPPT-2009-0477-0036 Sahar Osman-Sypher American Chemistry Council

EPA-HQ-OPPT-2009-0477-0037 W. Caffey Norman Patton Boggs LLP on behalf of PPG 

Industries, Inc.

EPA-HQ-OPPT-2009-0477-0038 Faye Graul Halogenated Solvents Industry Alliance, Inc.

EPA-HQ-OPPT-2009-0477-0039 Intertox, Inc. Intertox, Inc. on behalf of Perchlorate Study 

Group

EPA-HQ-OPPT-2009-0477-0040 Stephen L. Longacre FMC Corporation

EPA-HQ-OPPT-2009-0477-0041 Anthony D. Wagner American Chemical Council
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Document ID Commenter Name Organization

EPA-HQ-OPPT-2009-0477-0042 Andrew M. Jaques North American Polyelectrolyte Producers 

Association

EPA-HQ-OPPT-2009-0477-0044 Gregory R. Watson Acetochlor Registration Partnership

EPA-HQ-OPPT-2009-0477-0046 Anthony D. Wagner American Chemistry Council

EPA-HQ-OPPT-2009-0477-0047 D. Douglas Fratz Consumer Specialty Products Association

EPA-HQ-OPPT-2009-0477-0048 Robert J. Simon American Chemistry Council

EPA-HQ-OPPT-2009-0477-0049 Michael C. White Chemical Producers and Distributors 

Association

EPA-HQ-OPPT-2009-0477-0050 Wendelyn Jones CropLife America and Endocrine Policy 

Forum

EPA-HQ-OPPT-2009-0477-0051 Robert J. Fensterheim Acetaldehyde Working Group

EPA-HQ-OPPT-2009-0477-0052 Gregory Watson Monsanto Company

EPA-HQ-OPPT-2009-0477-0053 Kathleen M. Roberts Methyl Tertiary Butyl Ether (MTBE) 

Consortium

EPA-HQ-OPPT-2009-0477-0054 Niamh McMahon Dow AgroSciences LLC (DAS) 

EPA-HQ-OPPT-2009-0477-0055 Sarah Janssen Natural Resources Defense Council (NRDC)

EPA-HQ-OPPT-2009-0477-0056 Stephen P. Risotto American Chemistry Council (ACC)

EPA-HQ-OPPT-2009-0477-0058 Jean Kasakevich Dow Chemical Company (DOW)

EPA-HQ-OPPT-2009-0477-0060 Jean Kasakevich Dow Chemical Company (DOW)

EPA-HQ-OPPT-2009-0477-0061 Susan Van Volkenburg LANXESS Corporation

EPA-HQ-OPPT-2009-0477-0062 Fred Marashi Chevron Phillips Chemical Company LP 

(CPChem)

EPA-HQ-OPPT-2009-0477-0064 Michael Boucher McKenna Long & Aldridge LLP on behalf of 

Ferro Corporation

EPA-HQ-OPPT-2009-0477-0065 Dru Ann Toman EHS Global Product Leader, Performance 

Materials, Union Carbide Corporation 

(UCC), a subsidiary of The Dow Chemical 

Company (DOW)

EPA-HQ-OPPT-2009-0477-0066 The Bayer CropScience 

Endocrine Drive Team

Bayer CropScience LP

EPA-HQ-OPPT-2009-0477-0067 Jack Snyder Styrene Information and Research Center 

(SIRC)

EPA-HQ-OPPT-2009-0477-0068 Sherman Friedman Velsicol Chemical LLC (Velsicol)

EPA-HQ-OPPT-2009-0477-0069 Jean Kasakevich Dow Chemical Company (DOW)

EPA-HQ-OPPT-2009-0477-0072 McDermott Will & Emergy 

LLP on behalf Janet 

Ollinger

EBDC/ETU Task Force

EPA-HQ-OPPT-2009-0477-0073 Terry F. Quill Quill Law Group, LLC on behalf of Velsicol

Chemical, LLC
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2. Comments and EPA Responses by Comment Code

EPA Comment Code: 1000 Individual Comments

Individual Comments

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 1

EPA Comment Code: 1000

Comment: January 18, 2011

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, N.W.

Washington, DC. 20460

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477

Submitted via Federal eRulemaking Portal: http://www.regulations.gov

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

Dear Sir or Madam:

The American Chemistry Council (ACC) [FN1: The American Chemistry Council (ACC) represents the 

leading companies engaged in the business of chemistry. ACC members apply the science of chemistry 

to make innovative products and services that make people's lives better, healthier and safer. ACC is 

committed to improved environmental, health and safety performance through Responsible Care®, 

common sense advocacy designed to address major public policy issues, and health and environmental 

research and product testing. The business of chemistry is a $674 billion enterprise and a key element of 

the nation's economy. It is one of the nation’s largest exporters, accounting for ten cents out of every 

dollar in U.S. exports. Chemistry companies are among the largest investors in research and

development. Safety and security have always been primary concerns of ACC members, and they have 

intensified their efforts, working closely with government agencies to improve security and to defend 

against any threat to the nation’s critical infrastructure.] appreciates the opportunity to submit comments 

on EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the 

“Draft EDSP List 2”). Pursuant to EPA’s request for comments on the Draft EDSP List 2, 75 Fed. Reg. 

70248; 11/17/2010, (the “Listing Notice”), ACC provides a number of general comments related to the 

Draft EDSP List 2 and the Agency’s chemical prioritization approach. These comments do not address 

specific substances the Agency has chosen as candidates for the initial list. ACC panels and/or member 

companies will submit separate comments concerning some of those specific substances.

The American Chemistry Council (ACC) has played a constructive role in the Agency’s development of 

the EDSP and in furthering the goal of implementing the EDSP as quickly and efficiently as possible, in 

a manner consistent with the law and authoritative scientific policies and practices. To that end, ACC 
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has consistently supported increased funding for the Agency’s research and laboratory studies to 

develop, standardize and validate the screening and testing methods required for the EDSP. ACC also 

has sponsored technical studies to supply needed data for endocrine test development and validation, 

and has participated with the broader scientific and stakeholder communities on EPA’s standardization 

and validation advisory committees. Additionally, ACC has sponsored scientific research on the 

endocrine hypothesis through its Long-Range Research Initiative. As these actions demonstrate, ACC 

members take concerns about endocrine disruption seriously, as with any potential chemical risks.

ACC commends EPA on its care in accurately communicating what the draft list is and is not in its 

notice announcing the Draft EDSP List 2. We urge EPA to continue to carefully communicate accurate 

information at each stage of the EDSP process: listing of substances for screening/testing, issuance of 

test orders, results from Tier 1 screening and Tier 2 testing, and in hazard and risk characterization.

Response: Thank you for your comment.

Commenter Name: Francis Sherman

Commenter Organization: AkzoNobel

EPA Document ID: EPA-HQ-OPPT-2009-0477-0031

Comment Part: 1

EPA Comment Code: 1000

Comment: January 18, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency

1200 Pennsylvania Avenue, N.W.

Washington, DC. 20460-0001

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477

Submitted via Federal eRulemaking Portal: http://www.regulations.gov

RE: Comments on "Endocrine Disrupter Screening Program; Second List of

Chemicals for Tier 1 Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-0477; FRL-8848-7]

Dear Sir or Madam,

AkzoNobel is proud to be one of the world's leading industrial companies. Headquartered in 

Amsterdam, the Netherlands, we synthesise, formulate and supply a wide range of paints, coatings and 

specialty chemicals - 2008 revenue totalled €15.4 billion. In fact, we are the largest global paints and 

coatings company. As also a major producer of specialty chemicals we supply industries worldwide with 

quality ingredients for life's essentials.

The products manufactured by AkzoNobel are used to manufacture products for industrial, commercial 

and consumer markets in the United States and worldwide. Accordingly, AkzoNobel is a proud member 

of the American Chemistry Council (ACC). AkzoNobel fully supports ACC as it seeks to represent the 

interests of its member companies.
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In the matter referenced above, the ACC has submitted comments to EPA dated January 18, 2011. 

AkzoNobel strongly urges EPA to carefully consider the comments submitted by ACC in the matter. 

These comments were developed with significant input from the member companies with consideration 

for ensuring that sound scientific principles are applied and minimizing the cost impact on business.

AkzoNobel appreciates this opportunity to provide input on this important rulemaking process.

Sincerely,

Francis X. Sherman,

Country Director

Response: Thank you for your comment.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 5

EPA Comment Code: 1000

Comment: 4.0 PERCHLORATE IS NOT AN AGONIST OR ANTAGONIST TO ANTERIOR 

PITUITARY

OR THYROID HORMONES

A chemical that mimics the action of a hormone is fundamentally different than a chemical that can 

affect the function of an endocrine gland. A chemical that mimics hormonal action will add to (as an 

agonist) or negate (as an antagonist or mixed agonist/antagonist) endogenous hormonal effect. 

4.1 A brief historical context to Endocrine Disrupting Chemicals

Estrogens are comprised of a family of steroid compounds. Some members of the family are more 

potent than others in their effects; therefore, for some, only a small amount is needed to cause an effect 

in the body. The body produces endogenous estrogens. In females, estrogens regulate growth, 

reproduction, and other systems. Estrogens are generally female sex hormones and are more plentiful in 

females; however, estrogen is also produced in males. The most potent endogenous estrogen is 17β 

estradiol. Given to males in sufficient doses, estrogens can have powerful feminizing effects on the male 

body. 

In the body, estrogens exert their effects by binding to estrogen receptors. This binding triggers a chain 

reaction of biochemical events in the cell (e.g., increases or decreases the transcription of specific 

genes). In general, chemicals which behave like estrogens (i.e., mimic estrogens) will also bind to 

estrogen receptors. These estrogen mimetics can bind to the estrogen receptor and alter or prevent 

biochemical events in the cell. Those that mimic estrogen-like activities are estrogen agonists and those 

that inhibit these events are estrogen antagonists. Chemicals which have antagonist effects at the 

estrogen receptor are called antiestrogens. The same type of effect occurs for other receptor mediated 

hormones, such as thyroid hormones.
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Environmental exposure to estrogens has received a significant amount of attention from scientists, 

regulators, and the media. Estrogenic effects from industrial chemicals, pesticides, and pharmaceuticals 

have been reported to affect laboratory animals at low levels and can have a cumulative effect. The 

National Toxicology Program (NTP) was requested by US EPA to evaluate whether low dose effects 

(i.e., “biologic changes that occur in the range of human exposures or at doses lower than those typically 

used in the standard testing paradigm of the US EPA for evaluating reproductive and developmental 

toxicity;” Melnick et al., 2002) or non-standard dose-response curves occur with exposure to endocrine 

disrupting chemicals.

The thyroid gland produces and secretes two hormones: thyroxine (T4) and triiodothyronine (T3). Once 

secreted into the body, like estrogen, thyroid hormones are distributed throughout the body where they 

interact with thyroid hormone receptors.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language, general response to comment under EPA Code: 1050 Evaluation Criteria and the 

individual response to EPA Document ID: EPA-HQ-OPPT-2009-0477-0039, Comment Part: 3 of that 

section. Also, please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 10

EPA Comment Code: 1000

Comment: Second, nitrate has diverse sources and a distinct manufacturer for nitrate cannot be 

identified. Nitrate is found in the environment due to its use in fertilizers--Chilean nitrate fertilizer is 

used due to its high nitrate concentration, which plants require for growth. Nitrate used agriculturally 

can be found in food and drinking water. Other industrial uses of nitrate include as a food additive and 

as an oxidizer in gun powder, amateur rocket propellants, and fireworks.

Similar to perchlorate, the four remaining criteria do not apply to nitrate.

Based on the facts that nitrate is both naturally occurring and a manufacturer cannot be clearly 

identified, it meets the Agency’s scientific criteria for exclusion.

Like nitrate, another chemical that was excluded was bromate. Bromate is a water disinfection 

byproduct. It too is able to cause IUI with sufficient dose and duration (US EPA, 2010b). It has a MCL 

and was on the initial list that US EPA streamlined with the above criteria, although the specific reason 

for exclusion was not found. It is likely that bromate was excluded based on the second criterion: 

bromate has diverse sources and a distinct manufacturer is not identifiable.

Similar to perchlorate, the remaining criteria do not apply to bromate.
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Like nitrate, another chemical that was excluded from the November 17th list was chlorate. Chlorate is a 

water disinfection byproduct. It too is able to cause IUI with sufficient dose and duration (US EPA, 

2010b). It is on the CCL3 list and was on the initial list that US EPA streamlined. It is scientifically 

justified that chlorate was excluded from the final list based on the second criterion established by the 

Agency: chlorate has diverse sources, and a distinct manufacturer is not identifiable.

Similar to perchlorate, the remaining criteria do not apply to chlorate. 

In summary, US EPA has inconsistently applied its exclusion criteria by including perchlorate, while 

excluding other chemicals by the likely same exclusion criteria. US EPA should also exclude 

perchlorate.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review. Also, see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 4

EPA Comment Code: 1000

Comment: CropLife America/Endocrine Policy Forum Comments on Second List of Chemicals for Tier 

I Screening.

Docket ID: EPA-HQ-OPPT-2009-0477

Crop Life America [FN1: CropLife America (CLA) is a not-for-profit trade organization representing 

the nation's developers, manufacturers, formulators and distributors of plant science solutions for 

agriculture and pest management in the United States. Our member companies produce, sell and 

distribute virtually all the crop protection technology products used by American farmers and other 

consumers. We are committed to the safe and responsible use of the industry's products in order to 

provide safe and abundant food, as well as for the control of insect and plant disease vectors for the 

protection of human health, all providing valuable benefits back to the consumer]. and the Endocrine 

Policy Forum (EPF) [FN2: The Endocrine Policy Forum is a consortium of CLA members and nonmember stakeholders formed to address the aggregate needs of the group with respect to technical 

guidance and regulatory policy in response to the implementation of the EPA Endocrine Disruptor 

Screening Program.] are pleased to have this opportunity to submit comments on EPA's Endocrine 

Disruptor Screening Program; Second List of Chemicals for Tier I Screening, 75 Fed. Reg. 70248, Nov. 

17, 2010. These comments do not address specific substances the Agency has chosen as candidates for 

the initial list. Rather our comments are focused on the general approach outlined and implementation of 

the Endocrine Disruptor Screening Program (EDSP). 

Background

The 1996 Food Quality Protection Act (FQPA) directed EPA to develop a screening program, using 

appropriately validated test systems and other scientifically relevant information, to determine whether 

certain substances may have hormonal effects in humans. FQPA instructed EPA to determine the 

endocrine-disrupting potential of pesticide chemicals and other substances, and based on those findings, 
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to take action to protect the public health and the environment. EPA developed the EDSP in response. 

The determination that a chemical may or may not have the potential to interact with the endocrine 

system will be made on a weight of evidence basis taking into account data from the Tier I assays and/or 

other scientifically relevant information. Chemicals that go through Tier I screening and are found to 

have the potential to interact with the estrogen, androgen, or thyroid hormone systems will proceed to 

the next stage of EDSP where EPA will determine which, if any, of the Tier II tests are necessary. Tier I 

is intended by the Agency to serve as a screening battery. Tier II testing is designed to identify any 

adverse endocrine-related effects caused by the substance, and establish a quantitative dose-response 

relationship. The approval of EDSP mandated that EPA base its findings on appropriately validated test 

systems and other scientifically relevant information (OSRI) and to minimize duplicative testing. [FN3: 

http://www.reginfo.gov/public/do/PRAViewICR ?ref_ nbr=200904-2070-00 I] 

The status of the initial phase of EDSP Tier I test orders that EPA has already issued is available online 

[FN4: http://www.epa.gov/scipoly/oscpendo/pubs/edsp orders_ status.pdf] October 2011 is the current 

first deadline for complying with these test orders. Some OSRI applications, and EPA's responses to 

them, are available online [FN5: http://www.epa.gov/scipoly/oscpendo/pubs/EDSP OSRI_ Response_ 

Table.pdf] The test order recipients submitted timely OSRI applications (within the mandated 90 days 

for a single company or within 150 days for a consortium). However, with only a few remaining months 

until the first deadline for complying with the test orders, several CLA/EPF members do not know yet 

whether they will have to perform all or any of the Tier I tests.

In November 2010, EPA released in the Federal Register a series of draft documents relating to the 

expansion of the EDSP. The new list of chemicals[FN6: EPA, Endocrine Disruptor Screening Program; 

Second List of Chemicals for Tier 1 Screening 75 Fed. Reg. 70248, Nov. 17,2010 ("Draft List 2")] the 

amended information collection request [FN7: EPA, Agency Information Collection Activities; 

Proposed Collection; Comment Request; Addendum for the Second List of Chemicals; Tier 1 Screening 

of Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP); EPA ICR No. 

2249.02, OMB Control No. 2070-017675. Fed. Reg. 70568, Nov. 17, 2010 ("Draft ICR")] and the 

amended Draft Policies and Procedures [FN8: EPA, Endocrine Disrupt or Screening Program; Draft 

Policies and Procedures for Screening Safe Drinking Water Act Chemicals, 75 Fed. Reg. 70558, Nov. 

17,2010 ("Draft Phase 2 Policies and Procedures").] all refer to EPA's second phase of the EDSP. 

Presently CLA/EPF are providing public comment on EPA's draft second list of chemicals for Tier I 

screening of substances under the Endocrine Disruptor Screening Program (EDSP) pursuant to Section 

1457 of the Safe Drinking water Act (SDWA) and section 408(p) of the Federal Food, Drug, and 

Cosmetic Act (FFDCA) ("Phase 2"). 

Sharing the common goal of safety:

The EPA, state regulatory agencies and the crop protection industry all share the common goal of 

creating effective products that are environmentally safe and sustainable. When the process of 

development and registration for crop protection products is fully understood by the general public, their 

importance and safety are readily apparent. Crop protection technologies provide modem agriculture 

some of the tools necessary to feed the growing world population. An understanding of the current 

regulatory process and requirements under FIFRA provides an appreciation for the amount of data that 

exists on any given crop protection product that allows one to answer the question: "Does this product 

have the potential to interact with certain hormonal systems?" [the ultimate goal of EDSP Tier I 

screening].
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Response: Please see general response to comment under EPA Comment Code: 2005 Pesticides as a 

Group. Also, please see Response to Comments on the Public Review Draft of the Information

Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of 

Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is 

being published simultaneously with this comment response document.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 3

EPA Comment Code: 1000

Comment: COMMENTS ON THE INCLUSION OF ACETALDEHYDE (CAS NO. 75-07-0) IN 

“ENDOCRINE DISRUPTOR SCREENING PROGRAM: SECOND LIST OF CHEMICALS FOR 

TIER 1 SCREENING” 

75 FED. REG. 70248; NOVEMBER 17, 2010; EPA-HQ-OPPT-2009-0477

Submitted by the 

Acetaldehyde Working Group 

1250 Connecticut Ave., NW 

Suite 700 

Washington, DC 20036 

202.419.1500 

January 18, 2011

Comments on the Inclusion of Acetaldehyde (CAS No. 75-07-0) in “Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening” 

I. Introduction and Overview 

The Acetaldehyde Working Group (AWG) of the Vinyl Acetate Council (VAC) appreciates the 

opportunity to provide comments on the U.S. Environmental Protection Agency’s (EPA) November 17, 

2010 announcement of a second list of chemicals and substances for which EPA is considering issuing 

Test Orders under the Endocrine Disruptor Screening Program (EDSP) (75 FR 70248). AWG represents 

the major commercial manufacturers of acetaldehyde. AWG member companies[FN1: Members of the 

Acetaldehyde Working Group include: Celanese, Ltd.; The Dow Chemical Company; E.I. DuPont de 

Nemours; Eastman Chemical Company; LyondellBasell; and, Wacker Chemie.] have an interest in 

acetaldehyde because some members manufacture acetaldehyde for commercial purposes and because 

acetaldehyde is a metabolite of vinyl acetate monomer, an important commercial product manufactured 

and/or processed by members of the VAC. 

Acetaldehyde is a colorless liquid with a pungent, fruity odor. It is primarily used as a chemical 

intermediate, principally for the production of acetic acid, pyridine and pyridine bases, peracetic acid, 

pentaeythritol, butylene glycol, and chloral. Acetaldehyde is also a byproduct of numerous chemicals 

and other processes, as is evident by the fact that hundreds of companies emit acetaldehyde (as reflected 

in the Toxic Release Inventory) even though the majority of these companies did not manufacture (for 

commercial purposes) or purchase acetaldehyde.
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Response: Please see Endocrine Disruptor Screening Program; Final Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published simultaneously 

with this comment response document.

Commenter Name: Michael Boucher

Commenter Organization: McKenna Long & Aldridge LLP on behalf of Ferro Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0064

Comment Part: 3

EPA Comment Code: 1000

Comment: The CCL 3 implements section 1412(b)(1)(B) of the SDWA, which requires EPA to develop 

a list of unregulated contaminants that are known or anticipated to occur in public water systems and 

that may require regulation under the SDWA:

(B) Regulation of unregulated contaminants.-

(i) Listing of contaminants for consideration.-

(I) Not later than 18 months after August 6, 1996, and every 5 years thereafter, the Administrator, after 

consultation with the scientific community, including the Science Advisory Board, after notice and 

opportunity for public comment, and after considering the occurrence data base established under 

section 300j-4(g) of this title [the National Contaminant Occurrence Databases established under section 

1445(g) of the SDWA], shall publish a list of contaminants which, at the time of publication, are not 

subject to any proposed or promulgated national primary drinking water regulation, which are known or 

anticipated to occur in public water systems, and which may require regulation under this subchapter .

(II) The unregulated contaminants considered under subclause (1) shall include, but not be limited to, 

substances referred to in section 9601(14) of this title [the Comprehensive Environmental Response, 

Compensation, and Liability Act], and substances registered as pesticides under the Federal Insecticide, 

Fungicide, and Rodenticide Act [7 U.S.C. §§ 136-136y].[FN11: 42 U.S .C. § 300g-1(b)(1)(B)(i).]

To compile the CCL 3, EPA considered public water system monitoring data, data on ambient 

concentrations in surface water and groundwater, releases to the environment (for example, reporting 

data from the Toxic Release Inventory ("TRI")), and production volumes reported under the Toxic 

Substances Control Act's Inventory Update Rule ("IUR").[FN12: See 40 C.F .R. pt . 372, 40 CF.R. §§ 

710.23 to -.59] EPA acknowledged, however, that such data may not establish that a contaminant occurs 

in public water systems.[FN13: 74 Fed. Reg. at 51,851.]

Response: EPA acknowledged in 74 FR 51850 (USEPA, 2009c) that “While such data may not 

establish conclusively that contaminants are known to occur in public water systems, EPA believes these 

data are sufficient to anticipate that contaminants may occur in public water systems and to place them 

on the CCL”. Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Terry F. Quill

Commenter Organization: Quill Law Group, LLC on behalf of Velsicol Chemical, LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0073

Comment Part: 1
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EPA Comment Code: 1000

Comment: April 11, 2011

OPPT Document Control Office (DCO)

EPA East Bldg., Rm. 6428

1201 Constitution Ave., NW

Washington, DC 

Attention: Docket ID Number EPA-HQ-0PPT-2009-0477

Re: Supplemental Materials Submitted by Velsicol Chemical Concerning the

"Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1

Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

Dear Sir/Madam:

Velsicol Chemical LLC (Velsicol) is submitting this letter along with the attached CD containing 

relevant technical documents for inclusion in the above-referenced docket. Velsicol electronically 

submitted extensive, timely comments on EPA's Endocrine Disruptor Screening Program: Second List 

of Chemicals for Tier 1 Screening on January 17, 2011 . In response to recent discussions with the 

Agency concerning EPA's initial listing of Velsicol's chemicals (hexachlorocyclopentadiene, endrin, 

chlordane and heptachlor) on the EDSP Second List, Velsicol is submitting this supplemental 

information to assist the Agency in its consideration of Velsicol's comments and its assessment of 

Velsicol's chemicals for final listing.

Supplemental Technical Documents

Velsicol is submitting the following eleven technical documents. Those documents are copied in the 

enclosed CD labeled: Supplement to Comments of Velsicol - "Endocrine Disruptor Screening Program: 

Second List of Chemicals for Tier 1 Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; 

FRL-8848-71], April 8, 2011. Most of the technical documents are cited in Velsicol's January 17, 2011 

comments. Please note that Velsicol does not claim CBI protection for any of these documents.

1. Butz R.G., Yu C.C., Atallah Y.H. (1982): Photolysis of hexachlorocyclopentadiene in water. 

Ecotoxicol . Environ. Safety 6, 347-357. [Cited in footnote 9 of Velsicol's Jan. 17, 2011 Comments.]

2. Callahan, M.A., W.M. Slimak, N.W. Gabel, et al. Water-Related Environmental Fate of 129 Priority 

Pollutants. Volume II. EPA-440/4-79- 029b. Washington, D.C.: US Environmental Protection Agency. 

December 1997. [Cited in footnote 16 of Velsicol's Jan. 17, 2011 Comments.]

3. Chou S .F., Griffin R.A., Chou M.I. (1987) : Products of hexachlorocyclopentadiene (C-56) in 

aqueous solution. Environ. Toxicology and Chemistry 6, 371-376. [Cited in footnote 8 of Velsicol's Jan. 

17, 2011 Comments.]

4. US-EPA (1995): National Primary Drinking Water Regulations: Hexachlorocyclopentadiene. Office 

of Water, EPA 811-F-95-003t-T, October 1995. [This EPA document provides the relevant information 

found in the references cited in footnotes 17 (ACGIH 1986) and 18 (Chou, et al. 1983). In addition to 

being an Agency document, it is more recent.]
EPA-OGWDW Final EDSP List 2 February 2013

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5. European Union Risk Assessment Report: Hexachlorocyclopentadiene, Risk Assessment, July 2007 

("EU Hex Risk Assessment") [Cited in footnote 20 of Velsicol's Jan. 17, 2011 Comments.]

6. Korte (1978) : Photomineralization of hexachlorocyclopentadiene and ecotoxicological profile 

analysis of hexachlorocyclopentadiene . Unpublished report prepared for Velsicol Chemical 

Corporation, Chicago, IL. [Cited in footnote 11 of Velsicol's Jan. 17, 2011 Comments.]

7. Tabak H.H., Quave S.A., Mashni C.I. et al. (1981) : Biodegradability studies with organic priority 

pollutant compounds. J. Water Pollut . Control. Fed. 10, 1503-1518 . [Cited in footnote 15 of Velsicol's 

Jan. 17, 2011 Comments.]

8. US-EPA (1984): Health Assessment Document for HCCP. Final Report No. EPA-600/8-84- OO1F. 

U.S. Environmental Protection Agency, Cincinnati, OH, order No. PB 85-124915, National Technical 

Information Service (NTIS), Springfield, VA, 1-1 - 9-20, A-1-A-12 (IUCLID). [Cited in footnote 13 of 

Velsicol's Jan. 17, 2011 Comments.]

9. Wolfe N.L., Zepp R.G., Schlotzhauer P., Sink M. (1982): Transformation pathways of 

hexachlorocyclopentadiene in the aquatic environment. Chemosphere 11, 91-101. [Cited in footnote 7 of 

Velsicol's Jan. 17, 2011 Comments.]

10. Wolf 1982 [This document is identical to previous paper. It was inadvertently added to

CD]

11. Yu C.C and Atallah Y.H. (1977): Photoysis of hexachlorocyclopentadiene, Chicago, Velsicol 

Chemical Corporation Project No. 482428, Report No. 4 Laboratory Report. [Cited in footnote 10 of 

Velsicol's Jan. 17, 2011 Comments.]

Response: Thank you for your comment.
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EPA Comment Code: 1010 General Comments Agreeing with EPA

Individual Comments

Commenter Name: Thomas Curtis

Commenter Organization: American Water Works Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0028

Comment Part: 1

EPA Comment Code: 1010

Comment: Attached please find comments submitted on behalf of the American Water Works 

Association.

January 18, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, DC 20460

RE: Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening (Docket

ID No. EPA–HQ–OPPT–2009–0477)

Dear Sir or Madam:

The American Water Works Association (AWWA) is an international, nonprofit, scientific and 

educational society dedicated to the improvement of drinking water quality and supply. Founded in 

1881, the Association is the largest organization of water supply professionals in the world. Our 56,000-

plus members represent the full spectrum of the drinking water community: treatment plant operators 

and managers, environmental advocates, engineers, scientists, academicians, and others who hold a 

genuine interest in water supply and public health. Our membership includes more than 4,100 water 

systems that supply roughly 80 percent of the nation's drinking water. AWWA and its member utilities 

are dedicated to safe water. Regulations to ensure safe water must be developed through a transparent 

process, be based on good science, and provide meaningful risk reduction in an affordable manner.

AWWA appreciates the opportunity to comment on the November 17, 2010 Federal Register notice 

requesting comment on the proposed “Endocrine Disruptor Screening Program; Second List of 

Chemicals for Tier 1 Screening.” AWWA supports the Administrator’s strategy to leverage existing 

regulatory mechanisms to help ensure the safety and protection of our nation’s source waters and 

supports EPA’s effort to better understand the potential health implications from endocrine disrupting 

compounds (EDCs). The second screening list, as proposed [75 FR 70248], is an appropriate starting 

point since it is derived from current Safe Drinking Water Act (SDWA) regulated chemicals and the 

third Contaminant Candidate List (CCL3). We encourage the Agency to provide more detailed 

information on how the data obtained by test orders on these chemicals would be utilized in the 

regulatory development process, as that is not made clear in the notice. For example, it may be most 

appropriate to focus on those substances for which there is a shortage of information.
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Response: Please see general responses to comment under EPA Comment Codes: 1070 Increase 

Transparency and 1040 Complete List 1- Evaluate Tier 1 Screening Results before Proceeding with 

EDSP List 2.

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 1

EPA Comment Code: 1010

Comment: Please find attached NRDC’s comments on EPA’s EDSP Second List of Chemicals for Tier 

1 Screening.

Sarah Janssen, MD, PhD, MPH

Senior Scientist

Natural Resources Defense Council

111 Sutter St., 20th floor

San Francisco, CA 94104-4540

January 18, 2011 

Office of Pollution Prevention and Toxics (OPPT), EPA 

Submitted on-line through www.regulations.gov 

Re: Comments on “Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 

Screening”. Docket identification (ID): EPA–HQ–OPPT–2009-0477 

On behalf of the Natural Resources Defense Council (NRDC), we submit the following comments in 

general support of EPA’s proposed list of 134 chemicals for Tier 1 screening of endocrine disrupting 

potential under the authority of the Federal Food, Drug and Cosmetic Act (FFDCA), Safe Drinking 

Water Act (SDWA), and at the request of the House Appropriations Committee report for FY 2010 EPA 

appropriations. 

NRDC uses law, science, and the support of more than 1.2 million members nationwide to protect the 

planet's wildlife and wild places and to ensure a safe and healthy environment for all living things. 

NRDC has no direct or indirect financial or fiduciary interest in the manufacture or sale of any 

pesticides, pharmaceutical, industrial or HPV/Inert chemicals that may be selected for this second round 

of endocrine disruptor screening. More information is available at the NRDC website www.nrdc.org. 

General Comments on the EDSP and the second list of chemicals for Tier 1 Screening: 

The proposed list of 134 chemicals for screening of endocrine disrupting effects is based on priority 

chemicals identified through EPA’s drinking water and pesticide programs. Many of the chemicals in 

EPA’s proposed second list have already undergone a rigorous review within the Agency for exposure 

potential in vulnerable populations such as infants, children, pregnant women, the elderly, and 

individuals with pre-existing illness. However, though much of the population is likely to be exposed to 

these chemicals, there is incomplete toxicity data available for the majority of them. For many of the 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 24

chemicals on this list, very little toxicity data exists at all. The Endocrine Disruptor Screening Program 

(EDSP) will contribute important information about the endocrine disrupting potential of chemicals 

which have never been tested for sensitive endpoints in estrogen, androgen and thyroid hormone 

disruption. Interference with the normal actions of these chemicals could result in reproductive or 

neurodevelopment harm. 

The EDSP Tier 1 screens provide scientifically valid and distinct information from the information 

gained in whole-animal reproductive toxicity testing that is currently undertaken for pesticide chemicals.

Response: Thank you for your comment.

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 4

EPA Comment Code: 1010

Comment: EPA’s second list of chemicals includes 106 chemicals that are either currently regulated as 

drinking water contaminants or have been identified as priority contaminants for the drinking water 

program. The endocrine disrupting potential for the majority of these chemicals is unknown and is 

necessary information for understanding the impacts of these chemicals on wildlife living near polluted 

waters and for humans who rely on this water as a source of drinking water.

Response: Thank you for your comment.
EPA-OGWDW Final EDSP List 2 February 2013

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EPA Comment Code: 1020 Continue Use of Qualifying Language

General Response: EPA made every effort to state the purpose of the EDSP and Tier 1 and Tier 2 data 

in a clear, concise, and unambiguous manner in the Federal Register notice announcing the Final 

Second List of Chemicals and Substances for Tier 1 Screening Under the Endocrine Disruptor Screening 

Program. As stated in the Federal Register notice, the public should not presume that the listing of a 

chemical or substance indicates in any way that EPA currently suspects that such chemical or substance 

interferes with the endocrine systems of humans or other species simply because it has been listed for 

screening under the EDSP (75 FR 70248). EPA plans on maintaining this communication in future 

EDSP documents. Also, EPA conveys the various ways endocrine effects can occur on the EPA web 

site, at http://www.epa.gov/endo/pubs/edspoverview/whatare.htm.

Please see Response to Comments on the Public Review Draft of the Information Collection Request

(ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of Certain Chemicals 

Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is being published 

simultaneously with this comment response document. 

Individual Comments

Commenter Name: John Jachetta

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0014

Comment Part: 5

EPA Comment Code: 1020

Comment: Thank you for the opportunity to provide these comments. Further, DAS appreciates that the 

Agency continues to stress that chemicals subject to EDSP listing (either under List 1 or List 2) are not 

known to be endocrine disrupting chemicals and we encourage the Agency to continue to highlight this 

information.

Sincerely, 

John J. Jachetta, Ph.D.

Regulatory Sciences and Government Affairs Leader

Dow AgroSciences LLC

Phone: (317) 337-4686

Fax: (317) 337-4649

E-mail: jjjachetta@dow.com

References cited

1. http://www.epa.gov/enviro/html/sdwis/index.html

2. Summary pivot tables were accessed at:

http://water.epa.gov/scitech/datait/databases/drink/pivottables.cfm

3. USEPA (1995) Registration Eligibility Decision (RED) Picloram. USEPA Office of Prevention, 

Pesticides and Toxic Substances EPA 738-R95-019
EPA-OGWDW Final EDSP List 2 February 2013

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4. The online portal for the NAWQA program is at: http://water.usgs.gov/nawqa

5. Havens, PL.; Larsen, PL, Pottinger, MH, Lindsay, DA, and Schelle, GE (2003). State Groundwater 

Surveillance Monitoring Program for Picloram Herbicide, Final Report. Unpublished Report of Dow 

AgroSciences 980054.01I; USEPA MRID:

6. Barna-Lloyd, T., Swaim, L.D., Hinze, C.A., McDermott, M.C., Grandjean, M., Marek, J.W., and 

Jersey, G.C. (1982). Results of a One-Month Dietary Toxicity Study of (4-Amino-3,5,6-

Trichloropicolinic Acid) Administered in the Diet to Male and Female Beagle Dogs. Dow 

AgroSciences, LLC. Unpublished Report No. K-038323-27. April 30, 1982.

7. Gorzinski, S.J., Johnson, K.A., Campbell, R.A., and Park, C.N. (1982). Technical Grade Picloram: 

Results of a 13-Week Dietary Toxicity Study in Fischer 344 Rats. Dow AgroSciences, LLC. 

Unpublished Report No. K-038323-32. June 30, 1982.

8. Barna-Lloyd, T., Taylor, H.W., Swaim, L.D., Hinze, C.A., McDermott, M.C., Duke, R.L., and 

Grandjean, M. (1982). Results of a Six-Month Dietary Toxicity Study of Picloram (4-Amino-3,5,6-

Trichloropicolinic Acid) Administered in the Diet to Male and Female Beagle Dogs. Dow 

AgroSciences, LLC. Unpublished Report No. K-038323-28. June 9, 1982.

9. Tollett, J.T., Burek, J.D., Wade, C.E., Morden, D.C., Schuetz, D.J., Dittenber, D.A., Kalnins, R.V., 

Hermann, E.A. and Gorzinski, S.J. (1980). Picloram: Results of a 13-Week Toxicity Study in B6C3Fl 

Mice. Dow AgroSciences, LLC. Unpublished Report No. K-038323-14. July 30,1980.

10. Landry, T.D., Johnson, K.A., Cieszlak, F.S., Wolfe, E.L., and Kropscott, B.W. (1986). Picloram: A 

Two-Year Dietary Chronic Toxicity-Oncogenicity Study in Fischer 344 Rats. Dow AgroSciences, LLC. 

Unpublished Report No. K-38323-34. January, 1986..

11. Cosse, P.F., Stebbins, K.E., Sames, K.V., Stewart, H.S., Shabraing, S.N., and Corley, R.A. (1992). 

Picloram: Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats. Dow 

AgroSciences, LLC. Unpublished Report No. K038323-056. December 22, 1992.

12. Stott, W.T., Yano, B.L., Haut, K.T., and Shabrang, S.N. (1992). Picloram: Two-Year Dietary 

Oncogenicity Study in B6C3F1 Mice. Dow AgroSciences, LLC. Unpublished Report No. K-038323-

058. December, 24, 1992..

13. Schroeder, R.E. (1990). A Teratogenicity Study in Rats with Picloram K Salt. Dow AgroSciences 

LLC. Unpublished Report K050731-009. January 23, 1990.

14. Schroeder, E. (1990). A Teratogenicity Study in Rats with Picloram Triisopropanolamine. Dow

AgroSciences, LLC. Unpublished report K-049877-012, dated January 19, 1990

15. John, J.A., Ouellette, J.H., and Johnson, K.A. (1984). Picloram Potassium Salt: Oral Teratology 

Study in Rabbits. Dow AgroSciences, LLC. Unpublished Report No. K-050731-003. January 17, 1984.

16. Vedula, U, Stebbins, K.E. and Breslin, W.J. (1992). Picloram Triisopropanolamine Salt: Oral 

Gavage Teratology Study in New Zealand White Rabbits Dow AgroSciences, LLC. Unpublished report 

K-049877-015, dated August 11, 1992

17. Breslin, W.J., Zielke, G.J., and Kociba, R.J. (1991). Picloram: Two-Generation Dietary 

Reproduction Study in Sprague-Dawley Rats. Dow AgroSciences, LLC. Unpublished Report No. 

038323-057. October 2, 1991.

18. Mach, J.J. (2002): Avian Reproduction Study with Picloram Acid in Northern Bobwhite (Colinus 

virginianus). Genesis Laboratories, Inc., Colorado, USA. The Dow Chemical Company for Dow 

AgroSciences, unpublished report No. 011172, 01014, June 2002

19. Mayes, M.A., Dill, D.C. and Hopkins, D.L. (1983). The Toxicity of Technical Picloram to the 

Embryo, Larval, and Juvenile Stages of the Rainbow Trout (Salmo Gairdneri Richardson). Mammalian 

and Environmental Toxicology, Michigan, USA Dow AgroSciences, unpublished report number ESDR-0 114-1351-8, ES-703; MRID 00151784.

20. Weinberg, J.T., Hugo, J.M., Landre, A.M., Martin, M.D., Milazzo, D.P. (1996). Evaluation of the 

Toxicity of Picloram Triisopropanolamine (TIPA) Salt to the Early Life-Stages of the Fathead Minnow, 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 27

Pimephales promelas Rafinesque. The Environmental Toxicology Research Laboratory, Michigan, 

USA. Dow AgroSciences, unpublished report number DECO-ES-3037.

21. Boeri, R.L., D.C. Wyskiel and T.J. Ward. (2002). Picloram Acid: Life Cycle Study in the Daphnid, 

Daphnia magna. T.R. Wilbury Laboratories, Inc., Massachusetts, USA. Dow AgroSciences, unpublished 

report number 021029.

22. Gersich, FM, Hopkins, DL, Milazzo, DP (1984) The Acute And Chronic Toxicity Of Technical 

Picloram (4-Amino-3,5,6-Trichloropicolinic Acid) To Daphnia Magna Straus. The Environmental 

Toxicology Research Laboratory, Michigan, USA. Dow AgroSciences, unpublished report number ES690, MRID 00151783.

23. Putt, A.E. (2002) Picloram Acid - Full Life-Cycle Toxicity to Midge (Chironomus riparius) under 

Static Conditions. Springborn Laboratories, Inc., Massachusetts, USA. Dow AgroSciences unpublished 

report No. 011183, 12550.6157. 

24. Mallett, M.J. (2001): The Effects of Picloram on Reproduction and Growth in the Earthworm 

Eisenia foetida. CEM Analytical Services Ltd., Berkshire, UK. Dow AgroSciences unpublished report 

No. CEMS 1639 Dow AgroSciences Study no. GHE T-1148.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 1

EPA Comment Code: 1020

Comment: Comments to DOCKET ID NUMBER EPA-HQ-OPPT-2009-0477 ENDOCRINE 

DISRUPTOR SCREENING PROGRAM (EDSP)

January 13, 2011

Document Control Office

Office of Pollution Prevention and Toxics (7407M)

U. S. Environmental Protection Agency

One Potomac Yard

2777 S. Crystal Drive

Arlington, VA 22202

DOCKET ID NUMBER EPA-HQ-OPPT-2009-0477

ENDOCRINE DISRUPTOR SCREENING PROGRAM (EDSP)

Dow AgroSciences (DAS) appreciates the opportunity to submit comments on EPA’s Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the “Draft EDSP List 2”). 

Pursuant to EPA’s request for comments on the Draft EDSP List 2, Federal Register Vol. 75, No. 221, 

November 11, 2010, pp 70248-70254 (the “Listing Notice”), DAS provides the following comments 

related to the inclusion of herbicide active ingredient flumetsulam on the Draft EDSP List 2.

The priority selection process for Tier 1 test orders is currently based upon pesticide registration status 

or population exposure potential via drinking water. Including pesticides on List 2 erroneously suggests 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 28

to the public that the active ingredients are of concern in drinking water. Despite EPA’s best efforts to

accurately describe the criteria for inclusion, the perception is that the list is an endocrine disruptor list 

and misinterpretation does occur. DAS encourages the Agency to continue to stress the qualifying 

language that highlights that chemicals and substances subject to listing (either under List 1 or List 2) 

are not endocrine disrupting chemicals.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 6

EPA Comment Code: 1020

Comment: Thank you for the opportunity to provide these comments. DAS appreciates that the Agency 

continues to stress that chemicals subject to EDSP listing (either under List 1 or List 2) are not known to 

be endocrine disrupting chemicals, and we encourage the Agency to continue to highlight this 

information.

Sincerely,

Nneka T. Breaux, Ph.D.

Regulatory Leader, Regulatory Affairs

317-337-3248

317-337-4649 (FAX)

nbreaux@dow.com

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0026

Comment Part: 4

EPA Comment Code: 1020

Comment: Thank you for the opportunity to provide these comments. Further, DAS appreciates that the 

Agency continues to stress that chemicals subject to EDSP listing (either under List 1 or List 2) are not 

known to be endocrine disrupting chemicals, and we encourage the Agency to continue to highlight this 

information.

Sincerely,

Nneka T. Breaux, Ph.D.

Regulatory Sciences and Government Affairs Leader

Dow AgroSciences LLC

Phone: (317) 337-3248
EPA-OGWDW Final EDSP List 2 February 2013

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Page 29

Fax: (317) 337-4649

E-mail: ntbreaux@dow.com

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 6

EPA Comment Code: 1020

Comment: II. EPA Should Continue to Ensure Accurate, Complete and Consistent Communications 

Concerning the EDSP to the Public and Across the Agency

ACC believes EPA has done an excellent job thus far in communicating the meaning of its draft 

candidate list in the Listing Notice. ACC agrees with the Agency’s clear caution in its notice that “based 

on current information, the public should not presume that the listing of a chemical or substance 

indicates in any way that EPA currently suspects that such chemical or substance interferes with the 

endocrine systems of humans or other species simply because it has been listed for screening under the 

EDSP. At the present time, EPA believes that these chemicals or substances should be candidates, at 

least for screening purposes, under EDSP testing based only on their pesticide registration status and/or 

because such substances may occur in sources of drinking water to which a substantial population may 

be exposed.”[FN4: EPA (2010). Endocrine Disruptor Screening Program; Second List of Chemicals for 

Tier 1 Screening. Federal Register Volume 75, Number 221 (Wednesday, November 17, 2010), Pages 

70248-70254.]

The Agency must continue to communicate accurate and complete information about the substances on 

the list, however, even after the list is finalized. For example, when it issues the final EDSP List 2, EPA 

should also clarify that from a human health risk assessment perspective, the current lack of endocrine 

mechanistic information for any particular substance does not mean that the substance poses significant 

risks, even at environmentally relevant levels of exposure.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: James Lamb

Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0030

Comment Part: 5

EPA Comment Code: 1060

Comment: Further, we encourage the Agency’s continued use of qualifying language that highlights 

chemicals subject to listing (either under List 1 or List 2) are not endocrine disrupting chemicals. As the 

Agency is well aware, the purpose of Tier I testing is screening. The screening selection process is based 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 30

on potential exposure and not suspected endocrine activity. In all the formal communication from EPA 

on List 1, this was a point of emphasis; we urge EPA to continue this approach. 

Sincerely, 

James C. Lamb, IV, Ph.D., DABT, Fellow ATS 

Principal Scientist and Center Director 

Center for Toxicology and Mechanistic Biology

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 1

EPA Comment Code: 1020

Comment: Please see the attached submission from Intertox, Inc. on behalf of the Perchlorate Study 

Group in response to EPA-HQ-OPPT-2009-0447.

RESPONSE TO US ENVIRONMENTAL PROTECTION AGENCY’S ENDOCRINE DISRUPTOR

SCREENING PROGRAM SECOND TIER 1 SCREENING LIST

[EPA–HQ–OPPT–2009–0477; FRL–8848–7]

Prepared for

PERCHLORATE STUDY GROUP

January 18, 2011

Prepared by

INTERTOX, INC.

600 Stewart Street, Suite 1101

Seattle, WA 98101

206.443.2115 phone

206.443.2117 facsimile

Table of Contents

1.0 EXECUTIVE 

SUMMARY......................................................................................................................1

2.0 INTRODUCTION 

..................................................................................................................................2

3.0 GENERAL 

COMMENTS.......................................................................................................................3

4.0 PERCHLORATE IS NOT AN AGONIST OR ANTAGONIST TO ANTERIOR PITUITARY OR
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Page 31

THYROID 

HORMONES..............................................................................................................................3

4.1 A brief historical context to Endocrine Disrupting Chemicals .............................................................. 

4

4.2 Perchlorate is not consistent with the type of chemical US EPA has historically

examined....................................................................................................................................................... 

4

4.3 Perchlorate’s mechanism of action ........................................................................................................ 

4

5.0 PERCHLORATE EXCLUSION FROM THE ENDOCRINE DISRUPTOR SCREENING 

PROGRAM LIST

........................................................................................................................................................................

7

6.0 CHEMICALS SIMILAR TO PERCHLORATE WERE EXCLUDED FROM 

ANALYSIS....................................................................................................................................................

9

7.0 

CONCLUSIONS....................................................................................................................................10

8.0 REFERENCES 

......................................................................................................................................11

1.0 EXECUTIVE SUMMARY

The Food Quality Protection Act (FQPA) and Safe Drinking Water Act (SDWA) Amendments were 

both enacted in 1996 and direct US EPA to screen for chemicals with endocrine disruption potential. To 

facilitate this, the Endocrine Disruptor Screening Program (EDSP) has been congressionally mandated 

“to determine whether certain substances may have an effect in humans that is similar to an effect 

produced by a naturally occurring estrogen, or such other endocrine effect as [US EPA] may designate.” 

On November 17, 2010, US EPA released its tentative second list of chemicals for Tier 1 testing under 

EDSP [US EPA, 2010a; EPA–HQ–OPPT–2009–0477; FRL–8848–7]. Perchlorate was included on the 

November 17th list for Tier 1 Testing due to its inclusion on the Candidate Contaminant List 3 (CCL 3). 

Despite the goal of the EDSP, if a chemical is listed, US EPA states that

...the public should not presume that the listing of a chemical or substance indicates in any way that 

EPA currently suspects that such chemical or substance interferes with the endocrine systems of humans 

or other species simply because it has been listed for screening under the EDSP.

The Agency states that it has developed criteria for streamlining its November 17th EDSP list and has 

requested information that “...will inform the exclusion of a chemical from this list.”

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language, general response to comment under EPA Code: 1050 Evaluation Criteria and the 

individual response to EPA Document ID: EPA-HQ-OPPT-2009-0477-0039, Comment Part: 3 of that 

section. Also, please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.
EPA-OGWDW Final EDSP List 2 February 2013

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Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 4

EPA Comment Code: 1020

Comment: Inclusion on the November 17th list is, however, not based on potential for endocrine 

disruption. US EPA states in the Notice that:

...the public should not presume that the listing of a chemical or substance indicates in any way that 

EPA currently suspects that such chemical or substance interferes with the endocrine systems of humans 

or other species simply because it has been listed for screening under the EDSP. At the present time, 

EPA believes that these chemicals or substances should be candidates, at least for screening purposes, 

under EDSP testing based only on their pesticide registration status and/or because such substances may 

occur in sources of drinking water to which a substantial population may be exposed.

US EPA is interested in receiving information and comments that may influence the exclusion or 

inclusion of chemicals on the second EDSP list. In this document, we provide responses to the Agency’s 

request for information to remove the chemical perchlorate from the November 17th EDSP list. Given 

the guidelines provided by the Agency, we examine the scientific reasons for excluding perchlorate from 

further testing.

3.0 GENERAL COMMENTS

The public may confuse a chemical included on a list of chemicals for endocrine disruption screening 

with membership in the class. Even if listed for screening purposes, a chemical is likely to be perceived 

as an endocrine disruptor by the public. It will benefit the Agency to be particularly clear and consistent 

in its messaging. 

The scientific rationale for including or excluding a chemical on the November 17th list is not 

adequately transparent. The Agency does provide its criteria for streamlining its list from over 200 to 

134 chemicals. However, how the criteria were applied is not available in the docket. To illustrate this 

point, we demonstrate how perchlorate, which is listed in the November 17th list, meets the Agency’s 

criteria for exclusion. Further, we demonstrate that other regulated chemicals that were on the list of 

over 200 meet the same two criteria for exclusion as perchlorate and are absent from the November 17th 

list.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language, general response to comment under EPA Code: 1050 Evaluation Criteria and the 

individual response to EPA Document ID: EPA-HQ-OPPT-2009-0477-0039, Comment Part: 3 of that 

section. Also, please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 13

EPA Comment Code: 1020
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Comment: • Including a chemical on a list entitled “Second Endocrine Disruptor Screening Program 

List of Chemicals for Tier 1 Screening” is likely to be confusing to the public. Nothwithstanding the 

Agency’s statement that the listing does not imply endocrine effects, the inclusion of a chemical on this 

list creates an implication that the chemical is an endocrine disruptor.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 2

EPA Comment Code: 1020

Comment: * The ARP strongly encourages the Agency's continued use of appropriate qualifying 

language, emphasizing that chemicals subject to testing (either under List 1 or List 2) are not endocrine 

disrupting chemicals. Selection has been based primarily on exposure criteria and registration status. 

The screening selection process is not based on suspected endocrine activity. The Agency should also 

re-iterate that Tier 1 screening is only intended to detect the potential for endocrine disruption, and that 

Tier 2 testing (not yet even developed) will be required to determine whether a particular chemical 

actually behaves as an endocrine disruptor in the environment.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 11

EPA Comment Code: 1020

Comment: The Agency should continue to emphasize this is not a list of Endocrine Disruptors:

The ARP strongly encourages the Agency's continued use of appropriate qualifying language, 

emphasizing that chemicals subject to testing (either under List 1 or List 2) are not endocrine disrupting 

chemicals. Rather, the chemical selection process was based on potential exposure and not suspected 

endocrine activity. Specifically, during selection for the second list of chemicals for Tier 1 screening, the 

Agency focused on a subset of chemicals and substances that have been identified within the Agency's 

drinking water and pesticides programs. The EPA primarily identified candidate chemicals that are 

either contaminants regulated with a national primary drinking water regulation (NPDWR), are 

unregulated contaminants on the third Contaminant Candidate List (CCL 3), or are identified candidate 

chemicals from the Office of Pesticide Programs (OPP) based on pesticides that were scheduled for 

Registration Review during 2007 and 2008. Therefore, as stated by the EPA in the Federal Register 

notice for the second list of chemicals for Tier 1 screening, "the public should not presume the listing of 

a chemical or substance indicates it interferes with the endocrine systems of humans or other species 

simply because it has been listed for screening under the EDSP." The Agency made a similar statement 
EPA-OGWDW Final EDSP List 2 February 2013

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in the publication of the first list for screening in the Federal Register Notice of April 2009. In 2009, the 

EPA clearly stated: "This list should not be construed as a list of known or likely endocrine disruptors. 

Nothing in the approach for generating the initial list provides a basis to infer that by simply being on 

the list these chemicals are suspected to interfere with the endocrine systems of human or other species, 

and it would be inappropriate to do so." The EPA is to be commended for communicating to the public 

that the first and second lists do not represent a list of endocrine disruptors.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: D. Douglas Fratz

Commenter Organization: Consumer Specialty Products Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0047

Comment Part: 1

EPA Comment Code: 1020

Comment: January 18, 2010

Steve A. Owens

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

US EPA Headquarters Ariel Rios Building

1200 Pennsylvania Ave., NW

Washington, D.C. 20460

RE: CSPA Comments on Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening (75 Federal Register 70248, November 17, 2010). Docket ID: EPA–HQ–OPPT–2009–0477

Dear Mr. Owens:

The Consumer Specialty Products Association[FN1: 1 The Consumer Specialty Products Association 

(CSPA) is a voluntary, non-profit national trade association representing more than 240 companies 

engaged in the manufacture, formulation, distribution, and sale of consumer specialty products for 

household, institutional, commercial and industrial use. CSPA member companies' wide range of 

products includes home, lawn and garden pesticides, antimicrobial products, air care products, industrial 

and automotive specialty products, detergents and cleaning products, polishes and floor maintenance 

products, and various types of aerosol products. These products are formulated and packaged in many 

forms and are generally marketed nationally. CSPA and its member companies are committed to the safe 

manufacture, distribution, use and disposal of consumer products, and have instituted a product 

stewardship program, Product Care®, to promote the production and distribution of safe and effective 

formulated products that provide desirable benefits for household, commercial, institutional and 

industrial customers and consumers, and their families, pets and their environment.] appreciates the 

opportunity to comment on the notice proposing a second list (List 2) of 134 chemicals for Tier 1 

screening in the Agency’s Endocrine Disruptor Screening Program (EDSP). CSPA has been involved 

throughout the process of EPA’s development of the EDSP, and this proposed list, like the initial list, 
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includes chemicals that are of concern to many CSPA members. For these reasons, CSPA welcomes this 

opportunity to comment.

CSPA has also been involved in assisting its member companies in responding to the EDSP test orders 

issued for chemicals on the initial list of chemicals (List 1), especially through our Product Ingredient 

Review (PIR) Program, which currently has four groups responding to test orders. Those PIR groups are 

The Piperonyl Butoxide Task Force II, the Permethrin Data Development Group II, the Bifenthrin Task 

Force, and the Acephate Task Force. In addition, CSPA and its PIR groups are members of, and 

participate in, the Endocrine Policy Forum (EPF). CSPA therefore also supports the comments being 

filed by the EPF.

In the following sections, CSPA will provide its comments on a few of the key issues raised in EPA’s 

notice proposing additional chemicals for EDSP.

I. EPA Should Continue to Make it Clear that EDSP Chemical Lists are Not Suspected Endocrine 

Disruptors.

CSPA comments the Agency on its clarification in this notice that this proposed second list is not a list 

of substances that EPA suspects to be endocrine disruptors, and we continue to urge EPA to make this 

clear at every opportunity. We also continue to support EPA using exposure considerations in 

prioritizing chemicals for the EDSP.

We also urge EPA to clearly communicate several other related science policy messages at every 

opportunity, and to do so consistently throughout the Agency. One is that endocrine disruption is a 

mechanism by which adverse toxic effects to public health and the environment could occur, not a toxic 

endpoint in and of itself.[FN2: ECEROC Report TR106, “Guidance on Identifying Endocrine Disrupting 

Effects,” Technical Report No. 106, June 2009] Another key message that should be clearly conveyed is 

that the results of Tier 1 screening tests will not demonstrate chemicals to be endocrine disruptors, but 

rather to determine whether further (Tier 2) testing is needed to determine whether toxic effects could 

occur through an endocrine interaction mechanism. In addition, it may be important for EPA to convey 

that endocrine effects can be caused by other stressors (including other toxic responses), and convey a 

clearer understanding that toxic effects can cause endocrine effects, as well as visa versa. This latter 

knowledge could be important to understanding the results of some of the EDSP screening tests.

CSPA has seen evidence of public misunderstanding of these important science policy issues, sometimes 

even within EPA or other regulatory agencies. It is essential that EPA provides a clear and consistent 

understanding of endocrine disruption issues and the purpose of the EDSP.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language and general response to comment under EPA Comment Code: 1070 Increase 

Transparency. In addition, please see Response to Comments on the Public Review Draft of the

Information Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 

Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 

2012d) that is being published simultaneously with this comment response document.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 3

EPA Comment Code: 1020

Comment: Finally, we appreciate and support the Agency's continued use of qualifying language to 

emphasize that chemicals listed for purposes of screening under the EDSP are not endocrine disrupting 

chemicals, and that the purpose of Tier 1 screening is only to assess a chemical’s potential to interact 

with the human endocrine system.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 2

EPA Comment Code: 1020

Comment: We encourage the Agency's continued use of qualifying language that highlights chemicals 

subject to listing (either under List 1 or List 2) are not endocrine disrupting chemicals. As the Agency is 

well aware, the purpose of Tier I is screening. The screening selection process is based on potential 

exposure and not suspected endocrine activity. In all the formal communication from EPA on List 1, this 

was a point of emphasis; we urge EPA to continue this approach. Adherence to this approach is of vital 

importance to those firms that have compounds on the first and second list of compounds.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 6

EPA Comment Code: 1020

Comment: List 2 is not a list of endocrine disrupting chemicals: 

We encourage the Agency's continued use of qualifying language that highlights chemicals subject to 

listing (either under List 1 or List 2) as not being endocrine disrupting chemicals. Specifically, we 

congratulate the Agency in clearly stating that the public should not presume the listing of a chemical or 

substance indicates it interferes with the endocrine systems of humans or other species simply because it 

has been listed. As the Agency further notes, selection of chemical candidates for screening under Tier I 

reflect only their pesticide registration status or population exposure potential. As the Agency is well 

aware, the purpose of Tier I is screening. The screening selection process for the proposed substances on 

List 2 is based on potential exposure (SDWA chemicals) or registration review status (most pesticide 

active ingredients) and not based on suspected endocrine activity. 

Description of EDSP Tier I and Tier II:
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EPA should clarify and be consistent as to the purpose of Tier I screening and what the results of Tier I 

screening mean and do not mean. As EPA [FN10: EPA, Endocrine Disruptor Screening Program; 

Proposed Statement of Policy. 63 Fed. Reg. 71545 December 28, 1998.] noted in 1998, the purpose of 

Tier I is to identify substances that have the potential to interact with the estrogen, androgen, or thyroid 

hormone systems and the purpose of Tier II is to identify and establish a dose-response relationship for 

any adverse effects that might result from the interactions identified through the Tier I assays. Only after 

completion of Tier II testing will EPA be able to determine whether a particular chemical may have an 

effect in humans that is similar to an effect produced by naturally occurring estrogen, androgen, or 

thyroid hormones.

Within the various documents associated with Phase 2 of the EDSP, EPA is not consistent in how Tier I 

and Tier II are described. EPA clearly describes the purpose and structure of the EDSP with the Draft 

Phase 2 Policies and Procedures. The Draft Phase 2 Policies and Procedures states the EPA intends to 

use the data collected under the EDSP, along with other information to determine if a pesticide 

chemical, or other substances, may pose a risk to human health or the environment due to disruption of 

the endocrine system.

In the Draft Phase 2 Policies and Procedures, EPA describes the EDSP as a two-tiered testing program. 

"The purpose of Tier I screening is to determine whether a substance has the potential to interact with 

the estrogen, androgen or thyroid (EAT) systems." Substances that have the potential to interact with 

EAT systems will proceed on to Tier II, which is designed to "identify any adverse endocrine-related 

effects caused by the substance, and establish a quantitative relationship between the dose and that 

endocrine effect." EPA's description of the EDSP in the Draft Phase 2 Policies and Procedures is clear 

and accurate, and should be consistently used by all EPA offices and programs

Within the FR Notice for Draft List 2, EPA describes Tier I as "assays used to screen the chemicals for 

interaction with the [EAT] hormonal system." And for Tier II, EPA simply states "Tier II test assays are 

intended to test for more specific chemical effects on the endocrine system". This description of Tier II 

does not mention adverse effects or dose response. Within the second list of chemicals FR Notice, the 

difference between Tier I and Tier II is described as merely the specificity of the chemical effects 

detected in each tier. A naive reader might incorrectly conclude Tier I determines adverse effects. EPA 

should have simply repeated the description of the EDSP it used for the Draft Phase 2 Policies and 

Procedures when describing the EDSP. CLA/EPF is concerned that if EPA can be inconsistent in 

describing the EDSP in three related EDSP documents issued at the same time, it is unlikely EPA is 

consistently and accurately describing the EDSP across EPA offices and programs. CLAIEPF suggests 

that the specific language in the Draft Phase 2 Policies and Procedures document be used within all 

Phase 2 EDSP documents. 

Why does the exact description of the EDSP matter so much? The wording defining Tier I and Tier II 

within EPA documents must be consistent with Agency authority. As mandated by the Paperwork 

Reduction Act, EPA may not use the EDSP as a research program designed to gather information that 

has no practical use or utility. Rather, the purpose of the EDSP should be to collect data concerning 

endocrine risks posed by chemical substances. That data must be useful for managing risks to human 

health. In sum, the purpose of the EDSP should be to determine adverse effects and risk, not simply to 

determine whether substances may interact with the endocrine system, which does not determine risk or 

adverse effects. It is also important that EPA clearly describes the EDSP as a two-tiered program. 

Indeed, the purpose of the EDSP is not to merely determine whether a substance may interact with the 

endocrine system. Rather, the purpose is to determine whether substances cause adverse effects through 
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an endocrine mechanism. This understanding should underpin all Agency communications concerning 

the EDSP. It is critically important that EPA describe the purpose of EDSP as generating data that will 

determine adverse effects and risks. 

Defining endocrine disruptors to include adverse impacts on whole organisms:

We encourage the EPA to harmonize with the World Health Organization's definition of an endocrine 

disruptor: "An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the 

endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, 

or (sub)populations." Broader definitions only serve to unnecessarily alarm the public and perpetuate the 

waste of animals and resources extensively evaluating compounds that do not pose any real risk. The 

WHO definition is consistent with the scientific community's recognition that while substances may 

interact with the endocrine system, they may not adversely affect health or the ecosystem. Within the 

WHO definition, endocrine disruption is not considered a toxicological end point per se but a functional 

change that may lead to adverse effects. An adoption of an unnecessarily broad definition that suggests 

that any molecular or cellular response observed in animal or in vitro experiments is endocrine 

disruption provides no use or clarity. 

The endocrine system is complex and seeks to maintain homeostasis in a continually variable and 

fluctuating natural environment. Evidence that a substance interacts with a component of the endocrine 

system does not provide any information on whether that substance causes other biological changes, 

which may, in turn, cause adverse health effects. Within endocrine systems, natural variations in 

hormone levels and reversible or transient changes that are not considered adverse have been well 

documented. Endocrine interactions also must be looked at in the context of dose and timing of 

exposures. Importantly, studies must determine whether endocrine interactions are within the normal 

range of biological fluctuations or whether they are of such a magnitude as to overcome natural defense 

mechanisms and exert adverse effects. The interaction of a chemical with a component of the endocrine 

system may be insufficient to result in adverse health effects at environmentally relevant levels of 

exposure. Endocrine disruption should be defined more carefully as interactions with the endocrine 

system that result in adverse effects.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language. Also, please see Response to Comments on the Public Review Draft of the 

Information Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 

Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 

2012d) and the Response-to-Comments for the Endocrine Disruptor Screening Program’s Draft Policies 

and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c). Both of these 

documents are being published simultaneously with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 2

EPA Comment Code: 1020

Comment: * Monsanto strongly encourages the Agency’s continued use of appropriate qualifying 

language, emphasizing that chemicals subject to testing (either under List 1 or List 2) are not endocrine 

disrupting chemicals. Selection has been based primarily on exposure criteria and registration status. 
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The screening selection process is not based on suspected endocrine activity. The Agency should also 

re-iterate that Tier 1 screening is only intended to detect the potential for endocrine disruption, and that 

Tier 2 testing (not yet even developed) will be required to determine whether a particular chemical 

actually behaves as an endocrine disruptor in the environment.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 11

EPA Comment Code: 1020

Comment: The Agency should continue to emphasize this is not a list of Endocrine Disruptors: 

Monsanto strongly encourages the Agency’s continued use of appropriate qualifying language, 

emphasizing that chemicals subject to testing (either under List 1 or List 2) are not endocrine disrupting 

chemicals. Rather, the chemical selection process was based on potential exposure and not suspected 

endocrine activity. Specifically, during selection for the second list of chemicals for Tier 1 screening, the 

Agency focused on a subset of chemicals and substances that have been identified within the Agency’s 

drinking water and pesticides programs. The EPA primarily identified candidate chemicals that are 

either contaminants regulated with a national primary drinking water regulation (NPDWR), are 

unregulated contaminants on the third Contaminant Candidate List (CCL 3), or are identified candidate 

chemicals from the Office of Pesticide Programs (OPP) based on pesticides that were scheduled for 

Registration Review during 2007 and 2008. Therefore, as stated by the EPA in the Federal Register 

notice for the second list of chemicals for Tier 1 screening, “the public should not presume the listing of 

a chemical or substance indicates it interferes with the endocrine systems of humans or other species 

simply because it has been listed for screening under the EDSP.” The Agency made a similar statement 

in the publication of the first list for screening in the Federal Register Notice of April 2009. In 2009, the 

EPA clearly stated: “This list should not be construed as a list of known or likely endocrine disruptors. 

Nothing in the approach for generating the initial list provides a basis to infer that by simply being on 

the list these chemicals are suspected to interfere with the endocrine systems of human or other species, 

and it would be inappropriate to do so.” The EPA is to be commended for communicating to the public 

that the first and second lists do not represent a list of endocrine disruptors.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Niamh McMahon

Commenter Organization: Dow AgroSciences LLC (DAS)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0054

Comment Part: 2

EPA Comment Code: 1020
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Comment: DAS appreciates the opportunity to comment and continues to encourage the Agency to 

stress the qualifying language that highlights that chemicals subject to listing (either under List 1 or List 

2) should not be considered endocrine disrupting chemicals.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 1

EPA Comment Code: 1020

Comment: January 14, 2011

Steve A. Owens,

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

US EPA Headquarters Ariel Rios Building

1200 Pennsylvania Ave., NW

Mail Code: 7101M

Washington, D.C. 20460

RE: Bayer CropScience LP Comments on Second List of Chemicals for Tier 1 Screening. Docket ID: 

EPA–HQ–OPPT–2009–0477

Dear Mr. Owens:

Bayer CropScience LP would like to comment on the draft List 2 documents posted in the Federal 

Register (FR) Vol. 75, No. 221 on Wednesday, November 17, 2010. In the FR Notice, EPA announced 

the second list of chemicals and substances for which EPA intends to issue test orders under the 

Endocrine Disrupter Screening Program (EDSP). This second list of chemicals adds priority drinking 

water chemicals into the program for screening as authorized by SDWA section 1457 but also includes 

additional pesticides. In response to the Agency’s request for public comment on the second list of 

chemicals for Tier 1 screening under EDSP, we are hereby submitting our formal comments (Docket ID: 

EPA–HQ–OPPT–2009–0477).

List 2 is not a list of endocrine disrupting chemicals:

We encourage the Agency’s continued use of qualifying language that highlights chemicals subject to 

listing (either under List 1 or List 2) are not endocrine disrupting chemicals. As the Agency is well 

aware, the purpose of Tier 1 testing is screening. The screening selection process is based on potential 

exposure and not suspected endocrine activity.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.
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Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 3

EPA Comment Code: 1020

Comment: List 2 is not a list of endocrine disrupting chemicals:

We encourage the Agency's continued use of qualifying language that highlights chemicals subject to 

listing (either under List 1 or List 2) are not endocrine disrupting chemicals. Specifically, we 

congratulate the Agency in clearly stating that the public should not presume the listing of a chemical or 

substance indicates it interferes with the endocrine systems of humans or other species simply because it 

has been listed. As the Agency further notes, selection of chemical candidates for screening under Tier I 

reflects only their pesticide registration status or population exposure potential. As the Agency is well 

aware, the purpose of Tier 1 testing is screening. The screening selection process is based on potential 

exposure and not suspected endocrine activity.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.
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EPA Comment Code: 1030 General Comments Disagreeing with EPA

Individual Comments

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 2

EPA Comment Code: 1030

Comment: Furthermore, there is very little required toxicity information for non-pesticide chemicals 

such as those found in drinking water sources or otherwise known to have a high likelihood of exposure 

in the human population. The EDSP Tier 1 screens have undergone a rigorous and painstakingly slow 

validation process that in some cases has taken over 10 years to complete. As a result, the screens 

currently being used by the Agency have undergone a more thorough validation than any other test in 

use at the Agency. Therefore, we encourage the Agency to proceed expeditiously to finalize this second 

list of chemicals to undergo screening and proceed with implementation by issuing test orders so that 

important information about these chemicals can begin to be gathered. 

Although publication of this list is a step forward, NRDC is disappointed with the continued slow pace 

of implementation of the EDSP and EPA’s failure to meet agreed upon deadlines. EPA’s failure to 

adhere to the original timelines mandated by Congress in the FQPA and SDWA (See 21 U.S.C. § 

346a(p)(2) and 42 U.S.C. § 300j-17) was the subject of prior litigation between NRDC and EPA. In 

2001, EPA agreed in a settlement agreement with NRDC to establish new deadlines for implementing 

the EDSP, including commencement of screening of chemicals in Tier 1 by the end of 2003 and to begin 

testing in the Tier 2 tests by the end of 2004. However, EPA just began issuing test orders for the first 67 

chemicals in 2009 and did not finish issuing the first set of test orders until 2010, seven years after the 

court-mandated timeline. Furthermore, there is a 2 year deadline for submission of results, meaning the 

data for the first group of chemicals will not be compiled until well into 2012. And to date, the Tier 2 

tests are still not fully validated and there is no established timeline for when chemicals that are found to 

be positive in the Tier 1 screens will be required to undergo Tier 2 testing. At this rate, it will be at least 

another 5-7 years, and likely much longer, before a chemical can be determined to be an “endocrine 

disruptor” under the EDSP. This is too long to wait for information which can and should be gathered on 

a much quicker timeline.

Response: Please see the Response-to-Comments for the Endocrine Disruptor Screening Program’s 

Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that 

is being published simultaneously with this comment response document.

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 7

EPA Comment Code: 1030
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Comment: 4. The Agency should expeditiously finalize this second list of chemicals for screening and 

begin testing by immediately issuing test orders. 

The Agency is already over a decade behind in getting this program off the ground and results of the test 

orders are not expected to be finalized for many more years. The sooner that EPA finalizes this list of 

drinking water contaminants and pesticides for testing, the less time we will have to wait for information 

that is vitally important for public health. 

Thank you for the opportunity to comment and for your careful consideration of these comments. 

Sincerely, 

Sarah Janssen, MD, PhD, MPH 

Senior Scientist 

Natural Resources Defense Council

Response: Thank you for your comment.
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EPA Comment Code: 1035 Animal Testing

General Response: The tests for chemicals on the second EDSP list for Tier 1 screening are consistent 

with ensuring effective and efficient use of societal and government resources in generating and 

reviewing data, as well as minimizing the use of animals in regulatory testing, to achieve the information 

base needed to support a specified objective. EPA acknowledges that for some of the chemicals listed on 

the second EDSP list there may be existing data relevant to the Tier 1 screening test. Order recipients 

will have an opportunity to submit any relevant data to the Tier 1 assays or Other Scientifically Relevant 

Information (OSRI) as part of their initial response to receiving an order. For specific information on 

submitting or citing existing data or OSRI, please see the existing EDSP policies and procedures that 

were published in the Federal Register, 74 FR 17560, April 15, 2009 (USEPA, 2009b) and the 

Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening Safe Drinking 

Water Act Chemicals, 75 FR 70558, November 17, 2010 (USEPA, 2010a). Please also see Endocrine 

Disruptor Screening Program; Final Policies and Procedures for Screening Safe Drinking Water Act 

Chemicals (USEPA, 2012a) that is being published simultaneously with this comment response 

document.

Individual Comments

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals

EPA Document ID: EPA-HQ-OPPT-2009-0477-0008

Comment Part: 2

EPA Comment Code: 1035

Comment: This list of 134 chemicals includes a large number of pesticides, two perfluorocarbon 

compounds (PFCs), and three pharmaceuticals (erythromycin, nitroglycerin, and quinoline). This list 

also contains an assortment of other chemicals used in the production of pharmaceutical and personal 

care products. It is unconscionable to use animals to test chemicals that are already well characterized. 

In fact, at least three of these chemicals were used in the validation of Tier 1 assays for EDSP and many 

others have substantial databases of existing data that should be properly reviewed in response to 

publication of the second list. If all 134 chemicals are tested in the full Tier 1 battery, at least 77,000 

animals will be killed Our comments will address duplicative testing in an effort to greatly reduce these 

numbers.

We look forward to a positive response from the Agency. I may be reached at katew@peta.org or by 

telephone at (617)-522-3487.

Sincerely,

Catherine Willett, PhD

Science Policy Advisor

Regulatory Testing Division

cc: Stephen Owens, Office of Chemical Safety and Pollution Prevention
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Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.

Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 5

EPA Comment Code: 1035

Comment: To conclude, an extensive body of evidence available for the pesticide flumetsulam clearly 

demonstrates very low toxic hazard potential, no evidence of endocrine disruption, and minimal human 

exposure potential. The existing toxicology data would necessitate the conduct of EDSP studies at the 

limit dose, which has little relevance for extrapolation to humans. Moreover, a significant number of 

animals are needed to conduct the Tier l screening. DAS believes this is unjustified given all the 

scientific information that exists pertaining to the human health risk associated with exposure to 

flumetsulam. Based on these considerations, DAS respectfully requests flumetsulam be removed from 

List 2, or alternatively, not to be considered a priority for the EDSP.

We appreciate the opportunity to comment.

Sincerely,

Cindy Loy 

Regulatory Leader

Dow AgroSciences LLC

(317) 337-4655

e-mail: caloy@dow.com

References

Billington, R. and Gehen, S.C.. Toxicology of Triazolopyrimidine Herbicides, Hayes’ Handbook of 

Pesticide Toxicology 1865 – 1885, 2010.

Environmental Protection Agency (EPA). Flumetsulam. Amended Human Health Assessment Scoping 

Document in Support of Registration Review. August 12, 2008.

Stott, W.T.; Yano, B.L.; Beyer, J.E.; Kropskott, B.E.; and Eddy, S.L.. XRD-498: Two-Year Dietary 

Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats, Unpublished Report of Dow AgroSciences, 

Study 914917, May 18, 1991, MRID 41931707.

Yano, B.L.; Firchau, H.M.; Quast, J.F.; and Stott, W.T.. XRD-498: 4-Week Dietary Toxicity Study in 

Male Fisher 344 Rats, Unpublished Report of Dow AgroSciences, Study 884382, May 10, 1988.

Zempel, J.A.; Mensik, D.C.; Szabo, J.R.. XRD-498: Results of a Two Generation Reproduction Study in 

Fischer 344 Rats, Unpublished Report of Dow AgroSciences, Study 910132, Nov 1, 1990, MRID 

41931710.

Zielke, G.J.; Hanley, T.R., Jr.; Yano, B.L.. XRD-498: Dietary Teratology Study in Fischer 344 Rats, 

Unpublished Report of Dow AgroSciences, Study 887865, Nov 15, 1988, MRID 41263213.
EPA-OGWDW Final EDSP List 2 February 2013

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Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.

Please also see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0035

Comment Part: 4

EPA Comment Code: 1035

Comment: 5. Finally, and perhaps most importantly, the Panel believes that the use of additional 

experimental animals, as required by the proposed endocrine screening in vivo studies, is unnecessary 

and contrary to our, and EPA’s, efforts to reduce, refine, and replace animal testing, in particular to 

avoid unnecessary animal testing. [FN6: Typically, a lab conducting the EDSP Tier 1 battery will use a 

minimum of 162 rats per chemical for the uterotrophic, Hershberger, male pubertal and female pubertal 

assays in accordance with the requirements of the EPA EDSP Test Guidelines. However, experience has 

shown that dose-ranging pilot studies will almost always be necessary, and this will require some 40-50 

additional lab animals. Estimates for the frog assay indicate use of 300-400 tadpoles per assay, but in 

order to get to these numbers (the EPA Test Guideline requires the test tadpoles all be of a precisely 

defined staging) labs must to start with a total pool of several thousand to select those appropriate for 

assay. The fish reproduction assay requires approximately 100-120 adults, and typically close to 30,000 

embryos.] Rather, the Panel would recommend the use of these animal and laboratory resources only for 

substances which have a high potential to occur as drinking water contaminants, and whose potential 

long-term effects on development and reproduction in mammalian systems are not well understood.

Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 5

EPA Comment Code: 1035

Comment: 5. Finally, and perhaps most importantly, the Panel believes that the use of additional 

experimental animals, as required by the proposed endocrine screening in vivo studies, is unnecessary 

and contrary to our, and EPA’s, efforts to reduce, refine, and replace animal testing, in particular to 

avoid unnecessary animal testing. [FN5: Typically, a lab conducting the EDSP Tier 1 battery will use a 

minimum of 162 rats per chemical for the uterotrophic, Hershberger, male pubertal and female pubertal 

assays in accordance with the requirements of the EPA EDSP Test Guidelines. 

However, experience has shown that dose-ranging pilot studies will almost always be necessary, and this 

will require some 40-50 additional lab animals. Estimates for the frog assay indicate use of 300-400 

tadpoles per assay, but in order to get to these numbers (the EPA Test Guideline requires the test 

tadpoles all be of a precisely defined staging) labs must to start with a total pool of several thousand to 

select those appropriate for assay. The fish reproduction assay requires approximately 100-120 adults, 

and typically close to 30,000 embryos.] Rather, the Panel would recommend the use of these animal and 
EPA-OGWDW Final EDSP List 2 February 2013

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laboratory resources only for substances which have a high potential to occur as drinking water 

contaminants, and whose potential long-term effects on development and reproduction in mammalian 

systems are not well understood.

Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 4

EPA Comment Code: 1035

Comment: Additionally, the Panel believes that the use of additional experimental animals, in the 

proposed endocrine screening in vivo studies, is unnecessary and contrary to many member companies’ 

internal policies when existing animal studies show no histological or behavioral effects of potential 

endocrine disruption of ethylene glycol.

Ethylene glycol has been tested in several higher order animal studies for reproductive, developmental, 

and chronic toxicity and results indicate that it does not cause adverse effects suggestive of endocrine 

disruption.

Response: Please see general responses to comment under EPA Comment Codes: 1035 Animal Testing

and 2070 Contaminants Not Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 5

EPA Comment Code: 1035

Comment: Finally, and perhaps most importantly, Dow believes that the use of additional experimental 

animals, as required by the proposed endocrine screening in vivo studies, is unnecessary and contrary to 

our (and EPA's) efforts to reduce, refine, and replace animal testing, in particular to avoid unnecessary 

animal testing when existing animal studies show no histological or behavioral effects indicative of 

potential endocrine disruption following exposure to PDC. Rather, Dow would recommend the use of 

these animal and laboratory resources only for substances which have a high potential to occur as 

drinking water contaminants, and whose potential long-term effects on the endocrine system in 

mammalian and non-mammalian species are not well understood.

Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 7
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EPA Comment Code: 1035

Comment: Finally, and perhaps most importantly, Dow believes that the use of additional experimental 

animals, as required by the proposed endocrine screening in vivo studies, is unnecessary and contrary to 

our (and EPA's) efforts to reduce, refine, and replace animal testing, in particular to avoid unnecessary 

animal testing when existing animal studies show no histological or behavioral effects indicative of 

potential endocrine disruption following exposure to PO. Rather, Dow would recommend the use of 

these animal and laboratory resources only for substances which have a high potential to occur as 

drinking water contaminants, and whose potential long-term effects on the endocrine system in 

mammalian and non-mammalian species are not well understood.

Therefore, removing PO from the Endocrine Disruptor Screening Program is supported by the weightof-evidence of available data, as indicated by the details and references discussed above and provided 

below.

Sincerely,

Jean Kasakevich

Associate EH&S Product Stewardship Director

The Dow Chemical Company

Midland, MI 48674

References

Hackett, PL, Brown, M.G. Buschbom, RL., Clark, M.L., and Miller, RA. 1982. Teratogenic

study of ethylene and propylene oxide and n-butyl acetate. National Institute for Occupational

Safety and Health, Cincinnati, OH, NTIS PB 83-258-38.

Hansen, B.G., Munn, S.I., Pakalin, S., Heidorn, C.I.A., Allanou, R, Pellegrini, G., Anfossi, V.,

Berthault, F., Naughton, A., Praderio, L., and Loonen, L. (Eds.). 2002. European Union Risk

Assessment Report. Methyl oxirane (propylene oxide). CAS No. 75-56-9. EINIECS No. 200879-

2-EUR 29512/EN. Office for Official Publications of the European Communities,

Luxembourg.

Hardin, B., Niemeier, R, Sikov, M., and Hackett, P. 1983. Reproductive toxicologic assessment

of the epoxides ethylene oxide, propylene oxide, butylene oxide, and styrene oxide. Scand. J.

Work. Environ. Health 9:94-102.

Harris, S.B., Schardein, J.L., Ulrich, C.E., and Ridlon, S.A. 1989. Inhalation developmental

toxicity study of propylene oxide in Fischer 344 rats. Fundam. Appl. Toxicol. 13:232-331.

Hayes, W.C., Kirk, H.D. Gushow, T.S., and Young, J.T. 1988. Effect of inhaled propylene oxide

on reproductive parameters in Fischer 344 rats. Fundam. Appl. Toxicol. 10:82-88.

Kuper, c.F., Reuzel, P G., Feron, V.I., and Verschuuren, H. 1988. Chronic inhalation toxicity and

carcinogenicity study of propylene oxide in Wistar rats. Food Chern. Toxicol. 26: 159-167.

Lynch, D.W., Lewis, T.R, Moorman, W.I., Burg, J.R, Groth, D.H., Khan, A., Ackerman, L.I.,

and Cockrell, B.Y. 1984a. Carcinogenic and toxicologic effects of inhaled ethylene oxide and

propylene oxide in F344 rats. Toxicol. Appl. Pharmacol. 76:69-84.
EPA-OGWDW Final EDSP List 2 February 2013

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Page 49

Meylan W, Papa L, De Rosa CT, Stara JF. 1986. Chemical of current interest--propylene oxide:

health and environmental effects profile. Toxicol. Ind. Health. 2: 219-260.

NTP CERHR (National Toxicology Program Center for Evaluation of Risk to Human

Reproduction). 2004. NTP-CERHR Monograph on the Potential Human Reproductive and

Developmental Effects of Propylene Glycol. NIH Publication No. 04-4482.

NTP (National Toxicology Program). 1985. Toxicology and carcinogenesis studies of propylene

oxide (CAS no. 75-56-9) in F344/N rats and B6C3Fl mice (Inhalation studies). Technical Report

267. Research Triangle Park, NC.

Patil, S. 1999. Determination of Propylene Oxide Stability in USP Synthetic Human Gastric Juice

and in USP Synthetic Gastric Juice Mixture Modified to the Conditions of the Rat Forestomach,

Using (carbon-14)-Propylene Oxide: Pilot Study: Final Report: Lab Project Number: 0533-AC02.

Unpublished study prepared by SISTEK Research Laboratories. 49 p.

US EPA. 2006. Reregistration Eligibility Decision (RED) for Propylene Oxide. EPA 738-R-06029.192

pp.

Response: Oxirane, methyl- (propylene oxide) has been removed from the second EDSP list. Please see 

general response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters as 

Being or Potentially Incompatible with Test Assays. Also, please see general response to comment under 

EPA Comment Code: 1035 Animal Testing.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0069

Comment Part: 4

EPA Comment Code: 1035

Comment: Finally, and perhaps most importantly, Dow believes that the use of additional experimental 

animals, as required by the proposed endocrine screening in vivo studies, is unnecessary and contrary to 

our (and EPA's) efforts to reduce, refine, and replace animal testing, in particular to avoid unnecessary 

animal testing when existing animal studies show no histological or behavioral effects indicative of 

potential endocrine disruption following exposure to ECH. Rather, Dow would recommend the use of 

these animal and laboratory resources only for substances which have a high potential to occur as 

drinking water contaminants, and whose potential long-term effects on the endocrine system in 

mammalian and non-mammalian species are not well understood.

Response: Please see general response to comment under EPA Comment Code: 1035 Animal Testing.
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EPA Comment Code: 1040 Complete List 1- Evaluate Tier 1 Screening Results before

Proceeding with EDSP List 2

General Response: Please see Response to Comments on the Public Review Draft of the Information

Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of 

Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is 

being published simultaneously with this comment response document for information on the evaluation 

of EDSP Tier 1 screening results. Also, please see general response to comment under EPA Comment 

Code: 1060 SDWA 1457 for basis for including CCL3 contaminants (e.g., ethylene thiourea (ETU)) on 

the second EDSP list.

Individual Comments

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 3

EPA Comment Code: 1040

Comment: Prioritize assessment of key findings from List 1 data set.

Failure to critically evaluate the performance of the Tier 1 battery prior to issuing test orders for the 

second EDSP list is likely to lead to an unjustifiable, excessive waste of animals in testing. DAS 

proposes that the completion of evaluations of Tier 1 data sets for chemicals on List 1 is the optimal 

opportunity for EPA to engage in a “... timely re-evaluation of the battery of screening ...” as expressed 

in language within the House Appropriations Committee mandate to EPA.[FN8: Congress's House 

Appropriations Committee report for EPA’s FY 2010 appropriations (H.R. 2996, H. Rept. 111-180).] 

Finding an appropriate time in this ongoing endocrine program to pause and assess all of the 11 assays 

of Tier 1 in their entirety with a focus on the value each assay brings to the battery is unlikely. In 

addition, this re-evaluation would allow time to determine whether an assay should be replaced or 

revalidated before a screening battery is requested for the chemicals on draft List 2.

Determine suitability of timing and duration of test order issuance.

DAS requests EPA to use and evaluate real information including, for example, the Crop Life America

Endocrine Policy Forum comments on industry burden for OSRI preparation for chemicals on List 1, to 

ensure that timing and duration of test order issuance for draft list 2 is realistic and appropriate. An 

evaluation of the abilities of laboratories to cope with an additional 25 test orders per year should occur 

before scheduling and issuing the next set of test orders. The value for EPA of using feedback on 

laboratory capacity and testing progress from List 1 test order recipients within their one year progress 

reports and the percentage of on-time test order completions that will be known in late 2011 would give 

an opportunity to optimize test order language and re-assess test order duration. Concern for sufficient 

laboratory capacity to complete the testing in the two year mandated timeframe of the test orders

continues to be felt by industry. Setting a schedule for a second larger list could compound the capacity 

issues.
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Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 5

EPA Comment Code: 1040

Comment: In conclusion, the available information on oxyfluorfen as delineated in the RED has been 

deemed sufficient to register this active substance in the United States. Risk assessments have indicated, 

with ample safety margins, that the proposed uses of oxyfluorfen are not expected to pose any adverse 

effects to humans or the environment. Indeed, exposure to oxyfluorfen through drinking water is well 

below the levels of concern. In addition, its potential for producing endocrine disrupting effects is 

minimal, an important consideration for lowering its priority for endocrine screening. Furthermore, DAS 

encourages the Agency to acquire and apply intelligence gathered from evaluating Tier I data sets from 

active ingredients on List 1 to assess the suitability of distributing List 2 orders at this early date. DAS is 

committed to complying with the Agency’s EDSP initiative and seeks a deferral for listing oxyfluorfen 

until the data call-in is issued for Registration Review.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code:

1040 Complete List 1- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Marie Martinko

Commenter Organization: Society of the Plastics Industry, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0022

Comment Part: 1

EPA Comment Code: 1040

Comment: The Organic Peroxide Producers Safety Division (OPPSD) of the Society of the Plastics 

Industry, Inc. (SPI) appreciates the opportunity to submit the attached comments in response to the 

referenced notice issued by the Environmental Protection Agency.

Submitted via regulations.gov

January 18, 2011 

Document Control Office (7404M) 

Office of Pollution Prevention and Toxics (OPPT) 

Environmental Protection Agency 

1200 Pennsylvania Ave., NW

Washington, DC 20460-0001 

Attention: Docket ID No. EPA–HQ–OPPT–2009-0477 
EPA-OGWDW Final EDSP List 2 February 2013

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Re: Notice, Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; 75 

FR 70248 (November 17, 2010) and 75 FR 77869 (December 14, 2010); Docket No. EPA–HQ–OPPT–

2009-0477

To Whom It May Concern: 

The Organic Peroxide Producers Safety Division (“OPPSD”) of the Society of the Plastics Industry, Inc. 

(“SPI”) appreciates the opportunity to submit these comments in response to the referenced notice issued 

by the Environmental Protection Agency (“EPA”). Founded in 1937, SPI is the plastics industry trade 

association representing the third largest manufacturing industry in the United States. SPI's member 

companies represent the entire plastics industry supply chain, including processors, machinery and 

equipment manufacturers and raw materials suppliers. The U.S. plastics industry employs 1.1 million 

workers and provides nearly $379 billion in annual shipments.

Cumene hydroperoxide (CHP, CAS number[FN1: Chemical Abstract Services Registry Number] 80-15-

9) has been listed on the Second List of Chemicals for Tier 1 Screening for endocrine disruption. 

OPPSD members include companies that produce CHP and who would be affected if EPA were to issue 

a test order for this chemical under the Endocrine Disruptor Screening Program (EDSP). The following 

comments support our request that EPA allow time to review and evaluate the results of the Tier 1 

screening of the List 1 chemicals prior to requiring testing on additional chemicals.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Marie Martinko

Commenter Organization: Society of the Plastics Industry, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0022

Comment Part: 4

EPA Comment Code: 1040

Comment: The Agency should allow time to review and evaluate the results of the Tier 1 screening of 

the List 1 chemicals prior to requiring testing on additional chemicals. It is especially critical to 

determine the impact of non-specific physical/chemical properties on the integrity and specificity of the 

test systems for those materials with high chemical reactivity, like the powerful oxidizing properties of 

CHP. 

*****

SPI appreciates the opportunity to respond to this notice. Please contact me at (202) 974-5200 if you 

have questions or require additional information. 

Respectfully submitted,

Marie R. Martinko 

Director, Industry Affairs – Environment & Health
EPA-OGWDW Final EDSP List 2 February 2013

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Response: Please see general response to comment under EPA Comment Code: 1040 - Evaluate Tier 1 

Screening Results before Proceeding with EDSP List 2. Also, please see general response to comment 

under EPA Comment Code: 2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assay.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 4

EPA Comment Code: 1040

Comment: 2. EPA Has Ignored Concerns Expressed By The Office Of Management and Budget 

(OMB) And Failed to Follow OMB’s Directive To Consider And Report On Experience With The First 

List Of Substances Subject To EDSP Testing Before Publishing The Second EDSP List. 

As part of the Terms of Clearance for approval of EPA’s Information Collection Request for the first 

EDSP list of chemicals published on April 15, 2009 (74 Fed. Reg. 17579), OMB specifically requested 

that the Agency validate and re-estimate the burdens associated with the EDSP prior to initiating 

screening on additional chemicals. In particular, OMB stated that: 

This information collection is approved for the 67 chemicals published by EPA at 74 Fed. Reg. 17579 

(April 15, 2009). OMB appreciates the continuing dialog with respect to the practical utility of the Tier I 

battery of EDSP assays and the role that the results from these first 67 chemicals will play in ensuring 

practical utility for subsequent groups of chemicals. Nonetheless, under the principles of the PRA 

[Paperwork Reduction Act], EPA should promote and encourage test order recipients to submit Other 

Scientifically Relevant Information (OSRI) in lieu of performing all or some of the Tier I assays, and 

EPA should accept OSRI as sufficient to satisfy the test orders to the greatest extent possible. For this 

reason, and to further validate EPA’s burden estimates, OMB requests that EPA provide a report reestimating the burden of this information collection based on responses to the Tier I test orders, 

including the use of cost-sharing and data compensation, the submission and acceptance of existing data 

and OSRI, and description of any instances in which submission of OSRI was deemed insufficient to 

satisfy the testing order. OMB requests this report prior to or at the time of submission of revision of this 

information collection to cover additional chemicals. In addition, in order to ensure that EPA has 

maximized the practical utility of the Tier I assays as the program moves forward, EPA should ensure 

sufficient opportunity prior to submission of any revision to this collection for public comment and peer 

review of the EPA tools to be developed to guide agency decisions on whether a chemical must proceed 

to Tier II, including the Weight of the Evidence Approach and Standard Evaluation Procedures”. 

See Office of Information and Regulatory Affairs, ICR Reference No: 200904-2070-001 (emphasis 

added). 

Recently, CropLife America and the Endocrine Policy Forum provided EPA with a Preliminary Burden 

Report with estimates of the time and cost associated with compliance with Tier 1 Test Orders issued in 

April 2009. This information, based on actual industry experience, demonstrates that EPA has 

significantly underestimated both time and cost burdens associated with the development of initial 

responses to Tier 1 Test Orders. EPA’s time and costs estimates appear to be only one third to one fifth 

of the actual burden experienced by Order recipients. See Attachment 3. 
EPA-OGWDW Final EDSP List 2 February 2013

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In light of this new information, EPA should withdraw the proposed listing of additional chemicals until 

it can complete a more accurate and realistic assessment of time and cost burdens of Tier 1 Test Orders 

in compliance with OMB’s Terms of Clearance for the ICR request associated with the first EDSP list.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 7

EPA Comment Code: 1040

Comment: In closing, EPA’s initial selection of 67 pesticide chemicals for Phase 1 of EDSP screening 

was consistent with the SAB/SAP guidance set forth in the July 1999 SAB/SAP Review of the EPA's 

Proposed Environmental Endocrine Disruptor Screening Program which recommended that the Agency 

consider piloting the EDSP with a set of 50 to 100 chemicals. The SAB/SAP also recommended that 

EPA convene an external panel of independent scientists to review the initial screening data for the 

purpose of evaluating whether the Tier 1 screening program could be improved or optimized. EPA 

should follow the SAB/SAP advice and await completion of the EDSP Phase 1 to conduct the 

SAB/SAP-recommended review prior to requiring screening for any additional substances. A staged 

implementation of EDSP screening would allow the Agency to modify and/or replace Tier 1 assays as 

necessary based on the Agency’s Phase 1 experience. It would also allow the Agency time to review the 

available data on benzene and MTBE and confirm that Tier 1 studies are not necessary given the already 

extensive database. 

If you have any questions or require further information regarding this letter please do not hesitate to 

contact me.

Sincerely, 

Howard J. Feldman

REFERENCES 

U.S. Agency for Toxic Substances and Disease Registry’s (ATSDR) 2007 Toxicology Profile of 

Benzene. Document Webpage: http://www.atsdr.cdc.gov/ToxProfiles/TP.asp?id=40&tid=14 

American Chemistry Council Benzene, Toluene and Xylene (BTX) VCCEP Consortium Letter 

Submitted to U.S EPA on March 30, 2006. Document Webpage: 

http://www.epa.gov/opptintr/vccep/pubs/chem2.html 

ENSR (1999). Early-life stage toxicity of methyl tertiary-butyl ether (MTBE) to the fathead minnow 

(Pimephales promelas) under flow-through test conditions: ENSR Environmental Toxicology 

Laboratory. Rep No 0300-036-041-002. ENSR, Fort Collins, CO. 
EPA-OGWDW Final EDSP List 2 February 2013

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EPA (2005). U.S EPA Report Titled: Monitored Natural Attenuation of MTBE as a Risk Management 

Option at Leaking Underground Storage Tank Sites (EPA/600/R-04/179) January 2005. Document 

Webpage: http://www.epa.gov/nrmrl/pubs/600r04179/600r04179.pdf 

EPA (2008). U.S EPA Report Titled: Regulatory Determinations Support Document for Selected 

Contaminants from the Second Drinking Water Contaminant Candidate List (CCL 2). June 

2008.DocumentWebage: http://www.epa.gov/safewater/ccl/pdfs/reg_determine2/report_ccl2-

reg2_supportdocument_full.pdf

The European Union Risk Assessment Report on MTBE (Third Priority List, Volume 19, 2002) 

Document Webpage: http://ecb.jrc.ec.europa.eu/documents/ExistingChemicals/RISK_ASSESSMENT/REPORT/mtbereport313.pdf 

E. R. Mancini, A. Steen, G. A. Rausina, D. C. L. Wong, W. R. Arnold, F. E. Gostomski, T. Davies, J. R. 

Hockett, W. A. Stubblefield, K. R. Drottar, T. A. Springer, and, P. Errico MTBE Ambient Water Quality 

Criteria Development: A Public/Private Partnership Environmental Science & Technology 2002 36 (2), 

125-129 

Wildlife International Ltd. (1999). Methyl tertiary-Butyl Ether - A flow-through life-cycle toxicity test

with the cladoceran (Daphnia magna): Report no 472A-105, Wildlife International Ltd

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0026

Comment Part: 3

EPA Comment Code: 1040

Comment: Prioritize assessment of key learnings from list 1 data set.

Failure to critically evaluate the performance of the Tier 1 battery prior to issuing test orders for the 

second EDSP list is likely to lead to an unjustifiable, excessive waste of animals in testing. DAS 

proposes that the completion of evaluations of Tier l data sets for chemicals on List 1 is the optimal 

opportunity for EPA to engage in a “ ... timely re-evaluation of the battery of screening ...” as expressed 

in language within the House Appropriations Committee mandate to EPA.[FN7: Congress's House 

Appropriations Committee report for EPA's FY 2010 appropriations (H.R. 2996, H. Rept. 111-180).] 

Finding an appropriate time in this ongoing endocrine program to pause and assess all 11 assays of Tier 

1 in their entirety with a focus on the value each assay brings to the battery is unlikely. In addition, this 

re-evaluation would allow time to determine whether an assay should be replaced or revalidated before a 

screening battery is committed to for the chemicals on draft List 2.

Determine suitability of timing and duration of test order issuance.

DAS requests EPA to use and evaluate real information including, for example, the Crop Life America

Endocrine Policy Forum comments on industry burden for OSRI preparation for chemicals on List 1, to 

ensure that timing and duration of test order issuance for draft list 2 is realistic and appropriate. An 

evaluation of the abilities of laboratories to cope with an additional 25 test orders per year should occur 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 56

before scheduling and issuing the next set of test orders. The value for EPA of using feedback on 

laboratory capacity and testing progress from List 1 test order recipients within their one year progress 

reports and the percentage of on-time test order completions that will be known in late 2011 would give 

an opportunity to optimize test order language and re-assess test order duration. Concern for sufficient 

laboratory capacity to complete the testing in the two year mandated timeframe of the test orders 

continues to be felt by industry. Setting a schedule for a second larger list could compound the capacity 

issues.

In conclusion, the available information on isoxaben has been deemed sufficient to register this active 

substance in the United States. Risk assessments have indicated, with ample safety margins, that the 

proposed uses of isoxaben are not expected to pose any adverse effects to humans or the environment. 

Indeed, exposure to isoxaben through drinking water is well below the levels of concern. In addition, its 

potential for producing endocrine disrupting effects is minimal, an important consideration for lowering 

its priority for endocrine screening. Furthermore, DAS encourages the Agency to acquire and apply 

intelligence gathered from evaluating Tier I data sets from active ingredients on List 1 to assess the 

suitability of distributing List 2 orders at this early date.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see general 

response to comment under EPA Comment Code: 2100 Pesticide Registration Review Issues.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 2

EPA Comment Code: 1040

Comment: With respect to the Agency’s efforts to implement all of the necessary components of the 

EDSP, considerable additional effort is needed to ensure scientifically reliable data is generated. EPA 

must build upon existing data sources to distinguish “data needs” from “data gaps” in a cost efficient 

manner that fully considers animal welfare issues. EPA must also follow clear and consistent approaches 

for interpreting the data within a weight of evidence construct and for applying the test results in risk 

assessments. The EDSP Tier 1 screening is an ambitious testing program that is being implemented 

under new policies and procedures. It will utilize a suite of newly validated – and expensive -- test 

methods. For the reasons discussed in more detail in our comments, we believe EPA should, consistent 

with the recommendations of the Agency’s independent scientific experts, the Science Advisory Board 

and Scientific Advisory Panel (SAB/SAP)[FN2: EPA (1999). Review of the Endocrine Disruptor 

Screening Program by a Joint Subcommittee of the Science Advisory Board and Scientific Advisory 

Panel. http://www.epa.gov/scipoly/sap/meetings/1999/finalrpt.pdf. “There was broad support among the 

Subcommittee for the concept that the Agency should convene a panel of independent scientists to 

review all the screening data for 50-100 compounds, with an eye towards revising the process and 

eliminating those methods that don’t work.” Page 2], pause after EDSP Phase 1 to first conduct a review 

of the Tier 1 assays before requiring screening of additional chemicals using these assays. Such a pause 

would allow the Agency to modify and replace Tier 1 assays as necessary based on the Agency’s Phase 

1 experience.
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Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 5

EPA Comment Code: 1040

Comment: Finally, we think it would be inappropriate if EPA were to issue screening orders for these 

new substances before EPA has reviewed the results of the screening battery being applied in Phase 1 of 

the EDSP. We believe EPA should follow the advice of the Agency’s Science Advisory Board and 

Scientific Advisory Panel (SAB/SAP)[FN3: Ibid.] by completing EDSP Phase 1, and conducting the 

SAB/SAP-recommended review of the performance of the Tier 1 assays and the Tier 1 battery prior to 

requiring screening for additional substances.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 8

EPA Comment Code: 1040

Comment: III. EPA Should Complete Screening of its First List of Chemicals before Ordering 

Additional EDSP Screening

While ACC does not object to EPA’s prioritizing additional substances for EDSP Tier 1 screening, ACC 

believes that EPA should not issue screening orders for these new substances before the Agency has 

collected and analyzed data from the initial set of EDSP substances. The Tier1 screening component of 

the EDSP is an ambitious testing program that is being implemented under new policies and procedures. 

It utilizes a suite of newly validated test methods with which the Agency and industry have little 

experience. Tier 1 screening costs alone may run as high as $500,000 to $1,000,000 per substance and 

utilize a significant number of lab animals; Tier 2 testing costs could reach several million dollars per 

substance. Given the lack of experience with the EDSP screening and testing assays and the Tier 1 

battery, it is imperative that the Agency proceed to collect and analyze data from the initial set of EDSP 

substances before proceeding to additional substances. That approach would allow EPA to examine and 

revise its Tier 1 assays, the Tier 1 battery and EDSP procedures, such as use of “functionally equivalent 

data” and “other scientifically relevant information” before undertaking additional testing that could 

result in the unnecessary use of resources and test animals.

We believe this approach is also consistent with the SAB/SAP’s recommendation to “pilot” the first 

round of EDSP screening with a limited number of chemicals. EPA’s initial selection of 67 pesticide 

chemicals for Phase 1 of EDSP screening was consistent with the SAB/SAP guidance set forth in the 

July 1999 SAB/SAP Review of the EPA's Proposed Environmental Endocrine Disruptor Screening 
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Program[FN20: EPA (1999). Review of the Endocrine Disruptor Screening Program by a Joint 

Subcommittee of the Science Advisory Board and Scientific Advisory Panel. 

http://www.epa.gov/scipoly/sap/meetings/1999/finalrpt.pdf. “There was broad support among the 

Subcommittee for the concept that the Agency should convene a panel of independent scientists to 

review all the screening data for 50-100 compounds, with an eye towards revising the process and 

eliminating those methods that don’t work.”] which recommended that the Agency consider piloting the 

EDSP with a set of 50 to 100 chemicals. The SAB/SAP also recommended that EPA convene an 

external panel of independent scientists to review the initial screening data for the purpose of evaluating 

whether the Tier 1 screening program could be improved or optimized. ACC agrees with EPA’s initial 

use of a manageable number of pesticide chemicals and with the SAB/SAP recommendation to convene 

an external panel to review the initial screening data.[FN21: Ibid] EPA’s reference to this SAB/SAP 

recommendation is contained in the Agency’s description of the EDSP in both the “Response to 

Comments on the DRAFT Endocrine Disruptor Screening Program (EDSP): Policies & Procedures for 

Initial Screening and Testing”[FN22: EPA (2009). Docket ID #: EPA-HQ-OPPT-2007-1080 Response 

to Comments on the DRAFT Endocrine Disruptor Screening Program (EDSP): Policies & Procedures 

for Initial Screening and Testing. Page 2. http://www.epa.gov/endo/pubs/pandp_r2c_041509.pdf] and 

the Final “Policies and Procedures for Initial Screening”[FN23: EPA (2009). Endocrine Disruptor 

Screening Program; Policies and Procedures for Initial Screening. Federal Register, Volume 74 Number 

71 (Wednesday, April 15, 2009) Page 17561] published in 2009. We have interpreted EPA’s reference 

to the SAB/SAP recommendation as an indication of EPA’s intent to comply with this recommendation 

as it proceeds with the EDSP.

EDSP Phase 1 testing is either still underway or results have not yet been compiled and reviewed by 

EPA. EPA should follow the SAB/SAP advice and await completion of the EDSP Phase 1 to conduct 

the SAB/SAP-recommended review prior to requiring screening for additional substances. A staged 

implementation of EDSP screening (in which new screening orders would be issued only after 

completion of the first phase of screening) would allow the Agency to modify and/or replace Tier 1 

assays as necessary based on the Agency’s Phase 1 experience.

In addition, in order to utilize the very promising ToxCast advanced high through-put and high-content 

endocrine screening techniques within the EDSP, EPA should accelerate the necessary determinations of 

relevance, reliability, sensitivity and specificity of these methods. A phased approach would allow EPA 

to complete these determinations. These methods hold great promise to increase the efficiency of EDSP 

Tier 1 screening, provide greater sensitivity and specificity at a lower cost and use fewer lab animals. 

Indeed, these techniques have already been used by EPA, in lieu of the Agency’s own EDSP Tier 1 

battery, to compare the dispersants available for use in the Deepwater Horizon oil spill for potential 

endocrine activity and relative toxicity to living cells. The methods used, EPA’s ToxCastTM and the 

Tox21 NIH Chemical Genomics Center molecular/cellular screening tests, are advanced techniques that 

have only recently become available. The power of those methods is exemplified by the Agency’s full 

reliance on those test results for purposes of the oil spill evaluation to conclude:

EPA's results indicated that none of the eight dispersants tested, including the product in use in the Gulf, 

displayed biologically significant endocrine disrupting activity. The tested dispersants alone had 

relatively low potential for cytotoxicity, with JD-2000 and SAFRON GOLD being the least 

cytotoxic.[FN24: EPA (2010). US EPA’s Oil Spill Dispersant Screening Results. Rapid Testing For 

Potential Endocrine Related Activity & Cytotoxicity. 

http://www.epa.gov/ncct/download_files/factsheets/Technical%20Fact%20Sheet%20EST%20paper%20

In%20Vitro %20Tests%208%20Oil%20Dispersants%207-6-2010.pdf]
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As a general matter, EPA can ensure efficient, cost effective generation of scientifically reliable 

endocrine data by implementation of the EDSP in a manner that builds upon existing data sources. In 

this regard, EPA must distinguish “data needs” from “data gaps.” It should focus efforts on filling only 

data needs, and it should do so in a cost efficient manner taking full consideration of protection of public 

health, the environment and animal welfare concerns.[FN25: Typically, a lab conducting the EDSP Tier 

1 battery will use a minimum of 162 rats per chemical for the uterotrophic, Hershberger, male pubertal 

and female pubertal assays in accordance with the requirements of the EPA EDSP Test Guidelines. 

However, experience has shown that dose-ranging pilot studies will almost always be necessary, and this 

will require some 40-50 additional lab animals. Estimates for the frog assay indicate use of 300- 400 

tadpoles per assay, but in order to get to these numbers (the EPA Test Guideline requires the test 

tadpoles all be of a precisely defined staging) labs must to start with a total pool of several thousand to 

select those appropriate for assay. The fish reproduction assay requires approximately 100-120 adults, 

and typically close to 30,000 embryos.] When needed data are generated, EPA must use clear and 

consistent objective criteria for determining data quality and study reliability coupled with a structured 

evaluative framework to provide a systematic approach for assessing the overall weight of the evidence 

for observed effects and the postulated mode of action.

Response: Please see general response to comment under EPA Comment Code: 1040 - Evaluate Tier 1 

Screening Results before Proceeding with EDSP List 2. Also, please see general response to comment 

under EPA Comment Code: 1050 Evaluation Criteria Review.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 4

EPA Comment Code: 1040

Comment: The Agency should allow time to review and evaluate the results of the Tier 1 screening of 

the List 1 chemicals prior to requiring testing on additional chemicals, especially those with high 

chemical reactivity, like the powerful reducing properties of hydrazine, to determine the impact of nonspecific physical/chemical properties on the integrity and specificity of the test systems.

c. The Physical and Chemical Properties of Hydrazine May Preclude Testing 

The EPA criteria for listing includes the provision that the "material is not strongly acidic or basic and 

therefore would not be incompatible with the testing assays." Hydrazine is a highly reactive and strongly 

basic chemical. The pH of a 1 mM solution of hydrazine (i.e., 32 mg/L) would be ~9.6 and that of a 100 

μM solution -9.06 [FN6: Kb = 1.3 E-06 = [N2H5(+))[0H(-)] / [N2H4] = [OH(-)Y^2 / 0.001 = 1.3 10-9: 

SQRT 1.3 10-9 = 3.61 10-5

-Log 3.61 = 4.44: 14-4.44 = 9.6. Similarly for 0.0001 M solution. (see: http://answers.yahoo.com

lquestion/index;_ylt=A vU3HMZt4Il84_5yW8HzE5MExgt.;_ylv=3?qid=20090408191922AAUV

bXU]. The Agency should allow time to review and evaluate the results of the Tier 1 screening of the 

List 1 chemicals prior to requiring testing on additional chemicals, especially those with high chemical 

reactivity, like the powerful reducing properties of hydrazine, to determine the impact of non-specific 

physical/chemical properties on the integrity and specificity of the test systems.
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Response: Please see general response to comment under EPA Comment Code: 1040 - Evaluate Tier 1 

Screening Results before Proceeding with EDSP List 2.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 8

EPA Comment Code: 1040

Comment: b. The Physical and Chemical Properties of TPTH May Preclude Testing

Triorganotin hydroxides behave not as alcohols, but more like inorganic bases. This is illustrated by the 

reported pH of 8.2 for an unneutralized aqueous solution of TPTH at the concentration of 1 mg/L (1 

ppm). [FN12: ibid.]

The Agency should allow time to review and evaluate the results of the Tier 1 screening of the List 1 

chemicals prior to requiring testing on additional chemicals.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see general 

response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters as 

Being or Potentially Incompatible with Test Assay.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 11

EPA Comment Code: 1040

Comment: b. The Physical and Chemical Properties of CHP May Preclude Testing

CHP is highly reactive at STP in the presence of metals and organic matter, a condition likely to occur in 

the Tier 1 tests. The Agency should allow time to review and evaluate the results of the Tier 1 screening 

of the List 1 chemicals prior to requiring testing on additional chemicals. It is especially critical to 

determine the impact of non-specific physical/chemical properties on the integrity and specificity of the 

test systems for those materials with high chemical reactivity, like the powerful oxidizing properties of 

CHP.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assay. Also, please see 

general response to comment under EPA Comment Code: 1040 Complete List 1- Evaluate Tier 1 

Screening Results before Proceeding with EDSP List 2.

Commenter Name: Stephen Longacre

Commenter Organization: FMC Corporation
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0040

Comment Part: 3

EPA Comment Code: 1040

Comment: General Comments on EPA's Proposed Second List for Endocrine Disruptor Screening:

1) Test Orders for Endocrine Screening of the Second List of Chemicals Should Be Issued Following 

Completion of EPA's Evaluation of the Endocrine Disruptor Screening Results of Chemicals on the First 

List:

Endocrine disruption screening of pesticides and high volume chemicals on the first list is in progress. 

The screening results of the initial list of chemicals and any subsequently required Tier 2 testing should 

be completed and reviewed prior to any subsequent screening to determine what modifications to the 

current endocrine screening battery should be made to provide the best scientific screen and to avoid the 

unnecessary use of animals in subsequent screens. This point was made by the SAP as captured on page 

11 in the Agency's 11 Jun08 Meeting Minutes of the SAP 25-26Mar08 review of the endocrine 

disruption screening assays: 

"In summary, the proposed set of Tier 1 assays are appropriate to begin screening for disruptors of the 

EAT axes. However, several assays do not represent the current state of the science, or the proposed 

screens do not fully address major modes of action and should be updated and extended as soon as 

possible. The EPA should consider this set of assays to be a work in progress. The Panel expects that the 

EPA will continue to develop, refine, and review of the battery."

It would be prudent and most efficient not to issue test orders for endocrine disruption screening for the 

second list of chemicals until the endocrine disruption evaluation of the initial list of chemicals has been 

completed.

Please contact me at 215-299-5930 or at stephen.longacre@fmc.com if you have any questions about 

these comments.

Respectively submitted,

Stephen L. Longacre, Ph.D.

Senior Regulatory Manager

FMC Corporation

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 1

EPA Comment Code: 1040
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Comment: ATTACHED ARE THE COMMENTS FROM THE ACETOCHLOR REGISTRATION 

PARTNERSHIP.

January 18, 2011

Steve A. Owens,

Assistant Administrator

Office of Chemical Safety and Pollution Prevention (OCSPP)

US EPA Headquarters Ariel Rios Building

1200 Pennsylvania Ave. NW

Mail Code: 7101M

Washington, D.C. 20460

Re: Comments from the Acetochlor Registration Partnership (ARP) on the EPA proposal to issue a 

Second List of Chemicals for Tier 1 Screening under the Endocrine Disruptor Screening Program, 

Docket ID: EPA-HQ-OPPT-2009-0477

The Acetochlor Registration Partnership (ARP[FN1: The ARP member companies are Dow 

AgroSciences LLC and Monsanto Company (Managing Agent).]) appreciates the opportunity to provide 

comments to the EPA on the Second List of Chemicals for Tier 1 Screening (List 2). Docket ID: EPAHQ-OPPT -2009- 0477. The ARP is submitting comments with regard to the herbicide active ingredient 

Acetochlor (CAS number 34256-82-1) and two of its degradates, Acetochlor ethanesulfonic acid (ESA) 

(CAS number 187022-11-3) and Acetochlor oxanilic acid (OA) (CAS number 194992-44-4).

In response to the Agency's request for public comment on List 2 chemicals for Tier 1 screening under 

the EDSP, the ARP is hereby submitting our formal comments (Docket ID: EP A-HQ-OPPT -2009-

0477). The general comments provided by the ARP in this cover letter are followed by expanded 

comments in the attached document. Additionally, ARP member companies are members of Crop Life 

America's Endocrine Policy Forum (CLA-EPF) and comments raised by CLA-EPF are incorporated 

herein.

General comments:

* It is imperative that the EPA meet the OMB terms of clearance and SAB/SAP recommendation for 

List 1 chemicals before proceeding with List 2. The 'learn as we go' approach taken by OSCPP with List 

1 should be fully concluded before test orders are issued for List 2.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 5

EPA Comment Code: 1040
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Comment: * Significant information is still required to complete implementation of the EDSP. This 

information includes standard evaluation procedures (SEPs) for evaluating other scientifically relevant 

information (OSRI) that can be submitted to meet one or more of the Tier 1 screens; resolution of errors 

identified within the 890 Series Test Guidelines; SEPs for the 890 Series assay reports; and further 

clarity on how the Agency will consider the overall weight of evidence in the interpretation of Tier 1 

screening data. Additionally, significant work is still required to complete development and validation of 

the Tier 2 tests required for compounds that are concluded to be positive in Tier 1 testing. Consequently, 

it is premature to issue test orders for List 2 compounds before development and validation of Tier 2 

tests, using the List 1 chemicals.

* The Agency itself has already indicated in its comments on List 1 that it would be premature to 

include degradates, such as Acetochlor ESA and Acetochlor OA, for any EDSP screening and testing. 

The ARP encourages the EPA to continue with this approach until the List 1 results have been fully 

interpreted.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see Response-toComments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published simultaneously 

with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 10

EPA Comment Code: 1040

Comment: Expanded comments to the EPA's Endocrine Disruptor Screening Program Second List of

Chemicals for Tier I Screening ("List 2"):

Time is needed to realize lessons learned from initial Tier 1 screening with List 1 Chemicals before 

proceeding with List 2:

The ARP would like to emphasize the need for a comprehensive external review of EDSP results on an 

assay by assay basis as well as the performance of the Tier 1 Battery for List 1 chemicals before 

additional test orders are issued for List 2. Final data submissions for the first 67 chemicals undergoing 

Tier I screening will not begin until October 2011, with current submission deadlines continuing into 

2012. By prematurely issuing List 2, the Agency did not provide a sufficient period of time to 

adequately evaluate and improve the overall EDSP testing methodology before initiating valid and 

efficient testing for List 2 chemicals. Given the extraordinary overall cost of EDSP testing (both to the 

EPA and industry) for such a large number of compounds, the EPA should be prudent and judicious in 

its approach before issuing List 2 Test Orders. A tremendous number of test animals and a vast 

expenditure of limited financial and manpower resources will be wasted unless the EPA shows more 

restraint in its regulatory approach.

From the above, it is evident that the EPA rushed the publication of List 2, with a Congressional staff 

committee report serving as the only Legislative justification. It is imperative that the EPA meet the 

OMB terms of clearance and SAB/SAP recommendation for List 1 before proceeding with List 2. If the 
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Comment Response Document

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EPA chooses not to implement the SAB/SAP recommendation to review results for List 1 chemicals 

before issuing additional test orders for List 2, all benefits of such a review would be unrealized. The 

'learn as we go' approach taken by OSCPP with List 1 should be fully concluded before test orders are 

issued for List 2.

Additionally, significant information is still required to complete implementation of the program. This 

information includes standard evaluation procedures (SEPs) for evaluating other scientifically relevant 

information (OSRI) that can be submitted to meet one or more of the Tier 1 screens (and which the EPA 

is obligated to consider); resolution of errors identified within the 890 Series Test Guidelines for Tier 1 

screening; SEPs for the 890 Series assay reports; and further clarity on how the agency will consider the 

overall weight of evidence in the interpretation of Tier 1 screening data.

The ARP recommends that focus be placed on resolving all of the many pending issues with the EDSP 

implementation List 1 chemicals before test orders are issued for List 2. This approach will ultimately 

enhance the scientific rigor and integrity of the EDSP program.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see Response-toComments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published simultaneously 

with this comment response document. 

Commenter Name: D. Douglas Fratz

Commenter Organization: Consumer Specialty Products Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0047

Comment Part: 2

EPA Comment Code: 1040

Comment: II. EPA Should Review and Evaluate the Results of List 1 Testing Prior to Issuing 

Additional EDSP Test Orders.

CSPA believes that prior to finalizing List 2, and issuing test orders requiring additional EDSP Tier 1 

tests, the Agency should evaluate the results of List 1 chemicals and consider what changes are 

necessary before continuing to implement the program. Before additional companies are required to 

spend $500,000 to $1,000,000 per chemical to run these screening tests, EPA should evaluate what has 

been learned during the initial phase of testing. We believe that a full review of those data is needed to 

answer many questions regarding the EDSP test battery, including:

Are any revisions needed in the test protocols?

• Are any of the tests unreliable and therefore should be removed from the battery for some or all types 

of substances?

• Are any of the Tier 1 test results well predicted by other chronic toxicity tests (or other data) that make 

specific Tier 1 tests unnecessary for some or all chemicals?

• Are some test protocols redundant, giving the same answers as other Tier 1 tests, and can therefore be 

removed from the battery?
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• Can more refined weight-of-evidence criteria be developed that use the results of various tests or the 

battery as a whole in determining the need for Tier 2 tests?

• Can the Other Scientifically Relevant Information (OSRI) and Tier-1 Bypass policies be modified to 

consider other information in lieu of Tier 1 tests?

• Can ToxCast high-through-put endocrine screening techniques be used to obviate the need for some or 

all tests for some or all chemicals?

The results of the initial phase of testing may demonstrate the need for significant changes in the EDSP 

test battery, test protocols, and the interpretation of results, including further consideration of animal 

welfare issues. However, those initial phase test results will not be available at least until October 2011, 

with some due later in 2012. It would not seem reasonable to initiate additional testing while the initial 

phase of testing is ongoing. The approach CSPA recommends would be fully consistent with the advice 

provided by EPA’s Science Advisory Board and Scientific Advisory Panel.

Response: Please see general responses to comment under EPA Comment Codes: 1040 Complete List 

1- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2 and 1050 Evaluation Criteria 

Review. Also, please see Response-to-Comments for the Endocrine Disruptor Screening Program’s 

Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that 

is being published simultaneously with this comment response document.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 4

EPA Comment Code: 1040

Comment: EPA Should Complete Screening of the First List of Chemicals before Requiring Ordering 

Additional EDSP Screening 

EPA intends to expand the EDSP effort by requiring that screening begin on an additional 134 chemicals 

(“SDWA chemicals”) [FN2: EPA uses this term in the companion “policies and procedures” document 

(75 Fed. Reg. 70558; November 17, 2010) and we use it here for consistency.] before receiving and 

evaluating the results of the current screening effort on pesticide chemicals. This significant expansion 

of Tier 1 screening is neither required by statute nor prudent in light of EPA’s failure to timely develop 

functional weight of evidence guidance, more detailed evaluation procedures for other scientifically 

relevant information (“OSRI”), and the need for sufficient information about the successes and failures 

of the initial screening approach to inform future decisions about the EDSP. CPDA does not object to 

EPA’s appropriately prioritizing additional chemicals for future Tier 1 screening; however, we do object 

to the Agency rushing to issue new test orders for twice the numbers of chemicals in the first screening 

effort without first evaluating that effort and improve the EDSP. 

In the List 2 Notice, EPA sets forth its authority for developing the list of SDWA chemicals, citing 

section 408(p) of the Federal Food, Drug, and Cosmetic Act (“FFDCA”), [FN3: 21 U.S.C. § 346(a)(p)] 

section 1457of the Safe Drinking Water Act (“SDWA”), [FN4: 42 U.S.C. § 300j-17] and a House 

Appropriations Committee report. [FN5: U.S. House of Representatives. 2009. Committee on 

Appropriations Report 111-180 on Department of the Interior, Environment, and Related Agencies 

Appropriation Bill, 2010.] However, neither the FFDCA nor the SDWA contains a mandated time 
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period or a deadline for EPA to begin EDSP screening generally or for SDWA chemicals specifically. 

Moreover, EPA incorrectly interprets language in the Appropriations Committee report as a 

constitutionally valid legislative mandate to initiate EDSP screening. This rush to screen additional 

chemicals without a statutory deadline is premature and will undermine the valuable opportunity the 

initial Tier 1 screening can provide for future experience and science-based to improvements to this 

highly complex program.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 6

EPA Comment Code: 1040

Comment: Until the screenings on the first list has concluded, and EPA is in a position to make

decisions informed by that experience, the Agency should not undertake this major expansion of the 

program. The EDSP is a new and ambitious testing program. It orders the use of a battery of new and 

controversial test methods with which the Agency, laboratories and industry have little experience. Tier 

1 screening costs alone will run $500,000 to $1,000,000 per chemical and Tier 2 costs could reach 

several million dollars per chemical. Given the expense of, and lack of experience with, EDSP screening 

and testing, it is imperative that the Agency collect and analyze data from the pesticide chemicals 

currently being screened before expanding screening to additional chemicals. This approach would 

allow EPA to examine and revise the Tier 1 assays, the complete Tier 1 battery and EDSP policies and 

procedures to address issues such as “functional equivalence” and “other scientifically relevant 

information,” before undertaking additional testing. We believe this approach is supported with EPA’s 

Science Advisory Board/Science Advisory Panel recommendation to “pilot” the EDSP a limited number 

of chemicals:

“There was broad support among the Subcommittee for the concept that the Agency should convene a 

panel of independent scientists to review all the screening data for 50-100 compounds, with an eye 

towards revising the process and eliminating those methods that don’t work.” [FN10: EPA, Review of 

the EPA’s Proposed Environmental Endocrine Disruptor Screening Program. Joint Subcommittee of the 

Science Advisory Board and Scientific Advisory Panel, EPPA-SAB-EC-99-013, July 1999.]

Therefore, CPDA requests that EPA suspend further actions to issue test orders for the List 2 chemicals 

until the Tier 1 screening effort currently underway has been completed. EPA is under no statutory 

mandate to begin screening chemicals under the SDWA at this time.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049
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Comment Part: 10

EPA Comment Code: 1040

Comment: Conclusion

CPDA believes that EPA has unnecessarily rushed forward with Tier 1 screening of SDWA chemicals 

and requests that EPA suspend all action to issue test orders for the List 2 chemicals until the current 

Tier 1 screening effort has been completed. This would provide the Agency with timely information to 

improve the EDSP.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 3

EPA Comment Code: 1040

Comment: As the EDSP evolves in Phase 1 and the EPA further refines Phase 2, we recommend that 

the Agency apply lessons learned from initial Phase 1 Tier I testing. Final data submissions for the first 

67 chemicals undergoing EDSP Tier I screening are not due until beginning in October 2011 with 

deadlines continuing into 2012. Thus, the timing of List 2 test orders should take into account the time 

EPA will need to evaluate the initial Tier I data. It is premature to continue requesting data generation 

until the Tier I testing has yielded results. Further, inclusion of specific pesticides included in the list 

should take into account the schedule in place for Registration Review as EPA has stated this is the 

program under which the EDSP testing will be evaluated. 

CLA/EPF members have encountered a number of issues in the required EPA screening methods with 

List 1. It does not make sound scientific sense to begin testing a new group of chemicals (as proposed in 

List 2) until these issues have been resolved. Therefore, CLA/EPF proposes that EPA delay Phase 2 

EDSP until the unanswered questions regarding the EDSP Tier I screens are resolved. 

CLA/EPF appreciates the opportunity to provide input to the Agency on implementation of the EDSP, in 

particular these comments regarding the second list. We urge the Agency to consider these concerns and 

suggestions as it implements the Phase 2 of its EDSP. These are contained in the attached detailed 

comments.

Please contact me at wjones@croplifeamerica.org or at 202-872-3885 if you have any questions.

Sincerely,

Wendelyn Jones, Ph.D.

Senior Director, Human Health Policy

CropLife America

Attachment
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Comment Response Document

Page 68

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 10

EPA Comment Code: 1040

Comment: Recommendation to apply lessons learned from initial Tier I testing prior to issuance of any 

further EDSP test orders:

Final data submissions for the first 67 chemicals undergoing EDSP Tier I screening are not due until 

beginning in October 2011 with deadlines continuing into 2012. However, this timeline is expected to be 

extended due to delays in receiving EPA responses to waiver requests based on OSRI. Given the above, 

EPA is not likely to complete its evaluation of these Tier I data until sometime in 2013. Also, CLA/EPF 

members have encountered a number of issues in the required EPA screens with List 1. It does not make 

sound scientific sense to begin testing a new group of chemicals (List 2) until these issues have been 

resolved. Therefore, consistent with the SAB/SAP recommendations (in the SAB EDSP Report) to 

initially screen 50-100 substances and to evaluate the performance of the individual assays and the 

battery as a whole, CLA/EPF encourages EPA to not issue test orders for List 2 chemicals or any other 

substances, until this assessment has been completed and issues with the initial Tier I screens are 

resolved. 

CLA/EPF is providing these comments to encourage EPA to proceed in a considered step-wise manner 

before issuing test orders on this new list of chemicals and initiate Phase 2 of the EDSP. We would like 

to note that under the first list of chemicals under the EDSP (in Phase 1), the test order recipients are still 

seeking the following information to best help with compliance by industry and implementation by the 

Agency: 

• Agency criteria used for evaluating ORSI submitted by Phase 1 test order recipients,

• Resolution of errors within the 890 Series Test Guidelines,

• Standard Evaluation Protocols for the 890 Series assay reports,

• Further clarity on the procedures the agency will use to consider the overall weight of evidence.

CLA/EPF echoes the sentiment from Executive Branch's Office of Management and Budget (OMB) 

Terms of Clearance [FN14: http://www.reginfo.gov/public/do/PRA View!CR ?ref_ nbr=200904-2070-

00 I] by encouraging EPA to implement OMB's specified terms. We believe that an initial focus on 

resolving many of the pending issues with the EDSP implementation under the first list of chemicals 

will ultimately enhance the integrity of the EDSP program.

Thank you for the opportunity to provide these comments. Please contact Dr. Wendelyn Jones at 

wjones@croplifeamerica.org or at 202-872-3885 if you have any questions.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see Response-toComments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published simultaneously 

with this comment response document.
EPA-OGWDW Final EDSP List 2 February 2013

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Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 1

EPA Comment Code: 1040

Comment: Comments from Monsanto Company on Alachlor EDSP Listing

January 18, 2011 

Steve A. Owens, 

Assistant Administrator 

Office of Chemical Safety and Pollution Prevention (OCSPP) 

US EPA Headquarters Ariel Rios Building 

1200 Pennsylvania Ave. NW 

Mail Code: 7101M 

Washington, D.C. 20460 

Re: Comments from Monsanto on the EPA proposal to issue a Second List of Chemicals for Tier 1 

Screening under the Endocrine Disruptor Screening Program, Docket ID: EPA-HQ-OPPT-2009-0477 

Monsanto appreciates the opportunity to provide comments to the EPA on the Second List of Chemicals 

for Tier 1 Screening (List 2). Docket ID: EPA–HQ–OPPT–2009–0477. Monsanto is submitting 

comments with regard to the herbicide active ingredient Alachlor (CAS number 15972-60-8) and two of 

its degradates, Alachlor ethanesulfonic acid (ESA) (CAS number 142363-53-9) and Alachlor oxanilic 

acid (OA) (CAS number 171262–17–2). 

In response to the Agency’s request for public comment on List 2 chemicals for Tier 1 screening under 

the EDSP, Monsanto is hereby submitting our formal comments (Docket ID: EPA–HQ–OPPT–2009–

0477). The general comments provided by Monsanto in this cover letter are followed by expanded 

comments in the attached document. Additionally, Monsanto is a member of Crop Life America’s 

Endocrine Policy Forum (CLA-EPF) and comments raised by CLA-EPF are incorporated herein. 

General comments: 

* It is imperative that the EPA meet the OMB terms of clearance and SAB/SAP recommendation for 

List 1 chemicals before proceeding with List 2. The „learn as we go‟ approach taken by OSCPP with 

List 1 should be fully concluded before test orders are issued for List 2.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company
EPA-OGWDW Final EDSP List 2 February 2013

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EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 5

EPA Comment Code: 1040

Comment: * Significant information is still required to complete implementation of the EDSP. This 

information includes standard evaluation procedures (SEPs) for evaluating other scientifically relevant 

information (OSRI) that can be submitted to meet one or more of the Tier 1 screens; resolution of errors 

identified within the 890 Series Test Guidelines; SEPs for the 890 Series assay reports; and further 

clarity on how the Agency will consider the overall weight of evidence in the interpretation of Tier 1 

screening data. Additionally, significant work is still required to complete development and validation of 

the Tier 2 tests required for compounds that are concluded to be positive in Tier 1 testing. Consequently, 

it is premature to issue test orders for List 2 compounds before development and validation of Tier 2 

tests, using the List 1 chemicals. 

* The Agency itself has already indicated in its comments on List 1 that it would be premature to 

include degradates, such as Alachlor ESA and Alachlor OA, for any EDSP screening and testing. 

Monsanto encourages the EPA to continue with this approach until the List 1 results have been fully 

interpreted.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see Response-toComments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published simultaneously 

with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 10

EPA Comment Code: 1040

Comment: Expanded comments to the EPA’s Endocrine Disruptor Screening Program Second List of 

Chemicals for Tier I Screening (“List 2”): 

Time is needed to realize lessons learned from initial Tier 1 screening with List 1 Chemicals before 

proceeding with List 2: 

Monsanto would like to emphasize the need for a comprehensive external review of EDSP results on an 

assay by assay basis as well as the performance of the Tier 1 Battery for List 1 chemicals before 

additional test orders are issued for List 2. Final data submissions for the first 67 chemicals undergoing 

Tier I screening will not begin until October 2011, with current submission deadlines continuing into 

2012. By prematurely issuing List 2, the Agency did not provide a sufficient period of time to 

adequately evaluate and improve the overall EDSP testing methodology before initiating valid and 

efficient testing for List 2 chemicals. Given the extraordinary overall cost of EDSP testing (both to the 

EPA and industry) for such a large number of compounds, the EPA should be prudent and judicious in 

its approach before issuing List 2 Test Orders. A tremendous number of test animals and a vast 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 71

expenditure of limited financial and manpower resources will be wasted unless the EPA shows more 

restraint in its regulatory approach. 

From the above, it is evident that the EPA rushed the publication of List 2, with a Congressional staff 

committee report serving as the only Legislative justification. It is imperative that the EPA meet the 

OMB terms of clearance and SAB/SAP recommendation for List 1 before proceeding with List 2. If the 

EPA chooses not to implement the SAB/SAP recommendation to review results for List 1 chemicals 

before issuing additional test orders for List 2, all benefits of such a review would be unrealized. The 

“learrn as we go” approach taken by OSCPP with List 1 should be fully concluded before test orders are 

issued for List 2. 

Additionally, significant information is still required to complete implementation of the program. This 

information includes standard evaluation procedures (SEPs) for evaluating other scientifically relevant 

information (OSRI) that can be submitted to meet one or more of the Tier 1 screens (and which the EPA 

is obligated to consider); resolution of errors identified within the 890 Series Test Guidelines for Tier 1 

screening; SEPs for the 890 Series assay reports; and further clarity on how the agency will consider the 

overall weight of evidence in the interpretation of Tier 1 screening data. 

Monsanto recommends that focus be placed on resolving all of the many pending issues with the EDSP 

implementation List 1 chemicals before test orders are issued for List 2. This approach will ultimately 

enhance the scientific rigor and integrity of the EDSP program.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see Response-toComments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published simultaneously 

with this comment response document.

Commenter Name: Kathleen Roberts

Commenter Organization: Methyl Tertiary Butyl Ether (MTBE) Consortium

EPA Document ID: EPA-HQ-OPPT-2009-4077-0053

Comment Part: 1

EPA Comment Code: 1040

Comment: Comments submitted by Kathleen M. Roberts, Manager, MTBE Consortium

January 18, 2011

Via E-Mail

Document Control Office (7407M)

Office of Pollution Prevention and Toxics

United States Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460-0001
EPA-OGWDW Final EDSP List 2 February 2013

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Re: Comments on Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 

Screening, EPA-HQ-OPPT-2009-0477

To Whom It May Concern:

These comments are submitted on behalf of the Methyl Tertiary Butyl Ether (MTBE) Consortium. 

[FN1: Consortium members include: Enterprise Operating LLC; Huntsman Corporation;

LyondellBasell Industries; and TPC Group.] The MTBE Consortium appreciates the opportunity to 

comment on the U.S. Environmental Protection Agency’s November 17, 2010, Federal Register notice 

announcing the second list of chemicals and substances for which EPA intends to issue test orders under 

the Endocrine Disruptor Program (EDSP). [FN2: 75 Fed. Reg. 70248 (Nov. 17, 2010).] The MTBE 

Consortium supports the identification, assessment, and management of substances that may pose a risk 

to human health or the environment due to disruption of the endocrine system. EPA’s tiered EDSP is an 

important step, but its purpose and goals will be compromised if EPA does not review available 

scientifically relevant information to ensure that appropriate substances are selected and evaluated in the 

EDSP. EPA should, where relevant information exists to satisfy Tier 1 screening and Tier 2 testing, take 

these results into account before deciding to devote additional time, effort, and other resources to basic 

Tier 1 screening. The Consortium urges EPA to focus its EDSP screening on requiring testing (with 

concomitant cost and animal use) for substances that do not already have available data under Tier 1 or 

Tier 2.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review. Also, please see general response to comment under EPA Comment Code: 1040 

Complete List 1- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Niamh McMahon

Commenter Organization: Dow AgroSciences LLC (DAS)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0054

Comment Part: 1

EPA Comment Code: 1040

Comment: Dow AgroSciences is submitting a comment to request consideration of a stepwise 

implementation for List 2 of EDSP

January 18, 2011

Document Control Office

Office of Pollution Prevention and Toxics (7407M)

U. S. Environmental Protection Agency

One Potomac Yard

2777 S. Crystal Drive

Arlington, VA 22202

ENDOCRINE DISRUPTOR SCREENING PROGRAM (EDSP): Comments on Second List of 

Chemicals for Tier 1 Screening

DOCKET ID NUMBER EPA-HQ-OPPT -2009-0477
EPA-OGWDW Final EDSP List 2 February 2013

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Page 73

Dow AgroSciences (DAS) appreciates the opportunity to submit comments on EPA's Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the "Draft EDSP List 2") 

as a fully engaged participant who is already responding to test orders issued under List 1 of this 

program. DAS is committed to conducting Tier 1 screening battery assays as best fits within the 

framework of currently available extensive toxicity and ecotoxicity datasets which pesticides are already 

required to have to obtain and maintain registration under FIFRA. As an active member of the 

Endocrine Policy Forum [FN1: The Endocrine Policy Forum is a consortium of CLA members and nonmember stakeholders formed to address the aggregate needs of the group with respect to technical 

guidance and regulatory policy in response to the implementation of the EPA Endocrine Disruptor 

Screening Program.] at Crop Life America we also endorse comments made by that organization in 

response to Federal Register Vol. 75, No. 221, November 11, 2010, pp 70248-70254.

In addition DAS would like to encourage EPA to consider proceeding in a step-wise manner taking into 

account progress made and experience gained on List 1 of EDSP before issuing test orders for List 2 

chemicals. The expected benefits of this approach are many and include enhancing the scientific and 

regulatory integrity of the entire EDSP:

• A 'timely re-evaluation of the battery of screening'

• Ability to assess the universe of chemicals for best practices for priority setting

• Real indication of laboratory capacity and appropriateness of current test order duration

• Creation and implementation of clear decision criteria using experience gained via evaluation of Tier 1 

for chemicals on List 1

Encouragement to take on board lessons learned from phase 1 of this program before moving forward 

has been message delivered to EPA by Congress, the SAB/SAP reviewing EDSP and OIRA in their 

Terms of Clearance for ICR for List 1 of EDSP.[FN2: http://www.reginfo.gov/public/do/PRA 

ViewICR?ref nbr=200904-2070-001] The strongest caution in this regard came from SAB/SAP on the 

potential detrimental nature of expanding the scope of this program too fast. 'Developing massive 

amounts of screening information on a large universe of chemicals does not necessarily expedite the 

development of the appropriate scientific underpinning that the Agency needs to broaden this effort. 

Consequently, the Subcommittee recommends that EPA should not expand the set of agents until it has 

validated systems and can apply clear decision criteria. [FN3: 3 

http://yosemite.epa.gov/sab%5Csabproduct.nsf/C8AB 

D41OE357DBCF85257193004C42C4/$File/ec13.pdf]

• DAS proposes that the optimal opportunity for EPA to engage in a 'timely re-evaluation of the battery 

of screening replacing outdated ones with updated, more efficient screens that have been validated' as 

mandated by House appropriations language [FN4: 'Congress's House Appropriations Committee report 

for EPA FY 2010 appropriations' (H.R. 2996, H. Rept. 111- 180)] is upon receipt of data from List 1 test 

order recipients. It is unlikely that there will be a more appropriate time in this ongoing endocrine 

program to pause and assess all 11 assays of Tier 1 in their entirety with a focus on the value each assay 

brings to the battery. In addition it would allow time to evaluate whether an assay should be replaced or 

revalidated before a screening battery commences for the chemicals on List 2.

• The same recommendation was made by the SAP/SAB for a mid-course evaluation: “There was broad 

support among the Subcommittee for the concept that the Agency should convene a panel of 

independent scientists to review all the screening data for 50-100 compounds, with an eye towards 
EPA-OGWDW Final EDSP List 2 February 2013

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revising the process and eliminating those methods that don't work. , [FN5: 

http://yosemite.epa.gov/sab%5Csabproduct.nsf/C8ABD41OE357DBCF8525 

7193004C42C4/$File/ec13.pdf ] Failure to critically evaluate the performance of the Tier 1 battery prior 

to issuing test orders for List 2 could lead to excessive waste of animals in testing. 

• The SAB/SAP has also suggested [FN6: "The Subcommittee strongly encourages the Agency to 

include more and better-detailed case studies in the evolution of the priority-setting scheme. This will 

facilitate a realistic test of the plan, checking the sensitivity of the system and its practicality to prioritize 

properly chemicals for further testing. "] that case studies are needed to evolve the priority setting for the 

long term success of the program and such case studies could be provided by full assessment of the Tier 

1data from the chemicals on List 1. These data could be used then to establish a science based priority 

listing for a second list of chemicals. Furthermore, evolving relevant scientific tools (e.g. ToxCast) may 

assist in prioritizing chemicals for future proposals for entry into the EDSP

• By waiting to issue a second round of test orders EPA would gain an opportunity to optimize test order 

language and duration based on experiences from the first 67 chemicals through Tier 1 of the program. 

By late 2011 it will be clear if current test order recipients can complete Tier 1 test orders within 2 years. 

Concern for sufficient laboratory capacity to be able to complete the testing in the mandated timeframe 

continues to be felt by industry and setting a schedule for a second larger list could compound the 

capacity issues. At a minimum evaluation of the ability of laboratories to cope with an additional 25 test 

orders per year should be carried out to ensure that timing and duration of test order issuance for List 2 

is realistic and appropriate.

• DAS, as an active participate in Tier 1 data collection, continues to seek clarity on the evaluation and 

decision making implications of data gathered within Tier 1. 'Clear decision criteria' from EPA for a 

chemical to move into Tier II of the program remains elusive to participants in the program. The draft 

Weight of Evidence (WoE) documentation published on Nov 4th2010 in the Federal Register [FN7: 

Federal Register,Volume 75, Number 2l3, pages 67963-67965] offers only general considerations and 

standard evaluation procedures remain unavailable. Without this guidance for List 1 chemicals DAS 

intreprets OIRA's Terms of Clearance for the Tier 1 screening ICR as unsatisfied and thus a hurdle to 

issuance of List 2 test orders. [FN8: http://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=200904-

2070-001]

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Also, please see general 

response to comment under EPA Comment Code: 2100 Pesticide Registration Review Issues. In 

addition, please see Response-to-Comments for the Endocrine Disruptor Screening Program’s Draft 

Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) and

Response to Comments on the Public Review Draft of the Information Collection Request (ICR) entitled: 

“Addendum for the Second List of Chemicals; Tier 1 Screening of Certain Chemicals Under the 

Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that are being published 

simultaneously with this comment response document.

Commenter Name: Niamh McMahon

Commenter Organization: Dow AgroSciences LLC (DAS)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0054

Comment Part: 3
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Page 75

EPA Comment Code: 1040

Comment: At this interim stage in the program DAS would welcome, above all else, tools to be 

developed and made available that will guide agency decisions on whether a chemical must proceed to 

Tier II, including the Weight of the Evidence Approach and Standard Evaluation Procedures. It is a 

critical step and DAS encourage EPA to focus full attention on this area for List 1 before expanding the 

scope of the program to List 2.

Sincerely,

Niamh McMahon

Regulatory Leader

Dow AgroSciences LLC

(317) 337-4609

e-mail: nmcmahon@dow.com

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Susan Van Volkenburg

Commenter Organization: LANXESS Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0061

Comment Part: 1

EPA Comment Code: 1040

Comment: January 14, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, DC 20460-0001

Submitted via Federal eRulemaking Portal: http://www.regulations.gov RE: Comments on "Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening" [75 FR 70248; 

11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

Dear Mr. Owens;

Thank you for the opportunity for LANXESS Corporation to comment on the EPA's Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening. LANXESS is concerned 

that the EPA may be issuing test orders for these new substances prematurely. The EDSP is still a new 

testing program that is being implemented under new statutory authority. It requires a suite of newly 

validated test methods with which the Agency and industry have little experience. Tier 1 screening costs 

may run as high as $500,000 to $1,000,000 per substance and utilize a significant number of lab 

animals; Tier 2 testing costs could reach several million dollars per substance. Given the expense of 

endocrine screening and testing, and the lack of experience with the EDSP screening and testing assays 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 76

and the Tier 1 battery, it is imperative that the Agency proceed to collect and analyze data from the 

initial set of EDSP substances before proceeding to additional substances.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 5

EPA Comment Code: 1040

Comment: Full evaluation of Tier 1 utility should be conducted before testing additional substances:

Final data submissions for the first 67 pesticides or pesticide inerts undergoing EDSP Tier 1 screening 

are not due until beginning in October 2011 with deadlines continuing into 2012. However, this timeline 

is expected to be extended due to delays in receiving EPA responses to waiver requests based on OSRI. 

Given the above, EPA is not likely to complete its evaluation of these Tier I data until sometime in 

2013. EPA will not have an opportunity to apply "lessons learned" from the List 1 Tier I testing program 

before issuing List 2 test orders.

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 1

EPA Comment Code: 1040

Comment: January 18, 2011

Office of Science Coordination and Policy

Environmental Protection Agency

1200 Pennsylvania Ave. NW

Washington, DC 20460-0001

Attention: Docket No. EPA-HQ-OPPT-2009-0477

Comments: Endocrine Disruptor Screening Program (EDSP) Lis1 2 of Chemicals for Tier 1 Screening 

(Ethylene thiourea) 75 Federal Register, November 17, 2010 (70248-70254).

Dear Sir/Madam:

These comments address the potential inclusion of ethylene thiourea (ETL) on the second list of 

chemicals (List 2) for Tier I screening to be included in the Endocrine Disruptor Screening Program 

(EDSP). The comments arc submitted by the EBDC FTC Task Force, whose members include BASF 

Corporation, Dow AgroSciences, .LC, E.I du Pont de Nemours and Company and United Phosphorus, 

inc. The members of the E BDC/ETU Task Force are not manufacturers or suppliers of ETU. Rather, the 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 77

members are registrants of an ethylene bisdithiocarbamate (EBDC) fungicide (either rnancozeb or 

metiram), used to protect various specialty crops against various fungi. ETU is a minor impurity, 

common metabolite and breakdown product of the EBDC fungicides.

On November 17, EPA published a list of chemicals to be included in the second list of chemicals for 

Tier I screening for the EDSP (75 FR 70248-70254) (“List 2”). ETU was included in List 2 on the basis 

of the Safe Drinking Water Act (SDWA). (ibid) Pursuant to EPA’s request for comments, we do not 

believe it is appropriate to include ETU on List 2 for the reasons described below. ETU is rarely found 

in drinking water. Additionally, a considerable database of toxicology studies already exists for ETU. 

Additional, extensive studies are underway in response to Data-Call-In Requirements that will provide 

significant information on the endocrine effects of ETU. 

As the EDSP evolves, we recommend that the Agency apply lessons learned from initial Tier 1 testing 

Final data submissions for the first 67 chemicals undergoing EDSP Tier 1 screening are not due until 

beginning in October 2011, with deadlines continuing into 2012. Thus, the timing of List 2 test orders 

should take into account the time EPA will need evaluate the initial Tier 1 data. It is premature to 

continue requesting data generation until the Tier 1 resting has yielded results. Further, pesticides 

included in the list should take into account the schedule in place for Registration Review as EPA has 

stated this is the program under which the EDSP testing will be evaluated.

The program requires tremendous resources both by the regulated industry and by the Agency, and we 

believe that public dialogue is key to the successful implementation of the EDSP. As members of the 

EPA know first hand, Tier I screening costs between $500,000 and $ 1,000,000 per chemical (not 

including efforts to comply with a Test Order which the EPA has determined is significant just to 

respond to the Test Order initially and Submit Other Scientifically Relevant Information [FN1: 

www.regulations.gov Docket Number EPA-HQ-OPPT-2007-1081]).

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. Please see general response to 

comment under EPA Comment Code: 2100 Pesticide Registration Review Issues.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 6

EPA Comment Code: 1040

Comment: Additionally, we urge EPA to refrain from listing or issuing new test orders until the Agency 

has had an opportunity to properly evaluate functioning of the Tier I batter. This recommendation is in 

line with the SAP/SAB recommendation to collect and analyze data from List I before proceeding to 

additional substances. 

Given that the focus of List 1 is potential presence of a chemical in drinking water and potential 

substantial exposure to the human population, we recommend that pesticides which do not fulfill both 

criteria as outlined in Table 1 (page 70252) of the Federal Register Notice (FR 75, No 221 Wednesday, 

November 17, 2010) be removed from List 2. In describing the method for inclusion of chemicals on 

List2, an emphasis is placed on potential contamination of drinking water.
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Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code: 

1040 Complete List 1- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 9

EPA Comment Code: 1040

Comment: Recommend to apply lessons learned from the initial Tier 1 testing:

Final data submissions for the first 67 chemicals undergoing EDSP Tier I screening are not due until 

beginning in October 2011 with deadlines continuing into 2012. However, this timeline is expected to be 

extended due to delays in receiving EPA responses to waiver requests based on OSRI. Given the above, 

EPA is not likely to complete its evaluation of these Tier I data until sometime in 2013. EPA will not 

have an opportunity to apply “lessons learned” from the List I Tier I testing program before issuing List 

2 test orders. We believe it is inappropriate to begin any testing of List 2 materials until EPA has had 

sufficient time to review the results from List I.

In addition, contact lab availability due to the extensive test requirements of the EDSP assays has led to 

numerous extensions in the testing of List I compounds. 

Finally, as part of lessons learned there are numerous problems encountered with the validation and test 

protocols of the Tier I assays to the point where registrants and testing contract labs have reached a 

standstill in the testing of list I molecules until the issues are resolved. 

We therefore request no new testing occur until all issues with the Tier I EDSP assays are resolved and 

all List 1 molecules have been tested and EPA has had a chance to review all results from the List 1 

molecules to make sure the assays are in fact meeting the goal of the EPA -- to identify the potential 

endocrine disruptors. 

The Task Force is providing these comments to encourage EPA to proceed in a considered step-wise 

manner before issuing new test orders on List 2 chemicals including ETU. Case in point: List 1 test 

order recipients are still seeking the following information to best help with compliance by industry and 

implementation by the Agency:

*SEPs for OSRI,

*resolution of errors with the 890 Series Test Guidelines,

*SEPs for 890 Series assay reports,

*further clarity on how the agency will consider the overall weight of evidence.

We believe that an initial focus on resolving many of the pending issues with the EDSP implementation 

under the first list of chemicals will ultimately enhance the integrity of the EDSP program and thus ask 

that testing be suspended for list 2 until this occurs for List 2.

In conclusion, it is not appropriate to include ETU on List 2 for the EDSP.
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Please contact me at (215) 361-0355 or janetollinger@cs.com if you have any questions.

Sincerely,

Janet Ollinger, PhD

Chairperson

EBCD/ETU Task Force

Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2. 
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EPA Comment Code: 1050 Evaluation Criteria Review

General Response: EPA intends to use the best available data and will consider the scientific 

robustness of exposure data sources for future efforts. However, EPA’s intentions during the 

development of the second EDSP list were not to list “chemicals with the greatest potential to disrupt 

endocrine systems.” As described in the draft second list of chemicals for Tier 1 screening, 75 FR 

70248, November 17, 2010 (USEPA, 2010b), the chemicals to be screened under EDSP are priority 

chemicals for both the drinking water and pesticide programs. The basic criteria for list 2 chemical 

selections were chemicals that 1) met the criteria of SDWA 1457 and/or 2) were pesticides scheduled for 

Registration Review for years FY 2007 and 2008. The chemical selection process used to develop the 

second EDSP list did not place any weight on the chemicals potential endocrine disruptor effects. At this 

time EPA believes that these chemicals or substances should be candidates, at least for screening 

purposes, under EDSP testing based only on their pesticide registration status and/or because such 

substances may occur in sources of drinking water to which a substantial population may be exposed. 

The agency explained in the Federal Notice, 72 FR 33486, June 18, 2007 (USEPA, 2007), the 

difficulties in implementing the Endocrine Disruptor Screening and Testing Advisory Committee 

(EDSTAC) recommendations at that time noting: EPA anticipates that it may, in the future, modify its 

approach to selecting chemicals for screening. Information and factors that EPA may consider in 

selecting chemicals could include: public input; the results of testing chemicals on the initial list; 

management considerations to increase the integration of screening with other regulatory activities 

within the agency; implementation considerations flowing from a decision to extend screening to 

additional categories of chemicals (e.g., non-pesticide chemical substances); and the availability of new 

priority-setting tools (e.g., High-Throughput Pre-Screening (HTPS) or Quantitative Structure Activity 

Relationship (QSAR) models). 

EPA acknowledges that for some of the chemicals listed on the second EDSP list there may be existing 

data relevant to the Tier 1 screening test. Some of these data may have been used in EPA’s health 

assessments. For information on data used in EPA’s health assessments, visit http://www.epa.gov/IRIS/. 

In addition, data from the second group of EDSP chemicals and substances may have some utility in the 

context of drinking water regulations. Please see general response to comment under EPA Comment 

Code: 1070 Increase Transparency for additional information. 

Order recipients will have an opportunity to submit any relevant data to the Tier 1 assays or Other 

Scientifically Relevant Information (OSRI) as part of their initial response to receiving an order. For 

specific information on submitting or citing existing data or other OSRI, please see Endocrine Disruptor 

Screening Program; Final Policies and Procedures for Screening Safe Drinking Water Act Chemicals, 

(USEPA, 2012a) that is being published simultaneously with this comment response document.

EPA is currently developing new capabilities that utilize computational toxicology methods. An 

EDSP21 Work Plan has been developed that describes an approach for using computational or in silico

models and molecular-based in vitro high-throughput (HTP) assays to prioritize and screen chemicals to 

determine their potential to interact with the estrogen, androgen or thyroid (E, A, or T) hormonal 

systems. This work plan can be accessed at 

http://www.epa.gov/endo/pubs/edsp21_work_plan_summary%20_overview_final.pdf.

Please also see general response to comment under EPA Comment Code: 1020 Continue Use of 

Qualifying Language.
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Individual Comments

Commenter Name: Sushma Bhatia et al.

Commenter Organization: San Francisco REACH Team

EPA Document ID: EPA-HQ-OPPT-2009-0477-0012

Comment Part: 1

EPA Comment Code: 1050

Comment: Please find attached comments on the Second list of chemicals for tier 1 screening (EPA 

Docket # EPA-HQ-OPPT-2009-0477). If you have any questions, please contact Sushma Bhatia at 

415.355.3758.

December 17, 2010

William Wooge, 

Office of Pollution Prevention and Toxics (OPPT)

Document Control office (7407M)

U.S. Environmental Protection Agency (EPA)

1200 Pennsylvania Ave.

NW. Washington, DC 20460–0001

RE: Endocrine Disruptor Screening program (EDSP) - Second list of chemicals for tier 1 screening; 

EPA Docket # EPA-HQ-OPPT-2009-0477 

Dear Mr. Wooge, 

We, the San Francisco Fellows of the UCSF-EPA REACH Fellowship program, respectfully submit 

comments to the second list of chemicals for Tier 1 screening published on 11/17/10. We applaud the 

EPA’s work to build momentum on the Endocrine Disruptor Screening Program (EDSP), and support 

EPA's efforts to provide the public with this essential information. While we recognize that this list 

represents a tremendous leap forward in identifying chemicals to screen for endocrine disruption 

impacts, we are concerned that the second list is inadequate to meet the goal of evaluating chemicals for 

endocrine disrupting properties because it excludes some of the most strongly suspected endocrine 

disrupting chemicals and are disappointed that it underutilizes the opportunity presented by the EDSP to 

proactively protect human health. The EPA’s efforts to identify endocrine disrupting chemicals have the 

potential to serve a vital role in protecting human health and reducing disproportionate impacts on 

vulnerable communities and populations. However, the success in attaining this potential requires that 

chemicals that undergo Tier 1 testing include those with strong suspicion of endocrine disrupting 

properties. 

According to the 1998 EDSTAC final report[FN1: EPA (1998). Endocrine Disruptor Screening and 

Testing Advisory Committee (EDSTAC) Final Report. 

http://www.epa.gov/endo/pubs/edspoverview/finalrpt.htm]

“Only some chemicals are likely to cause endocrine disruption, and only some of these chemicals will 

be produced or used in such a fashion that humans or other living organisms will be exposed to them. 

Because screening and testing can be such a resource-intensive process for both the public and private 
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sectors, priorities must be set carefully to ensure that the chemicals of greatest concern are given priority 

“ 

Although EPA intends to identify the chemicals with the greatest potential to disrupt endocrine systems, 

it is clear from the methodology used to develop the second list that only chemicals that have been 

identified for reasons aside from endocrine disrupting properties are being considered for screening. 

Since chemicals whose primary modes of concern emerge as a result of their capacity to disrupt 

hormones are not included in the screening, the second list falls short of EPA’s goal.

In the comments below, we provide details on our two central concerns about the second list -

1. The inadequacy of the methodology used to develop the list and the resulting exclusion of chemicals 

with strong evidence of endocrine disruption properties (in Section 1.0); and 

2. The lack of clarity on the timeline for implementation (Section 2.0) and the lack of integration into 

existing EPA protocols. 

In Section 3.0, we provide examples of chemicals that we propose adding to the list for Tier 1 testing, 

along with technical references to support their addition, and propose an alternate mechanism for 

identifying chemicals for Tier 1 screening and integrating screening into existing EPA protocols in 

Section 4.0.

1.0 Methodology used to develop the second list is unclear and inadequate 

* According to EPA, the second list is a compilation of the pesticides that were scheduled for 

registration review during fiscal year 2007-2008 and chemicals listed in CCL3. By only considering new 

pesticides and potential drinking water contaminants, EPA has excluded a number of chemicals (or 

chemical groups) for which there is strong evidence of endocrine disruption and does not allow for 

inclusion of several potential endocrine disruptors based on emerging science. Some examples detailed 

below include: phthalates, bisphenol A (BPA) and triclosan. 

* Although EPA selected over 200 data sources to identify contaminants for CCL3, the data sources 

ultimately considered for inclusion were ones that represented a reasonable pathway to drinking water 

occurrence, in addition to adverse health impacts. Of the 5100 chemicals with only heath impact data, 

EPA ultimately included only 122 chemicals posing the greatest toxicologic concerns, i.e. the endocrine 

disruption properties were not considered in the selection process. In addition, in an effort to refine the 

diverse list of chemicals, while taking into account their production and health impact data, EPA 

considered only chemicals that were produced in quantities greater than 1 billion pounds on an annual

basis. 

* There is no mechanism for addition of non-pesticide chemicals of high public concern prior (due to 

evidence of bioaccumulation and exposure and/or high consumption) to the month-long public comment 

period on a developed list. 

*EPA does not explain why only new pesticide registration candidates for 2007-2008 are included in 

this list.
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Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Sushma Bhatia et al.

Commenter Organization: San Francisco REACH Team

EPA Document ID: EPA-HQ-OPPT-2009-0477-0012

Comment Part: 3

EPA Comment Code: 1050

Comment: 3.0 Timelines for implementation should be clearly outlined 

The deadline set for EPA by the U.S. Congress for creating and implementing the second list of 

chemicals for Tier 1 screening is inadequate. The House Appropriations Committee report for EPA’s FY 

2010 appropriations directed EPA to “publish within 1 year of enactment a second list of no less than 

100 chemicals for screening . . . and issue 25 orders per year for the testing of these chemicals.” This 

broad and open-ended timeline provides little direction to affected agencies, and fails to ensure that the 

protection of public health is EPA’s highest priority. 

We respectfully request that EPA develop a more precise timeline for implementing changes and 

additions to the EDSP and communicate it to all relevant federal agencies, as well as the public. More 

specifically, we propose that EPA establish and publish in the Federal Register by July 1, 2011 its 

annual performance measures and goals for creating and implementing the second list of chemicals for 

Tier 1 screening. We also propose that EPA publish an update every year on July 1, beginning on July 1, 

2013. These measures and goals should include: (1) the current status of the testing of the second list of 

chemicals (e.g., the number of chemicals on the second list that have been tested), (2) the future 

schedule for testing the remainder of chemicals on the second list in both the current and succeeding 

fiscal years, and (3) the projected year of completion of the testing of the entire second list of chemicals.

Response: Please see the U.S. Environmental Protection Agency Endocrine Disruptor Screening 

Program Comprehensive Management Plan (USEPA, 2012e). Also, please see general response to 

comment under EPA Comment Code: 1050 Evaluation Criteria Review.

Commenter Name: John Jachetta

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0014

Comment Part: 2

EPA Comment Code: 1050

Comment: SDWA specifies that the list (CCL) must include contaminants that are not subject to any 

proposed or promulgated NPDWRs, are known or anticipated to occur in public water systems (PWSs), 

and may require regulation under SDWA [73 FR 33486, February 21, 2008 p. 9629]. With a stated 

scope that includes 'anticipated' presence in public water systems, DAS does not believe that CCL3 is an 

appropriate selection for prioritization of a list 2 for the EDSP program, which clearly specifies that the 

administrator needs to determine that a 'substantial population may be exposed to such a substance'. 

DAS believes that chemicals listed on CCL3 do not a priori meet that SDWA requirement for testing 
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under EDSP and therefore, List 2 is not a definitive, scientifically rigorous list of chemicals with a high 

potential for human exposure.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 2

EPA Comment Code: 1050

Comment: The chemicals on the second list were selected from those designated as priority chemicals 

by either the Office of Water or the Office of Pesticide Programs. EPA began with drinking water 

contaminants, both regulated (85 chemicals), and unregulated contaminants listed on the third 

Contaminant Candidate List (CCL 3) (116 chemicals). EPA has determined that CCL 3 chemicals “may 

occur in sources of drinking water,” and that “a substantial population may be exposed to such 

substance...” (emphases added) (EPA 2010a).

EPA stated that election of pesticides was based on those that were scheduled for Registration Review 

during FY 2007 and 2008 (59 chemicals). From this potential list of 260 chemicals, 113 were selected 

for inclusion in the second list of potential chemicals for EDSP screening. 

Screening all 113 chemicals in the battery of 11 Tier 1 tests would kill more than 67,000 animals and 

cost anywhere from $53 to $144 million. Justification thus far provided for the need and use of 

endocrine related information does not support a testing program of this magnitude. Our comments 

present information available for a subset of the chemicals on the second list that would preclude the 

need for testing those chemicals in the EDSP Tier 1 assays. 

Exemptions 

In this FR notice, EPA cites only one general exemption, the exemption from FFDCA for substances 

that are “anticipated not to produce any effect in humans similar to an effect produced by a naturally 

occurring estrogen.” (21 U.S.C. 346 a(p)(4)). In contrast, the description of the first list of chemicals 

contained an expanded and clarified exemption, excluding “substances anticipated to have low potential 

to cause endocrine disruption (e.g., certain Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 

List 4 inerts, most polymers with number average molecular weight greater than 1,000 daltons, strong 

mineral acids, and strong mineral bases).” EPA also excluded from the first list “’positive control’ 

substances that are being used by EPA to validate screening assays proposed for the Tier 1 battery” and 

“chemicals that are no longer produced or used in the U.S.” The draft supporting statement for the 

Information Collection Request that applies to this Phase I chemical list describes a potential response to 

testing orders as “Additional EDSP screening is unnecessary because the chemical is an endocrine 

disruptor or was used as a “positive control” in the EDSP validation effort” (EPA 2010b). These 

additional exemptions should be listed here as well.
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During the selection of chemicals for the second list, the list of potential chemicals was “streamlined” by 

excluding: 1) biological and naturally occurring substances, 2) chemicals for which manufacturer, 

importer or registrant cannot be identified, 3) chemicals on first EDSP list, 4) hormones with confirmed 

endocrine effects, 5) chemicals not likely to be biologically active or have properties incompatible with 

testing, and 6) pesticides scheduled for registration review after FY 2008. 

Many of the chemicals on this list have significant existing information that would preclude further 

testing. In addition, several are no longer in production or use in the U.S., and therefore mitigation by 

restricting use is not possible. For these chemicals there is also the question of whether a substantial 

population is, in fact, exposed, and who would be responsible for testing (i.e., who would receive the 

test orders). Rather than issuing blanket test orders for this extensive list of chemicals, existing 

toxicological and exposure information should be evaluated to determine the regulatory need for 

information regarding endocrine disrupting potential prior to consideration of further testing.

EPA has begun using (Q)SAR and read-across to bolster information on chemicals under the purview of 

it pesticides program, after using similar strategies in the “toxics” program for decades. In its proposed 

rule to revise Part 158W [antimicrobial pesticide] testing requirements, it stated its interest in using 

QSAR and read-across to fill data gaps where appropriate (EPA 2008a). Furthermore, within the High 

Production Volume (HPV) Challenge Program and the Chemical Assessment and Management Program 

(ChAMP), EPA has had relatively good success utilizing categorization and read-across to cut down on 

the amount of testing (and thus animals and time used) while assessing large numbers of chemicals at 

once. Indeed a few of the substances on this second list were tested under the HPV challenge (1,2,4-

trichlorobenzene and 1,2-dichloropropane). We urge the agency to use QSAR and read-across 

technology and concepts for easily grouped candidate chemicals—such as the organochlorides—instead 

of ordering testing for each substance for each assay

Response: The agency has an obligation to minimize testing and plans on issuing exemptions in the 

future; however, as of June 25, 2012, the agency has not issued any FFDCA exemption orders. The 

exclusion of a chemical from a list of chemicals designated to receive FFDCA orders is not an FFDCA 

408(p) exemption order. The agency will take the other commenter’s exemption suggestions under 

advisement. Lastly, the full context of the exemption language associated with the release of the List 1 

chemicals for Tier 1 screening provided in the EDSP policies and procedures notice published April 15, 

2009 (74 FR 17560) are provided below [emphasis added]:

Request an exemption under FFDCA section 408(p)(4). EPA recognizes that FFDCA section 

408(p)(4) provides that “the Administrator may, by order, exempt from the requirements of this 

section a biologic substance or other substance if the Administrator determines that the substance 

is anticipated not to produce any effect in humans similar to an effect produced by a naturally 

occurring estrogen.” In 1998, the agency assessed the need to develop a specific list of 

substances to be exempted from EDSP testing or an exemption process for those substances that 

might not be anticipated to produce endocrine effects in humans (See Unit VI.L. of the 

December 1998 notice at 63 FR 71542). In the 1998 FR notice, EPA also provided several 

examples of substances that might possibly be exempted. As the EDSP has evolved and more 

endocrine research has been conducted, it has become evident that, at this time, development of 

criteria to exempt certain substances or to otherwise identify any pre-determined or blanket

exemptions from endocrine disruptor testing is premature.

For the initial screening, EPA is not aware of sufficient data that would allow the agency to 

confidently determine that a chemical meets the statutory standard for an exemption--i.e., that it 

is not anticipated to interact with the endocrine system. Although a relatively broad range of 
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toxicity data are available for pesticide active ingredients regulated under FIFRA, in most cases 

EPA has not yet established how the available data might be confidently used to predict the 

endocrine disruption potentials of these chemicals. This may be due to the non-specific nature of 

an effect or effects observed, questions related to whether the mode of action in producing a 

given effect or effects is or are endocrine system-mediated in whole or in part, or the lack of 

relevant data to make a judgment altogether.

However, if an order recipient believes that this showing can be made for its chemical, the 

agency would consider requests to issue such an exemption order on a case-by-case or chemicalby-chemical basis in response to individual submissions. In order for the agency to make the 

necessary statutory finding to issue the exemption, the request would need to provide any 

hazard-related information that you believe would allow EPA to determine that your chemical is 

anticipated to not be an endocrine disruptor, i.e., is not anticipated “to produce any effect in 

humans similar to an effect produced by a naturally occurring estrogen”.

Please also see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review and general response to comment under EPA Comment Code: 2020 Contaminants No Longer 

Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled Registrations. 

Please also see Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published simultaneously with this 

comment response document.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 16

EPA Comment Code: 1050

Comment: IV. Substances screened in ToxCastTM assays 

Of the proposed chemicals slated for Phase II EDSP Tier 1 testing, 30 (acetochlor, alachlor, bensulide, 

clofentzine, clomazone, coumaphos, cyanamide, cyromazine, dicrotophos, diuron, ethylene thiourea, 

fenamiphos, fenarimol, fenoxycarb, flumetsulam, hexythiazox, isoxaben, lactofen, lindane, 

methoxychlor, molinate, oxyfluorfen, paclobutrazol, perfluoctane sulfonic acid, perfluorooctanoic acid, 

picloram, profenofos, propetamophos , quinclorac, thiophanate-methyl, triflumizole, vinclozolin) have 

been screened in ToxCast for many endpoints, including endocrine activity. ToxCast is a rapid screening 

tool that can be used to prioritize substances based on in vitro data combined with existing in vivo, 

biological pathway and exposure information (Reif, Martin et al. 2010). It has been used to evaluate 

chemical activities and effects across a broad spectrum of chemical classes (Reif, Martin et al. 2010; 

Judson, Houck et al. 2010a). ToxCast has been successfully used to screen for potential endocrine 

activity in oil dispersants used in the Gulf of Mexico following the Deepwater Horizon oil spill in 2010. 

Because of the urgent need for toxicity data on essentially uncharacterized commercial oil dispersants, a 

rapid assessment was necessary and highly effective for determining the endocrine disrupting potential 

of these substances. Judson et al concluded that “...we were able to detect specific bioactivities in 

complex chemical mixtures for time-sensitive environmental issues and using high-throughput screening 

assays” (Judson, Martin et al. 2010b). During the October, 2010 NTP Board of Scientific Counselors 

meeting, Director Birnbaum noted that the methods employed in Tox21 (which includes ToxCastTM) 
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offer a “huge opportunity” to screen a large number of environmentally relevant mixtures, with the 

information gained being used to reduce the number of animal studies required. 

In the above mentioned analysis of ToxCast focusing on endocrine activity, methoxychlor and its more 

active metabolite, HPTE, scored among the highest of the 309 chemicals tested (Reif, Martin et al. 

2010). Bensulfide and coumaphos scored relatively high; in contrast, flumetsulam and picloram were 

predicted to have little to no endocrine activity. Dicrotophos was predicted to be very active in 

reproductive and developmental assays. This information must be applied to prioritize chemicals on the 

second list and considered as OSRI for these chemicals.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 20

EPA Comment Code: 1050

Comment: Moreover, there is no rationale for requiring information on the possible endocrine activity 

of chemicals whose major toxicity has already been well characterized (e.g. the neurotoxic activity of 

acrylamide or the carcinogenic activity of benzene), especially substances banned or severely restricted 

due to their extreme hazards. This includes other listed chemicals, such as benzo(a)pyrene which 

although not covered in these comments, also fall into this category. In such cases, any testing to 

ascertain the likelihood of endocrine activity or mechanism of action is extremely unlikely to affect the 

chemical’s over-all risk analysis and is therefore a waste of resources and animals. With testing of the 

second list of chemicals having the potential to kill approximately 70,000 animals, any and all steps 

toward streamlining the testing must be taken. 

Thank you for considering our comments and we look forward to the agency’s positive response. 

Sincerely, 

Catherine Willett, PhD 

Science Policy Advisor 

Regulatory Testing Division 

People for the Ethical Treatment of Animals

Kristie Sullivan, MPH 

Science & Policy Advisor 

Physicians Committee for Responsible Medicine

Sue A. Leary 

President 

Alternatives Research & Development Foundation

Nina Mak 
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Research Analyst 

American Anti-Vivisection Society

References 

Abraham, P., G. Wilfred, et al. (1999). Oxidative damage to the lipids and proteins pf the lungs, testis 

and kidney of rats during carbon tetrachloride intoxication. Clin Chim Acta 289(1-2): 177-179. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10636716. 

Acquavella, J. F., S. G. Riordan, et al. (1996). Evaluation of mortality and cancer incidence among 

alachlor manufacturing workers. Environ. Health Perspect 104: 728–733. 

Agency for Toxic Substances and Disease Registry (ATSDR) (2000). Toxicological Profile for 

Polychlorinated Biphenyls (PCBs). (Division of Toxicology/Toxicology Information Branch, US 

Department of Health and Human Services): http://www.atsdr.cdc.gov/ToxProfiles/tp17.pdf. 

http://www.atsdr.cdc.gov/ToxProfiles/tp17.pdf. 

Alvarez-Pedrerol, M., N. Ribas-Fito, et al. (2008). Thyroid disruption at birth due to prenatal exposure 

to beta-hexachlorocyclohexane. Environ Int 34(6): 737-740. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

18207242. 

Andersen, H. R., E. C. Bonefeld-Jorgensen, et al. (2006). Estrogenic effects in vitro and in vivo of the 

fungicide fenarimol. Toxicol Lett 163(2): 142-152. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

16324804. 

Andrews, L. S., E. W. Lee, et al. (1977). Effects of toluene on the metabolism, disposition and 

hemopoietic toxicity of [3H]benzene. Biochem Pharmacol 26(4): 293-300. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

849319. 

ATSDR (2003). Toxicological Profile for Carbon Tetrachloride. (U.S. Department of Health and Human 

Services. Public Health Services, Atlanta, G.A.). 

ATSDR (2007). Toxicological Profile for Benzene.‖ U.S. Department of Health and Human Services. 

http://www.atsdr.cdc.gov/toxprofiles/tp3.pdf. 

Badejo, A. M., Jr., C. Hodnette, et al. (2010). Mitochondrial aldehyde dehydrogenase mediates 

vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. 

Am J Physiol Heart Circ Physiol 299(3): H819-826.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20543077. 

Barton, H. A. and H. J. Clewell, 3rd (2000). Evaluating noncancer effects of trichloroethylene: 

dosimetry, mode of action, and risk assessment. Environ Health Perspect 108 Suppl 2: 323-334. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10807562. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 89

Battelle, R. W. Brueggemeier, et al. (2007). Integrated summary report on aromatase. 

http://www.epa.gov/endo/pubs/aromatase_isr.pdf. 

Bauer, E. R., N. Bitsch, et al. (2002). Development of an immuno-immobilized androgen receptor assay 

(IRA) and its application for the characterization of the receptor binding affinity of different pesticides. 

Chemosphere 46(7): 1107-1115. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

11999774.

BCERF Program on Breast Cancer and Environmental Risk Factors (2004). Pesticides and breast cancer 

risk: Dibromochloropropane (DBCP) Factsheet #50. Cornell University. 

http://envirocancer.cornell.edu/FactSheet/pesticide/fs50.dbcp.cfm. 

Beard, A. P. and N. C. Rawlings (1999). Thyroid function and effects on reproduction in ewes exposed 

to the organochlorine pesticides lindane or pentachlorophenol (PCP) from conception. J Toxicol Environ 

Health A 58(8): 509-530. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10632142. 

Berger, T. and C. M. Horner (2003). In vivo exposure of female rats to toxicants may affect oocyte 

quality. Reprod Toxicol 17(3): 273-281. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

12759095. 

Bingham, E., B. Cohrssen, et al. (2001). Aliphatic nitro, nitrate, and nitrite compounds: nitroglycerin. 

Patty’s Toxicology. New York, John Wiley and Sons Volume 1-9: 5th ed. 

Blair, R. M., H. Fang, et al. (2000). The estrogen receptor relative binding affinities of 188 natural and 

xenochemicals: structural diversity of ligands. Toxicol Sci 54(1): 138-153. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10746941. 

Bond, J. A., J. P. Chism, et al. (1981). Induction of hepatic and testicular lesions in Fischer-344 rats by 

single oral doses of nitrobenzene. Fundam Appl Toxicol 1(5): 389-394. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7185588. 

Bruckner, J. V., R. Ramanathan, et al. (2002). Mechanisms of circadian rhythmicity of carbon 

tetrachloride hepatotoxicity. J Pharmacol Exp Ther 300(1): 273-281. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

11752126. 

Bryant, C. and M. DeLuca (1991). Purification and characterization of an oxygen-insensitive NAD(P)H 

nitroreductase from Enterobacter cloacae. J Biol Chem 266(7): 4119-4125. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

1999405. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 90

Burns, L. A., S. G. Bradley, et al. (1994). Immunotoxicity of nitrobenzene in female B6C3F1 mice. 

Drug Chem Toxicol 17(3): 271-315. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7988385. 

Bustard, M. A., G. Ryan, et al. (2003). Human maternal and fetal plasma glyceryl trinitrate 

concentrations. Am J Obstet Gynecol 189(6): 1777-1778. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

14710114. 

Cattley, R. C., J. I. Everitt, et al. (1994). Carcinogenicity and toxicity of inhaled nitrobenzene in 

B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol 22(3): 328-340. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8050629. 

Centers for Disease Control and Prevention (CDC) (2005). Third National Report on Human Exposure 

to Environmental Chemicals.

Chadwick, R. W., R. L. Cooper, et al. (1988). Possible antiestrogenic activity of lindane in female rats. J 

Biochem Toxicol 3: 147-158. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

2462049. 

Cheek, A. O., K. Kow, et al. (1999). Potential mechanisms of thyroid disruption in humans: interaction 

of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. 

Environ Health Perspect 107(4): 273-278. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10090705. 

Chico Galdo, V., C. Massart, et al. (2006). Acrylamide, an in vivo thyroid carcinogenic agent, induces 

DNA damage in rat thyroid cell lines and primary cultures. Mol Cell Endocrinol 257-258: 6-14. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

16859826. 

Cioroiu, M., D. Tarcau, et al. (2010). Organochlorine pesticides in colostrums in case of normal and 

preterm labor (Iasi, Romania). Sci Total Environ 408(13): 2639-2645. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20378154. 

Colborn, T., F. S. vom Saal, et al. (1993). Developmental effects of endocrine-disrupting chemicals in 

wildlife and humans. Environ Health Perspect 101(5): 378-384. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8080506. 

Commission for Environmental Cooperation (CEC) (2006). North American Regional Action Plan 

(NARAP) on lindane and other hexachlorocyclohexane (HCH) isomers. 

http://www.cec.org/files/PDF/POLLUTANTS/LindaneNARAP-Nov06_en.pdf. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 91

Cooper, R. L., R. W. Chadwick, et al. (1989). Effect of lindane on hormonal control of reproductive 

function in the female rat. Toxicol Appl Pharmacol 99(3): 384-394. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

2473543. 

Cosby, N. C. and W. R. Dukelow (1992). Toxicology of maternally ingested trichloroethylene (TCE) on 

embryonal and fetal development in mice and of TCE metabolites on in vitro fertilization. Fundam Appl 

Toxicol 19(2): 268-274. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

1516784. 

Dang, S. S., B. F. Wang, et al. (2007). Inhibitory effects of saikosaponin-d on CCl4-induced hepatic 

fibrogenesis in rats. World J Gastroenterol 13(4): 557-563. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

17278221. 

Dawson, B. V., P. D. Johnson, et al. (1993). Cardiac teratogenesis of halogenated hydrocarboncontaminated drinking water. J Am Coll Cardiol 21(6): 1466-1472. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8473657. 

Daxenberger, A. A. (2002). Pollutants with androgen-disrupting potency. Eur J Lipid Sci Technol 

104(2): 124–130. 

De Guzman, N. P., P. Hendley, et al. (2005). The acetochlor registration partnership state ground water 

monitoring program. J Environ Qual 34(3): 793-803. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843642. 

Di Consiglio, E., A. De Angelis, et al. (2009). Effect of lindane on CYP-mediated steroid hormone 

metabolism in male mice following in utero exposure. Journal of Applied Toxicology 29(8): 648-655. 

Dreher, D. and A. F. Junod (1996). Role of oxygen free radicals in cancer development. Eur J Cancer 

32A(1): 30-38. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8695238. 

Dybing, E. and T. Sanner (2003). Risk assessment of acrylamide in foods. Toxicol Sci 75(1): 7-15. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

12805639. 

Einert, C., W. Adams, et al. (1963). Exposure to Mixtures of Nitroglycerin and Ethylene Glycol 

Dinitrate. Am Ind Hyg Assoc J 24: 435-447. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

14059263. 

Ellis, H. V., 3rd, C. B. Hong, et al. (1984). Subacute and chronic toxicity studies of trinitroglycerin in 

dogs, rats, and mice. Fundam Appl Toxicol 4(2 Pt 1): 248-260. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 92

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

6427046. 

Engeler, E. (2009). UN: Treaty expanded by 9 more dangerous chemicals. Associated Press. May 9, 

2009. 

Environmental Protection Agency (EPA) (1987). Trinitroglycerol health advisory. (Office of Drinking 

Water, Washington, DC). 

http://yosemite.epa.gov/water/owrccatalog.nsf/e673c95b11602f2385256ae1007279fe/0d790163ac04d29

385256b06007255ec!OpenDocument. 

EPA (1998). Alachlor Reregistration Eligibility Decision (RED) - December 1998. (Office of 

Prevention, Pesticides and Toxic Substances. Washington, DC). 

www.epa.gov/oppsrrd1/REDs/0063.pdf. 

EPA (2000a). Testing of Certain High Production Volume Chemicals (65 FR 81657). 

http://www.epa.gov/fedrgstr/EPA-TOX/2000/December/Day-26/t32497.htm. 

EPA (2000b). 1,2-Dibromo-3-Chloropropane (DBCP) Hazard Summary. 

http://www.epa.gov/ttnatw01/hlthef/dibromo-.html. 

EPA (2002). Interim Reregistration Eligibility Decision (IRED): Fenamiphos. EPA 738-R-02-004, May 

2002. (Office of Prevention, Pesticides and Toxic Substances, Washington, DC). 

EPA (2004a). Cancellation of pesticides for non-payment of Year 2004 maintenance fees (69 FR 

62666). Docket No. EPA-HQ-OPP-2004-0338. http://www.regulations.gov/#!documentDetail;D=EPAHQ-OPP-2004-0338-0001. 

EPA (2004b). Methoxychlor Reregistration Eligibility Decision (RED). (EPA Publication No. EPA 738-

R-04-010). http://www.epa.gov/oppsrrd1/REDs/methoxychlor_red.htm. 

EPA (2006a). Cumulative Risk from Chloroacetanilide Pesticides (Acetochlor and Alachlor). (Office of 

Pesticide Programs - Health Effects Division, Washington, DC). 

www.epa.gov/pesticides/cumulative/chloro_cumulative_risk.pdf.

EPA (2006b). Pesticide News Story: Lindane Registrations Cancelled. 

http://www.epa.gov/oppfead1/cb/csb_page/updates/2006/lindane-order.htm. 

EPA (2006c). Addendum to the 2002 Lindane Reregistration Eligibility Decision (RED). 

http://www.epa.gov/oppsrrd1/REDs/lindane_red_addendum.pdf. 

EPA (2007a). EPA 40 CFR Parts 9 and 158: Pesticides; Data Requirements for Conventional Chemicals 

(72 FR 60934). http://www.gpo.gov/fdsys/pkg/FR-2007-10-26/pdf/E7-20826.pdf. 

EPA (2007b). Pyridate; Notice of Receipt of Requests to Voluntarily Cancel and to Terminate Uses of 

Certain Pesticide Registrations (72 FR 19491). Docket No. EPA-HQ-OPP-2007-0103. 

http://edocket.access.gpo.gov/2007/E7-7258.htm. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 93

EPA (2007c). Pyridate; Product Cancellation Order to Terminate Uses of Certain Pesticide Registrations 

(72 FR 65573). Docket No. EPA–HQ–OPP–2007–0103. http://edocket.access.gpo.gov/2007/pdf/E7-

22663.pdf. 

EPA (2007d). Chloroneb, Cypermethrin, Methidathion, Nitrapyrin, Oxyfluorfen, Pirimiphos-methyl, 

Sulfosate, Tebuthiuron, Thiabendazole, Thidiazuron, and Tribuphos; Proposed Tolerance Actions (72 

FR 24198). Docket No. EPA-HQ-OPP-2007-0036. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2007-0036-0001. 

EPA (2007e). Chloroneb, Cypermethrin, Methidathion, Nitrapyrin, Oxyfluorfen, Pirimiphos-methyl, 

Sulfosate,Tebuthiuron, Thiabendazole, Thidiazuron, and Tribuphos; Tolerance Actions (72 FR 53455). 

Docket No. EPA-HQ-OPP-2007-0036-0015. http://www.regulations.gov/#!documentDetail;D=EPAHQ-OPP-2007-0036-0015. 

EPA (2007f). Integrated summary report for the validation of an androgen receptor binding assay as a 

potential screen in the endocrine disruptor screening program. (Office of Science Coordination and 

Policy). http://www.epa.gov/scipoly/oscpendo/pubs/ar_binding_isr.pdf. 

EPA (2007g). Integrated summary report for validation of a test method for assessment of pubertal 

development and thyroid function in juvenile female rats as a potential screen in the endocrine disruptor 

screening program tier-1 battery. (Office of Science Coordination and Policy and Office of Research and 

Development). http://www.epa.gov/scipoly/oscpendo/pubs/female_isr_v4.1c.pdf. 

EPA (2007h). Integrated Summary Report for Validation of a Test Method for Assessment of Pubertal 

Development and Thyroid Function in Juvenile Male Rats as a Potential Screen in the Endocrine 

Disruptor Screening Program Tier-1 Battery. http://www.epa.gov/endo/pubs/male_pubertal_isr.pdf. 

EPA (2007i). Validation of the fish short-term reproduction assay: Integrated summary report. 

http://www.epa.gov/scipoly/oscpendo/pubs/fish_assay_isr.pdf. 

EPA (2008a). Proposed revisions to U.S. pesticide data requirements for antimicrobial chemicals (73 FR 

59382). Docket No. EPA-HQ-OPP-2008-0110. http://www.gpo.gov/fdsys/pkg/FR-2008-10-08/pdf/E8-

23127.pdf. 

EPA (2008b). Fenamiphos; Amendment to Use Deletion and Product Cancellation Order (73 FR 

75097). Docket No. EPA-HQ-OPP-2003-0200. http://edocket.access.gpo.gov/2008/E8-29223.htm. 

EPA (2009a). EPA’s Approach for Considering Other Scientifically Relevant Information (OSRI) under 

the Endocrine Disruptor Screening Program (EDSP). Docket No. EPA–HQ–OPPT–2007–1080-0032. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2007-1080-0032.

EPA (2009b). Petition to Revoke Tolerances for 13 Pesticides; Notice of Availability (74 FR 45200). 

Docket. No. EPA-HQ-OPP-2009-0629. http://www.gpo.gov/fdsys/pkg/FR-2009-09-01/html/E9-

21124.htm. 

EPA (2009c). Toxicological review of nitrobenzene: in support of summary information on the 

Integrated Risk Information System (IRIS). http://www.epa.gov/ncea/iris/toxreviews/0079tr.pdf. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 94

EPA (2010a). EPA Endocrine Disruptor Screening Program; Second List of Chemicals for Tier1 

Screening (75 FR 70248). http://www.epa.gov/endo/pubs/stakeholder/notices.htm. 

EPA (2010b). Supporting Statement for an Information Collection Request in: EPA Agency Information 

Collection Activities; Proposed Collection; Comment Request; Addendum for the Second List of 

Chemicals; Tier 1 Screening of Certain Chemicals under the Endocrine Disruptor Screening Program; 

IPA ICR No.: 2249.02 (75 FR 70568). Docket No. EPA-HQ-OPPT-2007-1081. 

http://69.175.53.6/register/2010/Nov/17/2010-28815.pdf. 

EPA (2010c). Technical Factsheet: Alachlor. 

http://www.epa.gov/safewater/pdfs/factsheets/soc/tech/alachlor.pdf. 

EPA (2010d). Consumer Factsheet on: 2,4,5-TP (Silvex). 

http://water.epa.gov/drink/contaminants/basicinformation/historical/upload/Archived-ConsumerFactsheet-on-2-4-5-TP.pdf. 

Erkekoglu, P. and T. Baydar (2010). Toxicity of acrylamide and evaluation of its exposure in baby 

foods. Nutr Res Rev 23(2): 323-333. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20843409. 

European Union - DG SANCO (2002). EU Pesticides Database. 

Felsot, A. S. (1998). Dinoseb – Banned But Not Forgotten: the Tale of An Unusually Hazardous 

Pesticide. Agrichemical and Environmental News. June, 1998, Washington State University: 

http://aenews.wsu.edu/June98AENews/Dinoseb--Banned.html. 

Gallagher, S. P., J. B. Beavers, et al. (1999a). Alachlor: A reproductive study with the Northern 

bobwhite (Colinus virginianus). Monsanto report number WL-97-142 Monsanto IIA, 8.1.3/01. 

Gallagher, S. P., J. B. Beavers, et al. (1999b). Alachlor: A reproductive study with the mallard (Anas 

platyrhynchos). Monsanto report number WL-97-144 Monsanto IIA, 8.1.3/02. 

Ghanayem, B. I., R. Bai, et al. (2010). Diet-induced obesity in male mice is associated with reduced 

fertility and potentiation of acrylamide-induced reproductive toxicity. Biol Reprod 82(1): 96-104. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

19696015. 

Goldstein, R. and e. al (1983). Pathophysiology of splenic toxicity in mice and rats following oral 

nitrobenzene (NB) administration. Toxicologist 3: 125 (Abstr). 

Guo, Y., R. Xie, et al. (2010). Maternal transdermal nitroglycerin use and early childhood development. 

J Obstet Gynaecol Can 32(12): 1147-1152. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

21176326. 

Gutteridge, J. M. (1995). Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin 

Chem 41(12 Pt 2): 1819-1828. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 95

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7497639.

Hackett, A. G., D. I. Gustafson, et al. (2005). The acetochlor registration partnership surface water 

monitoring program for four corn herbicides. J Environ Qual 34(3): 877-889. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843651. 

Hassold, E. and T. Backhaus (2009). Chronic toxicity of five structurally diverse demethylase-inhibiting 

fungicides to the crustacean Daphnia magna: a comparative assessment. Environ Toxicol Chem 28(6): 

1218-1226. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

19132812. 

Hines, M. (1992). Surrounded by estrogens? Considerations for neurobehavioral development in human 

beings. In: Chemically induced alterations in sexual and functional development: the wildlife/human 

connection. T. Colborn and C. Clement. Princeton, NJ, Princeton Scientific Publishing: pp. 261-281. 

Hoffmann, F. and W. Kloas (2010). An environmentally relevant endocrine-disrupting antiandrogen, 

vinclozolin, affects calling behavior of male Xenopus laevis. Horm Behav 58(4): 653-659. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20600051. 

Holder, J. W. (1999). Nitrobenzene carcinogenicity in animals and human hazard evaluation. Toxicol 

Ind Health 15(5): 445-457. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10487355. 

Horn, M. M., A. R. Ramos, et al. (2006). Seminiferous epithelium of rats with food restriction and 

carbon tetrachloride-induced cirrhosis. Int Braz J Urol 32(1): 94-99; discussion 99. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

16519836. 

Humphreys, E. H., S. Janssen, et al. (2008). Outcomes of the California ban on pharmaceutical lindane: 

clinical and ecologic impacts. Environ Health Perspect 116(3): 297-302. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

18335094. 

Imoto, S., M. Kuramoto, et al. (1986a). [Percutaneous chronic toxicity study of 10% nitroglycerin (NT-1 

ointment) in rabbits]. J Toxicol Sci 11 Suppl 2: 31-57. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

3093691. 

Imoto, S., M. Nakao, et al. (1986b). [Teratological test of 10% nitroglycerin (NT-1 ointment) in rabbits]. 

J Toxicol Sci 11 Suppl 2: 59-70. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

3093692. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 96

Integrated Risk Information System (IRIS) (2007). Benzene. (Integrated Risk Information System. 

Washington, DC: U.S. Environmental Protection Agency). http://www.epa.gov/iris/subst/0276.htm. 

Jerina, D., J. Daly, et al. (1968). Role of arene oxide-oxepin system in the metabolism of aromatic 

substances. I. In vitro conversion of benzene oxide to a premercapturic acid and a dihydrodiol. Arch 

Biochem Biophys 128: 176-183.

Jin, L., D. Q. Tran, et al. (1997). Several synthetic chemicals inhibit progesterone receptor-mediated 

transactivation in yeast. Biochem Biophys Res Commun 233(1): 139-146. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9144411.

Judson, R. S., K. A. Houck, et al. (2010a). In vitro screening of environmental chemicals for targeted 

testing prioritization: the ToxCast project. Environ Health Perspect 118(4): 485-492. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20368123. 

Judson, R. S., M. T. Martin, et al. (2010b). Analysis of eight oil spill dispersants using rapid, in vitro 

tests for endocrine and other biological activity. Environ Sci Technol 44(15): 5979-5985. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20602530. 

Kelce, W. R., E. Monosson, et al. (1994). In vitro and in vivo evidence that vinclozolin (V) is an 

environmental antiandrogen. Biology of Reproduction 50: 102. 

Khan, M. A., C. A. Davis, et al. (1999). Changes in thyroid gland morphology after acute acrylamide 

exposure. Toxicol Sci 47(2): 151-157. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10220851. 

Khan, M. R. and D. Ahmed (2009). Protective effects of Digera muricata (L.) Mart. on testis against 

oxidative stress of carbon tetrachloride in rat. Food Chem Toxicol 47(6): 1393-1399. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

19327381. 

Klotz, D. M., B. S. Beckman, et al. (1996). Identification of environmental chemicals with estrogenic 

activity using a combination of in vitro assays. Environ Health Perspect 104(10): 1084-1089. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8930550. 

Kojima, H., E. Katsura, et al. (2004). Screening for estrogen and androgen receptor activities in 200 

pesticides by in vitro reporter gene assays using Chinese hamster ovary cells. Environ Health Perspect 

112(5): 524-531. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15064155. 

Konings, E. J., A. J. Baars, et al. (2003). Acrylamide exposure from foods of the Dutch population and 

an assessment of the consequent risks. Food Chem Toxicol 41(11): 1569-1579. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 97

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

12963010. 

Kumar, A., R. Correll, et al. (2010). Toxicity of selected pesticides to freshwater shrimp, Paratya 

australiensis (Decapoda: Atyidae): use of time series acute toxicity data to predict chronic lethality. 

Ecotoxicol Environ Saf 73(3): 360-369. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

19914717.

La Sala, G., D. Farini, et al. (2010). Estrogenic in vitro assay on mouse embryonic Ledig cells. Int J Dev 

Biol 54: 717-722. 

Lash, L. H., J. W. Fisher, et al. (2000a). Metabolism of trichloroethylene. Environ Health Perspect 108 

Suppl 2: 177-200. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10807551. 

Lash, L. H., J. C. Parker, et al. (2000b). Modes of action of trichloroethylene for kidney tumorigenesis. 

Environ Health Perspect 108 Suppl 2: 225-240. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10807554. 

Lemaire, G., B. Terouanne, et al. (2004). Effect of organochlorine pesticides on human androgen 

receptor activation in vitro. Toxicol Appl Pharmacol 196(2): 235-246. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15081270. 

Levin, A. A. and J. G. Dent (1982). Comparison of the metabolism of nitrobenzene by hepatic 

microsomes and cecal microflora from Fischer-344 rats in vitro and the relative importance of each in 

vivo. Drug Metab Dispos 10(5): 450-454. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

6128191. 

Lindstrom, A. B., K. Yeowell-O'Connell, et al. (1997). Measurement of benzene oxide in the blood of 

rats following administration of benzene. Carcinogenesis 18(8): 1637-1641. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9276641. 

LoPachin, R. M. (2004). The changing view of acrylamide neurotoxicity. Neurotoxicology 25(4): 617-

630. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15183015. 

LoPachin, R. M., R. C. Jones, et al. (2003). Application of proteomics to the study of molecular 

mechanisms in neurotoxicology. Neurotoxicology 24(6): 761-775. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

14637371. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 98

M.H., M.M., et al. (2005). Preliminary report- Response of H295R Cells to the Exposure to Four Model 

Chemicals (Prochloraz, Aminoglutethimide, Forskolin, and Vinclozolin). 

http://www.epa.gov/scipoly/oscpendo/pubs/preliminary_report_method_development_studiesmodel_chemicals.pdf. 

Manson, J. M., M. Murphy, et al. (1984). Effects of oral exposure to trichloroethylene on female 

reproductive function. Toxicology 32(3): 229-242. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

6474485. 

Maples, K. R., P. Eyer, et al. (1990). Aniline-, phenylhydroxylamine-, nitrosobenzene-, and 

nitrobenzene-induced hemoglobin thiyl free radical formation in vivo and in vitro. Mol Pharmacol 

37(2): 311-318. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

2154677. 

McKinlay, R., J. A. Plant, et al. (2008). Endocrine disrupting pesticides: implications for risk 

assessment. Environ Int 34(2): 168-183. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

17881056. 

Meyer, K. J., J. S. Reif, et al. (2006). Agricultural pesticide use and hypospadias in eastern Arkansas. 

Environ Health Perspect 114(10): 1589-1595. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

17035148. 

Miller, K. P., R. K. Gupta, et al. (2006). Methoxychlor metabolites may cause ovarian toxicity through 

estrogen-regulated pathways. Toxicol Sci 93(1): 180-188. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

16760418. 

Mitsumori, K., Y. Kodama, et al. (1994). Confirmation study, using nitrobenzene, of the Combined 

Repeat Dose and Reproductive/Developmental Toxicity Test protocol proposed by the Organization for 

Economic Cooperation and Development (OECD). J Toxicol Sci 19(3): 141-149. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7966451. 

National Agricultural Statistics Service (NASS) (2010). NASS database agricultural chemical statistics 

search—By year [Online]. (USDA NASS, Washington, DC). 

www.pestmanagement.info/nass/app_statcs1_year.cfm 

National Cancer Institute (NCI) (1976). Carcinogenesis Bioassay of Trichloroethylene. PB-254 

122(Washington, D.C.). 

National Research Council (NRC) (2006). Assessing the health risks of trichloroethylene. National 

Academies Press(Washington, D.C.). 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 99

National Toxicology Program (NTP) (1983). Technical Report on the Carcinogenesis Bioassay of 

Trichloroethylene in F344/N Rats and B6C3F1/N Mice. NIH Pub, No, 82-1799(Washington, D.C.). 

Nebert, D. W., A. L. Roe, et al. (2002). NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, 

exposure to benzene, and predisposition to disease: a HuGE review. Genet Med 4(2): 62-70. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

11882782. 

Needleman, P., D. J. Blehm, et al. (1971). The metabolic pathway in the degradation of glyceryl 

trinitrate. J Pharmacol Exp Ther 179(2): 347-353. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

5002725. 

Netke, S. and e. al. (1997). Ascorbic acid protects guinea pigs from acute aflatoxin toxicity. Toxicol 

Appl Pharmacol 143: 429-435. 

Nimrod, A. C. and W. H. Benson (1997). Xenobiotic interaction with and alteration of channel catfish 

estrogen receptor. Toxicol Appl Pharmacol 147(2): 381-390. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9439733. 

NovaDel Pharma Inc. (2004). FDA CDER New Drug Application #21-780. 

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021780s000PharmR.pdf. 

NTP (1988). Toxicology and Carcinogenesis Studies of Trichloroethylene (Cas No, 79-01-6) in Four 

Strains of Rats (ACI, August, Marshall, Osborne-Mendel) (Gavage studies). PB88-218896(Research 

Triangle Park, N.C.).

Okubo, T., Y. Yokoyama, et al. (2004). Estimation of estrogenic and antiestrogenic activities of selected 

pesticides by MCF-7 cell proliferation assay. Arch Environ Contam Toxicol 46(4): 445-453. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15253041. 

Organisation for Economic Co-operation and Development (OECD) (2003). Draft report of the OECD 

validation of the rat uterotrophic bioassay: Phase-2: Testing of potent and weak Oestrogen agonists by 

multiple laboratories. 

http://www.epa.gov/scipoly/oscpendo/pubs/edmvac/uterotrophic_oecd_rodent_validation_p2_3_5_2003

.pdf 

OECD (2004). Draft report of the OECD validation of the rat Hershberger bioassay: Phase-2: Testing of 

androgen agonists, androgen antagonists and a 5α-reductase inhibitor in dose response studies by 

multiple laboratories. http://www.epa.gov/scipoly/oscpendo/pubs/hershberger_phase2_report.pdf. 

Pahler, A., J. Parker, et al. (1999). Dose-dependent protein adduct formation in kidney, liver, and blood 

of rats and in human blood after perchloroethene inhalation. Toxicol Sci 48(1): 5-13. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10330678. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 100

People for the Ethical Treatment of Animals (PETA) et al. (2008). Comments on Draft List of Initial 

Pesticide Active Ingredients and Pesticide Inerts to be Considered for Screening under the Federal Food, 

Drug and Cosmetic Act (72 FR 33486). (Docket No. EPA-HQ-OPPT-2004-0109). 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2004-0109-0073.1. 

Percy, M. J., N. V. McFerran, et al. (2005). Disorders of oxidised haemoglobin. Blood Rev 19(2): 61-68. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15603910. 

Petit, F., P. Le Goff, et al. (1997). Two complementary bioassays for screening the estrogenic potency of 

xenobiotics: recombinant yeast for trout estrogen receptor and trout hepatocyte cultures. J Mol 

Endocrinol 19(3): 321-335. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9460653. 

Primiano, T., T. R. Sutter, et al. (1997). Antioxidant-inducible genes. Adv Pharmacol 38: 293-328. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8895814. 

Raizada, R. B., P. Misra, et al. (1980). Weak estrogenic activity of lindane in rats. J Toxicol Environ 

Health 6(3): 483-492. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

6158575. 

Rawlings, N. C., S. J. Cook, et al. (1998). Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, 

lindane, triallate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine and reproductive 

endocrine system in ewes. J Toxicol Environ Health A 54(1): 21-36. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9588346.

Reif, D. M., M. T. Martin, et al. (2010). Endocrine profiling and prioritization of environmental 

chemicals using ToxCast data. Environ Health Perspect 118(12): 1714-1720. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20826373. 

Rhodes, J. E. and M. Muckerman (1984). Early life-stage toxicity of alachlor to rainbow trout 

(Oncorhynhus mykiss) under flow-through conditions. Monsanto report number AB-94-280 Monsanto 

IIA, 8.2.2.1/02. 

Rickert, D. E. (1987). Metabolism of nitroaromatic compounds. Drug Metab Rev 18(1): 23-53. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

3311683. 

Rinsky, R. A., R. W. Hornung, et al. (2002). Benzene exposure and hematopoietic mortality: A longterm epidemiologic risk assessment. Am J Ind Med 42(6): 474-480. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

12439870. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 101

Rinsky, R. A., A. B. Smith, et al. (1987). Benzene and leukemia. An epidemiologic risk assessment. N 

Engl J Med 316(17): 1044-1050. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

3561457. 

Rinsky, R. A., R. J. Young, et al. (1981). Leukemia in benzene workers. Am J Ind Med 2(3): 217-245. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7345926. 

Rodwell, D. E. (1980). Alachlor: Teratology study in rats (technical alachlor). Monsanto report number 

IR-79020 Monsanto IIA, 5.6.2/01. 

Ross, D. (2000). The role of metabolism and specific metabolites in benzene-induced toxicity: evidence 

and issues. J Toxicol Environ Health A 61(5-6): 357-372. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

11086940. 

Ruprah, M., T. G. Mant, et al. (1985). Acute carbon tetrachloride poisoning in 19 patients: implications 

for diagnosis and treatment. Lancet 1(8436): 1027-1029. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

2859473. 

Santos, A. M., M. R. Ferraz, et al. (2004). Effects of undernutrition on serum and testicular testosterone 

levels and sexual function in adult rats. Horm Metab Res 36(1): 27-33. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

14983403. 

Schroeder, R. E. (1988). Alachlor: Teratology study in rabbits (final report). Monsanto report number 

BR-87-88 Monsanto IIA, 5.6.2/02. 

Schroeder, R. E. and G. K. Hogan (1981). Alachlor: A three generation reproduction in rats (final 

report). Monsanto report number BDN-77-422 Monsanto IIA, 5.6.1. 

Scippo, M. L., C. Argiris, et al. (2004). Recombinant human estrogen, androgen and progesterone 

receptors for detection of potential endocrine disruptors. Anal Bioanal Chem 378(3): 664-669. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

14579009.

Shimo, T., H. Onodera, et al. (1994). [A 28-day repeated dose toxicity study of nitrobenzene in F344 

rats]. Eisei Shikenjo Hokoku(112): 71-81. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8854905. 

Smith, A. G. (1991). Chlorinated Hydrocarbon Insecticides. In Handbook of Pesticide Toxicology. W. J. 

Hayes, Jr. and E. R. Laws, Jr. New York, Academic Press Inc. 

Smith, M. T. (1996a). Overview of benzene-induced aplastic anaemia. Eur J Haematol Suppl 60: 107-

110. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 102

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8987251. 

Smith, M. T. (1996b). The mechanism of benzene-induced leukemia: a hypothesis and speculations on 

the causes of leukemia. Environ Health Perspect 104 Suppl 6: 1219-1225. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9118896. 

Smith, R. (1996c). Toxic responses of the blood. Casarett and Doull’s Toxicology: the basic science of 

poisons. C. Klaassen. New York, McGraw-Hill: 335–354. 

Snyder, R. and C. C. Hedli (1996). An overview of benzene metabolism. Environ Health Perspect 104 

Suppl 6: 1165-1171. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9118888. 

Sonnenschein, C. and A. M. Soto (1998). An updated review of environmental estrogen and androgen 

mimics and antagonists. J Steroid Biochem Mol Biol 65(1-6): 143-150. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9699867. 

Soto, A. M., C. Sonnenschein, et al. (1995). The E-SCREEN assay as a tool to identify estrogens: an 

update on estrogenic environmental pollutants. Environ Health Perspect 103 Suppl 7: 113-122. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8593856. 

Stockholm Convention (2008). Summary of the forth meeting of the persistant organic pollutants review 

committee of the Stockholm Convention. Earth Negotiations Bulletin 15(161). 

Storrs, S. I. and J. M. Kiesecker (2004). Survivorship patterns of larval amphibians exposed to low 

concentrations of atrazine. Environ Health Perspect 112(10): 1054-1057. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15238276. 

Sugni, M., P. Tremolada, et al. (2010). Chemical fate and biological effects of several endocrine 

disrupters compounds in two echinoderm species. Ecotoxicology 19(3): 538-554. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

19937112. 

Sundari, P. N., G. Wilfred, et al. (1997). Does oxidative protein damage play a role in the pathogenesis 

of carbon tetrachloride-induced liver injury in the rat? Biochim Biophys Acta 1362(2-3): 169-176.

Thorpe, K. L., R. Benstead, et al. (2007). Associations between altered vitellogenin concentrations and 

adverse health effects in fathead minnow (Pimephales promelas). Aquat Toxicol 85(3): 176-183. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

17942165. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 103

U.S. Congress (2009). House Report 111–180. Department of the Interior, Environment, and Related 

Agencies Appropriations Bill, 2010. pp. 105 – 106. http://www.gpo.gov/fdsys/pkg/CRPT111hrpt180/pdf/CRPT-111hrpt180.pdf 

Van Thiel, D. H., J. S. Gavaler, et al. (1980). Is feminization in alcoholic men due in part to portal 

hypertension: a rat model. Gastroenterology 78(1): 81-91. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

7350040. 

Verna, L., J. Whysner, et al. (1996). 2-Acetylaminofluorene mechanistic data and risk assessment: DNA 

reactivity, enhanced cell proliferation and tumor initiation. Pharmacol Ther 71(1-2): 83-105. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8910950. 

Vinggaard, A. M., H. Jacobsen, et al. (2005). Antiandrogenic effects in short-term in vivo studies of the 

fungicide fenarimol. Toxicology 207(1): 21-34. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15590119. 

Vogel, E. and H. Günther (1967). Benzene oxide-oxepin valence tautomerism. Angew Chem Int Ed 

Engl 6(5): 385-476. 

Vonier, P. M., D. A. Crain, et al. (1996). Interaction of environmental chemicals with the estrogen and 

progesterone receptors from the oviduct of the American alligator. Environ Health Perspect 104(12): 

1318-1322. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

9118873. 

Wang, G., X. Zhang, et al. (2010a). Acute toxicity and mutagenesis of three metabolites mixture of 

nitrobenzene in mice. Toxicol Ind Health. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20858646. 

Wang, G., X. Zhang, et al. (2010b). Four-week oral toxicity study of three metabolites of nitrobenzene 

in rats. Drug Chem Toxicol 33(3): 238-243. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

20429802. 

Wartenberg, D., D. Reyner, et al. (2000). Trichloroethylene and cancer: epidemiologic evidence. 

Environ Health Perspect 108 Suppl 2: 161-176. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

10807550. 

Wauchope, R. D., T. M. Buttler, et al. (1992). The SCS/ARS/CES pesticide properties database for 

environmental decision-making. Rev Environ Contam Toxicol 123: 1-155. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

1732992.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 104

Weber, L. W., M. Boll, et al. (2003). Hepatotoxicity and mechanism of action of haloalkanes: carbon 

tetrachloride as a toxicological model. Crit Rev Toxicol 33(2): 105-136. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

12708612. 

World Health Organization (WHO) (1986). Diseases caused by toxic nitro and amino derivatives of 

benzene and its homologues. Early detection of occupational diseases. Geneva, World Health 

Organization: Ch. 9. 

WHO (2002). FAO/WHO Consultation on the Health Implications of Acrylamide in Food. (WHO, 

Geneva, Switzerland). http://www.who.int/foodsafety/publications/chem/acrylamide_june2002/en/. 

WHO (2003a). Alachlor in Drinking-water: Background document for development of WHO Guidelines

for Drinking-water Quality. WHO/SDE/WSH/03.04/31(World Health Organization, Geneva, 

Switzerland). http://www.who.int/water_sanitation_health/dwq/chemicals/en/alachlor.pdf. 

WHO (2003b). Environmental health criteria 230, Nitrobenzene. 

http://whqlibdoc.who.int/ehc/WHO_EHC_230.pdf. 

Wilson, A. G., D. C. Thake, et al. (1996). Mode of action of thyroid tumor formation in the male LongEvans rat administered high doses of alachlor. Fundam Appl Toxicol 33(1): 16-23. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

8812207. 

Wilson, V. S., M. C. Cardon, et al. (2004). Cloning and in vitro expression and characterization of the 

androgen receptor and isolation of estrogen receptor alpha from the fathead Minnow (Pimephales 

promelas). Environ Sci Technol 38(23): 6314-6321. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15597887. 

Wu, K. L. and T. Berger (2007). Trichloroethylene metabolism in the rat ovary reduces oocyte 

fertilizability. Chem Biol Interact 170(1): 20-30. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

17673192. 

Wu, K. L. and T. Berger (2008). Ovarian gene expression is stable after exposure to trichloroethylene. 

Toxicol Lett 177(1): 59-65. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

18249509. 

Yang, H. J., S. H. Lee, et al. (2005). Toxicological effects of acrylamide on rat testicular gene 

expression profile. Reprod Toxicol 19(4): 527-534. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15749267. 

Zenick, H., K. Blackburn, et al. (1984). Effects of trichloroethylene exposure on male reproductive 

function in rats. Toxicology 31(3-4): 237-250. 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 105

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

6740699.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Linda Ferguson

Commenter Organization: American Pacific Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0021

Comment Part: 2

EPA Comment Code: 1050

Comment: II. Exclusion for chemicals for which the manufacturer, importer or registrant cannot be 

clearly identified

Isotopic fingerprinting, while effective at distinguishing between natural and anthropogenic sources, has 

limitations in distinguishing the identity among various manufactured sources. Because of the variety of 

derivations of perchlorate currently being manufactured (aluminum, magnesium, potassium, sodium and 

lithium) accurate identification of the manufacturer, importer, or registrant becomes more difficult. 

While defense activities have often been assumed to be the dominant fraction of perchlorate's 

environmental presence, military contributions alone cannot be the explanation for the geographically 

dispersed detection of the compound. Although there is one manufacturer of ammonium perchlorate in 

the US (American Pacific Corporation), the other sources of perchlorate found environmentally are 

diverse, and fall into one or all categories: (1) natural, (2) import from outside the US, (3) a byproduct in 

Chilean nitrate fertilizer, (4) a byproduct of some municipal water treatments (e.g., hypochlorite) and (5) 

other manufactured applications. Even amongst natural sources, the source is varied. 

• One significant source of perchlorate in ground water is from agricultural use of imported Chilean 

nitrate fertilizer that contains perchlorate. This type of fertilizer is used in organic farming. The amount 

of perchlorate in typical Chilean nitrate fertilizer is approximately 0.1% by weight (Dasgupta et al., 

2005). One study estimated that over the past 60 years, the source strength from Chilean nitrate fertilizer 

in food was an average 0.75 Gg per year (approximately 800 tons per year) and natural sources 

contributed 0.13 - 0.64 Gg per year (approximately 150 – 700 tons per year) (Dasgupta et al., 2006).

• Kelp fertilizer, like Chilean nitrate fertilizer, is often used in organic farming. Kelp has been reported 

to have up to 885,000 ppb perchlorate (USGS, 2003).

• Perchlorate is as a contaminant of hypochlorite used to disinfect drinking water. Hypochlorite is also 

used agriculturally as a preservative and to control microbial risks. Perchlorate is an oxidation product of 

hypochlorite and is found in concentrations of up to 8,000 ppb in household bleach (MA DEP, 2006), 

6,750 ppb in water treatment plant hypochlorite solutions (MA DEP, 2006), and 23,400 ppb in 

agricultural hypochlorite solutions (Sanchez et al., 2009). Perchlorate was detectable in over 90% of 

hypochlorite used in water treatment plants (Sanchez et al., 2009).

• While there are clear instances where industrial practices of the past have led to industrial 

contamination, the attribution of source of perchlorate at these sites is different than previously thought 
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in some cases. In the US Southwest, groundwater and desert soil samples had isotopic fingerprints that 

were distinct from Chilean and industrial sources suggesting the source was neither agricultural nor 

industrial

(Sturchio et al., 2009).

Response: 

Please refer to Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published simultaneously with this 

comment response document. EPA agrees that “Because of the variety of derivations of perchlorate 

currently being manufactured that identification of the manufacturer, importer, or registrant becomes 

more difficult.” However, for the first list EPA determined that pesticides existing as salts and esters in 

the end use product, the acid moiety of the pesticide may be tested if environmental fate data show 

dissociation of the salt and hydrolysis of the ester to form an acid moiety, which is the active ingredient. 

For the initial list, Tier 1 testing could generally be conducted on the acid moiety of the salt or ester of 

the pesticides in the end use product. The similar approach will be used for perchlorate on the second 

EDSP list. 

Please also see general response to comment under Comment Code: 2040 Naturally Occurring 

Contaminants. Also, please see general response to comment under EPA Comment Code: 1050 

Evaluation Criteria Review.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 5

EPA Comment Code: 1050

Comment: 3. EPA Cannot Ignore Comments Pertaining To The Findings Required By SDWA Section 

1457, Which Provide the Predicate For EPA To List Substances For Testing Under The EDSP 

In the preamble to the current Federal Register notice, EPA explains how the Agency determined which 

substances should be included on the EDSP List pursuant to SDWA Section 1457. Specifically, EPA 

explains that the Agency compiled the EDSP List by relying on CCL 3 -- a list of “unregulated 

contaminants” which had previously been compiled by the Agency under a different section of the 

SDWA: Section 1412(b)(1). Under that section, EPA is directed to compile a list of substances that are 

“known or anticipated” to occur in public water systems, and that “may” require regulation under the 

SDWA [FN4: EPA periodically updates the CCL, and the last update (which constituted the third 

iteration of the CCL – or “CCL 3”) was published in October of 2009. 74 Fed. Reg. 51,850 (Oct. 8, 

2009).] 

EPA explains in the current Federal Register notice that methanol and other “SDWA chemicals” were 

included on the EDSP List because they previously had been added to CCL 3. See 75 Fed. Reg. 70,250-

51. Moreover, according to the Agency, the inclusion of these substances on CCL-3 satisfies the 

findings required for inclusion in the EDSP List under SDWA Section 1457. 

In the CCL listing, EPA already has made the component of the SDWA section 1457 determination that 

such substances may occur in sources of drinking water. The final CCL 3 listing also represents EPA’s 
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determination that a substantial population may be exposed to such substances for the purposes of 

SDWA 1457. [FN5: 75 Fed. Reg. 70,251.]

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review and 1060 SDWA 1457.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 7

EPA Comment Code: 1050

Comment: Moreover, the criteria that EPA applies in evaluating whether a substance should be added 

to the CCL under SDWA Section 1412 (namely, whether a substance is “known or anticipated” to occur 

in public water systems and “may” require regulation under the SDWA) are not the same criteria that 

EPA must apply in determining whether a substance should be included on the EDSP list pursuant to 

SDWA Section 1457 (namely, whether a substance may be a contaminant of drinking water, to which a 

substantial population may be exposed). Thus, despite EPA’s suggestions to the contrary, the Agency 

cannot simply assert that a CCL3 listing satisfies the criteria for inclusion on the EDSP list, since the 

two types of listings apply two different sets of criteria.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.

Commenter Name: Thomas Curtis

Commenter Organization: American Water Works Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0028

Comment Part: 3

EPA Comment Code: 1050

Comment: Some chemicals that are registered pesticides are also disinfectants that provide a barrier to 

waterborne pathogens and prevent the transmission of waterborne diseases in public drinking water and 

produce disinfection by-products as a result of their use. Policies and practices under this program need 

to ensure that the supply of chemicals essential to the water industry, such as sodium hypochlorite, is not 

adversely impacted. The withdrawal of manufacturers, re-packagers, re-labellers, etc. from the supply 

chain due to economic provisions of the screening program (e.g., cost sharing or direct testing costs) 

could exacerbate the challenges that water utilities face to supply safe drinking water.

A firm understanding of the specific compounds of concern and the specific exposure contribution from 

drinking water is needed to make appropriate regulatory decisions the future and to avoid unintended 

consequences. The policies in both the Office of Pollution Prevention and Toxics (OPPT) and the Office 

of Ground Water and Drinking Water (OGWDW) must assure that the use patterns of these chemicals 

are managed appropriately. This requires some balancing of risks and risk tradeoffs
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Additionally, AWWA encourages EPA to specify the entities for which this action may apply as there is 

ambiguity in what triggers action given the notice provides no clear definition to the terms “produce, 

manufacture, use, consume, work with, or import” when used to describe the potentially impacted 

entities. For example, farmers may apply acetochlor that degrades in the two acids, ESA and OA. Using 

this example, AWWA questions if this would be considered “manufacturing.”

In summary, AWWA supports EPA’s regulatory programs for protecting human health, and actions 

preventing exposure to harmful EDCs may be necessary, if shown to be needed by future health effects 

and occurrence data. Future EPA regulatory actions resulting from the EDSP should protect drinking 

water sources from potential contamination from EDCs. We appreciate the agency’s consideration of 

our recommendations. If there are any questions, please direct them to Cynthia Lane, AWWA, at (202) 

326-6122. 

Best regards,

Thomas W. Curtis

Deputy Executive Director

AWWA Government Affairs

cc: Peter Silva, EPA/OW

Cynthia Dougherty, EPA/OGWDW

Response: EPA recognizes the essential use of disinfectants in the drinking water treatment process. 

However, current FFDCA section 408(p)(3)(A) statute requires the “testing of all pesticides” under 

EDSP. The statute does not a make any distinctions among types of pesticides.

The policies and procedures for SDWA chemicals more specifically explain the identification of order 

recipients; please see Endocrine Disruptor Screening Program; Final Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published simultaneously 

with this comment response document. Please also see general response to comment under EPA 

Comment Code: 1050 Evaluation Criteria Review.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 4

EPA Comment Code: 1050

Comment: Furthermore, ACC believes that the Agency’s criteria for evaluating substances, for both 

initial inclusion on the Draft EDSP List 2 and for subsequent exclusion from the Draft EDSP List 2 (due 

to such scientific criteria as “ not likely to be biologically active” or “incompatible with testing assays 

for various reasons due to one or more of their physiochemical properties”), and the final EDSP List 2 

itself, should undergo scientific peer review, in accordance with the requirements of EPA’s Peer Review 

Handbook, Peer Review Policy and the Agency’s Information Quality Guidelines.

ACC has several additional comments about the selection processes for substances included in the Draft 

EDSP List 2 EDSP as well as issues related to screening and implementation of the EDSP. We urge the 
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Agency to consider these concerns, and suggestions as it implements the second phase of its EDSP. 

These are contained in ACC’s detailed comments, which are attached.

ACC appreciates the opportunity to provide comments to the Agency on implementation of the EDSP. 

Please do not hesitate to contact us should you require additional information/clarification on any of the 

provided comments. I can be reached by phone at 202- 249-6405 or by e-mail at 

Rick_Becker@americanchemistry.com.

Sincerely,

Richard A. Becker, Ph.D., DABT

Senior Toxicologist and Senior Director

Regulatory and Technical Affairs Department

American Chemistry Council

Attachment: Comments of the American Chemistry Council on “Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA-HQOPPT2009-0477; FRL-8848-7]

Comments of the American Chemistry Council “Endocrine Disruptor Screening Program; Second List 

of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-

7] 

January 18, 2011

The American Chemistry Council (ACC) is pleased to have this opportunity to submit comments on 

EPA’s Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening (the 

“Listing Notice”) 75 Fed. Reg. 70248, Nov. 17, 2010. Pursuant to EPA’s request for comments, ACC 

provides the following general comments related to EPA’s Endocrine Disruptor Screening Program 

Second List of Chemicals for Tier 1 Screening (the “Draft EDSP List 2”) and chemical prioritization 

approach. These comments do not address specific substances the Agency has chosen as candidates for 

the initial list. ACC panels and/or member companies will submit separate comments concerning some 

of those specific substances.

I. Introduction

ACC commends EPA on its care in accurately describing the draft list in its Listing Notice. ACC 

encourages EPA to continue to frame its activities under the EDSP in the proper context. ACC agrees 

with EPA’s decision to focus solely on exposure potential when selecting substances for EDSP 

screening. If EPA had included other factors, such as evidence of potential endocrine activity or toxicity, 

it would have created uncertainty concerning the significance of the list and may have lead the public to 

misinterpret the list as a list of endocrine disruptors or a list of hazardous substances, thereby creating 

significant communication challenges for the Agency and harming the regulated community.

Although ACC agrees with the Agency’s approach to focus on exposure potential in compiling the Draft 

EDSP List 2, EPA must also improve its process for determining exposure potential. Specifically, EPA 

should more critically consider the scientific robustness of the exposure data sources it relies on. As 

discussed below, ACC believes EPA should undertake a critical review of its exposure databases prior to 

further prioritization efforts.
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Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 7

EPA Comment Code: 1050

Comment: Further, while ACC agrees that it makes sense to base EDSP prioritization on exposure 

potential, ACC also believes that EPA should emphasize in all of its EDSP communications that, for 

many if not all of the substances on the EDSP List 2, the Agency already has data and information on 

relevant apical tests that are used for risk assessment purposes, including tests for reproduction and 

developmental toxicity (potential effects which are mediated by endocrine pathways). EPA already has a 

large amount of toxicity data on all pesticide chemicals. Furthermore, many of the commodity chemicals 

identified on the draft EDSP List 2 have had health risk assessments developed as part of the Agency’s 

drinking water regulatory program and a majority have been assessed in the Agency’s Integrated Risk 

Information System. Even if specific endocrine screening has not yet been conducted on certain 

compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., 

outcomes such as pathologic states indicative of disease conditions) covers all modes of action, 

including endocrine pathways.

II.A. Communication about Data Already Available to the Agency

As EPA is well aware, endocrine activity, as determined by Tier 1 screening, is not a distinct 

toxicological hazard per se, but rather a measure of a compound’s ability to interact with components of 

the endocrine system. Interaction with or modulation of endocrine processes may or may not give rise to 

adverse effects. It is the apical tests, the EDSP Tier 2 tests or similar toxicology tests that determine 

adverse effects and dose response that are to be used for hazard identification and risk assessment. As 

EPA has stated:

EPA developed a two-tiered approach to implement the statutory testing requirements. The purpose of 

Tier 1 screening (referred to as “screening”) is to identify substances that have the potential to interact 

with the estrogen, androgen, or thyroid hormone systems using a battery of assays. The fact that a 

substance may interact with a hormone system, however, does not mean that when the substance is used, 

it will cause adverse effects in humans or ecological systems. The purpose of Tier 2 testing (referred to 

as “testing”), is to identify and establish a dose-response relationship for any adverse effects that might 

result from the interactions identified through the Tier 1 assays.[FN5: EPA (2009). Endocrine Disruptor 

Screening Program; Policies and Procedures for Initial Screening. Federal Register Volume 74, Number 

71 (Wednesday, April 15, 2009) Pages 70248-70254. 

http://www.epa.gov/endo/pubs/revised_pandp_frn_041509.pdf] (Emphasis added.)

In the Agency’s EDSP Policy Statement EPA clearly indicates that toxicity testing – evaluation of apical 

endpoints for adverse effects -- is central to determining “whether a particular substance may have an 

effect in humans that is similar to an effect produced by a naturally occurring EAT [estrogen, androgen 

thyroid], that is, that the substance is an endocrine disruptor.”[FN6: EPA (1998). Endocrine Disruptor 

Screening Program: Statement of Policy. Federal Register Volume 63, Number 248 (Monday, December 
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28, 1998) page 71542.] Existing toxicity test results that have evaluated established apical adverse effect 

endpoints, primarily reproductive and developmental toxicity endpoints, are relevant to the EDSP. In 

this regard, the toxicity information on apical endpoints developed by ACC members as part of product 

stewardship and regulatory programs is directly pertinent to evaluating hazards and risks, including 

potential effects mediated by endocrine pathways, to health of individuals, including children. Such data 

typically includes: 1) identification and definition of possible hazards upon all major organ systems from 

both acute and repeated exposures; 2) detection of potential hazards arising from in utero exposures; 3) 

evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a 

substance to damage DNA. The acute toxicity studies, while critical to ensure correct packaging, 

labeling and handling to prevent poisoning incidents, are not directly relevant for determining endocrine 

disruption. The developmental and reproductive toxicity studies, however, are relevant for determining 

endocrine disruption because they assess risks that could affect normal prenatal and postnatal growth, 

development and maturation.

Hazard information from apical toxicity tests are available for many of the commodity chemicals 

included in the draft EDSP List 2. Such hazard evaluation studies (i.e., outcomes such as pathologic 

states indicative of disease conditions) cover all modes of action, including endocrine pathways. When 

toxicity test results are available that provide information on apical endpoints (e.g., identify dose levels 

that cause adverse effects, irrespective of a substance’s mode of action), the Agency has the data needed 

for understanding the dose-response relationship between exposure and adverse health effects for risk 

assessment purposes. Of the commodity chemicals included in the Draft EDSP List 2, for every 

substance that is a regulated drinking water contaminant EPA has conducted a hazard evaluation based 

on apical toxicity data to set a Maximum Contaminant Level Goal (MCLG). The MCLG is “the 

maximum level of a contaminant in drinking water at which no known or anticipated adverse effect on 

the health of persons would occur, and which allows an adequate margin of safety.”[FN7:

http://water.epa.gov/lawsregs/rulesregs/regulatingcontaminants/basicinformation.cfm] In addition, 

approximately 70% are included in the OECD HPV chemical list,[FN8: OECD (2004). The 2004 OECD 

List of High Production Volume Chemicals. http://www.oecd.org/dataoecd/55/38/33883530.pdf] and 

available hazard information for these substances can be accessed on the e-ChemPortal.[FN9: 

http://www.echemportal.org/echemportal/index?pageID=0&request_locale=en] What's more, greater 

than 75% of these chemicals have been assessed by EPA and included in the Agency’s Integrated Risk 

Information System (IRIS http://www.epa.gov/IRIS/). IRIS assessments include evaluation of apical 

toxicity tests, and, IRIS establishes Oral Reference Doses which are an “estimate of a daily oral 

exposure for a given duration to the human population (including susceptible subgroups) that is likely to 

be without an appreciable risk of adverse health effects over a lifetime.”[FN10: 

http://www.epa.gov/IRIS/] For chemicals with potential carcinogenic activity, IRIS establishes Oral 

Slope Factors for use in deriving estimates of upper bound lifetime cancer risks. The Agency relies on 

IRIS assessments in a number of programs, including the Drinking Water Office, for assessing and for 

determining risk management options.[FN11: 

http://water.epa.gov/action/advisories/drinking/upload/dwstandards2009.pdf] Therefore, because 

Agency decisions on these substances are based on adverse effects in the toxicology studies that cover 

all modes of action, and the Agency already has the results of such studies in hand for a majority of the 

commodity chemicals included in the draft EDSP List 2, there should be little concern that potential 

significant risks have not been accounted for.

ACC believes that it is important for the public to understand the extent of toxicity data that is relevant 

to endocrine disruption that is already available for the commodity chemicals included in the EDSP. By 

not referencing existing, publicly available sources of hazard and risk information, such as Drinking 
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Water Standards and Health Advisories,[FN12: Ibid.] IRIS and the e- ChemPortal, the Agency has 

missed an opportunity to inform the public and policy makers of the extent of existing toxicity 

information already in the public domain concerning the EDSP Draft List 2 candidates. This oversight 

should be corrected when the Agency publishes the final EDSP List 2, by including references and links 

to relevant Agency hazard and risk information data sources.

II.B. Ensuring Consistent Communications about Endocrine Disruptors and the EDSP Across the 

Agency

ACC urges EPA to accurately communicate EDSP related issues across the Agency. The definition of 

“endocrine disruptor” is a case in point. EPA did not adequately discuss the purpose of Tier 1 and Tier 2 

testing in the Listing Notice. EPA should be clear as to what the purpose of Tier 1 screening is and what 

the results of Tier 1 screening mean. As EPA has correctly stated in other places, the purpose of Tier 1 is 

to identify substances that have the potential to interact with the estrogen, androgen, or thyroid hormone 

systems and the purpose of Tier 2 is to identify and establish a dose-response relationship for any 

adverse effects that might result from the interactions identified through the Tier 1 assays.

It is clear from EPA’s long-standing policy statements that “endocrine disruptors” are substances that 

adversely affect the organ systems by interacting with the endocrine system. Therefore, substances that 

have an adverse impact on the endocrine system as a secondary effect of some other toxicity (e.g., 

hepatotoxicity) are not endocrine disruptors - they do not exert an adverse effect by a primary mode of 

action of interaction with the endocrine system. Indeed, any frank toxicity often results in some 

endocrine response, which may be no more than a homeostatic response. It would be illogical to term all 

substances that may exert a toxic effect at any dose an “endocrine disruptor.”

Unfortunately, communications across the Agency with regard to its definition of “endocrine disruptor” 

have not been consistent with EPA’s descriptions of Tier 1 and Tier 2 testing in EPA’s policy statement 

on the EDSP. For example, EPA’s Office of Research and Development (ORD) has described 

“endocrine disruptors” in various ways on the ORD website 

(http://epa.gov/ncer/science/endocrine/#eds):

* Endocrine disruptors are basically chemicals with the potential to interfere with the function of 

endocrine systems.

* Endocrine disrupting chemicals (EDCs) have been defined as exogenous agents that interfere with the 

production, release, transport, metabolism, binding, action, or elimination of the natural hormones in the 

body responsible for the maintenance of homeostasis and the regulation of developmental processes.

* EDCs can include man-made chemicals such as pesticides and plasticizers, natural chemicals found in 

plants (phytoestrogens), pharmaceuticals, or hormones that are excreted in animal or human waste.

Absent from ORD’s description is the notion that endocrine disruptors cause adverse effects, rather than 

simply interfering with the endocrine system. Any definition of endocrine disruption that does not 

include both the requirement for the direct interaction with the endocrine system and adverse effects is 

irrational. Not only is the ORD description inconsistent with EPA’s described purpose of Tier 1 and Tier 

2 testing, it is inconsistent with EPA’s definition of “endocrine disruptor” in its EDSP Policy Statement:
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The purpose of Tier 1 is to identify substances that have the potential to interact with the endocrine 

system. The purpose of Tier 2 is to determine whether the substance causes adverse effects, identify the 

adverse effects caused by the substance, and establish a quantitative relationship between the dose and 

the adverse effect. At this stage of the science, only after completion of Tier 2 tests will EPA be able to 

determine whether a particular substance may have an effect in humans that is similar to an effect 

produced by a naturally occurring EAT, that is, that the substance is an endocrine disruptor.[FN13: EPA 

(1998). Endocrine Disruptor Screening Program: Statement of Policy. Federal Register Volume 63, 

Number 248 (Monday, December 28, 1998) page 71542.]

In addition to ORD, it now appears that EPA’s Design for Environment (DfE) program is completely 

ignoring the Office of Chemical Safety and Pollution Prevention’s (OCSPP) EDSP and its definition of 

“endocrine disruptor” by proposing to apply results of EDSP Tier 1 screening for product risk 

management actions. In the DfE proposed standard, which is now being circulated for review and 

comment, the Agency proposes action based solely on “interaction” or “perturbation” of the endocrine 

system:

4.5.5 Potential endocrine effects. Chemicals that are candidates for endocrine screening will be part of 

the review. Chemicals found to interact with or perturb the endocrine system—potentially leading to 

reproductive, developmental, carcinogenic, systemic, hormonal or other effects—will not be allowed 

based on the toxicological hazards they pose.[FN14: EPA, OCSPP, Design for the Environment (2010). 

Proposed Enhancements to the Design for the Environment (DfE) Standard for Safer Products. EPA’s 

DfE Standard for Safer Cleaning Products (SSCP) 

http://www.epa.gov/dfe/proposed_enhancements_to_dfe_standard_for_safer_products.html and 

http://www.epa.gov/dfe/standard_for_safer_cleaning_products_revisions_updated_oct_26_2010.pdf] 

(Emphasis added.) 

The DfE proposed risk management action is wholly inappropriate and inconsistent with EPA’s EDSP 

policy. In the two-tiered EDSP, Tier 1 is specifically designed to maximize the sensitivity to detect any 

interaction with components of the estrogen, androgen and thyroid systems. The EDSP Tier 2 is 

designed to identify adverse effects and dose response and it is the Tier 2 results that are to be used for 

risk assessment and risk management. The EDSP Tier 1 assays, which determine the potential of a 

chemical to interact with components of the endocrine system, are not intended to signal a concern for 

health risks that would lead to bans or substitutions. EPA OCSPP is very clear on this point.

EPA developed a two-tiered approach to implement the statutory testing requirements. The purpose of 

Tier 1 screening (referred to as “screening”) is to identify substances that have the potential to interact 

with the estrogen, androgen, or thyroid hormone systems using a battery of assays. The fact that a 

substance may interact with a hormone system, however, does not mean that when the substance is used, 

it will cause adverse effects in humans or ecological systems. The purpose of Tier 2 testing (referred to 

as “testing”), is to identify and establish a dose-response relationship for any adverse effects that might 

result from the interactions identified through the Tier 1 assays.[FN15: EPA (2009). Endocrine 

Disruptor Screening Program; Policies and Procedures for Initial Screening. Federal Register Volume 

74, Number 71 (Wednesday, April 15, 2009) Pages 70248-70254. 

http://www.epa.gov/endo/pubs/revised_pandp_frn_041509.pdf] (Emphasis added.)

The description and proposed actions regarding endocrine in the draft DfE Standard, as currently 

written, would base action on Tier 1 EDSP screening results, and would promote regulation based 

merely on the potential of interactions rather than on adverse effects and risk, thus shifting the Agency’s 
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well established, scientifically grounded, risk-based chemical management paradigm. This is 

inappropriate. Even the NRC panel which used the term “perturbation” is clear that it did not envision 

regulatory actions would be triggered by any finding of a perturbation. The National Research Council’s 

(NRC) experts stated in “Toxicity Testing in the 21st Century: A Vision and a Strategy”:

Biological responses viewed as the result of an intersection of exposures with biological functions. The 

intersection leads to perturbations of biological pathways. When perturbations are sufficiently large or 

when host is unable to adapt because of underlying nutritional, genetic, disease or life-stage status, 

biological function is compromised (Emphasis added.).[FN16: Toxicity Testing in the 21st Century: A 

Vision and a Strategy (2007). The National Academies Press, Washington, DC, 20001. Page 49.]

The point is an adverse effect (an effect that warrants use as an endpoint for risk assessment and the 

basis for determining product stewardship or risk management or consideration for possible substitution 

of a chemical in a product), is not merely any known biochemical or chemical change, or even any 

known or measureable precursor along the pathway that could lead to some degree of perturbation. The 

NRC Committee clearly indicated that consideration of adversity occurs when perturbations are 

sufficiently large.

EPA OCSPP has an obligation to ensure that other EPA programs follow the Agency’s policies in 

describing what EDSP Tier 1 screening results are and are not, and that they use the information 

generated in the Tier 1 EDSP appropriately. ACC urges EPA to ensure accurate, complete and 

consistent communications about the list of substances to be screened – both to external audiences and 

across the agency as EPA moves forward to implement the EDSP. The OCSPP must work to improve its 

communications about endocrine disruption and the EDSP and work to ensure that the policies set 

within the EDSP, including the policies for the use of screening data and the interpretation and 

communication of screening results, are followed by all EPA programs and offices.

II.C. EPA Should Consistently Describe EDSP Tier 1 And Tier 2 in Agency Policy

Documents, Including the EDSP Notices Issued in The Federal Register.

As EPA moves forward with the EDSP, it is important that the Agency use consistent descriptions of the 

purpose of Tier 1 and Tier 2. In the Listing Notice EPA describes the EDSP Tier 1 and Tier 2 as:

Tier I test assays are used to screen the chemicals for interaction with the estrogen (E), androgen (A) or 

thyroid (T) hormonal systems. Tier II test assays are intended to test for more specific chemical effects 

on the endocrine system, and are currently in the process of being developed and validated. Further 

information regarding EDSP and requirements for Tier I and Tier II can be found on the Agency's 

EDSP.[FN17: EPA (2010). Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 

1 Screening (2010). Federal Register Volume 75, Number 221 (Wednesday, November 17, 2010), Pages 

70248-70254.]

ACC requests that in each future EDSP notice, EPA consistently use the definitions of EDSP, Tier 1 and 

Tier 2 adopted by the Agency in its Policy Statement, to wit,

The purpose of Tier 1 is to identify substances that have the potential to interact with the endocrine 

system. The purpose of Tier 2 is to determine whether the substance causes adverse effects, identify the 

adverse effects caused by the substance, and establish a quantitative relationship between the dose and 

the adverse effect. At this stage of the science, only after completion of Tier 2 tests will EPA be able to 
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determine whether a particular substance may have an effect in humans that is similar to an effect 

produced by a naturally occurring EAT, that is, that the substance is an endocrine disruptor. Therefore, 

both Tier 1 and Tier 2 are essential elements of the screening program mandated by the FQPA.[FN18: 

Endocrine Disruptor Screening Program; Policies and Procedures for Initial Screening (1999). Federal 

Register / Vol. 63, No. 248 / Monday, December 28, 1998, page 71545.]

EPA believes that the results from the entire battery of tests required in the Tier 1 screening and Tier 2 

testing stages (or their equivalents) are necessary to make the statutory determination of whether a 

particular substance “may have an effect in humans that is similar to an effect produced by a naturally 

occurring [hormone]”(21 U.S.C. 346a(p)). In other words, a positive result in the Tier 1 screening assays 

would not be adequate to make the determination “whether a substance may have an effect in humans 

that is similar to an effect produced by a naturally occurring [hormone].” Id. Conversely, a negative 

result in all Tier 1 screening tests will be adequate to determine that a particular substance is not likely 

to have an effect on the estrogen, androgen, and thyroid hormone systems (EAT) and, therefore, is not a 

priority for testing in Tier 2. The confirmatory tests in the Tier 2 testing stage are necessary to determine 

whether a substance may have an effect similar to that of a naturally occurring hormone.[FN19: Ibid.]

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Review Criteria. Also, please see general response to comment under EPA Comment Code: 1020 

Continue Use of Qualifying Language.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 11

EPA Comment Code: 1050

Comment: Furthermore, ACC believes that the Agency’s criteria for evaluating substances, both for 

inclusion and exclusion from the EDSP List 2, must undergo scientific peer review, in accordance with 

the requirements of EPA’s Peer Review Handbook , EPA’s Peer Review Policy and Information Quality 

Guidelines.[FN27: EPA (2006). U.S. Environmental Protection Agency Peer Review Handbook, 3rd 

Edition. http://www.epa.gov/peerreview/pdfs/peer_review_handbook_2006.pdf] [FN28: EPA (2002). 

Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information 

Disseminated by the Environmental Protection Agency. 

http://www.epa.gov/quality/informationguidelines/documents/EPA_InfoQualityGuidelines.pdf] The 

Agency’s policies and guidance on scientific peer review are clear: 1) Agency actions, such as the EDSP 

List 2, are included in the suite of Agency activities that meet the definition of dissemination of 

information to the public; 2) EPA’s Peer Review Policy states, “[p]eer review of all scientific and 

technical information that is intended to inform or support Agency decisions is encouraged and 

expected;” 3) EPA’s Peer Review Handbook states, “all influential scientific and technical work 

products used in decision making will be peer reviewed;” and 4) the EPA EDSP List 2 criteria, both the 

inclusion criteria and the exclusion criteria, meet the definition of “influential scientific information” in 

that use of such criteria will have a clear and substantial impact on important public policies or private 

sector decisions, since such action will result in Agency determinations that, as proposed, would trigger 

issuance of EDSP Tier 1 screening test orders.
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VI. EPA Must Interpret Key SDWA Provisions Before it Lists Phase 2 Chemicals and Before it Issues 

Phase 2 Orders

EPA, in the Listing Notice, has described its process for prioritizing chemicals for EDSP List 2. ACC, 

however, does not agree with EPA’s assertion that a chemical on the CCL3 list per se meets the criteria 

of the 1996 endocrine amendments to the Safe Drinking Water Act (SDWA) that a substance “may be 

found in sources of drinking water” and to which a “substantial population” may be exposed. The 

identification of candidates for EDSP List 2 should conform to the Agency’s authority specified in the 

SDWA. We refer EPA to ACC’s discussion of this matter in our comments on EPA’s Draft Policies and 

Procedures For Screening Safe Drinking Water Act Chemicals (75 Fed. Reg. 70558, Nov. 17, 2010), 

which have been filed separately.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Review Criteria. Also, please see general response to comment under EPA Comment Code: 1060 

SDWA 1457.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 14

EPA Comment Code: 1050

Comment: IX. EPA Should Undertake a Critical Review of its Exposure Databases Prior to

Further Prioritization Efforts

Further, with respect to the appropriateness of using the CCL3 list in general, ACC is concerned that 

EPA has not fully accounted for data quality by relying on certain databases for asserting substances on 

the CCL3 list automatically satisfy the SDWA endocrine statutory requirements. When utilizing any 

data source, EPA should undertake a rigorous analysis of data strengths and weaknesses prior to using 

that data in Agency programs. To ensure its analyses are reproducible, EPA should use only data sources 

that are publicly available. In evaluating the data sources it relies upon to prioritize substances for EDSP 

screening, EPA should analyze each database in terms of:

* The extent to which the database represents the current U.S. population (e.g., EPA should consider 

who was sampled, where samples were collected and sample size).

* Sampling design (including whether sufficient controls were used).

* Quality of the data (e.g., sensitivity and specificity of the chemical analytic techniques; adequacy of 

the quality assurance/quality control procedures for sample collection, storage, analysis, archiving and 

record keeping).

* Time frame of sample collection to determine current relevance. EPA should determine whether there 

have been major changes in production or use patterns, or in regulatory requirements that would impact 

current exposure circumstances.
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* Frequency of occurrence of measured concentrations within the database (e.g., whether the data 

represent an isolated incident and whether the data are statistically significant).

* Concentration ranges of the samples in the database.

* Identity of a chemical as a parent chemical as opposed to a metabolite of a different chemical.

* Public availability of the data.

Importantly, EPA should not conclude, without adequate written scientific justification, that the 

information it relies on to assess potential exposure for purposes of prioritization can be extrapolated to 

the general population and to current, present-day exposure circumstances. EPA has focused 

considerable attention on information quality issues, and the Agency has adopted a number of policies, 

procedures and guidelines to guide Agency actions in collecting, evaluating, disseminating and using 

environmental data, including:

* EPA Quality Manual for Environmental Programs 5360 A1. May 2000. 

http://www.epa.gov/quality/qs-docs/5360.pdf

* EPA/260R-02-008, December 2002, Guidelines for Ensuring and Maximizing the Quality, 

Objectivity, Utility and Integrity for Information Disseminated by the Environmental Protection Agency 

http://www.epa.gov/oei/qualityguidelines/EPA-OEIIQGFINAL-10.2.pdf

EPA should ensure all of its actions are consistent with its general policy, procedures and guidelines 

related to information quality. For the draft EDSP List 2, EPA has not adequately dealt with these data 

quality issues. For example, the reliance on the National Drinking Water Chemical Occurrence Database 

(NCOD) is problematic given the following limitations of this database:

* The NCOD is a compilation of data sets developed using different sampling strategies and study 

design. Therefore, comparison of the data among data sources may not be possible. In addition, the 

extrapolation of these data nationwide may be limited.

* The extent of QA/QC in the NCOD is not clear from the available data and supporting materials.

* Information to assess the reliability of these data regarding detection limits, sample custody, and 

sample storage and preservation are lacking.

* Raw-water monitoring data may not be very useful in assessing potential human exposure to drinking 

water because water treatment methods may affect concentrations of these compounds.

* The age of some of the data compiled in the NCOD may decrease the usefulness and

relevance of the data to current potential exposures due to differences in analytical

methods and temporal differences in environmental contaminants.

Overall, the process EPA has used to determine that a substance “may be found in sources of drinking 

water” and that a “substantial population” may be exposed should be revised to rely on more relevant 

and accurate exposure data sources. Because EPA has asserted that the CCL3 list informs the 1457 
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Screening program, the reliance on the list involves an action based on science. SDWA Section 

1412(b)((3)(A) requires that when, and to the extent such agency action is based on science, EPA must

(i) use the best available peer reviewed science and studies conducted in accordance with sound and 

objective scientific practices; and

(ii) data collected by accepted methods, or the best available methods, (if the reliability of the method 

and nature of the decision justifies the use of the data.)

This same standard has been incorporated into EPA's IQA Guidelines. Therefore, the data EPA relies on 

should meet the Agency's guidelines for data quality, should be publicly available and should be used in 

a manner that is scientifically justified. The listing criteria contained in the current list proposal fail to 

meet these basic EPA standards, and are not in accord with the statutory authority for the drinking water 

program in general.

***************************************

The American Chemistry Council appreciates the opportunity to comment on EPA’s draft initial

list of substances for EDSP screening. If you have questions regarding these comments, please

contact Dr. Richard Becker by e-mail at Rick_Becker@americanchemistry.com or by phone at

202-249-6405.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review. 

Commenter Name: James Lamb

Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0030

Comment Part: 3

EPA Comment Code: 1050

Comment: • Further, we believe that the Agency must show that a substance (1) is likely to be present 

in sources of drinking water and (2) there is an empirical basis - actual monitoring of finished drinking 

water or ambient water (that is an actual source of water that is delivered to consumers as finished 

water). In light of the fact that toxaphene is insoluble in water it is unlikely that toxaphene would be in 

drinking water or result in the exposure of a substantial population through that route.

EPA indicated that its initial procedures resulted in a list of 85 regulated drinking water contaminants 

with existing NPDWRs, and 116 unregulated contaminants listed on CCL 3. EPA next identified 

candidate chemicals from the Office of Pesticide Programs (OPP) based on pesticides that were 

scheduled for registration review during fiscal years (FY) 2007 and 2008. EPA states that this selection 

is part of its intent to expedite efficiently the testing of pesticides, by conducting the testing in parallel or 

as part of the OPP Registration Review Program. EPA consolidated the lists from the Office of Water 

(OW) and OPP, resulting in over 200 chemicals. 

EPA indicated that it streamlined this list by excluding any chemical that fell into one or more of the 

following categories:
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1. Biological agent and naturally-occurring chemicals (e.g., microbials, microbial toxins, inorganics, 

radionuclides). 

2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

disinfection byproducts or DBPs, microbes, microbial toxins, degradate compounds with more than one 

possible source etc.). 

3. Chemicals already included on the first EDSP list. 

4. Chemicals that are hormones with confirmed endocrine effects. 

5. Chemicals that are not likely to be biologically active or which are incompatible with testing assays 

for various reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or 

basic, solubility, vapor pressure molecular weight). 

6. Pesticides that are scheduled for registration review after FY 2008.

However, the manufacturer, importer or registrant of toxaphene found in the environment cannot be 

clearly identified, as there was more than one manufacturer of toxaphene-like materials, and toxaphene 

in the environment is degraded by nature of environmental weathering.

Further, chlorinated organic compounds have been shown to be transported significant distances through 

wind, or through the feces of migrating birds, and toxaphene degradation products in the US 

environment may have at least in part stemmed from other sources. Therefore, toxaphene should have 

been excluded from the List 2 chemicals on the basis of the second category cited by EPA. 

Against this background wherein the EPA has not yet defined needed terms, the Agency is introducing 

another term. EPA requested comment on whether and how to factor a chemical’s persistence in the 

environment into EDSP. It is not clear how EPA would incorporate persistence in determining whether a 

chemical may be found in sources of drinking water and whether a substantial population is exposed. 

Those findings should be based on actual data concerning the presence of a chemicals and a 

determination of what constitutes a substantial population. A chemical that meets those limitations will 

do so regardless of persistence. Trying to incorporate persistence is unnecessary. In addition, Hercules is 

not aware of any authority EPA has to add this criterion to the EDSP process.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. Also, please see general response to comment under EPA Comment Code: 1050 

Evaluation Criteria Review.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 1

EPA Comment Code: 1050

Comment: January 18, 2011
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Submitted Electronically to:

EPA Docket: EPA-HQ-OPPT-2009-0477

Steve A. Owens

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue, N.W.

Washington, DC 20460-0001

Re: Comments to "Endocrine Disrupter Screening Program: Second List of Chemicals

for Tier One Screening [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477] (the

Draft EDSP List 2")

Dear Mr. Owens:

Arkema Inc. ("Arkema") is a world class diversified chemical manufacturer with more than 2,000 

employees and 24 facilities in the United States. Arkema products are used in a varied range of end 

markets, including construction, paints, coatings and adhesives, electronics, automotive, packaging, 

energy, paper, health, hygiene and beauty, and agrichemicals. Arkema is an advocate of environmental 

regulations that protect environmental and human health while encouraging innovation and economic 

development. As a member of the American Chemistry Council ("ACC"), we are committed to the 

principles of product stewardship as set forth in ACC's Responsible Care® program.

Arkema appreciates the opportunity to submit comments to the Draft EDSP List 2. In general, Arkema 

supports and incorporates herein the comments submitted by the ACC and the Organic Peroxide 

Producers Safety Division of the Society of the Plastics Industry on the Draft EDSP List 2.

Arkema notes, as a preliminary matter, that the Safe Drinking Water Act (SDWA) provides that the 

Candidate Contaminant List (CCL) include contaminants that are known or anticipated to occur in 

public water systems. In contrast, the EDSP additionally requires that "a substantial population may be 

exposed" through drinking water. Under, these circumstances, mere inclusion of a substance on the 

CCL3 is not sufficient to satisfy the requirements for testing under the EDSP.

Arkema offers the following additional comments to highlight certain areas of the proposed rulemaking 

that may particularly affect the Company's business and operations. The EPA has identified three criteria 

for listing a chemical on the Second List of Chemicals for Tier 1 Screening for endocrine disruption.

A. The material appears on the Candidate Contaminate List 3 (CCL 3) of the Safe Drinking Water Act. 

(SDWA) [FN1: Office of Water (4607M) EPA 815-R-09-008 August 2009 www.epa.gov/safewater]

and" ... such substances may occur in sources of drinking water to which a substantial population may 

be exposed.” [FN2: Federal Register I Vol. 75, No. 221 I Wednesday, November 17, 2010 / Notices] 

b. The material has potential to interact with the estrogen (E), androgen (A) or thyroid (T) hormonal 

systems; and
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c. The material is not incompatible with testing assays for various reasons due to one or more 

physiochemical properties (e.g., gases, strongly acidic or basic, solubility, vapor pressure molecular 

weight) ..

The chemicals discussed hereinafter do not meet these criteria, and, therefore, should be removed from 

the Draft EDSP List 2.

Response: EPA disagrees with the commenter’s statement that “The EPA has identified three criteria 

for listing a chemical on the Second List of Chemicals for Tier 1 Screening for endocrine disruption.” 

As stated in the Federal Register notice, the agency considered priority chemicals contained on Office 

of Water (OW) and Office of Pesticide Programs (OPP) priority lists for inclusion on the second EDSP 

list. 

Also, see general responses to comment under EPA Comment Codes: 1050 Evaluation Criteria Review 

and 1060 SDWA 1457.

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 3

EPA Comment Code: 1050

Comment: B. Data Relevant to Determining Potential for Substantial Population Exposure

The plain language of the SDWA compels the conclusion that EPA is not to test for substances that 

hypothetically, or by some remote possibility "may be found in sources of drinking water," but rather 

that it is to test only for substances that are likely to be present in sources of drinking water, as 

demonstrated by monitoring of finished drinking water or ambient water that is an actual source of water 

that will be delivered to consumers as finished drinking water. In this regard, public water systems are 

required to monitor for a host of regulated and unregulated contaminants, and these data are recorded in 

occurrence databases for each individual public water system in each state. In order to ensure that such 

data are useful from a health risk and management perspective, EPA regulations expressly require that

monitoring be performed on water that is representative of the water that consumers will be drinking. 

While other programs such as the Clean Water Act may be concerned with broad-based pollutant issues 

affecting all waters (e.g., ecological impacts), the SDWA is concerned only with those waters that 

ultimately serve as a source of drinking water that may present human health risks. The universe of all 

ambient waters in the United States does not meet that test.

As described in greater detail below, EPA is required to establish maximum contaminant levels (MCLs) 

through the promulgation of national primary drinking water regulations at levels as close as feasible to 

the maximum contaminant level goals (MCLGs). Public water systems monitor these MCLs and 

MCLGs regularly using testing protocols mandated by the drinking water regulations to ensure the 

representativeness, accuracy and integrity of the data. As these data are (i) required of all public water 

systems, (ii) are system-specific, and (iii) can be traced directly to a water source, they are the only 

reliable indicator of potential source water contamination other than substantially similar testing of 

corresponding source water that may be conducted by the US Geological Survey. Moreover, testing for 

drinking water contaminants is ordinarily undertaken at or near the levels of detection, which for most 
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organic chemicals is one to two orders of magnitude below the MCL or MCLG, thus at the part-perbillion level or less. 

Given the extent and accuracy of the drinking water occurrence database, as well as EPA's reliance upon 

it to enforce the SDWA, it defies logic for the Agency to look to unreliable surrogate measures, such as 

Toxics Release Inventory (TRI) data, as alternative means of identifying human populations that are 

likely to be exposed to drinking water contaminants. TRI serves a number of legitimate purposes, but it 

is not a productive way to identify releases to sources of drinking water. EPA has offered no legal or 

scientific justification for using TRI in lieu of or in addition to its own accepted regulatory methodology 

for identifying regulated and unregulated contaminants that may pose risks in source waters. Certainly, 

where occurrence data are available, there is no reasoned basis for relying upon TRI data to reach a 

conclusion unsupported by those occurrence data.

Response: Please see general responses to comment under EPA Comment Code: 1060 SDWA 1457. 

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0035

Comment Part: 5

EPA Comment Code: 1050

Comment: In conclusion, the available information from previous risk assessments indicates low 

potential for exposure to MDA via drinking water, thereby leaving unsatisfied the criterion that a 

substantial population may be exposed to MDA. Whereas an assessment of the endocrine disrupting 

potential of this substance is partly informed by the existing dataset of studies reported by Tullner 

(1960) and repeated dose animal toxicity studies considered in risk assessments noted above, industry is 

presently further investigating this potential. Thus, the inclusion of this substance in the U.S. EPA 

endocrine screening program at this time may be regarded as an unnecessary duplication of efforts with 

the above information and programs. Therefore, we recommend that MDA should be removed from 

EPA’s Draft EDSP List 2. 

The Panel appreciates the opportunity to provide comments to the Agency on implementation of the 

EDSP. Please do not hesitate to contact me at (202) 249-6721 or Sahar_OsmanSypher@americanchemistry.com should you require additional information/clarification on any of the 

provided comments. 

Sincerely, 

Sahar Osman-Sypher 

Manager, Diisocyanates Panel

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review. Also, please see general response to comment under EPA Comment Code: 1070 

Increase Transparency to see how EPA may use EDSP information.

Commenter Name: W. Caffey Norman
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Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0037

Comment Part: 2

EPA Comment Code: 1050

Comment: B. Data Relevant to Determining Potential for Substantial Population Exposure

This statutory language compels the conclusion that EPA is not to test for substances that hypothetically, 

or by some remote possibility "may be found in sources of drinking water," but rather that it is to test for 

substances that are likely to be present in sources of drinking water, as demonstrated by monitoring of 

finished drinking water or ambient water that is an actual source of water that will be delivered to 

consumers as finished drinking water. In this regard, public water systems are required to monitor for a 

host of regulated and unregulated contaminants, and these data are reported and recorded in occurrence 

databases for each individual public water system in each state. In order to ensure that such data are 

useful from a health risk and management perspective, EPA regulations expressly require that 

monitoring be performed on water that is representative of the water that consumers will be drinking. 

While other programs such as the Clean Water Act may be concerned with broad based pollutant issues 

affecting all waters (e.g., ecological impacts), the SDWA is concerned only with those sources that 

ultimately serve as a source of drinking water that may present human health risks. The universe of all 

ambient waters in the United States does not meet that test.

EPA is required to establish maximum contaminant levels (MCLs) through the promulgation of national 

primary drinking water regulations at levels as close as feasible to the maximum contaminant level goals 

(MCLGs), which in turn must be "set at the level at which no known or anticipated effects on the health 

of persons occur and which allows an adequate margin of safety."[FN5: SDWA § 1412(b)(4); 42 U.S.C. 

§ 300g-1(b)(4).] Public water systems monitor these MCL and MCLG levels regularly using testing 

protocols mandated by the drinking water regulations to ensure the representativeness, accuracy and 

integrity of the data. As these data (i) are required of all public water systems, (ii) are system-specific, 

and (iii) can be traced directly to a water source, they are the only reliable indicator of potential source 

water contamination other than substantially similar testing of corresponding source water that may be 

conducted by the US Geological Survey. Moreover, testing for drinking water contaminants is ordinarily 

undertaken at or near the levels of detection, which for most organic chemicals is one to two orders of 

magnitude below the MCL or MCLG, thus at the part-per-billion level or less.

Given the extent and accuracy of the drinking water occurrence database, as well as EPA's reliance upon 

it to enforce the SDWA, it defies logic for the Agency to look to unreliable surrogate measures, such as 

Toxics Release Inventory (TRI) data, as an alternative means of; identifying human populations that are 

likely to be exposed to drinking water contaminants. TRI serves a number of legitimate purposes, but it 

is not a productive way to identify releases to sources of drinking water. EPA has offered no legal or 

scientific justification for using TRI in lieu of or in addition to its own accepted regulatory methodology 

for identifying regulated and unregulated contaminants that may pose risks in source waters. Certainly, 

where occurrence data are available, there is no reasoned basis for relying upon TRI data to reach a 

conclusion unsupported by those occurrence data.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.
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Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 3

EPA Comment Code: 1050

Comment: B. Data Relevant to Determining Potential for Substantial Population Exposure 

The plain language of the SDWA compels the conclusion that EPA is not to test for substances that 

hypothetically, or by some remote possibility "may be found in sources of drinking water," but rather 

that it is to test only for substances that are likely to be present in sources of drinking water, as 

demonstrated by monitoring of finished drinking water or ambient water that is an actual source of water 

that will be delivered to consumers as finished drinking water. In this regard, public water systems are 

required to monitor for a host of regulated and unregulated contaminants, and these data are recorded in 

occurrence databases for each individual public water system in each state. In order to ensure that such 

data are useful from a health risk and management perspective, EPA regulations expressly require that 

monitoring be performed on water that is representative of the water that consumers will be drinking. 

While other programs such as the Clean Water Act may be concerned with broad-based pollutant issues 

affecting all waters (e.g., ecological impacts), the SDWA is concerned only with those waters that 

ultimately serve as a source of drinking water that may present human health risks. The universe of all 

ambient waters in the United States does not meet that test. 

As described in greater detail below, EPA is required to establish maximum contaminant levels (MCLs) 

through the promulgation of national primary drinking water regulations at levels as close as feasible to 

the maximum contaminant level goals (MCLGs). Public water systems monitor these MCLs and 

MCLGs regularly using testing protocols mandated by the drinking water regulations to ensure the 

representativeness, accuracy, and integrity of the data. As these data (i) are required of all public water

systems, (ii) are system-specific, and (iii) can be traced directly to a water source, they are the only 

reliable indicator of potential source water contamination other than substantially similar testing of 

corresponding source water that may be conducted by the US Geological Survey. Moreover, testing for 

drinking water contaminants is ordinarily undertaken at or near the levels of detection, which for most 

organic chemicals is one to two orders of magnitude below the MCL or MCLG, thus at the part-perbillion level or less. 

Given the extent and accuracy of the drinking water occurrence database, as well as EPA's reliance upon 

it to enforce the SDWA, it defies logic for the Agency to look to unreliable surrogate measures, such as 

Toxics Release Inventory (TRI) data, as alternative means of identifying human populations that are 

likely to be exposed to drinking water contaminants. TRI serves a number of legitimate purposes, but it 

is not a productive way to identify releases to sources of drinking water. EPA has offered no legal or 

scientific justification for using TRI in lieu of or in addition to its own accepted regulatory methodology 

for identifying regulated and unregulated contaminants that may pose risks in source waters. Certainly, 

where occurrence data are available, there is no reasoned basis for relying upon TRI data to reach a 

conclusion unsupported by those occurrence data.

Response: Please see general responses to comment under EPA Comment Code: 1060 SDWA 1457. 

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.
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Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 3

EPA Comment Code: 1050

Comment:

• The public would naturally assume than any chemical placed on a list titled “Second Endocrine 

Disruptor Screening Program List of Chemicals for Tier 1 Screening” is an endocrine disruptor despite 

the Agency’s statement that the listing does not imply endocrine effects.

• The scientific rationale for including or excluding a chemical on the November 17th list is not 

adequately transparent even though US EPA has presented its criteria. We use the example of 

perchlorate to illustrate this point.

• The Agency has excluded other chemicals that interact directly with the thyroid in the same manner as 

perchlorate does. Nitrate, bromate, and chlorate are not on the November 17th EDSP list. The same 

exclusion criteria that apply to these chemicals also applies to perchlorate. However, these have been 

excluded and perchlorate has not.

We request that the Agency review its process, increase the transparency in its evaluation of chemicals, 

and in particular, streamline its list and exclude perchlorate.

2.0 INTRODUCTION

The FQPA and SDWA Amendments were both enacted in 1996 and direct US EPA to screen for 

chemicals with endocrine disruption potential. To facilitate this, the EDSP has been congressionally 

mandated “to determine whether certain substances may have an effect in humans that is similar to an 

effect produced by a naturally occurring estrogen, or such other endocrine effect as [US EPA] may 

designate.”

EDSP utilizes a two tier screening and testing process. Tier 1 aims to test for the ability of a chemical to

interact with the endocrine system, and Tier 2 determines possible effects within this system. 

Manufacturers of the chemicals are required to submit results of Tier 1 studies as directed by US EPA. 

Chemicals were included in the first EDSP list for Tier 1 testing based on an approach described by US 

EPA in a Federal Register Notice in 2005. The original list included pesticides and certain high 

production chemicals used as pesticide inert ingredients (US EPA, 2005). The first list of chemicals 

included in Tier 1 testing was released in 2007. There were 58 chemicals on the 2007 list and US EPA is 

currently collecting Tier 1 screening information on these. Perchlorate was not included on the first Tier 

1 Testing list.

On November 17, 2010, US EPA released its tentative second list of 134 chemicals for Tier 1 testing 

under EDSP [the Notice; EPA–HQ–OPPT–2009–0477; FRL–8848–7]. This list was generated from an 

initial compilation of US EPA Office of Water candidate chemicals, in contrast to the first list which 

focused on pesticides. US EPA identified candidate chemicals that were either listed as regulated 

contaminants on the national primary drinking water regulation (NPDWR) list (40 CFR part 141) or 

were listed as unregulated contaminants on the CCL 3. Perchlorate is listed in CCL 3; therefore, it was 

automatically included on the second list for Tier 1 Testing.
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There are over 200 chemicals that are either regulated under NPDWR or are on the CCL 3 list. US EPA 

reduced this list to 134 chemicals by excluding chemicals that met one or more of the following criteria:

i. Biological agents and naturally occurring chemicals (e.g., microbials, microbial toxins, inorganics, 

radionuclides).

ii. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

disinfection byproducts or DBPs, microbes, microbial toxins, degradate compounds with more than one 

possible source).

iii. Chemicals already included on the first EDSP list because these chemicals have already received an 

EDSP order.

iv. Chemicals that are hormones with confirmed endocrine effects.

v. Chemicals not likely to be biologically active or which are incompatible with testing assays for 

various reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or 

basic, solubility, vapor pressure molecular weight). 

vi. Pesticides that are scheduled for registration review after FY 2008.

Response: EPA agrees that perchlorate, like nitrate, bromate, and chlorate, has naturally occurring 

sources. However, unlike the other chemicals mentioned in the comment, perchlorate’s anthropogenic 

sources far outweigh its naturally occurring forms. A 2006 study by a Texas Tech researcher (Dasgupta 

et al., 2006) identifies three principal sources of the perchlorate in the environment: its use as an 

oxidizer (rocket propellants, fireworks, flares and explosives), its presence in Chilean nitrate fertilizer, 

and formation via atmospheric processes. Also, please see general response to comment under EPA 

Comment Code: 1050 Evaluation Criteria Review.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 14

EPA Comment Code: 1050

Comment: • The scientific rationale for including or excluding a chemical on the second list is not clear 

even though the Agency has made criteria available. Perchlorate’s presence on the November 17th list is 

illustrative of this point.

8.0 REFERENCES

Dasgupta PK, Dyke JV, Kirk AB, Jackson WA. 2006. Perchlorate in the United States. Analysis of 

relative source contributions to the food chain. Environ Sci Technol. 40(21):6608-14.
EPA-OGWDW Final EDSP List 2 February 2013

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Dasgupta PK, Martinelango PK, Jackson WA, Anderson TA, Kang T, TDCK RW, Rajagopalan S. 2005. 

The Origin of Naturally Occurring Perchlorate: The Role of Atmospheric Processes. Environ Sci 

Technol. 39(6):1569-1575.

hlke JK, Gu B, Hatzinger PB, Sturchio NC. 2010. Isotopic Composition and Origin of 

Indigenous Natural Perchlorate and Co-Occurring Nitrate in the Southwestern United States. Environ 

Sci Technol. 44(24):9597.

Li N, Wang D, Zhou Y, Ma M, Li J, Wang Z. 2010. Dibutyl phthalate contributes to the thyroid receptor 

antagonistic activity in drinking water processes. Environ Sci Technol. 44(17):6863-8.

MA DEP (Massachusetts Department of Environmental Protection). 2006. The occurrence and sources 

of perchlorate in Massachusetts; Massachusetts Department of Environmental Protection: Boston, MA.

Melnick R, Lucier G, Wolfe M, Hall R, Stancel G, Prins G, Gallo M, Reuhl K, Ho SM, Brown T, Moore 

J, Leakey J, Haseman J, Kohn M. 2002. Summary of the National Toxicology Program's report of the 

endocrine disruptors low-dose peer review. Environ Health Perspect. 110(4):427-31.

Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Hataya Y, Shimatsu A,

Kuzuya H, Nakao K. 2002. Thyroid hormone action is disrupted by bisphenol A as an

antagonist. J Clin Endocrinol Metab. 87(11):5185-90.

National Research Council of the National Academies (NRC). 2005. Health Implications of Perchlorate 

Ingestion. Committee to Assess the Health Implications of Perchlorate Ingestion, Board on 

Environmental Studies and Toxicology, Division on Earth and Life Studies. Washington, DC: The 

National Academies Press.

Orris GJ, Harvey GJ, Tsui DT, Eldrige JE. 2003. Preliminary analyses for perchlorate in selected natural 

materials and their derivative products. United States Geological Service.

Rajagopalan S, Anderson T, Cox S, Harvey G, Cheng Q, Jackson WA. 2009. Perchlorate in wet 

deposition across North America. Environ Sci Technol. 43(3):616-22.

Sanchez CA, Fonseca JM, Blount BC, Krieger RI. 2009. Hypochlorite treatments are not a significant 

source of perchlorate exposure in lettuce. J Agric Food Chem 57(6):2320-3.

Sturchio NC, Caffee M, Beloso AD Jr, Heraty LJ, Böhlke JK, Hatzinger PB, Jackson WA, Gu B, 

Heikoop JM, Dale M. 2009. Chlorine-36 as a tracer of perchlorate origin. Environ Sci Technol. 

43(18):6934-8.

Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P, Santini F, Crump K, and Gibbs J. 

2004. Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition 

of radioactive iodide uptake by the human sodium iodide symporter.Thyroid. 14(12):1012-9.

Urbansky ET, Brown SK, Magnuson ML, Kelty CA. 2001. Perchlorate levels in samples of sodium 

nitrate fertilizer derived from Chilean caliche. Environ Pollut. 112(3):299-302.
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US EPA. 2005. Endocrine Disruptor Screening Program; Chemical Selection Approach for Initial 

Round of Screening. OPPT–2004–0109 FRL–7716–9.

US EPA. 2010a. Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 

Screening. EPA–HQ–OPPT–2009–0477; FRL–8848–7.

US EPA. 2010b. Office of Inspector General, Scientific Analysis of Perchlorate. United States 

Environmental Protection Agency, Office of Inspector General. Washington, DC.

Response: Please see general response to comment EPA Document ID: EPA-HQ-OPPT-2009-0477-

0039, part 3 under this same comment code 1050.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 1

EPA Comment Code: 1050

Comment: Please find attached comments submitted by the Ethylbenzene Panel of the American 

Chemistry Council. 

January 18, 2011

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, N.W.

Washington, DC. 20460

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477

Submitted via Federal eRulemaking Portal: http://www.regulations.gov

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

To Whom It May Concern,

The American Chemistry Council’s Ethylbenzene Panel (Panel) [FN1: The American Chemistry 

Council’s Ethylbenzene Panel is comprised of: Americas Styrenics, INEOS NOVA, LLC, and TOTAL 

Petrochemicals ]. respectfully submits these comments on EPA’s Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening (the “Draft EDSP List 2”), pursuant to EPA’s 

request for comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010, (the “Listing Notice”). 

The Panel also endorses the comments of the American Chemistry Council that are being submitted 

separately. Panel members include manufacturers of ethylbenzene (CAS No. 100-41-4). 

Section 1457 of the Safe Drinking Water Act (SDWA) authorizes EPA to include substances in the 

EDSP “that may be found in sources of drinking water” if “a substantial population may be exposed to 

such substance.” EPA has indicated that it has included ethylbenzene on the Draft EDSP List 2 due to 

the existence of a national primary drinking water regulation for the substance, and a determination that 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 129

ethylbenzene “may occur in sources of drinking water to which a substantial population may be 

exposed.” 

In publishing the second list the Agency cautions that “the public should not presume that the listing of a 

chemical or substance indicates in any way that EPA currently suspects that such chemical or substance 

interferes with the endocrine systems of humans or other species simply because it has been listed for 

screening.” EPA also notes that certain drinking water substances were excluded from the second list 

because “information on endocrine effects is already available.”

Response: EPA excluded the following “hormones with confirmed endocrine effects”: 17alphaestradiol, equilenin, equilin, estradiol, estrone, ethinyl estradiol (17-alpha ethynyl estradiol), mestranol, 

and norethindrone. These chemicals differ from all of the remaining chemicals on the second EDSP 

because they are pharmaceuticals specifically designed for either estrogenic or progesteronic hormonal 

effects. Also, please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 3

EPA Comment Code: 1050

Comment: Further, ethylbenzene does not meet the statutory criteria for inclusion in the EDSP. While 

EPA has established a Maximum Contaminant Level (MCL) for ethylbenzene under the SDWA, 

indicating that it occurs in drinking water, this fact alone does not per se qualify it for EDSP screening. 

As discussed in more detail below, exposure to ethylbenzene in drinking water is not widespread and 

therefore a substantial population will not be exposed to it.

Response: For the purposes of the second EDSP, the primary occurrence information evaluated for 

ethylbenzene was the 1992 to 2001 United States Geological Survey (USGS) National Water Quality 

Assessment (NAWQA) study and the six-year Information Collection Rule (ICR) dataset. EPA analysis 

of the NAWQA data showed that ethylbenzene was detected in 5.7% of 6,055 samples and at 3.6% of 

4,335 sites. Analysis of the six-year ICR compliance monitoring data showed that 3.9% of the 50,447 

public water systems covered during the period from 1998 to 2005 had detections of ethylbenzene. The 

percentage of the population served by these PWSs with detections was 11.9% of over 200 million 

people. This percentage covered PWSs with both ground water and surface water sources. Based on this 

evidence that ethylbenzene has been detected in both ambient sources and PWSs, ethylbenzene meets 

the statutory requirements for a “substance that may be found in sources of drinking water” and to which 

a “substantial population may be exposed.” Also, please see general response to comment under EPA 

Comment Code: 1050 Evaluation Criteria Review.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 6

EPA Comment Code: 1050
EPA-OGWDW Final EDSP List 2 February 2013

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Comment: Finally, as a general matter, EPA can ensure efficient, cost effective generation of 

scientifically reliable endocrine data by implementing the EDSP in a manner that builds upon existing 

data sources. In this regard, EPA must distinguish “data needs” from “data gaps.” It should focus efforts 

on filling only data needs, and it should do so in a resource efficient manner taking full consideration of 

protection of public health, the environment and animal welfare concerns. [FN2: Typically, a laboratory 

conducting the EDSP Tier 1 battery will use a minimum of 162 rats per chemical for the uterotrophic, 

Hershberger, male pubertal and female pubertal assays in accordance with the requirements of the EPA 

EDSP Test Guidelines. However, experience has shown that dose-ranging pilot studies will almost 

always be necessary, and this will require some 40-50 additional lab animals. Estimates for the frog 

assay indicate use of 300-400 tadpoles per assay, but in order to get to these numbers (the EPA Test 

Guideline requires the test tadpoles all be of a precisely defined staging) labs must start with a total pool 

of several thousand to select those appropriate for assay. The fish reproduction assay requires 

approximately 100-120 adults, and typically close to 30,000 embryos. ]

For all of these reasons, the ACC Ethylbenzene Panel strongly urges EPA to remove ethylbenzene from 

the second list of chemicals for Tier 1 EDSP screening. If, however, EPA continues to include it in its 

second list, EPA should consider all potential manufacturers of ethylbenzene in drinking water to 

determine which should receive test orders. The ACC Ethylbenzene Panel represents companies that 

manufacture ethylbenzene, primarily from benzene and ethylene. Virtually all of the ethylbenzene 

manufactured by Panel members is used to produce styrene. Also, as discussed in the VCCEP 

assessment, ethylbenzene occurs naturally as a component of petroleum products, is present in gasoline, 

and is a component of hydrocarbon solvents, including commercial mixed xylenes. In these products, 

ethylbenzene is present because it is a component of refinery hydrocarbon steams

The Ethylbenzene Panel appreciates the opportunity to comment on the Listing Notice. If you have any 

questions, please contact me, at (202) 249-6708, or by email 

Anthony_wagner@americanchemistry.com. 

Sincerely,

Anthony D. Wagner

Manager, Ethylbenzene Panel

Attachment: Voluntary Children’s Chemical Evaluation Program (VCCEP): Tier 1 Pilot Submission for 

Ethylbenzene (CAS No. 100-41-4). Appendices available upon request.

Response: Please see general responses to comment under EPA Comment Codes: 1060 SDWA 

1457and 1050 Evaluation Criteria Review. Please also see Endocrine Disruptor Screening Program; 

Final Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is 

being published simultaneously with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 6

EPA Comment Code: 1050
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Comment: Upon review of the CCL3 Contaminant information sheets for the degradates of Acetochlor, 

it is clear that their presence on the CCL3 list is based entirely on data collected for the parent 

Acetochlor and that no data points have been assessed directly for these two substances. Therefore, the 

ARP asserts that the listing of Acetochlor ESA and Acetochlor OA on CCL3 is without scientific or 

regulatory basis. The EPA should not propagate such a regulatory error into the EDSP program, by 

blindly accepting the improper CCL3 listing of these two molecules as a justification for including them 

on EDSP List 2.

Response: EPA’s listing of contaminants on the CCL 3 list is discussed in the general response to 

comment under EPA Comment Codes: 1050 Evaluation Criteria Review and 1060 SDWA 1457.

Also, please refer to the following studies for information on detection of degradates:

De Guzman NP, Hendley P, Gustafson DI, van Wesenbeck I, Klein AJ, Fuhrman JD, Travis K, 

Simmons ND, Teskey WE, Durham RB. 2005. The acetochlor registration partnership state ground 

water monitoring program. J Environ Qual 34(3): 793-803. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843642. 

Hackett AG, Gustafson DI, Moran SJ, Hendley P, van Wesenbeeck I, Simmons ND, Klein AJ, 

Kronenberg JM, Fuhrman JD, Honegger JL, Hanzas J, Healy D, Stone CT. 2005. The acetochlor 

registration partnership surface water monitoring program for four corn herbicides. Journal of 

Environmental Quality 34(3): 877-889. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843651.

Kalkhoff SJ, Kolpin DW, Thurman EM, Ferrer I, Barcelo D. 1998. Degradation of Chloroacetanilide 

Herbicides: The Prevalence of Sulfonic and Oxanilic Acid Metabolites in Iowa Groundwaters and 

Surface Waters. Environmental Science and Technology 32: 1738-1740.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 16

EPA Comment Code: 1050

Comment: It would be premature to include pesticide degradates in List 2:

The EPA has previously addressed testing for degradates in their "Response to Comments" on the List 1, 

when the Agency stated: "Metabolites and degradation products were not considered for this first list of 

chemicals." This is consistent with the guidance given the Agency by the 1999 review of the proposed 

EDSP by the SAP/SAB to avoid levels of complexity that could be counterproductive, [72 FR 33486, 

June 18,2007 (FRL-8129-3)]. The ARP contends that with the endocrine program still in its initial phase 

of implementation, testing for degradates would create a level of complexity that is counterproductive 

and unnecessary and should be avoided until more information on the success of current screening 

techniques and interpretation of data from those screens are available. Perhaps after parent Acetochlor 

has been fully assessed in the EDSP, it would be appropriate to consider whether further evaluation of 

the degradates is necessary.
EPA-OGWDW Final EDSP List 2 February 2013

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Acetochlor degradates were improperly listed on CCL3:

Inspection of the CCL3 Contaminant information sheets for Acetochlor and its degradates as well as the 

summary table in appendix 2 of the document named, "Final CCL 3 Chemicals: Screening to a PCCL" 

dated August 2009, and available in docket EPA-HQ-OW-2007-1189-0193 [EPA 815-R-09-007], makes 

it clear that the presence of Acetochlor ESA and Acetochlor OA on the CCL3 list is based entirely on 

data collected for the parent Acetochlor and that no data points have been assessed directly for these two 

substances. Additionally, the occurrence attribute scores for Acetochlor ESA and Acetochlor OA are 

based solely on the occurrence data of the parent Acetochlor, which tabulate prevalence and magnitude 

scores of 1 and 1, respectively, for all 3 substances, which relates to LOW exposure potential. The 

attribute scores of potency and severity of 5 and 3, respectively, for both degradates are LOWER than 

those of Acetochlor (5 and 7, respectively) even as they are derived from health effects data of the 

Acetochlor parent molecule. Therefore, the ARP asserts that the listing of Acetochlor ESA and 

Acetochlor OA on CCL3 is without scientific or regulatory basis. The EPA should not propagate such a 

regulatory error into the EDSP program, by blindly accepting the improper CCL3 listing of these two 

molecules as a justification for including them on EDSP List 2.

Response: Please see general response to comment EPA Document ID: EPA-HQ-OPPT-2009-0477-

0044, part 6 under this same comment code 1050.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 19

EPA Comment Code: 1050

Comment: General comment on use of the CCL3 listing for creation of List 2:

The SDWA specifies that the Candidate Contaminant Lists (CCL) must include contaminants that are 

not subject to any proposed or promulgated NPDWRs, are known or anticipated to occur in public water 

systems (PWSs), and may require regulation under SDWA [73 FR 33486, February 21,2008 p. 9629]. 

With a stated scope that includes 'anticipated' presence in public water systems, the ARP does not 

believe that CCL3 is an appropriate selection for prioritization of a List 2 for the EDSP program, which 

clearly specifies that the administrator needs to determine that a 'substantial population may be exposed 

to such a substance'. The ARP believes that chemicals listed on CCL3 do not a priori meet that SDWA 

requirement for testing under EDSP and therefore, List 2 is not a definitive, scientifically rigorous list of 

chemicals with a high potential for human exposure.

Response: Please see general response to comment EPA Document ID: EPA-HQ-OPPT-2009-0477-

0014, part 2 under this same comment code 1050.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 1

EPA Comment Code: 1050
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Comment: January 18, 2011

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, N.W.

Washington, DC. 20460

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477

Submitted via Federal eRulemaking Portal: http://www.regulations.gov

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

To Whom It May Concern,

The American Chemistry Council’s Ethylene Glycols Panel (“Panel”) [FN1: The American Chemistry 

Council’s Ethylene Glycols Panel is comprised of: The Dow Chemical Company, Eastman Chemical 

Company, and Shell Chemical Company.] respectfully submits these comments on EPA’s Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the “Draft EDSP List 2”) 

pursuant to EPA’s request for comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010 (the 

“Listing Notice”). The Panel also endorses the comments of the American Chemistry Council that will 

be submitted separately. Panel members include manufacturers of ethylene glycol (CAS No. 107-21-1) 

which is used in many commercial and industrial applications including antifreeze and coolant. Ethylene 

glycol also is used as a raw material in the production of a wide range of products including polyester 

fibers for clothes, upholstery, carpet and pillows; fiberglass used in products such as jet skis, bathtubs, 

and bowling balls; and polyethylene terephthalate resin used in packaging film and bottles.

Section 1457 of the Safe Drinking Water Act (SDWA) authorizes EPA to include substances in the 

EDSP “that may be found in sources of drinking water” if “a substantial population may be exposed to 

such substance.” EPA has indicated that it has included ethylene glycol on the Draft EDSP List 2 

because it is listed on the third Contaminant Candidate List (CCL 3). EPA has concluded listing on the 

CCL 3 meets the SDWA Section 1457 criteria for inclusion in the EDSP.

In publishing the second list the Agency cautions that “the public should not presume that the listing of a 

chemical or substance indicates in any way that EPA currently suspects that such chemical or substance 

interferes with the endocrine systems of humans or other species simply because it has been listed for 

screening.” EPA also notes that certain drinking water substances were excluded from the second list 

because “information on endocrine effects is already available.”

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review and 1060 SDWA 1457.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 3

EPA Comment Code: 1050
EPA-OGWDW Final EDSP List 2 February 2013

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Comment: Additionally, the Panel believes that ethylene glycol does not meet the statutory criteria for 

inclusion in the EDSP as prolonged significant exposures to either humans or the environment is 

unlikely, based on the nature in which it is chiefly used and its environmental fate properties. Lastly, 

ethylene glycol should not be included on EPA’s CCL 3.

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review, 1060 SDWA, and 2030 Contaminants Unlikely to Persist in Drinking Water.

Commenter Name: D. Douglas Fratz

Commenter Organization: Consumer Specialty Products Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0047

Comment Part: 3

EPA Comment Code: 1050

Comment: III. EPA Should Continue to Review List 2 Chemicals and Remove Those That Do Not 

Meet the Appropriate Criteria.

EPA has outlined in its notice some of the criteria used in choosing the 134 substances being proposed 

for List 2 from various drinking water and pesticide registration lists. While the general criteria seem 

reasonable, it is far from clear what specific criteria were actually used and whether those criteria were 

applied consistently. While CSPA will not comment on all of the specific chemicals selected, we would 

like to note some instances where it appears that stated criteria were not applied, or where we think other 

criteria should be used for creating List 2.

• EPA states that it eliminated chemicals that were “naturally occurring chemicals,” but many chemicals 

on the proposed list are naturally-occurring chemicals whose existence in drinking water is probably 

primarily caused by their natural occurrence. Two obvious examples are methanol and 1-butanol, which 

are ubiquitous in the biosphere due to their occurrence in fruits, vegetables and other biomass and being 

natural biodegradation products. Acetaldehyde and proprionic acid are also widely found in nature from 

natural sources, and there are probably many others.

• EPA states that it excluded chemicals “for which a manufacturer...cannot be clearly identified,” 

specifically including “disinfection byproducts” and “degradate compounds.” Yet, in addition to the 

examples above, many of these proposed chemicals should meet these criteria. Many of the 

chlorocarbons included in the list may occur in drinking water primarily as disinfection byproducts. 

Many of the simple organics are common degradation products, and come from degradation of both 

natural biomass and landfills. Some of the chemicals listed here are “legacy” chemicals that are no 

longer manufactured or imported into the US. Others are primarily in water due to fuel use and 

combustion, not chemical manufacturing.

• EPA states that it excluded chemicals which may be incompatible with the testing assays due to one or 

more physiochemical properties, specifically citing gases, strong acids or bases, solubility, vapor 

pressure and molecular weight. While it is unclear what specific criteria were applied, a number of 

chemicals proposed could have been excluded based on these types of criteria.

• EPA states that it considered the degree of exposure potential, but the actual human and environmental 

exposure levels of these chemicals probably differ by many orders of magnitude. We believe that there 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 135

is room for further study regarding whether many of these chemicals represent significant levels of 

human and/or environmental exposure. 

We therefore urge EPA to make their criteria for exclusion more transparent and to continue reviewing 

this list to determine what chemicals should be removed prior to finalizing it for the next phase of EDSP 

testing. Choosing the correct chemicals for this second list is too important a task for the Agency to rush 

ahead and prematurely issue test orders for chemicals that should have been excluded.

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review, 2010 Contaminants Identified by Commenters as being or Potentially Incompatible 

with Test Assays, 2040 Naturally Occurring Contaminants, and 1070 Increase Transparency. 

Commenter Name: Robert Simon

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0048

Comment Part: 1

EPA Comment Code: 1050

Comment: January 18, 2011

Document Control Office (7407M)

Office of Pollution Prevention And Toxics (OPPT)

U. S. Environmental Protection Agency

1200 Pennsylvania Ave., NW,

Washington DC 20460-0001

RE: Comments on “Endocrine Disruptor Screening Program; Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals,” Docket EPA-HQ-OPPT-2007-1080; and “Endocrine 

Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening,” Docket EPA-HQ-OPPT2009-0477

To Whom It May Concern:

The American Chemistry Council (ACC) respectfully submits to the Environmental Protection Agency 

(EPA) these comments concerning the Agency’s approach to perfluorooctanoic acid (PFOA) under the 

Endocrine Disruptor Screening Program (EDSP). These comments are offered in response to two 

Federal Register Notices issued on November 17, 2010: (a) Draft Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals (75 Fed. Reg. 70558); and (b) Second List of Chemicals for Tier 1 

Screening (75 Fed. Reg. 70248) (“Draft EDSP List 2”). ACC represents broad sectors of chemistry 

including global fluoropolymer and/or fluorotelomer manufacturers: Asahi Glass Co., Ltd., Clariant 

International Ltd., Daikin Industries, Ltd., Dyneon LLC, and E.I. du Pont de Nemours and Company.

PFOA is a processing aid used to produce a wide range of high-performance fluoropolymer materials 

with benefits to society that include safety, emissions reductions and communications. It is a stable and 

persistent chemical that has been detected at low levels in the environment and in the blood of the 

general population. However, even though it has been detected, the Centers for Disease Control and 

Prevention (CDC) has cautioned that “the presence of an environmental chemical in people’s blood or 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 136

urine does not mean that it will cause esffects or disease. The toxicity of a chemical is related to its dose 

or concentration in addition to a person’s individual susceptibility. Small amounts may be of no health 

consequence, whereas larger amounts may cause adverse health effects”.[FN1: Fourth National Report 

on Human Exposure to Environmental Chemicals, 2009]

EPA included PFOA in the Draft EDSP List 2 as a “Drinking water chemical based on the CCL 3 List.” 

With respect to the criteria for developing the draft EDSP List 2, we refer EPA to the separate comments 

submitted by ACC on this issue. Accordingly, these comments do not address the rationale for listing of 

PFOA in the Draft EDSP List 2. Instead, we are focusing on the broader question of how PFOA should 

be addressed under the EDSP.

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review and 1060 SDWA 1457. 

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 1

EPA Comment Code: 1050

Comment: See attached cover letter and comments from the Acetaldehyde Working Group

January 18, 2011

Document Control Office (7407M) 

Office of Pollution Prevention & Toxics 

Environmental Protection Agency 

1200 Pennsylvania Avenue, NW 

Washington, DC 20460 

RE: Comments on Inclusion of Acetaldehyde (CAS No. 75-07-0) in “Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-0477] 

Dear Sir or Madam: 

The Acetaldehyde Working Group[FN1: The Acetaldehyde Working Group is organized 

administratively under the Vinyl Acetate Council.] (AWG) appreciates the opportunity to provide 

comments on the US Environmental Protection Agency’s (EPA) announcement of a second list of

chemicals for which EPA is considering issuing Test Orders in accordance with the Endocrine Disruptor 

Screening Program (EDSP). AWG member companies[FN#2: Members of the Vinyl Acetate Council 

and Acetaldehyde Working Group include: Celanese, Ltd.; The Dow Chemical Company; E.I. DuPont 

de Nemours; Eastman Chemical Company; LyondellBasell; and, Wacker Chemie.] have an interest in 

acetaldehyde because some members manufacture acetaldehyde for commercial purposes and 

acetaldehyde is a metabolite of vinyl acetate monomer, an important commercial product manufactured 

and/or processed by members of the Vinyl Acetate Council. 
EPA-OGWDW Final EDSP List 2 February 2013

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As discussed in the comments, the inclusion of acetaldehyde as a “drinking water contaminant” on the 

EDSP List 2, does not appear justified in light of the statutory directive of §1457 of the Safe Drinking 

Water Act since drinking water is a minor source of the public’s exposure to acetaldehyde. At the same 

time, the AWG would welcome the opportunity to meet with EPA to discuss the need for testing of 

acetaldehyde.

Response: EPA recognizes that there are exposure sources of acetaldehyde other than drinking water 

but relative source contribution was not a factor in selecting the list, nor is it a requirement of SDWA 

1457. However, the occurrence information evaluated for the second EDSP list is sufficient to lead EPA 

to believe that acetaldehyde “may be found in sources of drinking water” to which a “substantial 

population may be exposed.” EPA evaluated occurrence data from the Information Collection Rule 

databases for Disinfection By-Products (DBP ICR) and CAL DHS for occurrence in finished water. The 

maximum detection value in DBP ICR dataset was 18.3μ/L and the maximum detection value in CAL 

DHS dataset was 24μ/L. EPA also reviewed Toxic Release Inventory (TRI) data with 15,146,448 

pounds released per year in 2000 and Chemical Update System/Inventory Update Rule (CUS/IUR) data 

with more than 100-500 million pounds per year being released in 2002. Also, please see general 

responses to comment under EPA Comment Codes: 1050 Evaluation Criteria Review and 1060 SDWA 

1457.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 6

EPA Comment Code: 1050

Comment: Lastly, and most importantly, it would be woefully inappropriate for the Agency to issue 

Test Orders on acetaldehyde in light of the recently promulgated TSCA Section 4 Test Rule that EPA 

published on January 7, 2011 (76 Fed. Reg. 1067), which mandates that manufacturers of acetaldehyde 

conduct a reproductive/developmental effects screening study (40 CFR 9355) and an acute daphnid/algal 

toxicity study[FN2: EPA is requiring testing based on its findings under TSCA section 4(a)(1)(B)(ii) and 

(iii) relating to sufficient data and the need for testing (76 Fed. Reg. 1070). The exposures considered by 

the Agency to support the TSCA test rule should presumably include all sources of exposure.]. This Test 

Rule is directed at the same companies identified in the proposed EDSP testing program and requires the 

conduct of a reproductive and development screening study. The main difference is that the EDSP 

program employs an extensive battery of endocrine screening assays that will be used, in a still to be 

defined weight of evidence evaluation, to decide on the need for more extensive and robust in vivo 

reproductive effects testing that the protocol required by the TSCA rule.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 11

EPA Comment Code: 1050
EPA-OGWDW Final EDSP List 2 February 2013

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Comment: To assess the appropriateness of including acetaldehyde in EDSP List 2 pursuant to §1457 

SDWA, it is useful to compare the relative amount of exposure to acetaldehyde from drinking water in 

relation to other sources of exposure, most notably food. The following table contains estimates of the 

concentration of acetaldehyde in various beverages from published sources and present exposure 

estimates based on a typical serving. The WHO report also evaluated acetaldehyde exposure from food, 

noting, “on the basis of the ranges of concentrations determined in the Dutch survey, intake in food is 

estimated to range from just less than 10 to several hundred μg/kg body weight per day.”

[Table: Concentration of Acetaldehyde in Beverages; SEE DOCKET ID EPA-HQ-OPPT-2009-0477-

0051.2]

Based on the projected intake from food, one can compare estimates of total daily intake of acetaldehyde 

from drinking water, food and nonalcoholic beverages, alcoholic beverages and ambient air. If one uses 

the highest measurements reported in the EPA dockets for acetaldehyde in drinking water (recognizing 

that the majority of drinking water analyzed found non-detectable levels), and compares against levels 

of acetaldehyde typically found in food, less than 0.5% of the public’s aggregate daily exposure to 

acetaldehyde comes from drinking water, i.e., drinking water presents a de minimis source of exposure.

[Table: Summary of Daily Intake of Acetaldehyde from Air, Drinking Water, Food and Non-Alcoholic 

Beverages, and Alcoholic Beverages; SEE DOCKET ID EPA-HQ-OPPT-2009-0477-0051.2]

It is AWG’s contention that in order for EPA to impose a testing obligation pursuant to SDWA §1457, 

there should be greater justification than pointing to a chemical’s inclusion on a previous list and more 

than scant monitoring data. The statutory provision that a “substantial population may be exposed to 

such substance” must be read in the context of the overall purpose of the Act and, as such, should 

involve a substance where drinking water is the primary source of the public exposure. While 

acetaldehyde has been found in drinking water, measured concentrations are typically very low (in the 

part-per billion range) and must be considered de minimis when compared to other sources.

B. Acetaldehyde Meets EPA’s Exclusion Criteria 

AWG further questions why EPA did not exclude acetaldehyde from the proposed EDSP List 2 given 

that the compound appears to meet the exclusion criteria EPA established. According to the FR notice 

(page 70251), in reviewing the chemicals on the CCL 3, EPA: 

streamlined this initial second EDSP list by excluding any chemical that fell into one or more of the 

following categories: 

i. Biological agent and naturally occurring chemicals (e.g., microbials, microbial toxins, inorganics, 

radionuclides). 

Ii. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

disinfection byproducts or DBPs, microbes, microbial toxins, degradate compounds with more than one 

possible source etc.). 

Iii. Chemicals already included on the first EDSP list. 

Iv. Chemicals that are hormones with confirmed endocrine effects. 
EPA-OGWDW Final EDSP List 2 February 2013

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V. Chemicals that are not likely to be biologically active or which are incompatible with testing assays 

for various reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or 

basic, solubility, vapor pressure molecular weight). 

Vi. Pesticides that are scheduled for registration review after FY 2008. 

EPA is right to exclude biological and naturally occurring chemicals from EDSP. Humans and 

environmental organisms have been exposed to low levels of acetaldehyde throughout their entire 

evolutionary period and, as such, have developed both the metabolic means to create and eliminate 

acetaldehyde at reasonable levels without damaging organs. 

AWG believes that EPA’s exclusion criterion i. for “biological agent and naturally-occurring chemicals” 

is appropriately applied to acetaldehyde given its natural formation endogenously in the human body 

and in nature by a number of different organisms and should preclude the inclusion of acetaldehyde in 

the EDSP testing program.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general responses to comment under EPA Comment Codes: 1050 Evaluation Criteria 

Review and 2040 Naturally Occurring Contaminants.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 6

EPA Comment Code: 1050

Comment: Upon review of the CCL3 Contaminant information sheets for the degradates of Alachlor, it 

is clear that their presence on the CCL3 list is based entirely on data collected for the parent Alachlor 

and that no data points have been assessed directly for these two substances. Therefore, Monsanto 

asserts that the listing of Alachlor ESA and Alachlor OA on CCL3 is without scientific or regulatory 

basis. The EPA should not propagate such a regulatory error into the EDSP program, by blindly 

accepting the improper CCL3 listing of these two molecules as a justification for including them on 

EDSP List 2.

Response: EPA’s listing of contaminants on the CCL 3 list is discussed in the general response to 

comment under EPA Comment Codes: 1050 Evaluation Criteria Review and 1060 SDWA 1457.

Also, please refer to the following studies for information on detection of degradates:

De Guzman NP, Hendley P, Gustafson DI, van Wesenbeck I, Klein AJ, Fuhrman JD, Travis K, 

Simmons ND, Teskey WE, Durham RB. 2005. The acetochlor registration partnership state ground 

water monitoring program. J Environ Qual 34(3): 793-803. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843642. 

Hackett AG, Gustafson DI, Moran SJ, Hendley P, van Wesenbeeck I, Simmons ND, Klein AJ, 

Kronenberg JM, Fuhrman JD, Honegger JL, Hanzas J, Healy D, Stone CT. 2005. The acetochlor 

registration partnership surface water monitoring program for four corn herbicides. Journal of 
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Environmental Quality 34(3): 877-889. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843651.

Kalkhoff SJ, Kolpin DW, Thurman EM, Ferrer I, Barcelo D. 1998. Degradation of Chloroacetanilide 

Herbicides: The Prevalence of Sulfonic and Oxanilic Acid Metabolites in Iowa Groundwaters and 

Surface Waters. Environmental Science and Technology 32: 1738-1740.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 16

EPA Comment Code: 1050

Comment: It would be premature to include pesticide degradates in List 2: 

The EPA has previously addressed testing for degradates in their “Response to Comments” on the List 

1, when the Agency stated: “Metabolites and degradation products were not considered for this first list 

of chemicals.” This is consistent with the guidance given the Agency by the 1999 review of the 

proposed EDSP by the SAP/SAB to avoid levels of complexity that could be counterproductive, [72 FR 

33486, June 18, 2007 (FRL-8129-3)]. Monsanto contends that with the endocrine program still in its 

initial phase of implementation, testing for degradates would create a level of complexity that is 

counterproductive and unnecessary and should be avoided until more information on the success of 

current screening techniques and interpretation of data from those screens are available. Perhaps after 

parent Alachlor has been fully assessed in the EDSP, it would be appropriate to consider whether further 

evaluation of the degradates is necessary. 

Alachlor degradates were improperly listed on CCL3: 

Inspection of the CCL3 Contaminant information sheets for Alachlor and its degradates as well as the 

summary table in appendix 2 of the document named, “Final CCL 3 Chemicals: Screening to a PCCL” 

dated August 2009, and available in docket EPA-HQ-OW-2007-1189-0193 [EPA 815-R-09-007], makes 

it clear that the presence of Alachlor ESA and Alachlor OA on the CCL3 list is based entirely on data 

collected for the parent Alachlor and that no data points have been assessed directly for these two 

substances. Additionally, the occurrence attribute scores for Alachlor ESA and Alachlor OA are based 

solely on the occurrence data of the parent Alachlor, which tabulate prevalence and magnitude scores of 

1 and 1, respectively, for all 3 substances, which relates to LOW exposure potential. The attribute scores 

of potency and severity of 5 and 3, respectively, for both degradates are LOWER than those of Alachlor 

(5 and 7, respectively) even as they are derived from health effects data of the Alachlor parent molecule. 

Therefore, Monsanto asserts that the listing of Alachlor ESA and Alachlor OA on CCL3 is without 

scientific or regulatory basis. The EPA should not propagate such a regulatory error into the EDSP 

program, by blindly accepting the improper CCL3 listing of these two molecules as a justification for 

including them on EDSP List 2. 

Independent peer expert review panel finding on Alachlor degradates should be utilized: 

In May 2009, the Alliance for Risk Assessment assembled an independent peer expert review panel to 

review the toxicological profiles for the soil degradates of Alachlor and a closely-related herbicide, 
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acetochlor. In addition to staff from “Toxicology Excellence for Risk Assessment” (TERA), the panel 

included the following experts: 

*John P. Christopher, Department of Toxic Substances Control, California Environmental Protection 

Agency 

* Lebelle Hicks, Maine Board of Pesticides, Department of Agriculture 

* Santhini Ramasamy, Office of Water, U.S. Environmental Protection Agency 

* Stephen M. Roberts, Center for Environmental and Human Toxicology, University of Florida 

These highly respected State and Federal regulatory scientists reached firm conclusions on acceptable 

levels of human exposure to the Alachlor degradates in drinking water, which have now been published 

in the peer reviewed scientific literature. [FN5: Gadagbui, B., Maier, M., Dourson, M., Parker, A., 

Willis, A., Christopher, J.P., Hicks, L., Ramasany, S., Roberts, S.M. 2010. Derived Reference Doses 

(RfDs) for the Environmental Degradates of the Herbicides Alachlor and Alachlor: Results of an 

Independent Expert Panel Deliberation. Regulatory Toxicology and Pharmacology 57:220-234.] In 

determining the critical endpoints for establishment of reference doses, the expert panel 

comprehensively evaluated the available data on Alachlor ESA and Alachlor OA related to potential 

effects on multiple endocrine-sensitive tissues and parameters and did not indicate any concern for 

endocrine-mediated toxicity. When this finding is considered in light of the previously noted absence of 

any on-going human exposure, it is clear that EDSP testing for Alachlor degradates is unnecessary.

Response: Please see response to comment EPA Document ID: EPA-HQ-OPPT-2009-0477-0052, part

6, under this same comment code 1050. Also, please see general responses to comment under EPA 

Comment Codes: 1050 Evaluation Criteria Review and 1060 SDWA 1457.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 18

EPA Comment Code: 1050

Comment: General comment on use of the CCL3 listing for creation of List 2: 

The SDWA specifies that the Candidate Contaminant Lists (CCL) must include contaminants that are 

not subject to any proposed or promulgated NPDWRs, are known or anticipated to occur in public water 

systems (PWSs), and may require regulation under SDWA [73 FR 33486, February 21, 2008 p. 9629]. 

With a stated scope that includes ‘anticipated’ presence in public water systems, Monsanto does not 

believe that CCL3 is an appropriate selection for prioritization of a List 2 for the EDSP program, which 

clearly specifies that the administrator needs to determine that a ‘substantial population may be exposed 

to such a substance’. Monsanto believes that chemicals listed on CCL3 do not a priori meet that SDWA 

requirement for testing under EDSP and therefore, List 2 is not a definitive, scientifically rigorous list of 

chemicals with a high potential for human exposure.

Response: Please see general response to comment under EPA Comment Codes: 1050 Evaluation 

Criteria Review and 1060 SDWA 1457.

Commenter Name: Sarah Janssen
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Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 6

EPA Comment Code: 1050

Comment: 3. EPA should further develop the EDSP to incorporate a chemical nominations process by 

the public and to prioritize and test select common mixtures. 

Nominations from the public are an essential part of the prioritization process for the EDSP which has 

not yet been incorporated. We strongly urge EPA to set up a nominations process as soon as possible 

and allow members of the public to begin submitting suggestions for chemicals that should undergo 

screening and testing. These nominations can be compiled until the next round of chemical selection and 

inserted into the process at that time. 

In addition, EPA has indicated previously that it would include common mixtures in the EDSP. 

However, this notice does not comment on future chemical selection processes and contains no mention 

of assessing mixtures in the Tier 1 screens. Admittedly, the testing of mixtures does involve more 

complex scientific issues than the testing of individual chemicals; however it represents the real-world 

exposure for humans who are exposed to multiple chemicals from multiple sources every day. The 

screening of mixtures should begin with the very short list of high-priority mixtures identified by the 

EDSTAC, including selected common mixtures of chemicals found in breast milk, infant formula, and 

drinking water. 

In addition, we believe that certain chemical properties, such as environmental persistence, 

bioaccumulation potential, and octanol-water partition coefficient could be useful for chemical selection. 

Chemicals that are persistent and bioaccumulative are of great concern, especially if the data reveal that 

they have endocrine activity.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Stephen Risotto

Commenter Organization: American Chemistry Council (ACC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0056

Comment Part: 1

EPA Comment Code: 1050

Comment: January 18, 2011

Document Control Office

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460-0001

Re: Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening, EPA-HQOPPT- 2009-0477, 75 Federal Register 70248 (November 17, 2010)
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To Whom It May Concern:

The Phthalate Esters Panel of the American Chemistry Council (ACC PEP) appreciates the opportunity 

to submit comments on the second list of substances for which EPA intends to issue test orders in the 

Endocrine Disruptor Screening Program (EDSP). The Panel represents North American manufacturers 

of di(2-ethylhexyl) adipate (DEHA). These comments found on the basis for including DEHA on the 

second EDSP list. ACC PEP also endorses and incorporates by reference the comments of the American 

Chemistry Council that are being submitted separately.

As indicated in the November Federal Register notice, the second list of substances would expand the 

EDSP in an effort to include all pesticides, as required by Section 408(p) of the Federal Food, Drug, and 

Cosmetic Act (FFDCA), and to add priority drinking water substances as authorized by Section 1457 of 

the Safe Drinking Water Act (SDWA). SDWA Section 1457 authorizes EPA to include substances in 

the EDSP that may be found in sources of drinking water if “a substantial population may be exposed to 

such substance.” [FN 1: EPA has previously indicated that “it is necessary for the Agency to define 

[substantial population]” as used in FFDCA Section 408(p)(3)(B) and in SDWA Section 1457, but the 

Agency has yet to do so. (63 Federal Register 71562, December 28, 1998)] EPA has indicated that it has 

proposed to include DEHA on the second list on the basis of-

• The existence of a national primary drinking water regulation for the substance, and

• A determination that DEHA “may occur in sources of drinking water to which a substantial 

population may be exposed.”

In publishing the second list the Agency cautions that “the public should not presume that the listing of a 

chemical or substance indicates in any way that EPA currently suspects that such chemical or substance 

interferes with the endocrine systems of humans or other species simply because it has been listed for 

screening.” EPA also notes that certain drinking water substances were excluded from the second list 

because “information on endocrine effects is already available.”

EPA should not include DEHA on the second list for EDSP screening because available scientific 

evidence suggests that 

(1) DEHA does not meet the statutory criteria for inclusion since DEHA exposure in drinking water 

does not occur in a substantial population, and 

(2) DEHA should be exempted from the DESP since it is not anticipated to produce endocrine 

effects in humans

Specifically, EPA’s most recent review of the drinking water standards for the substance indicates that 

DEHA was found in less than one percent of monitoring samples taken from around the country. In 

addition, based on the results of in vitro and in vivo testing, there is no scientific basis for inclusion of 

DEHA on a candidate list of potential endocrine disruptors.

Response: Di(2-ethylhexyl)adipate is regulated with a National Primary Drinking Water standard. Most 

of the regulated drinking water contaminants with NPDWRs were designated by Congress under the 

1986 or the1996 SDWA amendments. Because Congress designated these contaminants for regulation 
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due to concerns about occurrence in drinking water and adverse impacts on human health, EPA believes 

that each such substance meets the statutory testing criteria from SDWA section 1457. As required by 

SDWA section 1412(b)(9), the agency periodically reviews the existing NPDWRs and revises them, if 

appropriate. This review is known as the six-year review. Data from the Six-Year Review-ICR were 

collected for di(2-ethylhexyl)adipate from 43 states. These data consist of 121,792 analytical results 

from 28,902 public water systems (PWSs) during the period from 1998 to 2005. The distribution of 

systems with detections of di(2-ethylhexyl)adipate is geographically dispersed. Seven states reported 

detections in more than 5 percent of their systems. In 10 states, between 1 percent and 5 percent of 

systems reported detections. For di(2-ethylhexyl)adipate, 1.754 percent of 28,902 systems reported 

detections. The percentage of the population served by the systems with detections is 6.767% of over 

18.4 million people.

Also, please see general responses to comment under EPA Comment Codes: 1050 Evaluation Criteria 

Review and 1060 SDWA 1457.

Commenter Name: Susan Van Volkenburg

Commenter Organization: LANXESS Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0061

Comment Part: 2

EPA Comment Code: 1050

Comment: Furthermore, LANXESS believes that the Agency's criteria for evaluating substances for 

inclusion on the Draft EDSP List 2 and for subsequent exclusion from the Draft EDSP List 2 should 

undergo scientific peer review. EPA already has a large amount of toxicity data on many of the 

chemicals which are on the Second List of Chemicals for Tier 1 Screening and there is a considerable 

amount of test data which is publicly available. Previously developed toxicity information as part of 

product stewardship and regulatory programs should be considered relevant to evaluating risks, 

including potential effects mediated by endocrine pathways. A scientific peer review should consider all 

of the available data and its relevance to Tier 1 testing.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria Review.

Commenter Name: Susan Van Volkenburg

Commenter Organization: LANXESS Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0061

Comment Part: 4

EPA Comment Code: 1050

Comment: Endocrine activity determined by Tier 1 screening does not identify a potential hazard but 

identifies a mode of action (MoA) of toxicity that could potentially result in a hazard. This mode of 

action typically manifests in the reproductive system. The EPA already has data and information on 

relevant apical tests which are used for risk assessment purposes, including tests for reproduction and 

developmental toxicity (potential effects which are mediated by endocrine pathways). Some of these 

substances identified on the draft EDSP List 2 have been reviewed as part of the High Production 

Volume program or as part of the EPA's IRIS program. The Agency has a large amount of toxicity data 
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on 1,2,4-trichlorobenzene (CAS# 120-82-1), benzyl chloride (CAS# 100-44-7), hydrazine (CAS# 302-

01-2), monochlorobenzene (CAS#108-90-7), nitrobenzene (CAS#98-95-3), o-dichlorobenzene (CAS# 

95-50-1), o-toluidine (CAS# 95-53-4) and p-dichlorobenzene (CAS# 106-46-7). Dossiers for o-toludiene 

and 1,2,4- trichlorobenzene were submitted to the EPA as part of the EPA HPV program. For chemicals 

included in the HPV Challenge program, EPA already has results of developmental toxicity and 

reproductive toxicity tests. p-Dichlorobenzene has been reviewed extensively by the EPA as part of the 

IRIS program. In addition, results of developmental toxicity and/or reproductive toxicity studies are 

readily available on 1,2,4-trichlorobenzene, benzyl chloride, hydrazine, nitrobenzene, and odichlorobenzene. These validated end point tests are designed to detect health hazards caused by any 

mode of action, including endocrine modes.

In reference to the fact that several chemicals which LANXESS produces are on the Second List of 

Chemicals for Tier 1 Screening. We would like to convey to the EPA that the following chemicals are 

used in strictly controlled conditions as chemical intermediates, solvents and monomers. Strictly 

controlled conditions can be defined as: the substance is contained by technical means during its whole 

lifecycle which includes manufacture, cleaning and maintenance of equipment, sampling, analysis, 

loading and unloading of equipment or vessels, waste disposal and storage. If the substance is 

temporarily not contained, for example during sampling, filling or loading operations, procedural and 

control technologies are used that minimize emission and any potential exposure. Only properly trained 

and authorized personnel handle these substances. In the case of cleaning and maintenance operations, 

special procedures such as purging and washing should be applied before the system is opened and 

entered. These strictly controlled conditions apply to the following chemicals: o-toluidine, benzyl 

chloride, 1,2,4-trichlorobenzene, p-dichlorobenzene (LANXESS' customer application), odichlorobenzene and monochlorobenzene.

The final EDSP List 2 will create new obligations for specific members of the chemical industry. EPA 

should have an obligation to avoid arbitrary and capricious actions when interpreting applicable law 

identifying chemicals for this program that will be subject to EDSP testing. Furthermore, additional 

testing could result in the unnecessary waste of resources and test animals. It is imperative that the 

Agency analyze data from the initial set of EDSP substances before proceeding to additional substances.

Due to the reasons discussed above, LANXESS respectfully requests that the EPA remove the following 

chemicals from the EDSP Second List of Chemicals for Tier 1 Screening: 1,2,4-trichlorobenzene (CAS# 

120-82-1), benzyl chloride (CAS# 100-44-7), hydrazine (CAS# 302-01- 2), monochlorobenzene (CAS# 

108-90-7), nitrobenzene (CAS# 98-95- 3), o-dichlorobenzene (CAS# 95-50-1), o-toluidine (CAS# 95-

53-4), and p-dichlorobenzene (CAS# 106-46-7). LANXESS appreciates the opportunity to comment on 

EPA's draft list of substances for EDSP screening.

Sincerely,

Susan Van Volkenburg

Director, Product Safety and Regulatory Affairs

Response: Please see general responses to comment under EPA Comment Codes: 1050 Evaluation 

Review Criteria, 1060 SDWA 1457, 1065 EPA’s Authority to Require Testing, 1040 Complete List 1-

Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2, and 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Sherman Friedman
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Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 8

EPA Comment Code: 1050

Comment: II. EPA Should Not Rely on NPDWR Contaminant Listing as Basis for EDSP Listing

EPA included a number of substances on its Draft EDSP List 2 solely because those substances are 

"regulated with a national primary drinking water regulation (NPDWR)." Listing Notice at 70250. [FN3: 

Among the substances EPA listed on its Draft EDSP List 2 based solely on NPDWR listing are 

hexachlorocyclopentadiene, endrine, heptachlor and chlordane. Velsicol manufactures or formerly 

manufactured those substances. They are discussed separately below.] EPA appears to assume those 

chemicals "meet[] the statutory testing criteria from SDWA section 1457 ... [b]ecause Congress 

designated these contaminants for regulation due to concerns about occurrence in drinking water and 

adverse impacts on human health., Id. EPA provides no actual evidence that these chemicals are " found 

in sources of drinking water” or that a "substantial population is exposed" to the chemicals. Indeed, as 

discussed above, EPA has not even attempted to define those phrases and, therefore, the scope of 

SDWA § 1457. If EPA intends to merely rely on the NPDWR Contaminant List to identify substances 

for its Draft EDSP List 2, it must at a minimum determine for each chemical (1) the basis for the 

original NPDWR listing; (2) whether the basis for the original NPDWR listing meets the criteria for 

EDSP listing (after EPA explicitly states the basis for EDSP listing); and (3) if the original NPDWR 

listing meets the criteria for EDSP listing, whether more recent data continue to support a finding that 

the chemical meets the criteria for EDSP listing. It should be noted that although the SDWA directs EPA 

to review and revise each NPDWR, it only allows the Agency to maintain or provide for greater 

protections. SDWA § 14129(b)(9). Therefore, substances that no longer occur in drinking water would 

be expected to remain on the NPDWR list. For that reason, there is no rational reason to simply assume 

substances on the NPDWR list are currently found in drinking water to which a substantial population is 

exposed. 

Velsicol believes EPA must make a science-based determination as to whether substances on its Draft 

EDSP List 2 are currently found in sources of drinking water to which a substantial population is 

exposed. EPA, however, provides no evidence it made any effort to collect and assess available 

occurrence and exposure data for the chemicals it proposes to include in its Draft EDSP List 2. Nor does 

the Agency cite any other source of data that might inform a determination as to whether a substance is 

found in sources of drinking water to which a substantial population is exposed. Rather, EPA merely 

adopted existing lists of priority chemicals in its drinking water program. It did not determine and assess 

the exposure- or occurrence-related bases for the current drinking water program listings. It also has not 

determined whether those bases arc relevant for determining whether substances may be listed for 

purposes of the EDSP. (Indeed, as discussed above, EPA will not be able to make that determination 

until it first determines the legal bases for listing chemicals for pursuant to Section 1457 of the SDWA.) 

Importantly, EPA also has not determined whether exposure and occurrence data used to support 

NPDWR listings are still relevant. Many chemicals were listed on the NPDWR two decades ago. To the 

extent those listings were based on accurate exposure and occurrence data at the time, those data are 

likely no longer accurate.

EPA should collect and assess current occurrence and exposure data for chemicals that may be found in 

sources of drinking water rather than relying on lists that arc likely outdated. As EPA is aware, some of 

the chemicals on the NPDWR list arc no longer used or manufactured. While those chemicals may or 
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may not be found in sources at this time (this would depend on a number of factors including 

environmental persistence and environmental release), it is likely levels of those chemicals have 

decreased dramatically in environmental media over the years. EPA must take this factor into 

consideration before simply adding a chemical from the NPDWR list to the Draft EDSP List 2. For 

chemicals that continue to be manufactured and used, EPA should expect that releases of those 

chemicals to environmental media have decreased over time due, in large part, to EPA's successful 

regulation of chemical releases to the environment. Again, to the extent those chemicals were in sources 

of drinking water when they were listed for the NPDWR, they may no longer be found in sources of 

drinking water. Further great strides in managing the Nation's water supply, including implementation of 

efficient water purification technology in response to effective Agency regulation, have likely decreased 

levels of NPDWR-listed chemicals in drinking water. EPA should have taken all of these factors into 

consideration before it simply moved chemicals from its NPDWR list to its Draft EDSP List 2. 

Public water systems are required by law to test for a host of regulated and unregulated contaminants, 

including those on the NPDWR list. One of the best available sources of information concerning 

whether and to what extent a substance may occur in drinking water is the extensive database of 

monitoring data that is recorded and reported to EPA by the nation's thousands of public water systems 

pursuant to Agency regulation. Given the extent and accuracy of that database, as well as EPA's reliance 

upon it to enforce the SDWA, it would have been logical for EPA to at least consider that data when 

creating its Draft EDSP List 2. Velsicol believes EPA should have utilized that data as well as other 

actual data to determine if substances are actually found in sources of drinking water. Velsicol cannot 

understand why EPA would ignore actual, readily available data and rely instead on dated, possible 

inaccurate, lists to develop its Draft EDSP List 2. To this regard, EPA's actions appear arbitrary, 

unscientific and contrary to law. 

When it does assess actual data for determining whether a substance may be found in sources of 

drinking water to which a substantial population is exposed, EPA should undertake a rigorous analysis 

of data strengths and weaknesses. EPA should do this when analyzing exposure and occurrence data 

underlying NPDWR listing as well as more recent occurrence data generated by public water systems. 

To ensure reproducible analyses, EPA should use only data sources that are publicly available. Further, 

in evaluating data sources it relies upon to prioritize substances for EDSP screening, EPA should 

analyze each database in terms of: 

• The extent to which the database represents the current U.S. population (e.g., EPA should consider 

who was sampled, where samples were collected and sample size).

• Sampling design (including whether sufficient controls were used).

• Quality of the data (e.g., sensitivity and specificity of the chemical analytic techniques; adequacy of 

the quality assurance/quality control procedures for sample collection, storage, analysis, archiving and 

record keeping).

• Time frame of sample collection to determine current relevance. EPA should determine whether there 

have been major changes in production or use patterns, or in regulatory requirements that would impact 

current exposure circumstances.

• Frequency of occurrence of measured concentrations within the database (e.g., whether the data 

represent an isolated incident and whether the data are statistically significant).
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• Concentration ranges of the samples in the database.

• Identity of a chemical as a parent chemical as opposed to a metabolite of a different chemical.

• Public availability of the data

Importantly, EPA should not simply assume that all the information it relies on to determine potential 

exposure for purposes of EDSP listing can be extrapolated to the general population and to current, 

present-day exposure circumstances. EPA has focused considerable attention on information quality 

issues, and the Agency has adopted a number of policies, procedures and guidelines to guide Agency 

actions in collecting, evaluating, disseminating and using environmental data. EPA should utilize those 

existing policies, procedures and guidelines when assessing data for purposes of EDSP listing. Those 

current Agency activities include: 

• EPA Quality Manual for Environmental Programs 5360 Al. May 2000. http://www.cpa.gov/quality/qsdocs/5360.pdf

• EPN260R-02-008, December 2002, Guidelines for Ensuring and Maximizing the Quality, Objectivity, 

Utility and Integrity for information Disseminated by the Environmental Protection Agency 

http://www.epa.gov/oei/qualityguidelincs/EPA-OEI-IQG-FINAL-l0.2.pdf

Although Velsicol urges EPA to rely on actual data when determining whether a substance "may be 

found in sources of drinking water" and a "substantial population” may be exposed, it should be mindful 

of limitation of specific databases. For example, the National Drinking Water Chemical Occurrence 

Database (NCOD) provides useful information, but has some limitations. For example:

• The NCOD is a compilation of data sets developed using different sampling strategies and study 

design. Therefore, comparison of title data among data sources may not be possible. In addition, the 

extrapolation of these data nationwide may be limited.

• The extent of QA/QC in the NCOD is not clear from the available data and supporting materials.

• Information to assess the reliability of these data regarding detection limits, sample custody and 

sample storage and preservation are lacking.

• Raw-water monitoring data may not be very useful in assessing potential human exposure to drinking 

water because water treatment methods may affect concentrations of these compounds.

• The age of some of the data compiled in the NCOD may decrease the usefulness and relevance of the 

data to current potential exposures due to differences in analytical methods and temporal differences in 

environmental contaminants

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review.
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Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 14

EPA Comment Code: 1050

Comment: VI. EPA Should Not Include Chlordane, Endrin, or Heptachlor on Its EDSP List2. 

EPA included Chlordane, Endrin and Heptachlor on its Draft EDSP List 2. EPA bases its listing of these 

substances solely on the fact that they are "regulated with a national primary drinking water regulation 

(NPDWR)." Listing Notice at 70250. EPA provides no evidence that it has actually determined that the 

substances “may be found in sources of drinking water" and “that a substantial population may be 

exposed" to the substances. Because EPA failed to make those determinations as required by law and to 

publish its factual determinations in that regard, the Agency should not have included Chlordane, Endrin 

and Heptachlor on its Draft EDSP List 2. Further as discussed in Comment IV above, EPA should not 

include Chlordane, Endrin and Heptachlor on its Draft EDSP List 2 because those substances are no 

longer manufactured in the United States. Finally, Velsicol believes Chlordane, Endrin and Heptachlor 

are not found in sources of drinking water to which a substantial population is exposed and, therefore, 

should not be placed on the EDSP List 2. 

A. EPA Failed to Determine Whether Chlordane, Endrin, and Heptachlor May Be Found in Sources of 

Drinking Water to Which a Substantial Population is Exposed 

For the reasons discussed in Section I of these comments, before it may list Chlordane, Endrin and 

Heptachlor on its EDSP List 2, EPA must determine that those substances "may be found in sources of 

drinking water" and "that a substantial population may be exposed.” EPA has failed, however, to make 

those determinations. Indeed, it appears EPA failed to assess any actual data concerning those 

substances for purposes of its EDSP listing. EPA merely relies on the fact that Hex is regulated with a 

NPDWR. For all the reasons discussed in Section II of these comments, EPA should not rely simply on 

NPDWR listing as the basis for listing Chlordane. Endrin, and Heptachlor on the EDSP List 2. 

Relying on the NPDWR listing, EPA simply assumes that Chlordane, Endrin and Heptachlor were found 

to occur in sources of drinking water and that a substantial population was exposed to those substances 

in drinking water when the NPDWRs were promulgated for those substances almost two decades ago. 

EPA provides no factual basis for that assumption. Even if the decades old NPDWR listings were based 

on sufficient exposure and occurrence information to warrant EDSP Listing, EPA failed to determine 

whether those substances are currently found in sources of drinking water to which a substantial 

population is exposed. EPA ignores that levels of Chlordane, Endrin and Heptachlor in sources of 

drinking water may have decreased dramatically over the last two decades. 

In sum, in listing Chlordane, Endrin and Heptachlor EPA (1) failed to define the terms “may be round in 

sources of drinking water" and "that a substantial population may be exposed"; (2) assumed (possibly 

incorrectly) those substances fell within the scope of those undefined terms two decades ago; and (3) 

assumed those substances still fall within the scope of those undefined terms today. Because EPA failed 

to properly define the scope of its authority under § 1457 of the SDWA and provided no support for its 

exposure assumptions concerning Chlordane, Endrin and Heptachlor, Velsicol believes EPA's listing of 

those substances is arbitrary. Chlordane, Endrin and Heptachlor should be removed from EPA's EDSP 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

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List 2 until EPA makes the appropriate legal and scientific findings that would support the listing of 

those substances on the EDSP List 2.

Response: Please see general responses to comment under EPA Comment Codes: 2020 Contaminants 

No Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations, 1050 Evaluation Criteria Review, and 1060 SDWA 1457.
EPA-OGWDW Final EDSP List 2 February 2013

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EPA Comment Code: 1060 SDWA 1457

General Response: EPA disagrees with comments stating that by EPA selecting a subset of chemicals 

from CCL 3 and chemicals regulated with National Primary Drinking Water standards it has not met the 

requirements of SDWA 1457. 

SDWA 1457 states that “the Administrator may provide for testing under the screening program 

authorized by section 408(p) of such Act, ...of any other substance that may be found in sources of 

drinking water if the Administrator determines that a substantial population may be exposed to such 

substance.” As stated in 75 FR 70248, November 17, 2010 (USEPA, 2010b), in listing drinking water 

contaminants on the CCL 3, EPA closely evaluated the nature of the occurrence and prevalence 

information supporting contaminants listed on the CCL 3 list. During the CCL 3 development process, 

EPA assessed the data sources used for relevance, completeness, redundancy, and availability to ensure 

that the agency used the best available scientific data. 

EPA considered and evaluated data based on occurrence in finished drinking water and ambient water. 

It is true that not all ambient waters are sources of drinking water. However, the ambient water data, 

along with other occurrence information, represents the best available scientific data. The National 

Drinking Water Chemical Occurrence Database (NCOD) was part of the occurrence information 

evaluated by an external peer review specific to the data sources. The data sources used for the CCL 3 

processes, including NCOD, were reviewed for the following four attributes: relevance, completeness, 

redundancy, and retrievability.

The agency also evaluated data related to the total releases to the environment, pesticide application 

rates, and production volumes (73 FR 9628, February 21, 2008) (USEPA, 2008). In deciding whether to 

move a possible drinking water contaminant from the preliminary CCL 3 to the proposed CCL 3, EPA 

scored each contaminant based on occurrence attributes, among other attributes (73 FR 9628, February 

21, 2008) (USEPA, 2008). The occurrence attributes were weighted more heavily based on a hierarchy 

representing prevalence of the contaminant in the water environment or likely release to the water 

environment. The results of that scoring are described at 73 FR 9644, February 21, 2008 (USEPA, 

2008). In 2009 EPA published the administrative record supporting the CCL 3. The administrative 

record includes contaminant-by-contaminant information sheets that document the occurrence that 

support the inclusion of contaminants on the CCL 3. The protocol that EPA used to develop CCL 3 was 

reviewed by internal experts, as well as external experts such as the National Drinking Water Advisory 

Council and the Science Advisory Board (NDWAC, 2004). The scientific basis for EPA's selection of 

contaminants on the CCL 3, therefore, also provides the basis for EPA's determination that a chemical 

may be found in sources of drinking water to which a substantial population may be exposed for the 

purposes of SDWA section 1457.

As stated in the November 2010 FR notice, most of the regulated drinking water contaminants with 

NPDWRs were designated by Congress under the 1986 or the 1996 SDWA amendments. Because 

Congress designated these contaminants for regulation due to concerns about occurrence in drinking 

water and adverse impacts on human health, EPA believes that each such substance meets the statutory 

testing criteria from SDWA section 1457.

SDWA section 1457 sets forth the criteria for the selection of substances for the screening program it 

authorizes. Section 1457 does not require the agency to promulgate regulations defining these criteria

and EPA has applied these statutory criteria as described in the November 2010 FR notice.
EPA-OGWDW Final EDSP List 2 February 2013

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Please note the Endocrine Disruptor Screening Program SDWA orders will not be issued under the 

authority of TSCA. Also, the EDSP is not a rulemaking process.

Individual Comments

Commenter Organization: American Chemistry Council Oxo Process Panel

EPA Document ID: EPA-HQ-OPPT-2009-0477-0027

Comment Part: 1

EPA Comment Code: 1060

Comment: Dear Sir or Madam:

The American Chemistry Council’s Oxo Process Panel appreciates the opportunity to submit the 

attached comments on the “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 

1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] regarding the listing 

of 1-butanol (CAS RN 71-36-3). If you have questions regarding these comments, please contact Leslie 

Berry at 202-249-6716 or by e-mail at Leslie_Berry@americanchemistry.com.

January 18, 2010 

OPPT Document Control Office (DCO) 

EPA East Building, Room 6428 

1201 Constitution Avenue, N.W. 

Washington, DC. 20460 

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477 

Submitted via Federal eRulemaking Portal: http://www.regulations.gov 

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] 

Dear Sir or Madam: 

The American Chemistry Council’s (“ACC”) Oxo Process Panel[FN1: The “Oxo Process” refers to an 

industrial synthesis process which is used to produce alcohols and related oxygenated compounds. The 

Panel members include BASF Corporation, Celanese Limited, The Dow Chemical Company, and 

Eastman Chemical Company.] (“Panel”) appreciates the opportunity to submit comments on EPA’s 

Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the “Draft 

EDSP List 2”). Pursuant to EPA’s request for comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 

11/17/2010, (the “Listing Notice”), the Panel supports the ACC’s general comments related to Draft 

EDSP Policies and Procedures, the Draft Information Collection Request, and EPA’s Draft EDSP List 2.

With regard to the listing of 1-butanol (CAS RN 71-36-3) on the draft EDSP list 2, EPA has not satisfied 

Section 1457 of the Safe Drinking Water Act (SDWA) because neither the Contaminant Candidate List 

3 (CCL3) or TRI data support the determination that 1-butantol “may be found in sources of drinking 

water” to which a “substantial population may be exposed”. Accordingly, the Panel requests that 1-

butanol be removed from EPA’s draft EDSP List 2. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

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I. 1-Butanol’s inclusion on the CCL3 does not meet the criteria of the 1996 endocrine amendments to 

the SDWA 

The Panel does not agree with EPA’s assertion that 1-butanol’s inclusion on the CCL3 per se meets the 

criteria of the 1996 endocrine amendments to the SDWA that a substance “may be found in sources of 

drinking water” and a “substantial population” has been exposed. Section 1457 of the SDWA is the 

statutory authority for the screening and testing of chemicals in drinking water for endocrine disruptive 

effect, the language providing for testing of “any other substance that may be found in sources of 

drinking water” must be read in light of the subsequent language requiring the Administrator to 

determine “that a substantial population may be exposed to such substance.” The language on its face 

and taken as a whole compels the conclusion that EPA is not to test substances like 1-butanol that 

hypothetically, or by some remote possibility “may be found in sources of drinking water,” but rather 

that it is to test for substances that are (1) likely to be present in sources of drinking water and (2) for 

which there is an empirical basis for that conclusion based on actual monitoring of finished drinking 

water or ambient water that is an actual source of water that is delivered to consumers as finished water. 

The CCL3 is a list of contaminants not regulated under the SDWA, but which may require a national 

drinking water regulation in the future. The CCL3 is used to prioritize research and data collection 

efforts to help EPA determine whether a specific contaminant should be regulated. A chemicals 

inclusion on the CCL3 does not mean the chemical is found in public drinking water sources to which a 

substantial population may be exposed. Accordingly, the listing of 1-butanol on the CCL3, by itself, 

does not constitute a rational basis for EPA to determine that a substantial population may be exposed to 

the chemical, and therefore, does not satisfy the statutory criteria of SDWA 1457.

II. EPA has not provided a rational basis for determining that 1-butanol may be found in sources of 

drinking water to which a substantial population may be exposed 

For 1-butanol, the CCL3 process uses TRI information and production data as the only indicator of 

“prevalence” in drinking water, not monitored data. In such cases, EPA clearly acknowledges “[T]he 

relationship between production or even environmental release data and the actual occurrence in 

drinking water is complex” and that many times the agreement between a CCL3 prevalence score based 

on actual measurements in potable water samples and a CCL3 prevalence score based on production or 

TRI data “was not good.”[FN2: EPA (2009). Final Contaminant Candidate List 3 Chemicals: 

Classification of the PCCL to CCL EPA-HQ-OW-2007-1189-0187. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OW-2007-1189-0187. Pages 23-24.]

Furthering this point, under TRI reporting of releases to surface water, there is no determination that any 

exposure to humans has or may occur, let alone that a “substantial population” may be exposed. Public 

health considerations and fundamental principles of water treatment and risk management dictate that 

public water suppliers screen source water supplies as a matter of course, independent of Section 1457, 

to eliminate potential water sources that may present a broad range of potential health concerns 

(pathogens, regulated contaminants). Given the host of geographic, topographic, water management, 

source water selection, and fate and transport considerations that serve to confound the nexus between 

TRI facilities and actual source waters, reliance on the TRI of gross production numbers for chemicals 

to identify chemicals for source water screening does not satisfy Section 1457 of the SDWA.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 154

Commenter Name: Leslie Berry

Commenter Organization: American Chemistry Council Oxo Process Panel

EPA Document ID: EPA-HQ-OPPT-2009-0477-0027

Comment Part: 3

EPA Comment Code: 1060

Comment: In summary, the Panel believes that 1-butanol should be removed from the EPA’s Draft 

EDSP List 2 because the chemical does not meet the endocrine SDWA requirements and EPA has not 

provided a rational basis for determining that 1-butanol may be found in sources of drinking water to 

which a substantial population may be exposed. As discussed in ACC’s overarching EDSP comments, 

the Panel believes the process EPA has used to determine that a substance “may be found in sources of 

drinking water” to which a “substantial population” may be exposed should be revised to rely on more 

relevant and accurate exposure data sources. We appreciated the opportunity provide these comments. If 

you have questions regarding these comments, please contact me at 202-249-6716 or by e-mail at 

Leslie_Berry@americanchemistry.com.

Sincerely, 

Leslie Berry 

Oxo Process Panel Manager, 

Chemical Products and Technology

References 

Barton HA, Deisinger PJ, English JC, Gearhart JN, Faber WD, Tyler TR, Banton MI, Teeguarden J, 

Andersen ME. 2000. Family Approach for Estimating Reference Concentrations/Doses for Series of 

Related Organic Chemicals. Toxicol Sci 54(1):251-261. 

EPA. (1994). Chemicals in the environment: 1-Butanol (CAS No. 71-36-3). Office of Pollution 

Prevention and Toxics (OPPT) Fact Sheet. 

Organization for Economic Cooperation and Development Screening Information Data Set Program 

2005. Review of n-butanol.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 1

EPA Comment Code: 1060

Comment: PHD Consulting 

9102 Riverside Drive, Fort Washington, MD 20744, Tel: 301-749-1307 

e-Mail: dugard4@msn.com 
EPA-OGWDW Final EDSP List 2 February 2013

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To Docket ID Number: EPA-HQ-OPPT-2009-0477 

Comments on the Inclusion of HCFC-22 (CAS No. 75-45-6) in the Second List of Chemicals for Tier 1 

Screening under the Endocrine Disruptor Screening Program (EDSP), 75FR 70248, Nov. 17 2010 

Comments filed by Paul H. Dugard, PhD, January 18, 2011

These comments have been filed on behalf of Arkema Inc., Honeywell International, Inc., and 

Mexichem Fluor, Inc., companies that are producers or importers of HCFC-22 (chlorodifluoromethane, 

CAS Number 75-45-6). 

HCFC-22 should not be included in the second list of chemicals for Tier 1 screening under the 

Endocrine Disruptor Screening Program (EDSP) for the following reasons:

1.HCFC-22 Does not Meet the Criteria “May be Found in Sources of Drinking Water and to Which 

Substantial Populations May be Exposed” Necessary to Support Listing 

The EDSP was established by EPA in response to Section 408(p) of the Federal Food, Drug and 

Cosmetic Act (FFDCA). The second list of chemicals for Tier 1 screening for endocrine disrupting 

activity responds to the directive in Section 1457 of the Safe Drinking Water Act (SDWA) to include in 

EDSP “any other substance that may be found in sources of drinking water if the Administrator 

determines that a substantial population may be exposed to such substance.” The authority for the 

selection of second list of chemicals for Tier 1 testing is thus based on this section of the SDWA and 

chemicals must meet the criteria of being “found in sources of drinking water” and that “a substantial 

population may be exposed.” The term “found” lacks clarity (sophistication of analytical techniques can 

make a difference as to whether or not a material is “found”) and “substantial population” is undefined. 

However, HCFC-22 does not fall into a “grey area” where the uncertainty regarding these terms is a 

concern.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457. 

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 1

EPA Comment Code: 1060

Comment: January 18, 2011

BY HAND

OPPT Document Control Office (DCO)

Environmental Protection Agency, East Building

Room 6428

1201 Constitution A venue, NW

Washington, DC

Re: EPA-HQ-OPPT-2009-0477

Dear Sirs:
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 156

The HAP Task Force represents manufacturers of 1,1,2-trichloroethane and ethylene dichloride (1,2-

dichloroethane or EDC) in connection with Enforceable Consent Agreements (ECAs) with EPA for the 

testing of these compounds. Both 1,1 ,2-trichloroethane and EDC appear on the second list of chemicals 

for Tier 1 screening under the Endocrine Disruptor Screening Program (EDSP), announced at 75 Fed. 

Reg. 70248 (November 17, 2010), comment period extended at 75 Fed. Reg. 77869 (December 14, 

2010). The HAP Task Force offers these comments in support of its position that both 1,1,2-

trichloroethane and EDC should be removed from this list.

A. Statutory Criterion for Screening/Testing

EPA established the EDSP in response to Section 408(p) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA).[FN121 U.S.C. § 346a(p)(4).]: The second list responds to the directive in Section 1457 of the 

SafeDrinking Water Act (SDWA) to include in EDSP "any other substance that may be found in sources 

of drinking water if the Administrator determines that a substantial population may be exposed to such 

substance." [FN2: 42 u.s.c. § 300j-17.] Thus, SDWA § 1457 is the statutory authority for the screening 

nd testing of chemicals in drinking water for endocrine disruption. Basic principles of statutory 

construction mandate that its language be read as a whole, as well as in the context of the overall 

purpose of the Act. The language providing for testing of "any other substance that may be found in 

sources of drinking water" must be read in light of the subsequent language requiring that the 

Administrator determine "that a substantial population may be exposed to such substance."

While "substantial population" is not defined in the SDWA, Section 4(a)(l)(B) of the Toxic Substances 

Control Act (TSCA),[FN3: 15 U.S.C. § 2603(a)(1)(B).] which requires EPA before issuing a test rule to 

find that a chemical substance (i) is produced "in substantial quantities," and (I) enters the environment 

"in substantial quantities," or (II) there is "significant or substantial human exposure" to the substance, is 

a comparable provision that EPA may look to for guidance in construing "substantial population" in 

SDWA § 1457. Since 1993, EPA has relied upon a statement of policy, known as "the B Policy" to 

articulate the standards and criteria for implementing its authority to require testing under the substantial 

production, release, and exposure provisions of TSCA. [FN4: 58 Fed. Reg. 28736 (May 14, 1993). The 

B Policy was developed after a US Court of Appeals remanded the TSCA § 4 test rule on cumene back 

to EPA to articulate the criteria the Agency uses to make "B" findings. CMA v. EPA, 899 F.2d 344 (5th 

Cir. 1990). Following the same reasoning, it is submitted that EPA must also articulate the criteria that 

will guide its decision that a substantial population may be exposed to a substance for purposes of 

requiring testing under SDWA § 1457.] The Agency set forth as general benchmarks for "substantial 

exposure" for purposes of TSCA § 4 exposure of 100,000 members of the public, 10,000 consumers, or 

1,000 workers. Some numerical criterion of this nature is necessary for EPA to avoid being arbitrary and 

capricious in its decisions as to which drinking water contaminants may reach a substantial population 

for purposes of EDSP.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457. 

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0035

Comment Part: 3

EPA Comment Code: 1060
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 157

Comment: 3. The Panel does not agree with EPA’s assertion that a chemical on the CCL3 list per se 

meets the 1996 endocrine amendments to the Safe Drinking Water Act (SDWA) that a substance “may 

be found in sources of drinking water” to which a “substantial population” may be exposed. 

* Toxics Release Inventory (TRI) reporting is the sole data source relied upon to include MDA on the 

CCL3 list based on the determination that it “may be found in sources of drinking water” and a 

“substantial population” may be exposed. In most, if not the vast majority of cases, TRI reporting of 

releases to surface water are over-conservative estimates, and not measured releases. Under TRI 

reporting of releases to surface water, there is no ascertainment that any exposure to humans has or may 

occur, let alone that a “substantial population” may be exposed. Furthermore, for 4,4’-MDA (CASRN 

101-77-9) TRI surface water emissions for reporting year 2009 totaled 1,906 lbs, and were associated 

with a single outfall of The Dow Chemical Company at Freeport, Texas. The surface water outfall 

associated with the estimated emissions at Freeport, TX occurs on the Brazos River, at a location where 

effluent is mixed with seawater prior to discharge, and is also influenced by tidal influx of seawater from 

the Gulf of Mexico. Therefore, the surface water occurring at, or downstream of, this outfall would 

contain salinity and other water quality attributes which prevent its use as a drinking water source. At a 

minimum, EPA should review the substances on the CCL3 List to determine which of these clearly 

show that a substance actually may make its way into a drinking water source and could lead to 

exposure of a “substantial population” before importing a substance on the CCL3 List into the EDSP. 

* The Panel is also concerned that EPA has not sufficiently accounted for data quality in relying on the 

TRI database for asserting substances on the CCL3 List automatically satisfy the SDWA endocrine 

statutory requirements. When utilizing any data source, EPA should analyze data strengths and 

weaknesses prior to using that data in Agency programs. Further, to ensure its analyses are both 

transparent and reproducible, EPA should use only data sources that are publicly available. 

4. EPA suggests that because the CCL3 List had previously been subject to notice and comment, and 

EPA response to same, that the Agency would not revisit those conclusions. This rationale is flawed, 

however, since the CCL3 was never developed to meet SDWA Section 1457 authority for testing 

substances that “may be found in sources of drinking water” to which a “substantial population” may be 

exposed. As the Agency is aware, the CCL3 was developed for different purposes of the SDWA. Being 

on the CCL3 does not necessarily mean the chemical is found in public drinking water sources to which 

a substantial population may be exposed. The Agency’s responses to previous comments on the CCL3, 

therefore do not justify the Agency’s plans not to respond to comments on the Draft EDSP List 2. 

Further, when the EDSP List 2 is final and integrated into individual EDSP test orders to manufacturers 

and importers, new duties and obligations for specific members of the regulated community will be 

created. Administrative efficiency, consistency with EPA’s approach in EDSP Phase I, and the open and 

transparent processes and practices envisioned by the Administrative Procedure Act, argue instead for 

EPA to respond to comment on the Draft EDSP List 2 that are submitted to this docket.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 4

EPA Comment Code: 1060
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 158

Comment: 3. The Panel does not agree with EPA’s assertion that a chemical on the CCL3 List per se 

meets the 1996 endocrine amendments to the SDWA that a substance “may be found in sources of 

drinking water” to which a “substantial population” may be exposed. In particular, the mere presence on 

the CCL3 List does not provide a rational basis for a determination that a substantial population may be 

exposed to TDI. 

* Toxics Release Inventory (TRI) reporting is the sole data source relied upon to include TDI on the 

CCL3 list based on the determination that it “may be found in sources of drinking water” to which a 

“substantial population” may be exposed. In most, if not the vast majority of cases, TRI reporting of 

releases to surface water are over-conservative estimates, not measured releases. The TRI reporting of 

releases does not assess whether any exposure to humans has or may occur, let alone that a “substantial 

population” may be exposed. Furthermore, for TDI substances (mixed isomers, CASRN 26471-62-5; 

2,4-TDI CASRN 584-84-9; 2,6-TDI, CASRN 91-08-7), TRI surface water releases for reporting year 

2009 totaled 716 lbs, and were associated with a single outfall of The Dow Chemical Company at 

Freeport, Texas. The surface water outfall associated with the emissions at Freeport, TX occurs on the 

Brazos River, at a location where effluent is mixed with seawater prior to discharge, and is also 

influenced by tidal influx of seawater from the Gulf of Mexico. Therefore, the surface water occurring 

at, or downstream of, this outfall would contain salinity and other water quality attributes which prevent 

its use as a drinking water source. It is recommended that EPA review the substances on the CCL3 List 

to determine which of these clearly show that a substance actually may make its way into a drinking 

water source and could lead to exposure of a “substantial population” before importing a substance on 

the CCL3 List into the EDSP. 

* The Panel is also concerned that EPA has not sufficiently accounted for data quality in relying on the 

TRI database for asserting substances on the CCL3 List automatically satisfy the SDWA endocrine 

statutory requirements. When utilizing any data source, EPA should analyze data strengths and 

weaknesses prior to using that data in Agency programs. Further, to ensure its analyses are both 

transparent and reproducible, EPA should use only data sources that are publicly available. 

4. EPA suggests that because the CCL3 had previously been subject to notice and comment, and EPA 

response to same, that the Agency would not revisit those conclusions. This rationale is flawed, 

however, since the CCL3 was never developed to meet SDWA Section 1457 authority for testing 

substances that “may be found in sources of drinking water” to which a “substantial population” may be 

exposed. As the Agency is aware, the CCL3 was developed for different purposes of the SDWA. Being 

on the CCL3 does not necessarily mean the chemical is found in public drinking water sources to which 

a substantial population may be exposed. The Agency’s responses to previous comments on the CCL3, 

therefore do not justify the Agency’s plans not to respond to comments on the Draft EDSP List 2. 

Further, when the EDSP List 2 is final and integrated into individual EDSP test orders to manufacturers 

and importers, new duties and obligations for specific members of the regulated community will be 

created. Administrative efficiency, consistency with EPA’s approach in EDSP Phase I, and the open and 

transparent processes and practices envisioned by the Administrative Procedure Act, argue instead for 

EPA to respond to comment on the Draft EDSP List 2 that are submitted to this docket.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: W. Caffey Norman
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 159

Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0037

Comment Part: 1

EPA Comment Code: 1060

Comment: January 18, 2011

BY HAND

OPPT Document Control Office (DCO)

Environmental Protection Agency, East Building

Room 6428

1201 Constitution Avenue, NW

Washington, DC

Re: EPA-HQ-OPPT-2009-0477

Dear Sirs:

On behalf of PPG Industries, Inc., we offer these comments on EPA's notice announcing a second list of 

chemicals for Tier 1 screening under the Endocrine Disruptor Screening Program (EDSP), 75 Fed. Reg. 

70248 (November 17,2010), comment period extended at 75 Fed. Reg. 77869 (December 14,2010). PPG 

manufactures trans-1,2-dichloroethylene and 1,1,1- trichloroethane, chemicals included in the second 

list.

A. Statutory Criterion for Screening/Testing 

EPA established the EDSP in response to Section 408(p) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA).[FNl: 21 U.S.C. § 346a(p)(4).] The second list responds to the directive in Section 1457 of the 

Safe Drinking Water Act (SDWA) to include in EDSP “any other substance that may be found in 

sources of drinking water if the Administrator determines that a substantial population may be exposed 

to such substance.”[FN2: 42 U.S.C. § 300j-17.] Thus, SDWA § 1457 is the statutory authority for the 

screening and testing of chemicals in drinking water for endocrine disruption. Basic principles of 

statutory construction mandate that its language be read as a whole, as well as in the context of the 

overall purpose of the Act. The language providing for testing of “any other substance that may be found 

in sources of drinking water” must be read in light of the subsequent language requiring that the 

Administrator determine “that a substantial population may be exposed to such substance.”

While “substantial population” is not defined in the SDWA, Section 4(a)(1)(B) of the Toxic Substances 

Control Act (TSCA),[FN3: 15 U.S.C. § 2603(a)(I)(B).] which requires EPA before issuing a test rule to 

find that a chemical substance (i) is produced “in substantial quantities,” and (I) enters the environment 

"in substantial quantities," or (II) there is "significant or substantial human exposure" to the substance, is 

a comparable provision that EPA may look to for guidance in construing "substantial population" in 

SDWA § 1457. Since 1993, EPA has relied upon a statement of policy, known as "the B Policy" to 

articulate the standards and criteria for implementing its authority to require testing under the substantial 

production, release, and exposure provisions of TSCA.[FN4: 58 Fed. Reg. 28736 (May 14, 1993). The B 

Policy was developed after a US Court of Appeals remanded the TSCA § 4 test rule on cumene back to 

EPA to articulate the criteria the Agency uses to make "B" findings. CMA v. EPA, 899 F.2d 344 (5th 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 160

Cir. 1990). Following the same reasoning, it is submitted that EPA must also articulate the criteria that 

will guide its decision that a substantial population may be exposed to a substance for purposes of 

requiring testing under SDW A § 1457.] The Agency set forth as general benchmarks for "substantial 

exposure" for purposes of TSCA § 4 exposure of 100,000 members of the public, 10,000 consumers, or 

1,000 workers. Some numerical criterion of this nature is necessary for EPA to avoid being arbitrary and 

capricious in its decisions as to which drinking water contaminants may reach a substantial population 

for purposes of EDSP.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 1

EPA Comment Code: 1060

Comment: January 18, 2011

BY HAND

OPPT Document Control Office (DCO)

Environmental Protection Agency, East Building

Room 6428

1201 Constitution A venue, NW

Washington, DC

Re: EPA-HQ-OPPT -2009-0477

Dear Sirs:

The Halogenated Solvents Industry Alliance, Inc. (HSIA) represents manufacturers of dichloromethane 

(methylene chloride), trichloroethylene, tetrachloroethylene (perchloroethylene ), and, for purposes of 

these comments, 1, 1-dichloroethylene (vinylidene chloride or VDC) and carbon tetrachloride. These 

compounds appear on the second list of chemicals for Tier 1 screening under the Endocrine Disruptor 

Screening Program (EDSP), announced at 75 Fed. Reg. 70248 (November 17, 2010), comment period 

extended at 75 Fed. Reg. 77869 (December 14, 2010). HSIA offers these comments in support of its 

position that these compounds should all be removed from the list.

A. Statutory Criterion for Screening/Testing

EPA established the EDSP in response to Section 408(p) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA). [FN1: 21 U.S.C. § 346 a(p)(4).] The second list responds to the directive in Section 1457 of 

the Safe Drinking Water Act (SDWA) to include in EDSP "any other substance that may be found in 

sources of drinking water if the Administrator determines that a substantial population may be exposed 

to such substance."[FN2: 42 U.S.C. § 300j-17.] Thus, SDWA § 1457 is the statutory authority for the 

screening and testing of chemicals in drinking water for endocrine disruption. Basic principles of 

statutory construction mandate that its language be read as a whole, as well as in the context of the 

overall purpose of the Act. The language providing for testing of "any other substance that may be found 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

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in sources of drinking water" must be read in light of the subsequent language requiring that the 

Administrator determine “that a substantial population may be exposed to such substance."

While "substantial population" is not defined in the SDWA, Section 4(a)(1)(B) of the Toxic Substances 

Control Act (TSCA), [FN3: 15 U.S.C. § 2603(a)(l)(B).] which requires EPA before issuing a test rule to 

find that a chemical substance (i) is produced "in substantial quantities," and (I) enters the environment 

"in substantial quantities," or (II) there is "significant or substantial human exposure" to the substance, is 

a comparable provision that EPA may look to for guidance in construing "substantial population" in 

SDWA § 1457. Since 1993, EPA has relied upon a statement of policy, known as "the B Policy" to 

articulate the standards and criteria for implementing its authority to require testing under the substantial 

production, release, and exposure provisions of TSCA. [FN4: 58 Fed. Reg. 28736 (May 14, 1993). The 

B Policy was developed after a US Court of Appeals remanded the TSCA § 4 test rule on cumene back 

to EPA to articulate the criteria the Agency uses to make "B" findings.CMA v. EPA, 899 F.2d 344 (5th 

Cir. 1990). Following the same reasoning, it is submitted that EPA must also articulate the criteria that 

will guide its decision that a substantial population may be exposed to a substance for purposes of 

requiring testing under SDWA § 1457.] The Agency set forth as general benchmarks for "substantial 

exposure" for purposes of TSCA § 4 exposure of 100,000 members of the public, 10,000 consumers, or 

1,000 workers. Some numerical criterion of this nature is necessary for EPA to avoid being arbitrary and 

capricious in its decisions as to which drinking water contaminants may reach a substantial population 

for purposes of EDSP.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 10

EPA Comment Code: 1060

Comment: F. Concluding Points

• Only a substance that occurs in drinking water so that substantial populations may be exposed to such 

substance may be subject to EDSP under the SDWA § 1457 authority; VDC, methylene chloride, and 

carbon tetrachloride do not meet this condition.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 2

EPA Comment Code: 1060

Comment: NAPPA also notes that EPA has not met the Congressional intent for EDSP that EPA 

consider substances where a “substantial population” is exposed. Numerous studies have shown no 
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detectable levels of acrylamide in drinking and surface waters. In fact, US and other health agencies 

have specifically concluded that drinking water is not a significant source of exposure to acrylamide.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 6

EPA Comment Code: 1060

Comment: II. Exposure to Acrylamide from Drinking Water is Negligible and As Such Does Meet the 

Statutory Criteria of SDWA 1457 

A. Polyacrylamides Provide Environmental Benefits for Water Treatment 

Polyacrylamides serve a critical role in the treatment of drinking water, wastewater, sludge, and other 

wastes as flocculants and coagulants for solid liquid separation processes, scale inhibitors, antifoams, 

odor control, heavy metal removal and color removal. They are used in municipal sewage treatment and 

effluent treatment for industries as diverse as petrochemicals, pharmaceuticals, textiles, food (dairy, 

sugar and brewery) and agriculture. 

Polyacrylamide flocculants in water treatment bind to particles or suspended material, forming an 

aggregate that can be removed by settlement or filtration. They may also be added to the resultant waste 

slurry or solids to facilitate dewatering and reduce the generated waste. 

For drinking water treatment the application rate of polyacrylamides is typically 0.5 - 1 ppm (0.5 - 1 

mg/L) in the treated water (NSF 2000; EU RAR 2002). The maximum concentrations of residual 

acrylamide monomer in polyacrylamides for drinking water treatment are typically 250-500 ppm (0.025 

– 0.05%), though in practice levels are typically lower. Assuming the maximum potential acrylamide 

residual, the concentrations in the treated water would be 0.125 to 0.5 ppb (NSF 2000, EU RAR 2002). 

These residual levels are based on theoretical maximums and are likely to be lower in actual use.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 7

EPA Comment Code: 1060

Comment: * We ask the EPA to define what is meant by "sources of drinking water" and a "substantial 

population" [that has been exposed to the chemical] in the amended language to the Safe Drinking 

Water Act (SDWA). A chemical listed on the CCL3 or on the Toxics Release Inventory does not a priori 

meet the EDSP SDWA requirement that the chemical is found within drinking water or that a substantial 

population has been exposed to the chemical.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.
EPA-OGWDW Final EDSP List 2 February 2013

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Page 163

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 18

EPA Comment Code: 1060

Comment: The EPA should define what is meant by "sources of drinking water" and "substantial 

population" under the Safe Drinking Water Act (SDWA):

In the Congressional amendments to the Safe Drinking Water Act (SDW A) in 1996, provisions called 

for the EPA to screen sources of drinking water contaminants to which substantial numbers of persons 

are exposed for potential endocrine modulating activity. The EPA needs to define what is meant by 

"sources 6 of drinking water." A chemical listed on the CCL3 or on the Toxics Release Inventory does 

not a priori meet the EDSP SDW A requirement that the chemical is found within drinking water. 

Reliance on the Toxics Release Inventory gross production numbers for chemicals or other chemical 

production data to trigger screening under the SDW A is not a scientifically rigorous approach. As 

pointed out above, there is extensive water monitoring information available from the EPA Office of 

Water to conclusively demonstrate that actual human exposure to Acetochlor and its degradates is 

negligible.

We also request the EPA to define what is meant by "substantial population" has been exposed. A 

chemical listed on the CCL3 or on the Toxics Release Inventory does not a priori mean the EDSP 

SDWA requirement that a "substantial population" has been exposed to the chemical. As noted, reliance 

on chemical production data to trigger screening under the SDW A is not a rational approach and does 

not necessarily correlate to population exposure.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 9

EPA Comment Code: 1060

Comment: Defining "sources of drinking water":

We ask EPA to define what is meant by "sources of drinking water." A chemical listed on the National 

Primary Drinking Water Regulation (NPDWR) or the third Candidate Contaminant List (CCL3) does 

not a priori meet the EDSP SDWA requirement that the chemical is found within drinking water.

SDWA specifies that the Candidate Contaminant List (CCL) must include contaminants that are not 

subject to any proposed or promulgated NPDWRs, are known or anticipated to occur in public water 

systems (PWSs), and may require regulation under SDWA [FN13: EPA, Drinking Water Contaminant 

Candidate List 3- Draft. 73 Fed. Reg. 9629, February 21, 2008.] [emphasis added]. With a stated scope 

for CCL3 that includes 'anticipated' presence in public water systems, such a listing cannot be 

considered an appropriate selection for prioritization of draft list 2 for the EDSP program, which clearly 

specifies that the administrator needs to determine that a 'substantial population may be exposed to such 
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Page 164

a substance'. This implies that deriving the EDSP Draft List 2 from such a list cannot produce a 

definitive, scientifically rigorous list of chemicals with a high potential for human exposure via drinking 

water. Chemicals listed on CCL3 do not a priori meet the SDWA requirement for testing under EDSP as 

a determination of regulation under SOW A may not actually have occurred.

For certain substances on List 2, environmental releases may occur from natural sources, from 

manufacturing and processing, and from such products as fuels. For such materials, EPA should first 

consider the relative contributions of potential water-borne exposures of each activity and then direct 

EOSP test orders to manufacturers and importers in a manner consistent with the exposure.

Before EPA can move forward with selecting substances for Phase 2, the Agency must interpret the 

SDWA consistent with procedures provided by the Administrative Procedures Act and subject to

judicial review. CLA/EPF notes that the Agency should not arbitrarily select substances for EDSP 

screening. The only way for EPA to ensure it acts within the authority granted by Congress is for the 

Agency to define the phrases "may be found in sources of drinking water" and "that a substantial 

population may be exposed." 

Defining "substantial population" which may be exposed:

We ask EPA to define what is meant by "substantial population may be exposed." A chemical listed on 

the NPDWR or CCL3 does not a priori mean the EDSP SDW A requirement that a "substantial 

population" has been exposed to the chemical has been met. 

Before EPA can move forward with selecting substances for Phase 2, the Agency must interpret the 

SDW A consistent with procedures provided by the Administrative Procedures Act and subject to 

judicial review. CLA/EPF notes that the Agency should not arbitrarily select substances for EDSP 

screening. The only way for EPA to ensure it acts within the authority granted by Congress is for the 

Agency to define the phrases "may be found in sources of drinking water" and "that a substantial 

population may be exposed."

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 7

EPA Comment Code: 1060

Comment: * We ask the EPA to define what is meant by “sources of drinking water” and a “substantial 

population” [that has been exposed to the chemical] in the amended language to the Safe Drinking 

Water Act (SDWA). A chemical listed on the CCL3 or on the Toxics Release Inventory does not a priori 

meet the EDSP SDWA requirement that the chemical is found within drinking water or that a substantial 

population has been exposed to the chemical.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Gregory Watson
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 165

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 17

EPA Comment Code: 1060

Comment: The EPA should define what is meant by “sources of drinking water” and “substantial 

population” under the Safe Drinking Water Act (SDWA): 

In the Congressional amendments to the Safe Drinking Water Act (SDWA) in 1996, provisions called 

for the EPA to screen sources of drinking water contaminants to which substantial numbers of persons 

are exposed for potential endocrine modulating activity. The EPA needs to define what is meant by 

“sources of drinking water.” A chemical listed on the CCL3 or on the Toxics Release Inventory does not 

a priori meet the EDSP SDWA requirement that the chemical is found within drinking water. Reliance 

on the Toxics Release Inventory gross production numbers for chemicals or other chemical production 

data to trigger screening under the SDWA is not a scientifically rigorous approach. As pointed out 

above, there is extensive water monitoring information available from the EPA Office of Water to 

conclusively demonstrate that actual human exposure to Alachlor and its degradates is negligible. 

We also request the EPA to define what is meant by “substantial population” has been exposed. A 

chemical listed on the CCL3 or on the Toxics Release Inventory does not a priori mean the EDSP 

SDWA requirement that a “substantial population” has been exposed to the chemical. As noted, reliance 

on chemical production data to trigger screening under the SDWA is not a rational approach and does 

not necessarily correlate to population exposure.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Susan Van Volkenburg

Commenter Organization: LANXESS Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0061

Comment Part: 3

EPA Comment Code: 1060

Comment: While reliance on lists of drinking water contaminants provide an easy method for the EPA 

to generate a list of potential substances for EDSP screening, those lists may not identify substances that 

"may be found in sources of drinking water" and "to which a substantial population may be exposed." 

EPA should rely on reasonable, probable scenarios or on actual data demonstrating that a substance is 

found in drinking water to which people are exposed. Due to the fact that sources of drinking water are 

carefully managed and there is a highly selective process of identifying water sources by professionals, 

EPA should define "sources of drinking water" as actual, rather than theoretical sources of drinking 

water. A scientific peer review of the Draft EDSP List 2 should be considered.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Michael Boucher

Commenter Organization: McKenna Long & Aldridge LLP on behalf of Ferro Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0064

Comment Part: 2
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Page 166

EPA Comment Code: 1060

Comment: LEGAL AND FACTUAL BACKGROUND

Section 1457 of the Safe Drinking Water Act, entitled "Estrogenic Substances Screening

Program," establishes criteria for screening substances under the EDSP:

In addition to the substances referred to in section 346a(p)(3)(B) of title 21 [section 408(p)(3)(B) of the 

Federal Food, Drug, and Cosmetic Act ("FFDCA")] the Administrator may provide for testing under the 

screening program authorized by section 346a(p) of title 21 [section 408(p) of the FFDCA], in

accordance with the provisions of section 346a(p) of title 21, of any other substance that may be found 

in sources of drinking water if the Administrator determines that a substantial population may be 

exposed to such substance.[FN6: 42 U.S .C . § 300j-17 (emphasis added).]

Thus, the SDWA's two criteria for EDSP screening are (1) that a substance "may be found in sources of 

drinking water" and (2) EPA's determination "that a substantial population may be exposed to such 

substance" in drinking water. In both of the foregoing cases, however, there must be some reasonable 

basis in fact for EPA to require screening of a substance under the EDSP.[FN7: 5 U.S .C. § 706(2)(A).]

EPA cites section 1457 of the SDWA as the Agency's authority to screen benzyl chloride under the 

EDSP.[FN8: 75 Fed. Reg. at 70,250.] EPA claims that the listing of benzyl chloride on the CCL 3 alone 

satisfies the EDSP screening criteria in section 1457 of the SDWA. Specifically, EPA claims that 

listings on the CCL 3 "are sufficient to anticipate contaminants that may occur in public water systems 

and furthermore, also represent those substances that may be found in sources of drinking water and to 

which a substantial population may be exposed."[FN9: Id.] In addition, EPA states as follows:

In the CCL listing, EPA already has made the component of the SDWA section 1457 determination that 

such substances may occur in sources of drinking water. The final CCL listing also represents EPA's 

determination that a substantial population may be exposed to such substance for the purposes of SDWA 

§ 1457.[FN10: Id. at 70,251.]

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 4

EPA Comment Code: 1060

Comment: Defining “sources of drinking water” and “substantial population has been exposed”:

We ask EPA to define what is meant by “sources of drinking water” and what is meant by “substantial 

population has been exposed.”

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman Friedman
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 167

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 1

EPA Comment Code: 1060

Comment: January 17, 2011

Steve A. Owens

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

1200 Pennsylvania Ave., N.W.

Washington, D.C. 20460-000 I

Re: Comments of Velsicol on "Endocrine Disruptor Screening Program: Second List of

Chemicals for Tier l Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-71]

Dear Mr. Owens:

Velsicol Chemical LLC (Velsicol) [FN1: Velsicol is a US based, medium sized chemical company, 

which supplies intermediates to the chemical industry globally. Among its core values is a strong 

commitment to product safety and stewardship. Velsicol currently manufacturers 

hexachlorocyclopentadiene, a substance included on EPA's Draft EDSP List 2. Velsicol is a former 

manufacturer of endrin, heptachlor and chlordane, also substances included on EPA's Draft EDSP List 

2] appreciates the opportunity to submit comments on EPA's Endocrine Disruptor Screening Program: 

Second List of Chemicals for Tier I Screening (the "Draft EDSP List 2"). Pursuant to EPA’s request for 

comments on the Draft EDSP List 2,[FN2: EPA, Endocrine Disruptor Screening Program; Second List 

of Chemicals for Tier 1 Screening, 75 Fed. Reg. 70248, Nov. 17, 2010 ("Listing Notice").] Velsicol, in 

the attached, provides a number of general comments related to the Draft EDSP List 2 and the Agency's 

approach for prioritizing Safe Drinking Water Act (SDWA) chemicals for its Endocrine Disruptor 

Screening Program (EDSP). Velsicol also provides specific comments concerning EPA's proposed 

listing of hexachlorocyclopentadiene, endrine, heptachlor and chlordane.

Velsicol believes that prior to creating its Draft EDSP List 2, EPA should have clearly defined the scope 

of Section 1457 of the SDWA and, therefore, explicitly determined the scope of its authority to require 

BDSP screening of SDWA substances. Specifically, the Agency should have interpreted key SDWA 

phrases: "may be found in sources of drinking water" and "that a substantial population may be 

exposed." It should have then assessed, individually, each substance it proposed to include in its Draft 

EDSP List 2 to ensure the substances it selected for that list were within the intended scope of SDWA 

Section 1457. Velsicol believes the process EPA used to create the Draft EDSP List 2, merely adopting 

existing lists of substances, was arbitrary and contrary to law, good science and good regulatory policy.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 4

EPA Comment Code: 1060
EPA-OGWDW Final EDSP List 2 February 2013

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Comment: Comments of Velsicol Chemical LLC On EPA's Endocrine Disruptor Screening Program 

Second List of Chemicals for Tier 1 Screening [EPA-HQ-OPPT-2009-0477; FRL-8848-7]

January 17,2011

Velsicol Chemical LLC [FN1: Velsicol is a US based, medium sized chemical company, which supplies 

intermediates to the chemical industry globally. Among its core values is a strong commitment to 

product safety and stewardship. Velsicol currently manufacturers hexachlorocyclopentadiene, a 

substance included on EPA's Draft EDSP List 2. Velsicol is a former manufacturer of endrin, heptachlor 

and chlordane, also substances included on EPA's Draft EDSP List 2] (Velsicol) is pleased to submit 

these comments on EPA's Second List of Chemicals for Tier 1 Screening under the Endocrine Disruptor 

Screening Program (EDSP) developed pursuant to Section 1457 of the Safe Drinking Water Act (SDW 

A) and Section 408(p) of the Federal Food, Drug, and Cosmetic Act (FFDCA) (the “Draft EDSP List 

2”). In response to EPA’s request for comments on the Draft EDSP List 2 [FN2: EPA, Endocrine 

Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening, 75 Fed. Reg. 70248, Nov. 

17, 2010 ("Listing Notice").] Velsicol provides general comments related to the Draft EDSP List 2 and 

specific comments related to EPA's proposed listing hexachlorocyclopentadiene, endrin, heptachlor and 

chlordane.

Velsicol believes EPA improperly listed hexachlorocyclopentadiene, endrin, heptachlor and chlordane 

on its Draft EDSP List 2 for a number of reasons. First, Velsicol believes EPA's Draft EDSP List 2 is 

legally deficient because the Agency failed to interpret language of the SDWA that defines its authority 

to list substances pursuant to the Act. The Agency also failed to determine whether substances it 

included on its Draft EDSP List 2 fall within the scope of the SDWA EOSP testing provisions. Velsicol 

believes EPA's current approach of merely adopting existing lists of substances is arbitrary and contrary 

to law

Prior to creating its Draft EDSP List 2, EPA should clearly define the scope of Section 1457 of the 

SDWA by interpreting the phrases "may be found in sources of drinking water" and "that a substantial 

population may be exposed." It should then assess individually each substance it proposes to include in 

its Draft EDSP List 2 to ensure the substances it selects for that list are within the intended scope of 

Section 1457 of the SDWA. Velsicol believes, for the reasons discussed below, that 

hexachlorocyclopentadiene, endrin, heptachlor and chlordane are not found in drinking water to which a 

substantial population are exposed and should, therefore, not be included in the EDSP List 2.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 7

EPA Comment Code: 1060

Comment: I. EPA Must Interpret Key SDWA Provisions That Define the Scope of Its Authority to 

Lists Chemicals Pursuant SDWA §1457
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The scope of the EDSP as it concerns screening of drinking water contaminants turns on EPA's 

interpretation of the phrases "may be found in sources of drinking water" and "that a substantial 

population may be exposed." EPA has not yet interpreted those phrases, which limit the Agency's 

authority to require EDSP screening pursuant to the SDWA. Instead, EPA merely relies at this time on a 

number of existing lists of drinking water contaminants to derive its Draft EDSP List 2. While reliance 

on those existing lists provide an easy method for EPA to generate a list of potential substances for 

EDSP screening and may provide one of many possible starting points for identifying potential 

substances for the Draft EDSP List 2, those lists may not accurately identify substances that "may be 

found in sources of drinking water” and "to which a substantial population may be exposed." Because 

EPA has not outlined the scope of its authority and has made no specific determinations as to whether 

chemicals on the lists it relies on meet SDWA requirements for EDSP listing, EPA's Draft EDSP List 2 

is an arbitrary selection or chemicals and is contrary to law, good science and sound policy. Therefore, 

before constructing a Draft EDSP 2 List EPA should properly determine the scope of its authority by 

clearly defining the phrases “may be found in sources of drinking water” and "that a substantial 

population may be exposed." EPA should then determine, based on actual scientific data, whether 

substances meet those criteria for EDSP listing.

Congress limited EPA's authority to require EDSP screening pursuant to the SDWA when it stated that 

EPA may provide for EDSP testing "of any other substance that may be found in sources of drinking 

water if the Administrator determines that a substantial population may be exposed to such substance." 

SDWA §300j-17, 42 USC §300j-I 7 (emphasis added). Congress did not define those key phrases, which 

clearly delineate the Agency's authority and the scope of the SDWA provision. Rather, Congress left it 

to the Agency to construe the meaning of the Act by defining those phrases consistent with sound 

science and policy. Before it can move forward with selecting substances for Phase 2, the Agency must 

first interpret the Act consistent with procedures provided by the Administrative Procedures Act. That 

interpretation is subject to judicial review. The Agency is not entitled to grant itself unfettered authority 

and may not arbitrarily select substances for EDSP screening. The only way for EPA to ensure it acts 

within the authority granted by Congress is for the Agency to define the phrases "may be found in 

sources of drinking water" and "that a substantial population may be exposed."

When defining the phrases "may be found in sources of drinking water" and "that a substantial 

population may be exposed" EPA should define separately (1) "may be found"; (2) "sources of drinking 

water"; (3) “substantial population"; and (4) "may be exposed." When defining "may be found" and 

“may be exposed," EPA should rely on reasonable, probable scenarios or on actual data demonstrating 

that a substance is found in drinking water to which people are exposed. EPA, when defining 

"substantial population," should keep in mind the potential risks to human health and should assess costs 

as well as benefits. EPA might want to look at how it has defined "substantial population" for other 

environmental programs such as TSCA. Finally, EPA should define "sources of drinking water” as 

actual, rather than theoretical, sources of drinking water. In the case of water supplied by public water 

systems, "drinking water” should refer to finished water rather than raw water. Although, it might be 

argued that any water (even a discharge to a POTW) is a "potential” source of drinking water and any 

chemical might find its way into some water body or aquifer from which drinking water might someday 

be drawn, too broad an interpretation of the phrase "sources of drinking water" would render the express 

Congressional limitations meaningless. If Congress wanted EPA to require EDSP testing for any 

chemical in any water it would have said so. EPA must assume, consistent with well established legal 

principles of statutory construction that Congress did not mean to include in the SDWA meaningless 

limitations on the Agency's authority.
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Basic principles of statutory construction mandate that EPA read the language or Section 1457 or the 

SDWA as a whole, as well as in the context of the overall purpose of the Act. Thus, the language 

providing for testing of "any other substance that may be found in sources of drinking water" must be 

read in light of the subsequent language requiring that the Administrator determine "that a substantial 

population may be exposed to such substance." The language on its face and taken as a whole compels 

the conclusion that EPA is not to require EDSP testing for substances that hypothetically, or by some 

remote possibility "may be found in sources of drinking water,” but rather that it may require EDSP 

testing of substances (1) that are likely to be present in sources of drinking water; and (2) for which 

there is some empirical basis to conclude the substances is likely to be present in sources of drinking 

water. Empirical bases would include actual monitoring of finished drinking water or actual monitoring 

of ambient water that is a source of water delivered to consumers as finished water.

In sum, Velsicol urges EPA to interpret the provisions of the SDWA that outline the Agency's authority 

by defining the key terms discussed above. It should also develop scientific and legal processes for 

determining what are "sources of drinking water" under the Act, whether substances are likely to be 

present on those sources, and whether a substantial population is exposed to those substances in those 

sources. Velsicol believes EPA must do this before it can identify substances for the EDSP List 2 and 

before it implements the second phase of its EDSP.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 11

EPA Comment Code: 1060

Comment: V. EPA Should Not Include Hexachlorocyclopentadiene on Its EDSP List 

EPA included hexachlorocyclopentadiene ("Hex") on its Draft EDSP List 2. EPA bases its listing of Hex 

solely on the fact that Hex is "regulated with a national primary drinking water regulation (NPDWR)." 

Listing Notice at 70250. EPA provides no evidence that it has actually determined that Hex "may be 

found in sources of drinking water" and "that a substantial population may be exposed" to Hex. Because 

EPA failed to make those determinations, as required by law, and to publish its factual determinations in 

that regard, the Agency should not have included Hex on its Draft EDSP List 2. In any event, Velsicol 

believes Hex is not found in sources of drinking water to which a substantial population is exposed and, 

therefore, should not be placed on the EDSP List 2. 

A. EPA Failed to Determine Whether Hex May Be Found in Sources of Drinking Water to Which a 

Substantial Population is Exposed

For the reasons discussed in Section I of these comments, before it may list Hex in its EDSP List 2, EPA 

must determine that Hex "may be found in sources of drinking water" and that a substantial population 

may be exposed." EPA has failed, however, to make those determinations. Indeed, it appears EPA failed 

to assess any actual data concerning Hex for purposes of its EDSP listing. EPA merely relies on the fact 

that Hex is regulated with a NPDWR. For all the reasons discussed in Section II of these comments, 

EPA should not rely simply on NPDWR listing as the basis for listing Hex on the EDSP List 2.
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Relying on the NPDWR listing, EPA simply assumes that Hex was found to occur in sources of drinking 

water and that a substantial population was exposed to Hex in drinking water when the NPDWR was 

promulgated for Hex two decades ago. EPA provides no factual basis for that assumption and Velsicol 

believes the original NPDWR listing did not consider exposure. Even if the decades old NPDWR listing 

for Hex was based on sufficient exposure and occurrence information to warrant EDSP Listing, EPA 

failed to determine whether 'Hex is currently found in sources of drinking water to which a substantial 

population is exposed. EPA ignores that levels of Hex in sources of drinking water may have decreased 

dramatically over the last two decades.

In sum, in listing Hex EPA (1) failed to define the terms "may be found in sources of drinking water" 

and "that a substantial population may be exposed"; (2) assumed (possibly incorrectly) Hex fell within 

the scope of those undefined terms two decades ago; and (3) assumed Hex still falls within the scope of 

those undefined terms today. Because EPA failed to properly define the scope of its authority under § 

1457 of the SDWA and provided no support for its exposure assumptions concerning Hex, Velsicol 

believes EPA's listing of Hex is arbitrary. Hex should be removed from EPA's EDSP List 2 until EPA 

makes the appropriate legal and scientific findings that would support the listing of Hex on the EDSP 

List 2.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 7

EPA Comment Code: 1060

Comment: Defining “sources of drinking water”:

We ask EPA to define what is meant by “sources of drinking water.” A chemical listed on the CCL3 or 

on the Toxics Release Inventory does not a priori meet the EDSP SDWA requirement that the chemical 

is found within drinking water. Reliance on the Toxics Release Inventory gross production numbers for 

chemicals or other chemical production data to trigger screening under the SDWA is not a rational 

approach.

For certain substances on List 2, environment releases may occur from natural sources, from 

manufacturing and processing, and from such products as fuels. For such materials, EPA should first 

consider the relative contributions of potential water-borne exposures of each activity and then direct 

EDSP test orders to manufacturers and importers in a manner consistent with the exposure.

Defining “substantial population has been exposed”:

We ask EPA to define what is meant by “substantial population has been exposed”. A chemical listed on 

the CCL3 or on the Toxics Release Inventory does not a priori mean the EDSP SDWA requirements that 

a “substantial population has been exposed” to the chemical. As noticed, reliance on chemical 

production data to trigger screening under the SDWA is not a rational approach and does not necessarily 

correlate to population exposure.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.
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EPA Comment Code: 1065 EPA's Authority to Require Testing

General Response: As stated in the Federal Register Volume 75, Number 21 (Wednesday, November 

17, 2010), EPA's authority for taking this action is based on several different Congressional actions, 

including the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Safe Drinking Water Act 

(SDWA). In addition, this action is in accordance with a directive from the House Appropriations 

Committee report for EPA's FY 2010 appropriations. EPA developed the EDSP in 1998 to implement 

FFDCA section 408(p), which requires EPA to “develop a screening program, using appropriate 

validated test systems and other scientifically relevant information, to determine whether certain 

substances may have an effect in humans that is similar to an effect produced by a naturally occurring 

estrogen, or such other endocrine effect as [EPA] may designate.” (21 U.S.C. 346a(p)). The statute

generally requires EPA to “provide for the testing of all pesticide chemicals” and gives EPA 

discretionary authority to “provide for the testing of any other substance that may have an effect that is 

cumulative to an effect of a pesticide chemical if the Administrator determines that a substantial 

population may be exposed to such a substance.” (21 U.S.C. 346a(p)(3)). The statute also authorizes 

EPA to exempt a chemical upon a determination that “the substance is anticipated not to produce any 

effect in humans similar to an effect produced by a naturally occurring estrogen.” (21 U.S.C. 

346a(p)(4)). The EDSP is not a rulemaking process.

Section 1457 of SDWA provides that “in addition to the substances” referred to in FFDCA section 

408(p)(3)(B), “the Administrator may provide for testing under the screening program authorized by 

section 408(p) of such Act, in accordance with the provisions of section 408(p) of such Act, of any other 

substance that may be found in sources of drinking water if the Administrator determines that a 

substantial population may be exposed to such substance.” (42 U.S.C. 300j-17). EPA used its authority 

under SDWA to identify a portion of the chemicals on the second EDSP list.

In addition, in Congress's House Appropriations Committee report for EPA's FY 2010 appropriations 

(H.R. 2996, H. Rept. 111-180), it directed EPA “to publish within 1 year of enactment a second list of 

no less than 100 chemicals for screening that includes drinking water contaminants, such as halogenated 

organic chemicals, dioxins, flame retardants (PBDEs, PCBs, PFCs), plastics (BPA), pharmaceuticals 

and personal care products, and issue 25 orders per year for the testing of these chemicals.”

The 1996 Food Quality Protection Act (FQPA) and SDWA, along with the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA), the Toxic Substances Control Act (TSCA), and FFDCA

provide testing authorities of chemicals for both human health as well as ecological effects. The 

Endocrine Disruptor Screening and Testing Authority Committee (EDSTAC) recommended that EDSP 

scope should include screening for adverse effects to wildlife, as well as humans, recognizing that 

wildlife are an inherently valuable element of ecosystems and their well-being can be an indication of 

the overall health of the environment in which humans live.

In September 2011, EPA published the Weight-of Evidence document. The document includes standard 

evaluation procedures for evaluating results of Tier 1 screening to identify the need for Tier 2 testing 

(USEPA, 2011). 

Individual Comments
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Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 3

EPA Comment Code: 1065

Comment: In addition, when describing the method for inclusion of chemicals, not pesticides, on List 2, 

an emphasis is placed on potential contamination of drinking water by those chemicals. Flumetsulam, a 

pesticide, is not identified as a concern based upon the Safe Drinking Water Act (SDWA) and does not 

appear on Candidate Contaminant List 3 (CCL3). Therefore, since a major criteria for listing a chemical, 

stated below, is missing for flumetsulam, a pesticide, DAS respectively requests that flumetsulam is 

removed from List 2. ’Publish within one year of enactment a second list of no less than 100 chemicals 

for screening that include drinking water contaminants, such as halogenated organic chemicals, dioxans, 

flame retardants (PBDEs, PCBs and PFCs), plastics (BPA), pharmaceuticals, personal care products, 

and issue 25 test orders per year for the testing of these chemicals. This process should also allow for 

public comment” Congress’ House Appropriations Committee report for EPA’s FY 2010 appropriations 

(H.R. 2996, H. Rept. 111–180)

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 5

EPA Comment Code: 1065

Comment: Moreover, the potential for human exposure to flumetsulam is minimal. The human health 

risk assessment using conservative and health protective estimates of exposure to flumetsulam in food 

and drinking water indicates that the chronic dietary risk for the general population is no more than 0.1% 

of the reference dose for flumetsulam, of which only 0.2% is used by the highest exposed group (US 

EPA 2008). US EPA thus concluded with reasonable certainty that "residues of flumetsulam in food and 

drinking water would not likely result in an aggregate chronic dietary risk above the Agency's level of 

concern, particularly to infants and children" (US EPA 2008).

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 1

EPA Comment Code: 1065
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Comment: Comments on the second list of chemicals for testing in the EDSP from the animal welfare 

community represented by PETA, PCRM, ARDF, and AAVS.

January 17, 2011 

Dr. William Wooge 

Office of Science Coordination and Policy (7201M) 

Environmental Protection Agency 

1200 Pennsylvania Ave. N.W. 

Washington, DC 20460-0001 

Re: 75 FR 70248, November 17, 2010, Docket ID number EPA-HQ-OPPT-2009-0477; Endocrine 

Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening

Dear Dr. Wooge: 

These comments are submitted on behalf of the more than two million members of Alternatives 

Research and Development Foundation, the American Anti-Vivisection Society, the People for the 

Ethical Treatment of Animals and the Physicians Committee for Responsible Medicine who share the 

common goal of promoting reliable and relevant regulatory testing methods and strategies that protect 

human health and the environment while reducing, and ultimately eliminating, the use of animals. These 

comments are in response to the Environmental Protection Agency’s (EPA) issuance of the second list 

of chemicals to be tested in the EPA’s Endocrine Disruptor Screening Program (EDSP).

The authority EPA is citing for issuing test orders for these chemicals is not only the Federal Food, Drug 

and Cosmetics Act (FFDCA) that created the EDSP and under which the test orders for the first list of 

chemicals were issued, but also the Safe Drinking Water Act (SDWA) and House Appropriations 

Committee report language for Fiscal Year (FY) 2010. The FFDCA allows testing of chemicals other 

than pesticides “that may have an effect that is cumulative to an effect of a pesticide chemical if the 

Administrator determines that a substantial population may be exposed.” In addition, the SDWA 

authorizes EPA to test “any other substance that may be found in sources of drinking water if the 

Administrator determines that a substantial population may be exposed...” (emphasis added). 

The House report language (U.S. Congress 2009) (which is non-binding) instructs EPA to “publish 

within one year of enactment a second list of no less than 100 chemicals for screening that includes 

drinking water contaminants, such as halogenated organic chemicals, dioxins, flame retardants (PBDEs, 

PCBs, PFCs), plastics (BPA), pharmaceuticals and personal care products, and issue 25 orders per year 

for the testing of these chemicals. This process also should allow for public input.” 

The House report language also instructs EPA to “engage in a timely re-evaluation of the battery of 

screening, replacing outdated ones with updated, more efficient screens that have been validated (for 

example, a recombinant receptor assay to replace the cytosolic receptor assay for estrogen receptor 

binding)” and “develop and publish criteria for evaluating the results of Tier I screening and determining 

whether a chemical should undergo Tier II analysis within one year of enactment,” neither of which the 

EPA has done.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.
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Commenter Name: James Lamb

Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0030

Comment Part: 2

EPA Comment Code: 1065

Comment: EPA states that the list of 134 chemicals "includes a large number of pesticides, two 

perfluorocarbon compounds (PFCs), and three pharmaceuticals (erythromycin, nitroglycerin, and 

quinoline). This list also consists of an array of other chemicals, ranging from those used for industrial 

manufacturing processes, as plasticizers, or in the production of pharmaceutical and personal care 

products (PPCPs)." The 134 chemicals also include a significant number of Toxic Substances Control 

Act (TSCA) chemicals that EPA has identified as priorities under the Safe Drinking Water Act (SDWA) 

and may be found in sources of drinking water where a substantial number of people may be exposed. 

In selecting chemicals for the second list, EPA first identified candidate chemicals that are either 

regulated with a national primary drinking water regulation (NPDWR) or are unregulated and listed on 

the third Contaminant Candidate List (CCL 3). [Toxaphene is included among chemicals regulated with 

a NPDWR.]

Hercules believes that EPA must better define the SDWA chemicals:

• The scope of the EDSP concerning screening of drinking water contaminants depends upon EPA’s 

interpretation of the phrases “may be found in sources of drinking water” and “that a substantial 

population may be exposed.” Congress limited EPA’s authority to require EDSP screening pursuant to 

the SDWA when it stated that EPA may provide for EDSP testing “of any other substance that may be 

found in sources of drinking water if the Administrator determines that a substantial population may be 

exposed to such substance.” SDWA §300j-17, 42 USC §300j-17. Congress did not define those key 

phrases, which define the scope of the SDWA provision. EPA has not yet interpreted those phrases, 

which limit the Agency’s authority to require EDSP screening pursuant to the SDWA. Rather, EPA 

relies at this time on a number of existing lists of drinking water contaminants. Those lists may not 

identify substances that “may be found in sources of drinking water” and “to which a substantial 

population may be exposed.” Until EPA clearly defines those key phrases, its selection of substances or 

use of existing lists of substances for Phase 2 screening is arbitrary. 

• Before EPA can move forward with selecting substances for Phase 2, the Agency must interpret the 

SDWA consistent with procedures provided by the Administrative Procedures Act and subject to 

judicial review. We note that the Agency should not arbitrarily select substances for EDSP screening. 

The only way for EPA to ensure it acts within the authority granted by Congress is for the Agency to 

define the phrases “may be found in sources of drinking water” and “that a substantial population may 

be exposed.” If Congress wanted EPA to require EDSP testing for any chemical it would have said so. 

EPA must assume, consistent with well established legal principles of statutory construction, Congress 

did not mean to include in the SDWA meaningless limitations on the Agency’s authority.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing. Also, please see general response to comment under EPA Comment Code: 1060 

SDWA 1457.
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Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 7

EPA Comment Code: 1065

Comment: 3. EPA Lacks Authority to Require Ecotoxicity Testing

EPA should not assume that the references above to existing ecotoxicity data in any way suggest that the 

HAP Task Force accepts that EPA may require such studies either under EDSP. FFDCA § 408(p)(1) 

requires EPA to "develop a screening program, using appropriate validated test systems and other 

scientifically relevant information, to determine whether certain substances may have an effect in 

humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine 

effect as [EPA] may designate" In order to develop the screening program, EPA established the 

Endocrine Disrupter Screening and Testing Advisory Committee (EDST AC), whose mission was to 

make recommendations on how to develop the screening and testing program. In establishing the scope 

of its recommended testing program, EDSTAC elected to look broadly at the various testing authorities 

under EPA's jurisdiction, including FFDCA, TSCA, and the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA). As a result, EDSTAC recommended that EPA's Endocrine Disrupter 

Screening and Testing Program (EDSTP) should address both human and ecological (wildlife) effects. 

EPA then adopted the EDSTAC recommendations and established a tiered approach (Tier 1 screening 

and Tier 2 definitive testing) to evaluate the effects of chemicals on the estrogen, androgen, and thyroid 

systems in humans, fish and wildlife. FFDCA § 408(p), however, grants EPA authority to require EDSP 

testing only to determine "whether certain substances may have an effect in humans." Screening/testing 

for wildlife and other ecological effects is outside the scope of this program. 

Similarly, the SDWA grants no authority to EPA to evaluate or regulate substances because of 

ecological effects. Had Congress intended to expand EDSP to the entire ecosystem, it would have 

incorporated the program into the Clean Water Act instead of the SDWA. While not necessarily 

eliminating all Tier 1 screening to the extent that those studies are deemed relevant to predicting human 

endocrine effects, this means that there is no basis to require conduct of the fish short-term reproduction 

study or any of the other Tier 2 studies being validated such as the amphibian multi-generation, avian 

multi-generation, fish lifecycle, or invertebrate (Mysid) lifecycle, none of which is directly relevant and 

necessary to assess human health effects.

E. Concluding Points

• Only a substance that occurs in drinking water so that substantial populations may be exposed to such 

substance may be subject to EDSP under the SDWA § 1457 authority; 1,1,2-trichloroethane and EDC 

do not meet this condition.

• Available data for both 1,1,2-trichloroethane and EDC are sufficient to conclude that they are unlikely 

to produce any effect in humans similar to those produced by a naturally occurring estrogen, thus they 

are exempt from testing.
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• The only Tier 2 study that EPA may lawfully require has already been done for 1,1,2-trichloroethane 

and is being conducted under an ECA for EDC.

• It is inconsistent with EPA's animal welfare policies and common sense for EPA to impose expensive 

and animal-intensive Tier 1 screening when the study requirement for which the screening is done has 

already been filled.

• Requiring screening/testing for endocrine effects for 1,1,2-trichloroethane and EDC serves no purpose, 

as the MCLs already must be as close to 3 ppb/zero as feasible based on other effects and the 

precautionary principle.

• Put another way, EPA has advanced no rationale for requiring information on the possible endocrine 

activity of chemicals whose principal toxicities have been well-characterized and which are already 

restricted in drinking water to the maximum extent. 

Respectfully submitted,

Peter E. Voytek, Ph.D.

Manager

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing. Please also see general responses to comment under EPA Comment Codes: 2070 

Contaminants Not Expected to Produce Estrogen-like Effect, 2060 Chemicals with Toxicity Data 

Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints, and 2080

Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 

1457 Requirements.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 8

EPA Comment Code: 1065

Comment: 3. EPA Lacks Authority to Require Ecotoxicity Testing

FFDCA § 408(p )(1) requires EPA to "develop a screening program, using appropriate validated test 

systems and other scientifically relevant information, to determine whether certain substances may have 

an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other 

endocrine effect as [EPA] may designate" In order to develop the screening program, EPA established 

the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), whose mission was to 

make recommendations on how to develop the screening and testing program. In establishing the scope 

of its recommended testing program, EDSTAC elected to look broadly at the various testing authorities 

under EPA's jurisdiction, including FFDCA, TSCA, and the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA). As a result, EDSTAC recommended that EPA's Endocrine Disruptor 

Screening and Testing Program (EDSTP) should address both human and ecological (wildlife) effects. 

EPA then adopted the EDSTAC recommendations and established a tiered approach (Tier 1 screening 

and Tier 2 definitive testing) to evaluate the effects of chemicals on the estrogen, androgen, and thyroid 

systems in humans, fish and wildlife. FFDCA § 408(p), however, grants EPA authority to require EDSP 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 178

testing only to determine "whether certain substances may have an effect in humans." Screening/testing 

for wildlife and other ecological effects is outside the scope of this program. 

Similarly, the SDWA grants no authority to EPA to evaluate or regulate substances because of 

ecological effects. Had Congress intended to expand EDSP to the entire ecosystem, it would have 

incorporated the program into the Clean Water Act instead of the SDWA. While not necessarily 

eliminating all Tier 1 screening to the extent that those studies are deemed relevant to predicting human 

endocrine effects, this means that there is no basis to require conduct of the fish short-term reproduction 

study or any of the other Tier 2 studies being validated such as the amphibian multi-generation, avian 

multi-generation, fish lifecycle, or invertebrate (Mysid) lifecycle, none of which is directly relevant and 

necessary to assess human health effects.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 9

EPA Comment Code: 1065

Comment: IV. No Basis for Ecological Effect Testing of Acrylamide is Presented and Existing 

Ecotoxicity Data are Sufficient 

A. SDWA §1457 Does Not Grant the Agency the Authority to Require Ecological Effects Testing 

There is no authority granted to EPA in SDWA to evaluate or regulate substances because of ecological 

effects. 

In 1996, Congress passed the Food Quality Protection Act (FQPA) and amendments to the Safe 

Drinking Water Act (SDWA) which collectively directed EPA to establish and initiate a screening and 

testing program of pesticides and other chemicals to assess possible endocrine disrupting effects in 

humans. In order to develop the screening program, EPA established the Endocrine Disruptor Screening 

and Testing Advisory Committee (EDSTAC), whose mission was to make recommendations on how to 

develop the screening and testing program. 

In establishing the scope of its recommended testing program, EDSTAC elected to look broadly at the 

various testing authorities under EPA’s jurisdiction; this included not only the endocrine provisions of 

FQPA and SDWA, but also those of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 

the Toxic Substances Control Act (TSCA), and the Federal Food, Drug, and Cosmetic Act (FFDCA). 

EDSTAC decided that “[T]ogether these acts provide testing authorities for a variety of chemicals for 

both human health as well as ecological effects.” As a result, EDSTAC recommended that EPA’s 

Endocrine Disruptor Screening and Testing Program (EDSTP) should “address both human and 

ecological (wildlife) effects.” 

In the present action, EPA has proposed to rely on the authority[FN3: EPA further explains that its 

present action to develop List 2 for EDSP screening was driven, in part, by the Congressional House 
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Appropriations Committee report for EPA’s FY 2010 appropriations (H.R. 2996, H. Rept. 111–180) 

(Ref. 1), which advocated EPA, “to publish within 1 year of enactment a second list of no less than 100 

chemicals for screening that includes drinking water contaminants, such as halogenated organic 

chemicals, dioxins, flame retardants (PBDEs, PCBs, PFCs), plastics (BPA), pharmaceuticals and 

personal care products, and issue 25 orders per year for the testing of these chemicals.”] provided by 

section 1457 of SDWA to expand the chemicals in the EDSP program by adding priority drinking water 

chemicals[FN4: On November 17, 2010, EPA issued a list containing 134 compounds, which contained 

both pesticides and non-pesticides that EPA proposed met the statutory authority for testing from section 

1457 SDWA.]. Section 1457 of SDWA states: 

In addition to the substances referred to in section 408(p)(3)(B) of the Federal Food, Drug, and Cosmetic 

Act (21 U.S.C. 346a(p)(3)(B)) the Administrator may provide for testing under the screening program 

authorized by section 408(p) of such Act, in accordance with the provisions of section 408(p) of such 

Act, of any other substance that may be found in sources of drinking water if the Administrator 

determines that a substantial population may be exposed to such substance. [42 U.S.C. 300j–17] 

While Congress authorized EPA to extend the endocrine screening program to drinking water 

contaminants, EPA was directed to select chemicals because of their presence in drinking water that 

could lead to a substantial portion of the US population being exposed. Nowhere within the statute does 

Congress authorize EPA to evaluate effects other than those associated with human health, i.e., 

chemicals found in drinking water need not be screened for wildlife and other ecological effects but 

should be limited to human health. 

As EPA is well aware, the overall purpose of the SDWA is to protect public health by regulating the 

nation’s public drinking water supply.2 SDWA authorizes EPA to set national health based standards for 

drinking water in order to protect the health of millions of American people who receive drinking water 

every day from public water systems. 

EDSTAC correctly recognized that EPA has various testing authorities stemming from a range of 

statutes, each with a different purpose, objective and finding, which need to be determined before testing 

can be initiated. The fact that EPA elected to expand the scope of testing for pesticide chemicals to 

include ecological effects pursuant to the authorities provided by FFDCA does not enable the Agency to 

expand the scope of testing authorized by §1457 SDWA, which should clearly be limited only to human 

health. For these reasons, EPA should eliminate from Test Orders any study that is not directly relevant 

and necessary to assess human health, including the Fish Short-term Reproduction study[FN5: Unlike 

the amphibian metamorphosis assay, which may provide useful information on the human thyroid, the 

fish short-term reproduction study appears relevant only to fish with essentially no nexus to people.] or 

any of the Tier 2 studies being validated such as Amphibian 2-Generation, Avian 2-Generation, Fish 

Lifecycle, and Invertebrate (Mysid) Lifecycle. There is no authority granted to EPA in SDWA to 

evaluate or regulate substances because of ecological effects. 

Had Congress intended to expand the EDSP program to the entire ecosystem, Congress would have 

incorporated the EDSP program into a different statute (e.g., Clean Water Act) instead of SDWA. As 

such, the only meaningful interpretation to SDWA §1457 is that Congress intended the Agency to direct 

its testing of drinking water contaminants to human health.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.
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Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 1

EPA Comment Code: 1065

Comment: Attached please find the public comments submitted by the Chemical Producers and 

Distributors Association for inclusion in docket ID Number EPA-HQ-OPPT-2009-0447.

January 18, 2011

VIA WWW.REGULATIONS.GOV 

Mr. William Wooge 

Office of Science Coordination and Policy 

U.S. Environmental Protection Agency (MC 7203M) 

1200 Pennsylvania Avenue, NW 

Washington, DC 20460-0001 

RE: Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Notice; 75 

Fed. Reg. 70248 (November 17, 2010); EPA-HQ-OPPT-2009-0477; FRL-8848-7. 

Dear Mr. Wooge: 

The Chemical Producers & Distributors Association (“CPDA”) appreciates this opportunity to comment 

on the above-referenced notice (“List 2 Notice”) for the second list of chemicals (“List 2”) to be 

screened under the Endocrine Disruption Screening Program (“EDSP”). CPDA is the primary advocate 

on federal legislative and regulatory issues for generic pesticide registrants, adjuvant and inert ingredient 

manufacturers, and product formulators and distributors.

Introduction 

As we discuss below, CPDA does not believe EPA is under any statutory mandate to test SDWA 

chemicals at this time. While we do not object to prioritizing chemicals for future screening, we do think 

that initiating Tier 1 screening for these chemicals now, however, is imprudent and will result in a 

missed opportunity to make experience and science--based improvements to improvements to the EDSP 

before additional testing.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 5

EPA Comment Code: 1065
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Comment: CPDA is particularly concerned about EPA’s unsupported reliance on a non-legislative 

Congressional directive to undertake this very costly information collection. EPA notes in the List 2 

Notice that a House Appropriations Committee report directed EPA “to publish within 1 year of 

enactment [of the appropriations bill] a second list of no less than 100 chemicals for screening...and 

issue 25 orders per year for the testing of these chemicals.” [FN6: List 2 Notice, p. 70250.] What EPA 

fails to disclose, however, is that reports issued by only the House or the Senate are not authoritative or 

binding on an agency. [FN7: Northwest Environmental Defense Center et al. v. Bonneville Power 

Administration, 447 F. 3d 668, ___ (9th Cir. 2007). (“The principle that committee report language has 

no binding legal effect is grounded in the text of the Constitution and in the structure of separated 

powers the Constitution created. Article I, section 7, clause 2 of the Constitution is explicit about the 

manner in which Congress can take legally binding action. Members of Congress cannot use committee 

report language to make an end run around the requirements of Article I. If Congress wishes to alter the 

legal duties of persons outside the legislative branch, including administrative agencies, it must use the 

process outlined in Article I” (internal footnotes omitted)....” “Treating legislative reports as binding 

law also undermines our constitutional structure of separated powers, because legislative reports do not 

come with the traditional and constitutionally-mandated political safeguards of legislation. As noted 

above, legislative reports are not acts of law satisfying the precise requirements of Article I, which were 

devised by the Framers to ensure separation of powers and a careful legislative process. By contrast, 

legislative reports may in some cases be written by an individual legislator, congressional staffers, or 

even lobbyists.13 Giving binding effect to passages in legislative reports may thus give binding legal 

effect to the unchecked will of a lone person, and that is not what our Constitution envisions.”) Id.] 

Moreover, the U.S. Supreme Court has expressly cautioned against treating legislative reports as binding 

law:

“[L]egislative materials like committee reports, which are not themselves subject to the requirements of 

Article I, may give unrepresentative committee members-or, worse yet, unelected staffers and lobbyistsboth the power and the incentive to attempt strategic manipulations of legislative history to secure 

results they were unable to achieve through the statutory text.” [FN8: Exxon Mobil Corp. v. Allapattah 

Services, Inc., 125 S. Ct. 2166, 2626 (2005).]

Therefore, EPA cannot rely on committee report language to infer a statutory duty or mandate, and its 

authority to impose testing requirements under the Safe Drinking Water Act is limited. [FN 9: SDWA 

§1457; 42 USC §300j-17. Generally, EPA must first show that a substance “may be found in sources of 

drinking water” and “that a substantial population may be exposed to such substance.” No such 

showings are presented in the Agency’s proposed listing decision (List 2 Notice).]

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 5

EPA Comment Code: 1065

Comment: To the extent that EPA decides to issue Test Orders for endocrine testing of acetaldehyde, 

such testing should not include wildlife and other ecological effects given that §1457 SDWA directed 
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EPA to address “human health” effects. Even though EDSTAC incorporated ecological testing in its 

screening battery, and the Agency elected to include the full battery of testing for EDSP List 1, this does 

not justify the Agency expanding the scope of testing authorized by SDWA to other ecological effects.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 12

EPA Comment Code: 1065

Comment: III. Section 1457 of the SDWA Does Not Grant the Agency the Authority to Require 

Ecological Effects Testing 

The development of the EDSP stems from the 1996 Food Quality Protection Act (FQPA) and 

amendments to the Safe Drinking Water Act (SDWA), which collectively directed EPA to establish and 

initiate a screening and testing program of pesticides and other chemicals to assess possible endocrine 

disrupting effects. 

FQPA incorporated section 408(p)(1) to the Federal Food, Drug and Cosmetic Act (FFDCA), which 

called on EPA to “develop a screening program, using appropriate validated test systems and other 

scientifically relevant information, to determine whether certain substances may have an effect in 

humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine 

effect as [EPA] may designate” [emphasis added]. In order to develop the screening program, EPA 

established the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), whose 

mission was to make recommendations on the screening and testing program. 

In establishing the scope of its recommended testing program, EDSTAC elected to look broadly at the 

various testing authorities under EPA’s jurisdiction; this included not only the endocrine provisions of 

FQPA and SDWA, but also those of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 

the Toxic Substances Control Act (TSCA), and the Federal Food, Drug, and Cosmetic Act (FFDCA). 

EDSTAC decided that “[T]ogether these acts provide testing authorities for a variety of chemicals for 

both human health as well as ecological effects. As a result, EDSTAC recommended that EPA’s 

Endocrine Disruptor Screening and Testing Program (EDSTP) should address both human and 

ecological (wildlife) effects and put forth a tiered approach to testing (Tier 1 screening and Tier 2 

definitive testing) to evaluate the effects of chemicals on the estrogen, androgen, and the thyroid system 

in humans, fish and wildlife.

The first list of chemicals to be screened in the EDSP was released on April 15, 2009[FN5 EPA-HQOPPT-2004-0109; FRL-8399-7]. EDSP List 1 addressed pesticide chemicals (actives and inerts) as 

called for by FFDCA section 408(p)(3)(A), which stated that EPA “shall provide for the testing of all 

pesticide chemicals.” Pursuant to its authority under FFDCA and FIFRA, EPA issued Test Orders for 

these pesticide chemicals, incorporating the full battery of tests relating to human health, wildlife and 

ecological effects. 
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In the present action, EPA has proposed to rely on the authority[FN6: EPA further explains that its 

present action to develop List 2 for EDSP screening was driven, in part, by the Congressional House 

Appropriations Committee report for EPA’s FY 2010 appropriations (H.R. 2996, H. Rept. 111–180) 

(Ref. 1), which advocated EPA, “to publish within 1 year of enactment a second list of no less than 100 

chemicals for screening that includes drinking water contaminants, such as halogenated organic 

chemicals, dioxins, flame retardants (PBDEs, PCBs, PFCs), plastics (BPA), pharmaceuticals and 

personal care products, and issue 25 orders per year for the testing of these chemicals.”] provided by 

section 1457 of SDWA to expand the chemicals in the EDSP program by adding priority drinking water 

chemicals[FN7: On November 17, 2010, EPA issued a list containing 134 compounds, which contained 

both pesticides and non-pesticides that EPA proposed met the statutory authority for testing from section 

1457 SDWA.]. While the statutory provisions of FQPA and SDWA are clearly intertwined, the fact that 

Congress placed these provisions into different statutes must be considered when defining the scope of 

the testing to be conducted under the different statutory authorities. Section 1457 of SDWA states: 

SEC. 1457. In addition to the substances referred to in section 408(p)(3)(B) of the Federal Food, Drug, 

and Cosmetic Act (21 U.S.C. 346a(p)(3)(B)) the Administrator may provide for testing under the 

screening program authorized by section 408(p) of such Act, in accordance with the provisions of 

section 408(p) of such Act, of any other substance that may be found in sources of drinking water if the 

Administrator determines that a substantial population may be exposed to such substance. [42 U.S.C. 

300j–17] 

Congress authorized EPA to extend the endocrine screening program to drinking water contaminants if 

the Agency determines that a “substantial population may be exposed,” although nowhere within the 

statute does Congress direct EPA to evaluate effects other than those associated with human health. As 

EPA is well aware, the overall purpose of the SDWA is to protect public health by regulating the 

nation’s public drinking water supply.2 SDWA authorizes EPA to set national health based standards for 

drinking water in order to protect the health of millions of American people who receive drinking water 

every day from public water systems. The only meaningful interpretation to section 1457 is that 

Congress intended the Agency to direct its testing of drinking water contaminants to human health. 

EDSTAC correctly recognized that EPA has various testing authorities stemming from a range of 

statutes, each with a different purpose, and findings that need to be determined before testing can be 

initiated. The fact that EPA elected to expand the scope of testing for pesticides to include ecological 

effects pursuant to the authorities provided by FFDCA, does not enable the Agency to expand the scope 

of testing authorized by §1457 SDWA beyond human health, i.e., there is no basis for EPA to require 

conduct of the Fish Short-term Reproduction study or any of the other Tier 2 studies being validated 

such as Amphibian 2-Generation, Avian 2-Generation, Fish Lifecycle, Invertebrate (Mysid) Lifecycle.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Linda Ferguson

Commenter Organization: American Pacific Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0021

Comment Part: 4

EPA Comment Code: 1065
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Comment: The growing body of evidence suggests that perchlorate sources should be reappraised, 

particularly in light of findings that perchlorate in fireworks, bleach, safety flares, and Chilean fertilizer 

may outweigh contamination from military-industrial applications. The new data on sources in the 

environment and releases to the environment should be used to better inform regulatory decisions on 

controlling exposure.

A continued focus on man-made contamination will not provide a complete analysis of the sources of 

perchlorate. The weight of evidence demonstrates there are substantial unattributed and natural sources 

of low-level perchlorate contamination across the U.S.

Linda G. Ferguson

Vice President, Administration

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing.

Commenter Name: Dru Ann Toman

Commenter Organization: Union Carbide Corporation (UCC), a subsidiary of The Dow Chemical 

Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0065

Comment Part: 2

EPA Comment Code: 1065

Comment: II. EPA Should Not Require Manufactures to Conduct Testing If No Significant Exposure Is 

Associated with their Manufacture of the Substance

When final, the EDSP List 2 will create significant new duties and obligations for manufacturers and 

importers of the listed substances. EPA noted its intention to issue Test Orders to companies that 

manufacture List 2 chemicals in accordance with reporting to the IUR. In the case of acrolein, UCC's 

manufacture and use account for an extremely minor portion of acrolein emissions to the environment, 

do not result in releases to surface water and are handled in a manner which prevents occupational 

exposures. UCC confirms manufacture and handling of acrolein is conducted under strictly controlled 

conditions:

Acrolein has been produced at the St Charles Operations Site in Hahnville, Louisiana since 1967. All of 

the acrolein produced is consumed on-site to produce derivatives that go into animal feed supplements 

and biocides. Acrolein is not sold as a product and is not shipped from the Site.

Acrolein is produced by the oxidation of propylene over a fixed bed catalyst. The acrolein is then 

recovered in a series of absorption, stripping and distillation steps to produce a refined product for use in 

the manufacture of derivatives.

The acrolein produced is fully contained within the process equipment. All normal vent gas streams are 

routed to a thermal oxidizer with destruction efficiency for acrolein of 99.9+%. Emergency relief 

devices are routed to a collection system and destroyed in a flare. Process waste water that may contain 

acrolein is treated in a caustic (sodium hydroxide) reactor, where the acrolein is destroyed through 

polymerization or reaction to less hazardous species. The pre-treated waste water is then discharged to 
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the Site Waste Water Treatment Plant for further treatment. The destruction efficiency of the caustic 

reactor approaches I 00%. Water used to clean process equipment is also treated in the caustic reactor.

Process samples are collected using a fully contained sampling system. Sample flushes are contained 

within the process piping, and vent gas from sampling is routed back to process equipment. The sample 

container is a closed bottle with a non-permeable rubber closure (septum). The bottle is filled and vented 

with injection needles inserted through the septum.

There is an on-site process and quality control laboratory for analyzing process samples and refined 

product samples. The laboratory has a small caustic reactor for treating all samples that contain acrolein 

before discharging the waste water to the Site Waste Water Treatment Plant.

In the event of a loss of containment, resulting in a release of acrolein in the process area, there is a 

sewer collection system routed to the area process water collection system (process sump). The process 

sump has facilities to inject caustic and dilution water into the discharge piping that transfers waste 

water from the process sump to the Waste Water Treatment Plant. R&D studies have confirmed that the 

reaction conditions and residence time in the pipeline are sufficient to achieve the same level of acrolein 

destruction that is obtained in the caustic reactor.

The refined acrolein is transferred by a dedicated pipeline from the production facility to the derivative 

plants. The derivative plants have similar facilities for vent collection and destruction, waste water and 

wash water is collected and treated in a caustic reactor before discharge to the Site Waste Water 

Treatment Plant.

EPA should not place the burden of testing on manufacturers of acrolein where the manufacture and use 

do not result in any significant release of acrolein to the environment.

To the extent that testing is needed for acrolein, requiring the IUR manufacturers to test would only 

make sense when the population exposure is associated with the manufacture or processing of acrolein 

and its downstream use. In the case of UCC's manufacture of acrolein, this is not the case and the 

issuance of a test order to UCC for this substance would not be appropriate. Therefore, if EPA does not 

drop Acrolein from this rulemaking, EPA should at least provide that manufacturers whose operations 

do not cause significant exposure will not be subject to test orders.

Response: Please see general response to comment under EPA Comment Code: 1065 EPA’s Authority 

to Require Testing. Also please refer to Endocrine Disruptor Screening Program; Final Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document.
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EPA Comment Code: 1070 Increase Transparency

General Response: The agency has reevaluated the list and has removed 25 contaminants. In the 

“General Response” sections of this document under EPA Codes: 2010 (Contaminants Identified by 

Commenters as Being or Potentially Incompatible with Test Assays) and 2020 (Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations) EPA provides rationale for removing contaminants from the second EDSP list. 

EPA also received comments requesting that EPA explain how data obtained by test orders would be 

used in the regulatory development process. For the drinking water regulatory program, EPA uses new 

and updated health assessments in the agency’s review and/or revision of currently regulated 

contaminants, the evaluation of unregulated contaminants to determine if regulation is needed (i.e., the 

Contaminant Candidate List and the Regulatory Determination processes), and the development of new 

regulations for unregulated contaminants. Therefore, EPA would consider data from Tier 1 and Tier 2 

assays along with other available data sources when conducting hazard identification and dose-response 

assessments, respectively. EPA may also consider data from EDSP when evaluating human health 

impacts associated with potentially sensitive populations. In addition, the data from EDSP could also 

assist the agency in determining potential drinking water research needs for unregulated and regulated 

drinking water contaminants. 

References to other sections within this document, or other EDSP-related support documents

Please see EPA Comment Code: 1020 Continue Use of Qualifying Language for additional information.

See EPA Comment Code: 1040 Complete List 1- Evaluate Tier 1 Screening Results before Proceeding 

with EDSP List 2 for additional information.

See EPA Comment Code: 2010 Contaminants Identified by Commenters as Being or Potentially 

Incompatible with Test Assays for additional information.

See EPA Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or Used in the US, 

also Includes Pesticides with Cancelled Registrations for additional information.

See EPA Comment Code: 2040 Naturally Occurring Contaminants for additional information.

Please also see Response to Comments on the Public Review Draft of the Information Collection

Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of Certain 

Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is being 

published simultaneously with this comment response document. 

Individual Comments

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 19

EPA Comment Code: 1070

Comment: A confounding factor in assessing the “added value” of EDSP screening is that it is yet 

unclear how EPA intends to use the information. For many of the Phase I chemicals, EPA has rejected 

the equivalent of Tier 2 information since those tests do not address mechanism of action, yet is unclear 

why such information is necessary. There is currently no requirement or explanation regarding EPA’s 

intent to regulate a chemical based on an endocrine mechanism of action, particularly when information 

is available regarding developmental and reproductive effects.

Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 10

EPA Comment Code: 1070

Comment: V. EPA Should Be Fully Transparent in the Procedures Used for Developing the Draft

EDSP List 2 of 134 Substances

Although EPA compiled a list of 201 substances as candidates for the EDSP List 2, the Agency has not 

been fully transparent in its basis for streamlining this candidate list to arrive at the 134 substances 

included in the Draft EDSP List 2. In the Listing Notice, EPA qualitatively describes the criteria it has 

employed, but the Agency has not published the actual physiochemical criteria and data it relied on to 

make the exclusion decisions. For full transparency, ACC requests that EPA publish the specific 

scientific criteria the Agency employed to determine a substance falls into a category of i) a biological 

agent or naturally occurring chemical; ii) a chemical for which the manufacturer, importer or registrant 

cannot be clearly identified; or iii) a chemical not likely to be biologically active or which are 

incompatible with testing assays for various reasons due to one or more of their physiochemical 

properties (e.g., gases, strongly acidic or basic, solubility, vapor pressure molecular weight). In this 

regard, it appears that EPA may not have consistently applied criteria iii) above, in that certain 

substances contained in the Draft EDSP List 2 appear to be highly reactive and/or highly irritating 

chemicals.[FN26: Highly reactive and irritating chemicals, like acids and bases, would be expected to 

react at the point of contact and may not be suitable at certain concentrations for administration by 

certain routes in some toxicity tests. Some highly reactive chemicals can react exothermically with air or 

water spontaneously, leading to rapid breakdown of such substances, making dose administration very 

difficult. In addition, a highly reactive substance would not be expected to persist in the environment as 

the parent molecule.] However, because the Agency has not provided the scientific basis for the 

Agency’s determinations for streamlining and removing some substances, independent verification of 

consistent application of such criteria by EPA is simply not possible at this time.

Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.
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Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 13

EPA Comment Code: 1070

Comment: VIII. EPA Should Establish a Transparent Policy to Provide Equitable Resolution of the 

Question of Who Should be Subject to EDSP Testing of Drinking Water Contaminants

For certain chemicals on the Draft EDSP List 2, occurrence in drinking water sources can result from 

natural sources, from manufacturing, processing and importing of a specific chemical, and from uses of 

other products and from other activities. Without addressing any particular chemicals on the Draft EDSP 

List 2, ACC urges EPA to consider policies that provide equitable resolution to the question of who 

should be subject to EDSP testing under EPA’s SDWA authority. These policies might address, for 

example, chemicals which may be found as contaminants in drinking water for which the major sources 

are from current commercial activities, not from the current manufacture or import of the specific 

chemical per se. In developing such a policy, EPA should clearly explain its considerations so the 

regulated community can understand the Agency’s rationale.

Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency. For additional information please see Response-to-Comments for the Endocrine 

Disruptor Screening Program’s Draft Policies and Procedures for Screening Safe Drinking Water Act 

Chemicals (USEPA, 2012c) and Endocrine Disruptor Screening Program; Final Policies and Procedures 

for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that are being published 

simultaneously with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 12

EPA Comment Code: 1070

Comment: The Agency should re-iterate the purpose of Tier 1 screening under the EDSP:

The EPA needs to further clarify and be consistent as to the purpose of Tier 1 screening and how to 

interpret the results of Tier 1 screening. As the .EPA[FN2: Federal Register / Vol. 63, No. 248/ Monday, 

December 28, 1998, page 71545.] noted in 1998, the purpose of Tier 1 is to identify substances that have 

the potential to interact with the estrogen, androgen, or thyroid hormone systems. The purpose of Tier 2 

testing is to identify and establish a dose-response relationship for any adverse effects that might result 

from the interactions identified through the Tier 1 assays. Only after completion of Tier 2 testing will the 

EPA be able to determine whether a particular chemical may have an effect in humans that is similar to 

an effect produced by a naturally occurring estrogen, androgen, or thyroid hormones and that the 

substance is an endocrine disruptor. However, significant work is still required to complete development 

and validation of the Tier 2 tests required for compounds that are concluded to be positive in Tier 1 

testing. Consequently, it is premature to proceed with List 2 compounds before development and 

validation of Tier 2 tests.
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Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 2

EPA Comment Code: 1070

Comment: We also address our concerns about the Agency’s need to be consistently and fully 

transparent while implementing the EDSP. The EDSP is a complex program, with ambitious testing 

requirements being implemented under new statutory authority. It is also a very costly program for 

which industry expects EPA to consistently make transparent decisions that demonstrate genuine 

consideration given to achieving the maximum practical utility of the data collected while minimizing 

the burden on those subject to testing requirements. [FN1: Paperwork Reduction Act of 1995, 44 U.S.C. 

chapter 35.]

Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency. Also, please see Endocrine Disruptor Screening Program; Final Policies and Procedures 

for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 8

EPA Comment Code: 1070

Comment: EPA Should Be Fully Transparent in the Procedures Used to Develop List 2

Although EPA has provided the initial list of “over 200” candidate chemicals it compiled, the Agency 

has not been fully transparent about the “streamlining” process used to reduce those 200 plus chemicals 

to the 134 chemicals on the draft List 2. In the List 2 Notice, EPA describes the categories of chemicals 

excluded from screening at this time, [FN15: List 2 Notice, p. 70251.] but the Agency has not disclosed 

the actual physiochemical criteria and data it relied on to make the exclusion decisions. Since the 

Agency has not provided the scientific basis for its decision to retain or remove chemicals, independent 

verification of EPA’s consistent application of the six specified categories is simply not possible at this 

time. Therefore, CPDA requests that EPA publish the specific criteria the Agency employed to 

determine whether or not a chemical falls into exclusion category (i) as a biological agent or naturally 

occurring chemical; exclusion category (ii) as a chemical for which the manufacturer, importer or 

registrant cannot be clearly identified; or exclusion category (v) as a chemical not likely to be 

biologically active or which is incompatible with testing assays for various reasons due to one or more 

of their physiochemical properties (e.g., gases, strongly acidic or basic, solubility, vapor pressure 

molecular weight).
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Response: Please see general response to comment under EPA Comment Code: 1070 Increase 

Transparency. Also, please see Response to Comments on the Public Review Draft of the Information

Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of 

Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is 

being published simultaneously with this comment response document.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 12

EPA Comment Code: 1070

Comment: The Agency should re-iterate the purpose of Tier 1 screening under the EDSP: 

The EPA needs to further clarify and be consistent as to the purpose of Tier 1 screening and how to 

interpret the results of Tier 1 screening. As the EPA [FN1: Federal Register / Vol. 63, No. 248 / 

Monday, December 28, 1998, page 71545.] noted in 1998, the purpose of Tier 1 is to identify substances 

that have the potential to interact with the estrogen, androgen, or thyroid hormone systems. The purpose 

of Tier 2 testing is to identify and establish a dose-response relationship for any adverse effects that 

might result from the interactions identified through the Tier 1 assays. Only after completion of Tier 2 

testing will the EPA be able to determine whether a particular chemical may have an effect in humans 

that is similar to an effect produced by a naturally occurring estrogen, androgen, or thyroid hormones 

and that the substance is an endocrine disruptor. However, significant work is still required to complete 

development and validation of the Tier 2 tests required for compounds that are concluded to be positive 

in Tier 1 testing. Consequently, it is premature to proceed with List 2 compounds before development 

and validation of Tier 2 tests.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue use of 

Qualifying Language and the Response to Comments on the Public Review Draft of the Information

Collection Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of 

Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is 

being published simultaneously with this comment response document. Also, please see general 

response to comment under EPA Comment Code: 1070 Increase Transparency.
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EPA Comment Code: 1075 Request for Formal Response

General Response: EPA previously stated in the November 17, 2010, Federal Register for the Second 

EDSP List of Chemicals for Screening that it did not plan to respond formally to comments. EPA 

reconsidered this position and is providing a formal response to comment, even though this action is not 

a rulemaking. EPA hopes that this response to comment document will help to provide more 

transparency for the EDSP process. In finalizing the list, EPA considered all comments and information 

received from the public concerning the inclusion or exclusion of chemicals on the second EDSP list, 

even those concerning CCL 3 chemicals. 

Individual Comments

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 6

EPA Comment Code: 1075

Comment: Later in the Federal Register preamble, EPA indicates that the Agency will not “respond 

formally” to information or comments that are submitted on the proposed EDSP List, and the Agency 

suggests that it will not consider comments that “re-open” the determinations that were made in the 

development of CCL 3. [FN6: EPA states that: “the Agency does not intend to re-open CCL 3 for public 

comment or any of the individual lists used to create the second list of EDSP chemicals and does not 

intend to respond to any such comments so submitted.” Id.]

EPA cannot refuse to consider comments on the EDSP List that pertain to the criteria for including a 

substance on the List – namely, whether the substance may be a contaminant of drinking water, and 

whether a substantial population may be exposed to the substance – even if those criteria were 

previously evaluated by the Agency during development of CCL 3. Under Section 553 of the APA, an 

agency is required to consider all relevant comments submitted in response to a proposed rule. See 

Thompson v. Clark, 741 F.2d 401, 409 (D.C. Cir. 1984). The fact that an agency may have evaluated the 

same set of facts, and accepted comments on those facts, in a prior rulemaking does not relieve the 

agency of its obligation to receive and consider comments in a subsequent rulemaking pertaining to the 

same set of facts.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 8

EPA Comment Code: 1075

Comment: Similarly, even if EPA did evaluate the EDSP criteria when it created the CCL3, under the 

APA it is impermissible for the Agency to refuse to consider comments in this new rulemaking 
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proceeding on whether the substances that EPA has decided to include on the EDSP list actually satisfy 

the EDSP listing criteria under SDWA Section 1457.

For all of the foregoing reasons, EPA should remove methanol from the proposed EDSP List, since the 

available data do not support the listing of methanol. In addition, EPA should withdraw the proposed 

listing of additional chemicals until the Agency complies with OMB’s request associated with the first 

EDSP list. Finally, EPA must review and respond to comments submitted on the proposed EDSP listing, 

and the Agency cannot simply rely on its findings under the CCL 3 rulemaking to justify the addition of 

substances to the EDSP list.

Thank you for your consideration. Please contact me if you have any questions or require any additional 

information.

Sincerely,

Gregory A. Dolan 

Executive Director

[Attachments: see PDF docket ID EPA-HQ-OPPT-2009-0477-0024.1; EPA-HQ-OPPT-2009-0477-

0024.3; EPA-HQ-OPPT-2009-0477-0024.4]

Response: Please see general responses to comment under EPA Comment Code: 1075 Request for 

Formal Response and EPA Comment Code: 1040 Complete List 1- Evaluate Tier 1 Screening Results 

before Proceeding with EDSP List 2. Also, please see Response to Comments on the Public Review 

Draft of the Information Collection Request (ICR) entitled: “Addendum for the Second List of 

Chemicals; Tier 1 Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program 

(EDSP)” (USEPA, 2012d) that is being published simultaneously with this comment response 

document. 

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 6

EPA Comment Code: 1075

Comment: In addition to the chemical specific comments noted above, EPA should also ensure that it 

will respond to public comments submitted on the Draft EDSP List 2. In the November 17th federal 

register notice, EPA stated that it was “... interested in receiving information and/or comment that may 

inform the exclusion or inclusion of chemicals on the second EDSP list.” However the notice also stated 

that the “...Agency does not plan to respond formally to information or comments that may be 

submitted...” (75 Fed. Reg 70248, 70251). API believes that EPA has an obligation to respond to 

submitted stakeholder comments in a timely manner.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Richard Becker
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Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 3

EPA Comment Code: 1075

Comment: ACC is disappointed in EPA’s statement that “[t]he Agency does not plan to respond 

formally to information or comments that may be submitted...” on the draft list. We think the rationale 

for this plan is flawed as well as inconsistent with open and transparent regulatory practices. For the 

reasons discussed below, ACC urges EPA to formally respond to comments received on the Draft EDSP 

List 2.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 9

EPA Comment Code: 1075

Comment: IV. EPA Should Respond To Comments Submitted on the Draft EDSP List 2

EPA states in its List 2 Notice that “The Agency does not plan to respond formally to information or 

comments that may be submitted...” on the draft list (75 Fed. Reg. 70248, 70251). Elsewhere in the 

notice, EPA suggests that because the CCL3 had previously been subject to notice and comment, and 

EPA response to same, that the Agency wouldn’t re-visit those conclusions. This rationale is flawed, 

however, since the CCL3 was never developed to meet the SDWA §1457 authority for testing 

substances that “may be found in sources of drinking water” to which a “substantial population” may be 

exposed. As the Agency is aware, the CCL3 was developed for different purposes of the SDWA. Being 

on the CCL3 does not necessarily mean the chemical is found in public drinking water sources to which 

a substantial population may be exposed. The Agency’s responses to previous comments on the CCL3 

(or the MCLs/MCLGs for that matter), therefore, does not justify the Agency’s plans not to respond to 

comments on the draft EDSP List 2.

Further, when the EDSP List 2 is final and integrated into individual EDSP test orders to manufacturers 

and importers, new duties and obligations for specific members of the regulated community will be 

created. These test orders may be challenged (presuming the Agency follows its currently non-binding 

policies and procedures to treat test orders as final agency action. See ACC’s separate comments on 

Policies and Procedures, Section X), including the Agency’s basis for testing a listed substance. But 

administrative efficiency, consistency with EPA’s approach in EDSP Phase 1, and the open and 

transparent processes and practices envisioned by the Administrative Procedure Act, argue instead for 

EPA to respond to comment on the draft EDSP List 2 that are submitted to this docket.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response. Please also see Endocrine Disruptor Screening Program; Final Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document.
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Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 3

EPA Comment Code: 1075

Comment: * The ARP notes that the Agency does not intend to respond to these public comments. The 

EDSP program is a significant and important undertaking for both the EPA and Industry. Therefore, we 

urge the Agency to reconsider and provide responses.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 9

EPA Comment Code: 1075

Comment: We appreciate the opportunity to provide these comments to EPA, and request that EPA 

provide a response.

Gregory Watson, Ph.D.

Chemical Regulatory Affairs Lead

Monsanto Company

Managing Agent, Acetochlor Registration Partnership

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 13

EPA Comment Code: 1075

Comment: The EPA should respond to comments on List 2 Chemicals:

The ARP notes that the Agency does not intend to respond to these public comments; however, we urge 

the Agency to reconsider and provide such responses. The EDSP program is a significant and important 

undertaking for both the EPA and industry. The decision by the Agency to include a chemical on List 2 

is the prelude to the Agency's issuance of binding EDSP Test Orders. When finalized, List 2 will create 

new obligations for specific members of the regulated community. The program requires tremendous 

numbers of animals and vast expenditure of resources, both by the regulated industry and by the 

Agency, and we believe that public dialogue is essential for any such undertaking. Thus, the EPA has 
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specific legal obligations. The ARP believes the EPA should adhere to the requisite notice and comment 

provisions of the Administrative Procedure Act (APA), and formally respond to comments received on 

List 2. By responding to the comments, the EPA can avoid the appearance of acting in an arbitrary and 

capricious manner and promote an open and transparent process with the regulated industry and other 

stakeholders.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: D. Douglas Fratz

Commenter Organization: Consumer Specialty Products Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0047

Comment Part: 4

EPA Comment Code: 1075

Comment: IV. EPA Should Respond to All Comments Submitted in Response to this Notice.

As a final issue, CSPA is highly concerned that EPA is not planning to respond formally to comments 

on this notice. We urge EPA to respond to all comments submitted. Whether a chemical is on this list or 

not is a matter of significant importance considering the high cost of EDSP testing and the risks from 

uncertainty regarding the interpretation of test results. EPA needs to assure that it is fully considering all 

public comments received.

V. Summary and Conclusions

CSPA continues to support the implementation of EPA’s EDSP as a science-based initiative to assure 

that chemicals do not have adverse impacts on human health or the environment through endocrine 

disruption. In these comments, we urge the Agency to move deliberately in developing a List 2 for 

further EDSP testing, awaiting the results on the first phase of Tier 1 testing to use the lessons learned to 

optimize the test battery and its interpretation, and carefully reviewing the list to assure that appropriate 

exclusions are made.

Thank you once again for this opportunity to comment further. Please do not hesitate to contact us if you 

have any questions or require further information.

Respectfully Submitted,

D. Douglas Fratz

Vice President, Scientific & Technical Affairs

CSPA

Beth L. Law

Assistant General Counsel 

CSPA

Susan E. Little, Executive Director

PIR Program
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cc: CSPA Scientific Affairs Committee Endocrine Issues Task Force

CSPA Pest Management Products Division

CSPA Product Ingredient Review Task Forces

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 7

EPA Comment Code: 1075

Comment: EPA Should Respond to Comments Submitted on the Draft EDSP List 2

EPA has stated in the List 2 Notice that “[t]he Agency does not plan to respond formally to information 

or comments that may be submitted on this document....” [FN11: List 2 Notice at p. 70251.] This 

position is contrary to the general public process envisioned by the Administrative Procedures Act 

(“APA”) [FN12: 5 U.S.C. §§ 500-706.] for federal agency actions and is inconsistent with open and 

transparent regulatory practices. When final, List 2 will create new duties and obligations for specific 

members of the regulated community, particularly when the Agency issues test orders. Consequently, 

EPA has a legal obligation under the APA to avoid arbitrary and capricious actions in interpreting 

applicable law and in identifying chemicals and manufacturers and importers that will be subject to 

enforceable EDSP testing requirements.

EPA’s actions related to issuing List 2 are, in essence, a rule making and the Agency should fully 

comply with the APA’s notice and comment provisions for thee important reasons. First, EPA’s decision 

to include a chemical on List 2 is the initial step in the process of issuing binding EDSP test orders and, 

as such, is a regulatory action subject to the APA. Second, EPA considers issuance of test orders “final 

agency action subject to review,” [FN13: 75 Fed. Reg. 70558, 70566 (November 17, 2010).] and the 

SDWA provides for general judicial review of EPA final actions. [FN14: SDWA § 1448.] Third, final 

review of agency actions is based on the relevant administrative record, of which EPA’s written 

responses to formally submitted comments are an important component. Therefore, EPA should engage 

in robust notice and comment on List 2, including a response to comments, to avoid the appearance of 

acting arbitrarily, to provide a proper administrative record, and to ensure an open and transparent 

process.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 1

EPA Comment Code: 1075
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Comment: January 18, 2010

Steve A. Owens,

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

US EPA Headquarters Ariel Rios Building

1200 Pennsylvania Ave., NW

Washington, D.C. 20460

RE: CropLife America/Endocrine Policy Forum Comments on Second List of Chemicals for Tier I 

Screening. Docket ID: EP A-HQ-OPPT -2009—0477

Dear Assistant Administrator Owens:

CropLife America [FN1: CropLife America (CLA) is a not-for-profit trade organization representing the 

nation 's developers, manufacturers, formulators and distributors of plant science solutions for 

agriculture and pest management in the United States. Our member companies produce, sell and 

distribute virtually all the crop protection technology products used by American farmers and other 

consumers. We are committed to the safe and responsible use of the industry's products in order to 

provide safe and abundant food, as well as for the control of insect and plant disease vectors for the 

protection of human health, all providing valuable benefits back to the consumer.] (CLA) and the 

Endocrine Policy Forum (EPF) [FN2: The Endocrine Policy Forum is a consortium of CLA members 

and non-member stakeholders formed to address the aggregate needs of the group with respect to 

technical guidance and regulatory policy in response to the implementation of the EPA Endocrine 

Disruptor Screening Program.] are committed to assisting their members in complying with the 

Agency's Endocrine Disruptor Screening Program (EDSP) including complying with the EDSP test 

orders. EPF is working diligently to facilitate communication between its members and EPA in order to 

maximize the efficient and effective use of the Agency's and our members' time and resources, and to 

help ensure timely compliance with the test orders. Within the Federal Register Vol. 75, No. 221 on 

Wednesday, November 17, 2010, EPA announced the second list of chemicals and substances for which 

EPA intends to issue test orders under the EDSP. With this FR Notice, EPA outlined the Agency's intent 

with regards to 'Phase 2' of the EDSP. EPA established the EDSP in response to section 408(p) of the 

Federal Food, Drug, and Cosmetic Act (FFDCA). This second list of chemicals expands the EDSP to 

include more pesticides and adds "drinking water chemicals" into the program for screening as 

authorized by Safe Drinking Water Act (SDWA) Section 1457. In response to the Agency's request for 

public comment on the second list of chemicals for Tier I screening under EDSP, we are pleased to 

hereby submit our formal comments (Docket ID: EPA-HQ-OPPT-2009-0477).

The second list of 134 chemicals includes a large number of pesticides, two perfluorocarbon compounds 

(PFCs), and three pharmaceuticals (erythromycin, nitroglycerin, and quinoline). Several of the 

compounds are no longer produced or manufactured in the United States. This list also consists of an 

array of other chemicals, ranging from those used for industrial manufacturing processes, as plasticizers, 

or in the production of pharmaceutical and personal care products (PPCPs). Given the fact that the entire 

first list of compounds included in the EDSP program were pesticides or inert compounds included with 

pesticides in end use products, the concentration on pesticides in the second list is surprising. 

Congressional mandates have directed EPA to include other classes of compounds in the EDSP. We 

urge the Agency to reconsider the compounds included on the list and provide responses to public 
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comments received on this second list. The EDSP program is significant and an important undertaking 

for both EPA and industry. The program requires tremendous resources, and we believe that public 

dialogue and transparency are key to the successful implementation of the EDSP. 

Contrary to what is stated in the Federal Register, we urge the Agency to reconsider and provide 

responses to public comments received on this second list. The EDSP program is significant and an 

important undertaking for both EPA and industry. The program requires tremendous resources, and we 

believe that public dialogue is key to the successful implementation of the EDSP.. The fact that EPA 

needs to process another Information Collection Request (ICR) indicates the significance of the 

publication of this list.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 5

EPA Comment Code: 1075

Comment: EPA should respond to comments on List 2 chemicals:

We note that the Agency does not intend to respond to these public comments, however, we urge the 

Agency to reconsider and provide responses. The decision by the Agency to include a chemical on List 2 

is the de facto prelude to the Agency's issuance of binding EDSP test orders. The EDSP program is a 

significant and important undertaking for both EPA and industry. The program requires tremendous 

resources both by the regulated industry and by the Agency, and we believe that public dialogue is key 

to the successful implementation of the EDSP. As members of the EPF know first hand, Tier I screening 

costs range between 500,000 and 1,000,000 US dollars per chemical. Additional costs are associated 

with the administrative efforts to comply with the test order and to develop and submit Other 

Scientifically Relevant Information (OSRI) [FN9: 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT -2007-1081-0037.2].

When finalized, List 2 will create new testing obligations for specific members of the regulated 

community. (The finalization of List 2 is one component to Phase 2 of EDSP by EPA.) Thus, EPA has 

specific legal obligations. CLA/EPF believes EPA should adhere to the requisite notice and comment 

provisions of the Administrative Procedure Act (APA), and formally respond to comments received on 

Draft List 2. By responding to the comments, EPA can avoid the appearance of acting in an arbitrary and 

capricious manner and promote an open and transparent process with the regulated industry and other 

stakeholders. The fact that EPA needs to process another Information Collection Request (ICR) 

indicates the significance of the publication of this list.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 2

EPA Comment Code: 1075

Comment: AWG members believe such a meeting should be arranged soon in light of the TSCA 

Section 4 Test Rule that EPA published on January 7, 2011 (76 Fed. Reg. 1067), which mandates that 

manufacturers of acetaldehyde conduct a reproductive/developmental effects screening study (40 CFR 

9355) and an acute daphnid/algal toxicity study. This Test Rule is directed at the same companies 

identified in the proposed EDSP testing program and requires the conduct of a reproductive and 

development screening study. The main difference is that the EDSP program employs an extensive 

battery of endocrine screening assays that will be used, in a still to be defined weight of evidence 

evaluation, to decide on the need for more extensive and robust in vivo reproduction effects testing than 

the protocol required by the TSCA rule. As such, AWG believes it is critically important for EPA 

(including the key Agency scientists and policy makers from both the TSCA Section 4 and EDSP) to 

meet with the affected industry to discuss comprehensively the various testing needs for acetaldehyde. If 

these programs are not coordinated, we believe the result will be a wasteful expenditure of both public 

and private sector resources and an inefficient use of animals that is not consistent with minimization of 

animal use in toxicity testing. 

If you have any questions regarding these comments, please contact me at (202) 419-1500 or 

rfensterheim@regnet.com. 

Sincerely, 

Robert J. Fensterheim 

Executive Director

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response. Please also see Endocrine Disruptor Screening Program; Final Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 7

EPA Comment Code: 1075

Comment: Given the apparent inefficiencies that would result and perceived lack of coordination within 

the Agency, AWG believes it is critically important for EPA (including the key Agency scientists and 

policy makers from both the TSCA section 4 and EDSP program) to meet with the affected industry to 

comprehensively discuss the various testing needs for acetaldehyde. AWG will separately submit a 

formal request for a meeting that should be organized as soon as practically feasible, to avoid a wasteful 

expenditure of both public and private sector resources and an inefficient use of animals that is not 

consistent with minimization of animal use in toxicity testing.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.
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Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 3

EPA Comment Code: 1075

Comment: * Monsanto notes that the Agency does not intend to respond to these public comments. The 

EDSP program is a significant and important undertaking for both the EPA and Industry. Therefore, we 

urge the Agency to reconsider and provide responses.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 9

EPA Comment Code: 1075

Comment: We appreciate the opportunity to provide these comments to EPA, and request that EPA 

provide a response. 

Gregory Watson, Ph.D. 

Chemical Regulatory Affairs Lead 

Monsanto Company

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 13

EPA Comment Code: 1075

Comment: The EPA should respond to comments on List 2 Chemicals: 

Monsanto notes that the Agency does not intend to respond to these public comments; however, we urge 

the Agency to reconsider and provide such responses. The EDSP program is a significant and important 

undertaking for both the EPA and industry. The decision by the Agency to include a chemical on List 2 

is the prelude to the Agency’s issuance of binding EDSP Test Orders. When finalized, List 2 will create 

new obligations for specific members of the regulated community. The program requires tremendous 

numbers of animals and vast expenditure of resources, both by the regulated industry and by the 

Agency, and we believe that public dialogue is essential for any such undertaking. Thus, the EPA has 

specific legal obligations. Monsanto believes the EPA should adhere to the requisite notice and 
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comment provisions of the Administrative Procedure Act (APA), and formally respond to comments 

received on List 2. By responding to the comments, the EPA can avoid the appearance of acting in an 

arbitrary and capricious manner and promote an open and transparent process with the regulated 

industry and other stakeholders.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 6

EPA Comment Code: 1075

Comment: EPA should respond to comments on List 2 chemicals:

We note that the Agency does not intend to respond to these public comments, however, we urge the 

Agency to reconsider and provide responses. The EDSP program is significant and an important 

undertaking for both EPA and industry. The program requires tremendous resources, and we believe that 

public dialogue is key to the successful implementation of the EDSP.

As a final comment, we would like to note that under the first list of chemicals under the EDSP, we are 

still seeking the following information to best help with compliance by industry and implementation by 

the Agency:

* guidance for OSRI,

* resolution of errors within the 890 Series Test Guidelines,

* SEPs for the 890 Series reports,

* an appropriately detailed weight of evidence approach.

We believe that an initial focus on resolving many of the pending issues with the EDSP implementation 

under the first list of chemicals will ultimately enhance the integrity of the EDSP program.

Sincerely,

The Bayer CropScience Endocrine Drive Team

Cc:

Dr. Frank Sanders

Mr. William Wooge

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 3
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EPA Comment Code: 1075

Comment: Finally, Velsicol believes EPA should formally respond to these and other comments 

concerning its Draft EDSP List 2. The Agency's plan not to "respond formally to information or 

comments that may be submitted" is inconsistent with open and transparent regulatory practices. It may 

also be contrary to law. Velsicol appreciates the opportunity to provide these comments on the Draft 

EDSP List 2. Please do not hesitate to contact me if you have questions. 

Very Truly Yours, 

Sherman Friedman 

Vice President Velsicol Chemical LLC 

Enclosure: Velsicol Comments

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 6

EPA Comment Code: 1075

Comment: Finally, for the reasons discussed below, Velsicol believes EPA should formally respond to 

these and other comments on its Draft EDSP List 2.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 9

EPA Comment Code: 1075

Comment: Ill. EPA Should Respond To Comments Submitted on the Draft EDSP List 2

The EDSP List 2 will create new duties and obligations for specific members of the regulated 

community. For example, EDSP listing may lead to product de-selection and to millions of dollars of 

screening and testing. As such, EPA has a legal obligation to avoid arbitrary and capricious actions in 

interpreting applicable law and in identifying chemicals, and consequently manufacturers and importers 

that will be subject to EDSP testing. Velsicol believes that EPA should utilize the notice and comment 

provisions of the Administrative Procedure Act (APA) when developing the EDSP List 2. In that regard, 

it should formally respond to comments received on the Draft EDSP List 2.
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EPA stated in the Listing Notice that "The Agency does not plan to respond formally to information or 

comments that may be submitted ... " (75 Fed. Reg 70248, 70251). This position is contrary to the open 

process envisioned by the EPA for agency actions and is inconsistent with open and transparent 

regulatory practices. Velsicol believes that the Agency action related to issuing the EDSP List 2 is, in 

essence, a rulemaking and EPA should comply with APA notice and comment provisions. The decision 

by the Agency to include a chemical on the EDSP List 2 is the first step in the process that may 

culminate in Agency issuance of binding EDSP Test Orders, which would lead to possibly millions of 

dollars of screening and testing. For these reasons, Velsicol believes EPA's development of an EDSP 

List 2 is a regulatory action subject to the APA. In any event, EPA should provide formal notice and 

comment, including a response to comments, to avoid the appearance of acting arbitrarily, and to ensure 

an open and transparent process.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 2

EPA Comment Code: 1075

Comment: When finalized, List 2 will create new obligations for specific members of the regulated 

community (with the issuance of test orders). Thus, EPA has specific legal obligations. The Task Force 

believes EPA should adhere to the requisite notice and comment provisions of the Administrative 

Procedure Act (APA), and formally respond to comments received on List 2. By responding to the 

comments, EPA can avoid the appearance of acting an arbitrary and capricious manner and promote an 

open and transparent process with the regulated industry and other stakeholders.

Response: Please see general response to comment under EPA Comment Code: 1075 Request for 

Formal Response.
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EPA Comment Code: 2005 Pesticides as a Group

General Response: EPA acknowledges that for some of the chemicals listed on the second EDSP list 

there may be existing data relevant to the Tier 1 screening. For test orders requiring Tier 1 screening 

assays, the agency decided not to issue tailored data requirements because, in EPA’s view, it is the order 

recipient’s responsibility to demonstrate that it does not need to conduct one or more of the specified 

assays to fulfill the order. Test orders specifically provide recipients the opportunity to provide “other 

scientifically relevant information” (OSRI) in lieu of conducting one or more of the required assays in 

the Tier 1 battery. EPA has been reviewing OSRI submissions and making its determinations public. 

Future test order recipients may obtain these determinations from the EPA Web site

(http://www.epa.gov/endo/pubs/EDSP_OSRI_Response_Table.pdf ) and use them to guide preparation 

of requests involving submission of other scientifically relevant information. 

Please also see Response to Comments on the Public Review Draft of the Information Collection

Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of Certain 

Chemicals Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is being 

published simultaneously with this comment response document.

Individual Comments

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 3

EPA Comment Code: 2005

Comment: I. Pesticides 

As pointed out in comments regarding the first list of chemicals (People for the Ethical Treatment of 

Animals (PETA) et al. 2008), pesticides are among the most highly data-rich substances in existence. 

For registration, pesticides currently are subject to dozens of separate animal tests, including 

reproductive and chronic/lifecycle studies in rodents, fish and birds (EPA 2007a). These tests kill 

thousands of animals and include many of the same endpoints addressed in the presumptive EDSP Tier 

2 tests. Similarly, EPA’s HPV Program also provides for the collection of data which may be germane 

to the assessment of potential reproductive toxicity (EPA 2000a). At an absolute minimum, chemicals 

should be exempted from EDSP Tier 1 screens for which equivalent or higher tier data are available. 

In its guidance on the acceptance of Other Scientifically Relevant Information (OSRI) in lieu of 

additional testing, EPA describes OSRI as any information that “informs the determination as to whether 

the substance may have an effect that is similar to an effect produced by a substance that interacts with 

the estrogen, androgen, and/or thyroid hormonal systems. OSRI may either be functionally equivalent to 

information obtained from the Tier 1 assays—that is, data from assays that perform the same function as 

EDSP Tier 1 assays—or may include data that provide information on a potential consequence or effect 

that could be due to effects on the estrogen, androgen or thyroid systems,” including “studies that 

correspond to the assays in Tier 1 or Tier 2; metabolism studies; or other vertebrate or invertebrate 

toxicity studies, including, but not limited to, developmental toxicity tests,” carcinogenicity tests, 
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toxicogenomic data, and reproductive toxicity tests", as well as testing conducted under 40 CFR Part 

158 data requirements to support a pesticide registration (EPA 2009a).

Following this reasoning, information requests should be tailored to individual chemicals and/or 

chemical classes. For example, Reproduction and Fertility effects (OPPTS 870.3880) and Prenatal 

Developmental Toxicity (OPPTS 870.3700) tests are required for both food-use and non-food-use 

pesticide Technical Grade of the Active Ingredients (TGAI). The simple mechanistic data produced by 

the Hershberger, uterotrophic, and the male and female pubertal assays will not provide additional 

information; indeed, chemicals tested according to OPPTS 870.3880 have, in effect, already been 

subject to EDSP Tier 2 mammalian testing. Thus, with the possible exception of mechanistic screening 

for thyroid effects, EDSP Tier 1 screens would appear to provide little or no value-added for pesticide 

chemicals.

Response: Please see general response to comment under EPA Comment Code: 2005 Pesticides as a 

Group. Also, please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 4

EPA Comment Code: 2005

Comment: * Screening pesticide active ingredients, such as Acetochlor, for endocrine disruption is 

redundant and unnecessary given FlFRA pesticide requirements. FlFRA already requires that pesticides 

undergo a broad and comprehensive battery of toxicology testing covering a spectrum of endocrine 

endpoints that are sufficient to detect endocrine disruption.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code: 

2005 Pesticides as a Group.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 7

EPA Comment Code: 2005

Comment: Inclusion of pesticides in List 2:

EPA issued the first list of 67 chemicals to be evaluated in Tier I assays under the EDSP on April 15, 

2009. This list included 58 pesticides and 9 high production volume chemicals and/or inert ingredients 

of pesticide products. The test screens are estimated to cost in the range of $500,000 to 

$1,000,000/chemical. List 2 contains 50 additional pesticide active ingredients (and several discontinued 

pesticide products). Pesticide active ingredients are approved for use under the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA). As mandated under FIFRA, the process of developing and 

registering crop protection products for commercial use is methodical and demanding. Collectively, sub-
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chronic and chronic toxicity studies in rats, mice and dogs, developmental toxicity studies in rats and 

rabbits, as well as reproduction studies in rats evaluate a wide array of estrogen-, androgen- and/or 

thyroid-sensitive tissues. Data are obtained on potential endocrine-mediated responses such as 

reproductive parameters (e.g. mating, fertility, and gestational indices), estrous cyclicity, sperm 

parameters, and histological alterations in a variety of endocrine controlled tissues, (e.g. epididymides, 

testes, ovaries, uteri, thyroid, adrenals, pituitary). The development of fetuses and offspring is also 

assessed by measuring endpoints related to growth, survival, and sexual development. Often additional 

endpoints such as hormone levels are included in study designs to better understand the toxicity profile 

of a compound. Data on endpoints pertaining to endocrine-mediated effects are also available from the 

studies performed on representative wildlife species, including fish and birds. Metabolism studies in 

rats, poultry, ruminant animals and fish demonstrate the extent of absorption and excretion of the 

pesticide over time as an indication of potential exposure and can help to identify any metabolites of 

concern. The extensive toxicity profile available on a pesticide across its FIFRA dataset provides an 

appreciable amount of information about patterns of effects and downstream outcomes all of which are 

relevant in the assessment of a compound's potential to interact with the endocrine system.

The Office of Pesticide Programs has indicated that, subsequent to the first list of substances to be 

evaluated in the Tier I screening battery, the EDSP for pesticide active ingredients will be implemented 

in conjunction with the Registration Review process. Given this decision, it is unnecessary to continue 

to list pesticides for screening. In fact, because the pesticides on the draft List 2 are from the 2007 and 

2008 registration review schedule, the listing comes very late in the Registration Review process for 

these products. To include them on a screening list at this late date has the potential to disrupt the 

Registration Review process for the pesticides listed. We would suggest that it is, therefore, unnecessary 

to include pesticides on List 2 and that EPA evaluate the appropriate timing and procedure for EDSP 

screening of pesticides within the existing pesticide registration review process.

Additionally, we urge EPA to refrain from listing or issuing new test orders for pesticide active 

ingredients, or any other chemical, until the Agency has had an opportunity to properly evaluate the 

performance of the Tier I screening battery based on the results of the first 67 chemicals on EPA's List 

1. This recommendation is consistent with the SAP/SAB recommendation to collect and analyze data 

from List I before proceeding to the evaluation of additional substances in the EDSP.[FN11: EPA, 

Review of the EPA 's Proposed Environmental Disrupt or Screening Program; Review of the Endocrine 

Disruptor Screening Program by a Joint Subcommittee of the Science Advisory Board and Scientific 

Advisory Panel. EPA-SAB-EC-99-013, July 1999 ("SAB EDSP Report").]

Given that the focus of List 2 is potential presence of a chemical in drinking water and potential 

substantial exposure to the human population, we recommend that pesticides which do not fulfill both 

criteria as outlined in Table 1 of the Federal Register Notice (FR 75, No 221, Wednesday, November 17, 

2010) be removed from List 2. In describing the method for inclusion of chemicals on List 2, an 

emphasis is placed on potential contamination of drinking water. This is clearly not the case because 29 

pesticides are not identified as a concern regarding the SDWA. They were listed solely due to the 

Registration Review schedule. To include these pesticides on List 2 erroneously suggests to the public 

that the active ingredients are of concern in drinking water. Despite EPA's best efforts to accurately 

describe the listing criteria, we know from experiences with List I and the perception that the list was an

endocrine disruptor list such misinterpretations do occur.

Response: The second EDSP list includes priority chemicals for both the drinking water program and 

the pesticide program within EPA. Please see general response to comment under EPA Comment Code:
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2100 Pesticide Registration Review Issues. Also, please see general response to comment under EPA 

Comment Code: 2005 Pesticides as a Group.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 4

EPA Comment Code: 2005

Comment: * Screening pesticide active ingredients, such as Alachlor, for endocrine disruption is 

redundant and unnecessary given FIFRA pesticide requirements. FIFRA already requires that pesticides 

undergo a broad and comprehensive battery of toxicology testing covering a spectrum of endocrine 

endpoints that are sufficient to detect endocrine disruption. In the specific case of Alachlor, the EPA 

itself already made this argument in 2006, in response to a petition from several States.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code: 

2005 Pesticides as a Group.

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 2

EPA Comment Code: 2005

Comment: Inclusion of pesticides in List 2:

EPA issued the first list of chemicals of 67 chemicals under the EDSP on April 15, 2009, that included 

58 pesticides and 9 inert compounds. List 2 contains an additional 50 pesticide active ingredients 

including several discontinued pesticides. As mandated under FIFRA, the process of developing and 

registering crop protection products for commercial use is methodical and demanding. The extensive 

toxicity profile available on a pesticide across its FIFRA dataset provides an appreciable amount of 

information about patterns of effects and downstream outcomes, all of which are relevant in the 

assessment of a compound’s potential to interfere with the endocrine system. The Office of Pesticide 

Programs has indicated that the EDSP will be implemented in the Registration Review process. 

Therefore, in our view, it is unnecessary to continue to list pesticides for screening. Instead, EPA should 

evaluate the appropriate timing and procedure for EDSP screening of pesticides within the existing 

pesticide evaluation and registration review processes. The listing of pesticides from the 2007 and 2008 

registration review schedule comes very late in the Registration Review process for these pesticides. To 

include them on a screening list at this late date has the potential to disrupt the Registration Review 

process for the pesticides listed. We would suggest pesticides in Registration Review not be included on 

List 2. Specifically, the following Bayer CropScience substances should be removed from List 2:

Fenamiphos,

Fenoxaprop-p-ethyl,

Fosetyl-Al, and

Glufosinate ammonium.
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Additionally, we urge EPA to refrain from listing pesticides for screening or issuing new test orders 

until the Agency has had an opportunity to properly evaluate the usefulness of the Tier 1 battery assays. 

In fact this recommendation applies to all chemicals, in line with the SAP/SAB recommendation to 

collect and analyze data from List 1 before proceeding to additional substances.

Further, given that the focus of List 2 is potential presence of a chemical in drinking water and potential 

substantial exposure to the human population, we particularly recommend that pesticides which do not 

fulfill both criteria as outlined in Table 1 (page 70252) of FR 75, No 221, Wednesday, November 17, 

2010 be removed from List 2. In describing the method for inclusion of chemicals on List 2, an 

emphasis is placed on potential contamination of drinking water. This is clearly not always the case 

because 29 pesticides are not identified as a concern regarding SDWA; rather they were listed solely due 

to the Registration Review schedule. To include these pesticides on List 2 erroneously suggests to the 

public that the active ingredients are of concern in drinking water. Despite EPA’s best efforts to 

accurately describe the inclusion criteria, we know from experiences with List 1 and the perception that 

the list was an endocrine disruptor list that such misinterpretation does occur.

Finally, there are 50 additional pesticide active ingredients on List 2, nearly doubling the total number of 

pesticides identified for Tier 1 screening. Therefore, at a minimum, any test orders for pesticides should 

be among the last group issued from List 2 in deference to the ongoing burden already shouldered by the 

pesticide industry.

Response: The second EDSP list includes priority chemicals for both the drinking water program and 

the pesticide program within EPA. Some pesticides were included on the second EDSP list solely based 

on their inclusion on the 2007 and 2008 Registration Review Schedule. Please see general responses to 

comment under EPA Comment Codes: 2005 Pesticides as a Group and 2100 Pesticide Registration 

Review Issues.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 4

EPA Comment Code: 2005

Comment: Inclusion of pesticides in List 2:

EPA issued the first list of chemicals of 67 chemicals under the EDSP on April 15, 2009. This list 

included 58 pesticides and 9 high production volume chemicals and/or inert ingredients of pesticide 

products. The test screens are estimated to cost up to approximately $1,000,000/chemical. ETU happens 

to be a chemical used in a variety of industries and also a metabolite of the EBDC fungicides. As such, 

EPA has investigated these materials under the Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA). As mandated under FIFRA, the process of developing and registering crop protection products 

for commercial use is methodical and demanding. A variety of toxicology and environmental tests have 

been done on ETU. A considerable database of toxicology studies already exists for ETU. Additional 

extensive studies are underway as required by Data Call-In Notices that will provide significant 

information on the endocrine effects of ETU.

Response: Please see general response to comment under EPA Comment Codes: 1050 Evaluation 

Criteria review, 2100 Pesticide Registration Review Issues, and 2005 Pesticides as a Group.
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EPA Comment Code: 2010 Contaminants Identified by Commenters as Being or 

Potentially Incompatible with Test Assays

General Response: EPA removed four chemicals from the second ESDSP list because of their highly 

reactive physiochemical properties and test assay incompatibility issues. The chemicals removed from 

the list are benzyl chloride, cumene hydroperoxide (CHP), oxirane, methyl- (propylene oxide or PO), 

and triethylamine (TEA). 

EPA received comments chlorodifluoromethane (HCFC-22) and toluene diisocyanate (TDI) should also 

be removed from the list due to testability issues. EPA decided to keep these chemicals and prioritize the 

test orders to allow time for test incompatibility issues to be resolved.

Individual Comments

Commenter Name: Marcy Banton

Commenter Organization: LyondellBasell Industries

EPA Document ID: EPA-HQ-OPPT-2009-0477-0011

Comment Part: 3

EPA Comment Code: 2010

Comment: 3. Propylene oxide may be incompatible with Tier 1 endocrine testing due to its hydrolysis 

to propylene glycol.

Propylene oxide spontaneously reacts with water to form propylene glycol. In several of the endocrine 

disruption screening program assay systems (e.g. androgen receptor binding, aromatase, estrogen 

receptor binding assay, estrogen receptor transcriptional activation assay, fish short-term reproduction 

assay, amphibian metamorphosis assay, steroidogenesis assay), propylene oxide would be added to 

aqueous media directly to cells or organisms (fish) or added to aqueous solutions for receptor binding 

using cellular cytosolic fractions. In all of these instances, it can be predicted that the chemical form 

available to interact with the cellular targets will be propylene glycol.

Propylene glycol has some unique features within these types of test systems. For example, propylene 

glycol is often added to cellular suspensions to stabilize cells (e.g. sperm used in vitro fertilization 

procedures) and their membranes prior to freezing or other potentially stressful techniques. Indeed, in 

one of the endocrine disruption screening program assays, propylene glycol is required and necessary 

for the optimal performance of the assay (see page 7 of the aromatase guidelines; OPPTS 890.1200). 

This suggests that propylene glycol (and hence propylene oxide), is having an effect within the assay 

system that is separate from inhibition of the aromatase enzyme. This raises the question as to how to 

conduct a study where the chemical being tested is forming a necessary component of the test system 

itself. As with any component of the assay system, the concentration of each component is optimized to 

allow the assay to function. Correspondingly, lower or higher concentrations of each component can 

lead to reduced function or less than optimal performance. This reduced function can be entirely 

separate from inhibition of the aromatase enzymatic reaction. How can the US EPA separate the reduced 

function of the assay system due to increased concentrations of a component of the test system from a 

true inhibition of aromatase enzymatic activity?
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Propylene glycol produced from the spontaneous conversion of propylene oxide can also affect other 

endocrine disruption screening program assay systems that contain cytosolic fractions or cell being 

cultured in vivo, as propylene glycol has an obvious role in affecting cells responding to stress (e.g. 

cryopreservation of sperm) or proteins within a suspension or cytosolic fraction (e.g. as propylene glycol 

effects the aromatase assay). For example, propylene glycol may affect tadpole larva or fish eggs in 

ways totally independent of the thyroid axis in frogs or endocrine systems within fish.

For these reasons, we question if propylene oxide can validly be tested in the Tier 1 in vitro tests and 

aquatic in vivo tests. Seemingly only in vivo testing of propylene oxide to inhalation exposures of whole 

animals (Herschberger assay, Pubertal development and thyroid function in intact juvenile/peripubertal 

female rats, Pubertal development and thyroid function in intact juvenile/peripubertal male rats and the 

uterotrophic assays) is achievable in the current Tier 1 test methods. For inhalation exposure tests, it can 

be assured that the effects observed are due to propylene oxide exposure and are not secondary to a 

nonspecific mechanism due to propylene glycol formed within the media or cytosolic fraction.

In conclusion, the above information supports that there is adequate data on the endocrine disrupting 

potential of propylene oxide already that exceed the intent of the Tier 1 screening battery. In addition, 

propylene oxide is not expected to be found in water and testing in the majority of the Tier 1 battery is 

incompatible given its hydrolysis to propylene glycol. Additionally, the Panel believes that the use of 

additional experimental animals, in the proposed endocrine screening in vivo studies, is unnecessary and 

contrary to appropriate use of animals when existing animal studies show no histological or behavioral 

effects of potential endocrine disruption of propylene oxide.

Accordingly, we believe that propylene oxide should be excluded from the second list of chemicals for 

Tier 1 Endocrine Disruptor Screening. However, if the Agency does not delete propylene oxide from the 

list, it should require only those endocrine studies that have not already been tested and can validly be 

tested.

If you have any questions on this information, please contact me by phone at 713-309-7192 or by email 

at marcy.banton@lyondellbasell.com.

Sincerely,

Marcy I. Banton, DVM, PhD, DABVT

Manager, Toxicology and Risk Assessment

LyondellBasell Industries

REFERENCES

Crews RC. (1974). Effects of propylene oxide on selected species of fishes. Testing laboratory: Eglin 

Air Force Base, US Air Force Armament Center, Florida 32542, USA. Report no.: NTIS/AD/A-003637. 

Report date: 1979-11-01.

Deneer JW, Sinnige TL, Seinen W, and Hermens JLM. (1988) Quantitative Structure-Activity 

Relationship for the Acute Toxicity of Some Epoxy Compounds to the Guppy. Aquatic Toxicology. 

13:195-204.
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European Union. (2002). European Union Risk Assessment Report. Methyl Oxirane (Propylene Oxide). 

CAS No. 75-56-9. EINIECS No. 200-879-2 - EUR 29512/EN. Office for Official Publications of the 

European Communities, Luxembourg.

Hansch C and Leo AJ. (1989). Medchem Project, Pomona College, Claremont CA. Hardin BD et al., 

(1983). Reproductive-toxicologic assessment of the epoxides ethylene oxide, propylene oxide, butylene 

oxide, and styrene oxide. Scand. J Work Environ. Health. 9:94-102.

Hardin B, Niemeier R, Sikov M and Hackett P. (1983). Reproductive-toxicologic assessment of the 

epoxides ethylene oxide, propylene oxide, butylene oxide, and styrene oxide. Scand. J Work Environ. 

Health. 9:94-102.

Harris SB, Schardein JL, Ulrich CE, Ridlon SA. (1989). Inhalation developmental toxicity study of 

propylene oxide in Fischer 344 rats. Fundam. Appl. Toxicol. 13:323-331.

Hayes WC, Kirk HD, Gushow TS and Young JT. (1988). Effect of inhaled propylene oxide on 

reproductive parameters in Fischer 344 rats. Fundam. Appl. Toxicol. 10:82-88.

MITI (Ministry of International Trade and Industry) Japan (1988). Biodegradation and bioaccumulation 

testing results on existing chemical substances. The Official Bulletin of the Ministry of International 

Trade and Industry. Report date: 1988-12-28.

NTP CERHR (National Toxicology Program Center for the Evaluation of Risks to Human 

Reproduction). (2004). NTP-CERHR Monograph on the Potential Human Reproductive and 

Developmental Effects of Propylene Glycol. NIH Publication No. 04-4482.

Shell Research Ltd. (1986). Propylene oxide: acute toxicity (Salmo gairdneri, Daphnia magna and 

Selenastrum capricornutum) and n-octanol/water partition coefficient. Testing laboratory: Sittingbourne 

Research Centre, Environmental Research Department, Kent ME9 8AG, United Kingdom. Study 

number: SBGR.85.250. Report date: 1986-04-14.

Sweeney LM, Kirman CR, Albertini RJ, Tan Y-M, Clewell III HJ, Filser JG, Csanady G, Pottenger LH, 

Banton MI, Graham CJ, Andrews II LS, Papciak RJ and Gargas ML. (2009). Derivation of inhalation 

toxicity reference values for propylene oxide using mode of action analysis: Example of a threshold 

carcinogen. Critical Reviews in Toxicology. 39(6):462-486.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Terry Medley

Commenter Organization: E.I. du Pont de Nemours and Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0016

Comment Part: 2

EPA Comment Code: 2010

Comment: 2. Pursuant to the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p)(1), 

testing conducted for the EDSP must be based on “validated test systems and other scientifically 
EPA-OGWDW Final EDSP List 2 February 2013

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relevant information.” [21 U.S.C. § 346a (p)(l)]. The screening assays in the EPA proposed EDSP Tier I 

screening battery are not designed for, nor have they been validated for, use with inhalation exposures. 

Under conditions where exposure would be expected, which are primarily in workplace production and 

use, HCFC-22 would be a gas, and testing of HCFC-22 in aqueous solutions is not practical given its 

low boiling point (-40.8 C).

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Marie Martinko

Commenter Organization: Society of the Plastics Industry, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0022

Comment Part: 3

EPA Comment Code: 2010

Comment: III. The Physical and Chemical Properties of CHP May Preclude Testing 

As noted above, CHP is highly reactive at STP in the presence of metals and organic matter, a condition 

likely to occur in the Tier1 tests.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 3

EPA Comment Code: 2010

Comment: 2. HCFC-22 is Unsuitable for Tier 1 Endocrine Testing 

The Federal Register notice of November 17, 2010 on page 70251 indicates that an initial list of more 

than 200 chemicals was “streamlined” to yield the published second list of 134 chemicals. Under item 

3.v., reasons for excluding chemicals are “Chemicals not likely to be biologically active or which are 

incompatible with testing assays for various reasons due to one or more of their physiochemical 

properties (e.g., gases, strongly acidic or basic, solubility, vapor pressure, molecular weight).” 

Biological activity is discussed below. We consider that HCFC-22 should have been removed from the 

list on physiochemical grounds during the streamlining process. HCFC-22 is a gas under ambient 

conditions with low affinity for water and it has a high vapor pressure (10,300 hPa at 24oC). The 

protocols for Tier 1 screens are unsuitable for testing a chemical with these properties. Methods 

involving inhalation administration or enclosed vapor techniques are required but these have not been 

established as yet. Such protocols would have to be developed with rigorous validation and 

standardization before being employed in the EDSP. Indeed, Section 408(p)(1) of the FFDCA requires 

EPA to “develop a screening program, using appropriate validated test systems and other scientifically 

relevant information...” and, as evidenced by the development of Tier 1 tests for non-gaseous 

substances, a robust validation process is anticipated in this mandate.
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Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 6

EPA Comment Code: 2010

Comment: b. The Physical and Chemical Properties of Triethylamine May Preclude Testing: 

The EPA criteria for listing includes the provision that the "material is not strongly acidic or basic and 

therefore would not be incompatible with the testing assays." TEA is highly corrosive [FN8: Corrosive 

after 3 minute application to the skin ofrabbits, TSCATS, 8EHQ-0892-5947] to tissue and a strongly 

basic chemical. This is substantiated by the measurement ofthe pH of 9.8 at 60 mg/L in aqueous 

solution. [FN9: Triethylamine Acute Toxicity To Rainbow Trout (Oncorhynchus Mykiss) Under FlowThrough Conditions, Machado MW, 1994 [Arkema sponsored unpublished data]]

The Agency should allow time to review and evaluate the results of the Tier 1 screening of the List 1 

chemicals prior to requiring testing on additional chemicals. It is especially critical to determine the 

impact of non-specific physical/chemical properties on the integrity and specificity of the test systems 

for those materials with high chemical reactivity, like the corrosive nature and strong alkalinity of TEA.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 14

EPA Comment Code: 2010

Comment: b. The Physical and Chemical Properties of HCFC 22 Preclude Testing

The Federal Register notice of November 17, 2010 indicates that reasons for excluding chemicals are 

"Chemicals not likely to be biologically active or which are incompatible with testing assays for various 

reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or basic, 

solubility, vapor pressure, molecular weight)." HCFC-22 is a gas under ambient conditions with low 

affinity for water and a high vapor pressure (10,300 hPa at 24°C). The protocols for Tier 1 screens are 

unsuitable for testing a chemical with these properties. Methods involving inhalation administration or 

enclosed vapor techniques would be required and these would have to be rigorously validated and 

standardized before being employed in the EDSP.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.
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Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 2

EPA Comment Code: 2010

Comment: * Each of the eleven endocrine screening tests required under the Tier 1 screening program 

involves introduction of the tested substance to test media containing water, proteins, solvents, etc. that 

are known to readily react with isocyanates. Thus, the testing of TDI in these assays would likely result 

in formation of reaction products and associated test results which have no relevance to the substance 

and its known modes of exposure, uptake, metabolism, and elimination in living organisms. Therefore, 

the endocrine screening tests specified would not provide information relevant to exposure to TDI.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 3

EPA Comment Code: 2010

Comment: 5) The physical-chemical properties of PO will be problematic for the EDSP Tier 1 assays, 

as PO is reactive and will bind to nucleophilic macromolecules including proteins and other 

nucleophiles that are present in a test matrix, thus limiting the extrapolation utility of any data collected 

and possibly invalidating the test system/results.

Details supporting each of these lines of evidence are provided below:

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 6

EPA Comment Code: 2010

Comment: 5) The physical-chemical properties of PO will be problematic for the EDSP Tier 1 in vitro 

assays. PO is a reactive compound that binds with nucleophilic sites, including proteins and other 

cellular macromolecules. PO-adducted macromolecules may interfere with the expected performance of 

the EDSP assays, especially in vitro assays which typically present higher concentrations (and higher 

potential for binding) of such macromolecules than in vivo situations. Furthermore, the identity and 

quantity of PO-adducted species occurring in these in vitro assays would not be expected to reflect the 
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same identity and quantity of PO-adducted species resulting from in vivo exposures. Thus there is a high 

likelihood of PO resulting in confounding assay performance, which will result in uninterpretable or 

erroneous results.

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.

Commenter Name: Fred Marashi

Commenter Organization: Chevron Phillips Chemical Company LP (CPChem)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0062

Comment Part: 2

EPA Comment Code: 2010

Comment: We would also like to echo comments submitted by the American Chemistry Council (ACC) 

in which they challenge the validity and the ability of the available tests to conclusively determine if a 

substance has endocrine disruption activity.

If you have questions regarding these comments, you may contact me at 832-813-4675 or by e-mail at 

marasm@cpchem.com.

Respectfully submitted,

Sincerely yours,

Fred Marashi

Response: Please see general response to comment under EPA Comment Code: 2010 Contaminants 

Identified by Commenters as Being or Potentially Incompatible with Test Assays.
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EPA Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or 

Used in the US, also Includes Pesticides with Cancelled Registrations

General Response: EPA received several comments claiming specific chemicals on the second EDSP 

list are banned, no longer manufactured or imported, or are cancelled pesticides and should therefore be 

excluded from the second EDSP list. The agency has taken the comments and supporting information 

into consideration and has removed the following 21 chemicals: 

1. 1,2 -Dibromo-3-chloropropane (DBCP) 12. Dimethipin

2. Chlordane 13. Fenamiphos

3. Ethylene dibromide 14. Molinate

4. 2,4,5-TP (Silvex) 15. Fenarimol

5. Dalapon 16. Fenoxycarb

6. Dinoseb 17. Propetamphos

7. Endrin 18. Pyridate

8. Heptachlor 19. Sodium tetrathiocarbonate

9. Heptachlor epoxide 20. Sulfosate

10. Methoxychlor 21. Temephos

11. Toxaphene 

For additional information please see Response-to-Comments for the Endocrine Disruptor Screening 

Program’s Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 

2012c) and Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening Safe 

Drinking Water Act Chemicals(USEPA, 2012a) that are being published simultaneously with this 

comment response document.

EPA also received comments suggesting the agency remove the following chemicals from the EDSP 

List 2: lindane, polychlorinated biphenyls (PCBs), methyl tert-butyl ether (MTBE), 1,1,1-trichlorethane, 

carbon tetrachloride, and hexachlorocyclopentadiene. The chemicals remain on the list for the following 

reasons:

1. Lindane: While lindane is no longer registered as an insecticide, it is a Food and Drug 

Administration registered product for scabies and lice treatment. Lindane has been detected in 

sources of drinking water. See EPA’s Web site for more information on lindane:

http://www.epa.gov/ttn/atw/hlthef/lindane.html.

2. Polychlorinated biphenyl (PCB): This chemical remains on the list so that orders can be issued 

should a manufacturer be identified or someone begins manufacturing. 

3. Methyl tert- butyl ether (MTBE): Growing concerns about MTBE pollution of ground water and 

drinking water led at least 25 states to pass laws banning or limiting the use of MTBE, with 

effective dates ranging from 2000 to 2009. Although MTBE production has been declining since 

1999 and the use of MTBE as a gasoline additive is far less common than it was in the 1990s, 

contamination of drinking water wells is likely to continue because of existing soil and ground 

water contamination and continued MTBE-contaminated plume movement. The production and 
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importation of MTBE in the United States was over 1 billion pounds for all IUR reporting cycles 

from 1986 to 2002. The highest total release reported TRI data for MTBE was in 1998 with over 

4 million pounds. TRI data indicate that total off-site and on-site releases of MTBE for 2008 

reporting was approximately 350 thousand pounds.

4. 1,1,1 – Trichloroethane: This chemical is currently being manufactured and therefore it will 

remain on the list. 

5. Carbon tetrachloride: This chemical is currently being manufactured and therefore it will remain 

on the list.

6. Hexachlorocyclopentadiene: This chemical is currently being manufactured and therefore it will 

remain on the list.

Individual Comments

Commenter Name: P. J. Snyder

Commenter Organization: Shell Downstream Inc., U.S.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0018

Comment Part: 1

EPA Comment Code: 2020

Comment: Comments on "Endocrine Disruptor Screening Program: Second List of Chemicals for Tier I 

Screening [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] 

Date: January 14, 2011

Steve A. Owens

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

1200 Pennsylvania Ave., N.W.

Washington, D.C. 20460-0001

SUBJECT: 

Re: Comments on "Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] 

Dear Mr. Owens,

Shell Companies[FN1: Shell Companies include Shell companies and Shell affiliated companies, 

including Shell Chemical LP, Shell Oil Products Company LLC, Shell Trading (US) Company, Motiva 

Enterprises LLC and the Deer Park Refining Limited Partnership.], ("Shell") appreciates the opportunity 

to submit comments on EPA's Endocrine Disruptor Screening Program: Second List of Chemicals for 

Tier I Screening (the "Draft EDSP List 2") pursuant to EPA's request for comments on the Draft EDSP 

List 2, 75 Fed. Reg. 70248; 11/17/2010. While these comments are limited to issues pertaining to one 

aspect of the Draft EDSP List 2, Shell is aware of more extensive comments provided by the American 

Chemistry Council (ACC). Shell is a member of ACC and is supportive of and incorporates herein the 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 218

comments ACC has provided. Other industry groups in which Shell participates are also submitting 

comments on specific substances and Shell endorses and incorporates those comments as well.

With respect to specific additional comments, Shell would like to address the listing of compounds, or 

compounds contained in products no longer manufactured by Shell. First, Shell specifically supports the 

ACC comment that the authority provided to the EPA under the Safe Drinking Water Act to require 

EDSP screening/testing is limited to current manufacturers and importers. Secondly, a number of the 

compounds on the EDSP List 2 were manufactured by Shell at one time but have not been manufactured 

by Shell for nearly a decade in some instances and several decades for others. Shell supports EPA's 

proposal to provide an opportunity for current manufacturers to opt out of screening/testing by agreeing 

to no longer manufacture a chemical (75 Fed. Reg. 70564; 11/17/2010) and, consistent therewith, that 

the prior cessation of manufacturing is sufficient to support no screening/testing.

For legacy compounds no longer on the market, current risk management has proceeded from the 

extensive toxicology databases and have produced conservative, often highly conservative, target 

investigation, remediation and/or or exposure standards in all media, standards that likely would not be 

influenced by additional screening assays or testing. Additionally, no additional product regulation 

would result for the underlying products are no longer on the market. Thus, the additional examination 

of these compounds under the current proposal would likely have no tangible value, would be a needless 

expenditure of resources and result in unnecessary animal testing. Finally, it would be difficult to 

imagine how appropriate test samples of these materials would be obtained as technical grade materials 

no longer exist for compounds such as 1,2 Dibromo, 3 chloropropane. 

Again, Shell appreciates the opportunity to provide comments to the Agency on the Draft EDSP List 2. 

The following person should be contacted if you have questions or a need for discussion:

Laurel Gingrich

Product Regulatory Support

Shell Downstream Inc, U.S.

910 Louisiana St.

Houston, TX 77002

Telephone No. 713-241-6030; Facsimile 713-241-1596

Email: laurel.gingrich@shell.com

Sincerely yours,

P.J. Snyder

Global Manager Product Stewardship

Shell Downstream Inc, U.S.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019
EPA-OGWDW Final EDSP List 2 February 2013

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Comment Part: 8

EPA Comment Code: 2020

Comment: II. Pesticides and chemicals no longer registered, manufactured or in use 

At least three of the 50 chemicals listed as registered pesticide active ingredients (fenamiphos, pyridate 

and sulfosate) are not currently registered (EPA 2010c). Hexachlorocyclopentadiene and its derivatives 

chlordane, endrin, and heptachlor, as well as all other derivatives, have been internationally banned or 

are under consideration for banning, according to the deliberations of the Stockholm Convention on 

Persistent Organic Pollutants (Stockholm Convention 2008). In addition, many more of SDWA 

regulated contaminants and CCL3 chemicals are no longer manufactured. For chemicals that are no 

longer manufactured, it is unclear who would perform the proposed testing. More importantly, since the 

purpose of the information from the EDSP is presumably to mitigate exposure to dangerous chemicals, it 

is unclear what EPA intends to do with additional information about chemicals that are no longer in 

production. In addition, there is already significant information regarding exposure, toxicity and 

potential endocrine activity for many of these chemicals including the pesticides that are no longer 

registered. Therefore we question the justification and utility of including these chemicals in Tier 1 

screening and request that they be exempted.

A. Fenamiphos 

Fenamiphos is an organophosphate, one of a group of related pesticides that affect the functioning of the 

nervous system. A nematicide and an insecticide, fenamiphos was used primarily to control nematodes 

and thrips on various agricultural crops (i.e., citrus, grapes, peanuts, pineapples, tobacco, etc.) and nonagricultural (i.e., turf and ornamentals) sites. Additionally, all uses were-soil incorporated, except for the 

pineapple use. There were no residential uses for fenamiphos. 

In the Interim Reregistration Eligibility Decision (IRED) for fenamiphos (EPA 2002), EPA determined 

that due to a number of unacceptable risk levels identified, the registrant would need to develop risk 

mitigation measures if it wished to continue the pesticide’s registration. Instead, Bayer Corporation, the 

sole registrant, requested voluntary cancellation and a 5-year phase-out of all existing fenamiphos 

registrations rather than committing to develop any additional data. A Use Deletion and Product 

Cancellation Order (FRL-7332-5) (68 FR 68901) for fenamiphos was published in the Federal Register 

on December 10, 2003, announcing that EPA granted the registrant’s request. All fenamiphos product 

registrations were cancelled and sale and distribution of manufacturing and end-use products by the 

registrant were prohibited effective May 31, 2007. 

Sale and distribution of all existing stocks by persons other than the registrant were to be prohibited 

effective May 31, 2008. However, as announced in an Amendment to Use Deletion and Product 

Cancellation Order published in the Federal Register on June 11, 2008 (FRL-8368-2), persons other than 

the registrant were allowed to continue to sell and distribute two fenamiphos products, Nemacur 10% 

Turf and Ornamental Nematicide (EPA Reg. No. 432-1291) and Nemacur 3 Emulsifiable Systemic 

Insecticide-Nematicide (EPA Reg. No. 264-731) until November 30, 2008. A December 2008 

amendment (EPA 2008b) provided that persons other than the registrant were permitted to sell and 

distribute existing stocks of Nemacur 3 Emulsifiable Systemic Insecticide-Nematicide (EPA Reg. No. 

264–731) until March 31, 2009. Tolerances in 40 CFR 180.349 for most commodities were revoked by 

December 31, 2009, with the exception of import tolerances for banana; fruit, citrus, group 10; garlic; 

grape; and pineapple, which will not have a U.S. registration as of December 31, 2009. On July 23, 
EPA-OGWDW Final EDSP List 2 February 2013

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2009, a petition from the American Bird Conservancy was submitted, requesting that EPA revoke 

tolerances established under the Federal Food, Drug and Cosmetic Act (FFDCA), section 408, for uses 

of 13 pesticides with no associated U.S. registrations (including fenamiphos), claiming that maintaining 

these tolerances allows Central and South American countries to continue using these pesticides on 

crops for which the United States has already determined there are unacceptable risks for U.S. protected 

migratory birds (EPA 2009b). EPA has yet to take action on this petition. 

Summary and conclusions regarding Fenamiphos: Fenamiphos is a canceled pesticide product that has 

not been produced since 2008 and any remaining stocks could not be sold after March 31, 2009. 

Tolerances on nearly all commodities were revoked in December 2009; any remaining tolerances will 

not have a U.S. registration as of December 31, 2009. There is a petition to revoke the remaining few 

tolerances for imported products. Again, it is questionable whether a substantial population is, in fact, 

exposed to fenamiphos in water and food. Since fenamiphos is no longer used as a pesticide in the US, 

and other uses are in question, information regarding its potential endocrine activity is of little value and

this chemical should not be included in the second list of chemicals for screening.

B. Pyridate

On April 18, 2007, EPA issued a notice of receipt of request by registrant Syngenta Crop Protection, 

Inc. to voluntarily cancel and to terminate uses of pyridate (EPA 2007b). The last remaining pyridate 

products registered under FIFRA Section 3 were cancelled in 2004 for failure to pay the required annual 

maintenance fees, but there were several Special Local Needs registrations for weed control on mint that 

were still active. On November 21, 2007, EPA issued notification in the Federal Register (EPA 2007c) 

of product cancellation and indicated that any existing stocks if pyridate could be sold and used until 

exhausted.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 10

EPA Comment Code: 2020

Comment: While this pesticide was considered to be a potential residue on fruits and vegetables at the 

time of the Okubo study, its registration has since been canceled and this, as well as any other sources of 

exposure are no longer of concern. The lack of likely exposure combined with proven lack of endocrine 

activity should exempt pyridate from further testing. 

C. Sulfosate

Sulfosate, a trimethylsulfonium salt of glyphosate, is an organophosphate herbicide that was used as a 

weed suppressor on a variety of commercially important crops. All sulfosate registered products were 

canceled on October 15, 2004 due to non-payment of registration maintenance fees, and a notice was 

published in the Federal Register on October 27, 2004 titled “Cancellation of pesticides for non-payment 
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of Year 2004 maintenance fees” (EPA 2004a). EPA stated that the registrant (Zeneca Ag. Products, now 

Sygenta Crop Protection) could continue to sell and distribute existing stocks until January 15, 2005; 

however the registrant later informed EPA that it did not produce sulfosate after 2002 and sold the 

remaining existing stocks of sulfosate in 2003 (EPA 2007d). Also, the registrant did not support 

continuing the import tolerance on bananas. Therefore, by 2004 EPA believed all existing stocks had 

been exhausted and any treated commodities had cleared the channels of trade. On May 2, 2007, EPA 

proposed amendments to revoke sulfosate’s existing tolerances in 40 CFR 180.489 (EPA 2007d), and 

finalized the revocation, after a 60-day comment period in which no comments were received, on 

September 19, 2007 (EPA 2007e).

Summary and conclusions: Sulfosate is a canceled pesticide product that has not been produced since 

2002 and the last stocks were sold in 2003. Tolerances on all commodities have been revoked. Since it is 

unlikely that a substantial population is exposed, information regarding the potential endocrine activity 

of this pesticide is of questionable value and this chemical should not be included in the second list of 

chemicals for screening. 

D. Lindane

Similarly, lindane is no longer registered as an insecticide and has been internationally banned from 

agricultural use since 2009 under the Stockholm Convention on Persistent Organic Pollutants (EPA 

2006b; Engeler 2009). Although lindane is still allowed sparingly as a second-line treatment for lice and 

scabies (Engeler 2009), it has not been manufactured in the US since the 1970s (Commission for 

Environmental Cooperation (CEC) 2006). As the agricultural use of lindane was restricted and 

eventually ceased, the levels of this substance in the environment and in human tissue have declined 

dramatically. Consistent with the calculated half-life of lindane isomers in human blood of 7.2 years 

(Hines 1992), as early as 2005 no detectible amounts of lindane could be found in a random sampling of 

about 5,000 people in the US (Centers for Disease Control and Prevention (CDC) 2005) and the amount 

of lindane introduced into the environment has been reduced by more than 99% since agricultural 

restrictions have been in place (Commission for Environmental Cooperation (CEC) 2006; EPA 2006c). 

State-specific bans on the pharmaceutical use of lindane and international efforts to discontinue lindane 

production are reducing the environmental load even further (Humphreys, Janssen et al. 2008). 

According to the Toxics Release Inventory, the remaining lindane waste in the US resides in a very 

limited number of hazardous waste recovery facilities that reported only 236 lbs of controlled lindane 

discharge in 2009. This minimal release would not result in a substantial population being exposed. 

As with the other pesticides mentioned above, there is no clear entity to whom testing orders would be 

issued for lindane and additional data would not alter mitigation strategies already successfully 

underway. These aspects alone should exempt lindane from testing in this program.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 12
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EPA Comment Code: 2020

Comment: E. 2-Dibromo-3-Chloropropane (DBCP) and 2,4,5-TP 

DBCP was banned as a pesticide on pineapple by the EPA in 1977 because of its known neurotoxicity 

and probable human carcinogenicity. In 1985 EPA cancelled all registrations and prohibited use of any 

stockpiles of DBCP (EPA 2000b). Although DBCP has been detected in ground water, filtration systems 

have been developed that can remove it from drinking water sources making human exposure to residual 

DBCP unlikely and easily mitigated (BCERF Program on Breast Cancer and Environmental Risk 

Factors 2004). Similarly, the herbicide 2,4,5-TP has been banned in the US since 1985. According to the 

EPA's own fact sheet, the physical properties of 2,4,5-TP make it very unlikely to leach into ground 

water and to accumulate in aquatic life. Even so, levels of 2,4,5-TP in drinking water are currently 

monitored and in the case of detection above action levels, would be easily removed with activated 

charcoal (EPA 2010d). 

Summary and conclusion: DBCP has not been used in the US for over 30 years; the only possible 

mitigation is by removal from drinking water supplies by filtration. Therefore information on endocrine 

activity of this chemical is not germane to its regulation and it should be removed from the second list 

for testing.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 14

EPA Comment Code: 2020

Comment: In addition to the extensive information available on its potential endocrine activity, 

methoxychlor was banned in the United States in 2003 (EPA 2004b) and in the European Union in 2002 

(European Union - DG SANCO 2002). Although these bans are comparatively recent, methoxychlor 

biodegrades relatively quickly in the environment and does not bioaccumulate (Smith 1991; Wauchope, 

Buttler et al. 1992) making it very unlikely that a substantial population would be exposed to levels of 

concern.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Patricia Casano

Commenter Organization: General Electric Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0023

Comment Part: 1

EPA Comment Code: 2020
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 223

Comment: Attached please find the comments of the General Electric Company.

January 18, 2011

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, N.W.

Washington, D.C.

(202) 564-8930

Attn: Docket ID Number EPA-HQ-OPPT-2009-0477

Re: Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening. 75 Fed.

Reg. 70248 (Nov. 17, 2010)

Dear Sir or Madam:

The General Electric Company (GE) appreciates the opportunity to respond to the Environmental 

Protection Agency's (EPA) request for "information and/or comment that may inform the exclusion or 

inclusion of chemicals on the second EDSP [Endocrine Disruptor Screening Program] list." Endocrine 

Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening, 75 Fed. Reg. 70248 (Nov. 

17, 2010). Polychlorinated biphenyls (PCBs) are among the chemicals that EPA is considering including 

on the second EDSP list. From the 1940's until 1977, GE manufactured equipment that contained PCBs 

purchased from another manufacturer.

As explained below, there is no practical utility to be derived by including PCBs on the second EDSP 

list. PCBs have not been manufactured intentionally in the United States since the mid-1970's. The use, 

distribution in commerce, storage and disposal of legacy PCBs have been subject to strict regulations for 

more than thirty years. Numerous actions to address PCBs that were released into the environment have 

been, and are being, conducted under federal and state law and voluntary programs. The result has been 

a dramatic reduction in exposures, and opportunities for exposures, to PCBs. PCBs also have been the 

subject of thousands of published studies, and currently are the subject of a risk assessment being 

conducted by EPA's National Center for Environmental Assessment. In short, every action that could be 

taken to investigate and address the potential risks of PCBs has been taken or is underway.

Exposures To PCBs Have Declined Dramatically

The manufacturing and importation of PCBs generally has been banned in the United States since 1979. 

15 U.S.C. § 2606(e)(3)(a)(i).[FN1: As the PCB rules acknowledge, PCBs can be generated inadvertently 

in some manufacturing processes. 40 CFR 761.3 (definition of "excluded manufacturing process"). Such 

inadvertent generation is subject to limitations on the concentration of PCBs in the final product and the

amount of PCBs that are discharged into the air or water. Id.] The use, distribution in commerce, storage 

and disposal of PCBs also have been subject to stringent regulation for more than thirty years. See 40 

CFR Part 761. In addition, many entities have voluntarily removed from service equipment that contains 

legacy PCBs. See, e.g., the Comments of the Utility Solid Waste Activities Group, which were recently 

submitted in response to EPA's 1 OPPT Document Control Office January 18, 2011 Advance Notice of 

Proposed Rulemaking for PCB Use Authorizations.[FN2: The comments are available at
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 224

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480b50086.] Thus, as 

EPA recently acknowledged, "The population of PCB-containing equipment is continually decreasing 

and will never grow or rebound." 75 Fed. Reg. at 17651.

In addition, substantial quantities of PCBs have been removed from the environment or otherwise 

addressed under CERCLA, RCRA and other programs at numerous sites around the country. Thus, 

levels of PCBs in the environment have declined substantially over time. See, e.g., Van Metre et al. 

(1998); Van Metre and Mahler (2005) ("Two broad conclusions about trends are evident from these 38 

lakes: DDT and PCB concentrations are decreasing, and PAH concentrations are increasing"). See also 

EPA, Great Lakes Monitoring-Contaminants in Top Predator Fish-Program Goals ("The most recent 

analytical results indicate that on average, total PCB concentrations in whole Great Lakes top predator 

fish have declined 5 percent annually between 1990 and 2003.")[FN3: 

www.epa.gov/glnpo/glindicators/fishtoxics/topfishb.html].

As a result of the ban on manufacturing and other restrictions in the rules, and concomitant reductions in 

the levels of PCBs in the environment, the dietary intake of PCBs - the main source of human exposure 

to PCBs - has declined dramatically. In 1978, the dietary intake of PCBs for an average adult was about 

0.03 micrograms per kilogram of body weight per day (ug/kg/day). ATSDR (2000), p. 15. By 1991, 

dietary intake had declined to less than 0.001 ug/kg/day. Id. This is a 30-fold decrease in exposure over 

only the first thirteen years of the TSCA PCB program.

As one would expect from these data, the human body burden of PCBs has declined radically over the 

last 30 years. As ATSDR has reported:

A time-trend analysis of the data [from the National Human Adipose Tissue Survey (NHATS)] also 

revealed that the percentage of the population having PCB concentrations from 1-3 ppm steadily

declined from over 62% in 1972 to less than 2% in 1984. The percentage of the population that had 

tissue levels > 3 ppm also declined during this same period from a high near 10% in 1978 to zero in 

1984 (Fensterheim 1993). PCB concentrations in human adipose tissues in the United States appear to 

have decreased significantly over the years. 

ATSDR (2000), p. 557.

The CDC's Fourth National Report on Human Exposure to Environmental Chemicals recently 

concluded:

“[H]uman serum levels of... PCBs have decreased by more than 80% since the 1980's .... The levels of 

polychlorinated dibenzo-p-dioxins, dibenzofurans, and coplanar and mono-ortho-substituted biphenyls 

seen in the U.S. population are generally well below the levels associated with occupational or 

unintentional exposures that have produced health effects. There are no firmly established relationships 

between concentrations (mainly considering TCDD) and health effects in people. "

CDC (2009), pp. 383-84. Hopf et al. (2009) similarly concluded that background population PCB serum 

levels peaked in 1979, and have declined since that time.

Including PCBs In The EDSP Is Unnecessary
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Page 225

The point of the EDSP is to screen chemicals for possible endocrine effects, but EPA already is 

assessing the potential noncancer effects of PCBs, including endocrine effects, in the context of EPA's 

Integrated Risk Information System. See Integrated Risk Information System (IRIS); Announcement of 

Availability of Literature Searches for IRIS Assessments, 75 Fed. Reg. 25239, 25240 (May 7, 2010). In 

support of that assessment, EPA has prepared a literature search that includes hundreds of studies, 

including studies that investigated hypothesized endocrine effects. Literature Search Product for 

Polychlorinated Biphenyls (non cancer) - Results of the May 2010 literature search arranged within the 

framework of an IRIS Toxicological Review (Chapter 2 through Section 4.5), available at 

http://www.epa.gov/ncea/iris/pdfs/Litsearch PCB.pdf. Including PCBs in the EDSP program would 

duplicate EPA's current effort under IRIS

In addition, the Tier 2 battery of tests in the EDSP rely heavily on in vivo studies as the definitive tests 

to validate and integrate biologically meaningful effects on the endocrine system. There are dozens of in 

vivo reproductive and developmental studies that have looked for effects from PCBs, with mixed results. 

There is no scientific rationale for conducting EDSP Tier 1 studies when there is an extensive existing 

literature base for making judgments on the potential endocrine impact from exposures to PCBs. At 

minimum, any testing of PCBs required under the EDSP should be carefully tailored to address any gaps 

in the existing body of relevant literature.

There Is No Obvious Candidate For A Test Order

EPA is proposing to include PCBs in the EDSP based on Section 1457 of the SDWA, which provides as 

follows:

SEC. 1457. In addition to the substances referred to in section 408(p)(3)(B) of the Federal Food, Drug, 

and Cosmetic Act (21 U.S.C. 346a(p)(3)(B)) the Administrator may provide for testing under the 

screening program authorized by section 408(p) of such Act, in accordance with the provisions of 

section 408(p) of such Act, of any other substance that may be found in sources of drinking water if the 

Administrator determines that a substantial population may be exposed to such substance. 

Section 1457 clearly authorizes EPA to include in the EDSP "any other substance that may be found in 

sources of drinking water if the Administrator determines that a substantial population may be exposed 

to such substance." That authority, however, must be exercised "in accordance with the provisions of 

section 408(p)" of the Federal Food, Drug and Cosmetic Act (FFFDCA), 21 U.S.C. § 346a(p).

Section 408(p) of the FFDCA provides:

IN GENERAL.-The Administrator shall issue an order to a registrant of a substance for which testing is 

required under this subsection, or to a person who manufactures or imports a substance for which testing 

is required under this subsection, to conduct testing in accordance with the screening program described 

in paragraph (1), and submit information obtained from the testing to the Administrator, within a 

reasonable time period that the Administrator determines is sufficient for the generation of the 

information. 

FFDCA § 408(p)(5)(A)(emphasis supplied). The operative language, underlined above, is written in the 

present tense, which means that EPA can issue test orders only to entities that currently are 

manufacturing or importing PCBs. As the Supreme Court recently stated:
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Page 226

Consistent with normal usage, we have frequently looked to Congress' choice of verb tense to ascertain a 

statute's temporal reach. See, e.g. , United States v. Wilson, 503 U. S. 329, 333 (1992) ("Congress' use 

of a verb tense is significant in construing statutes"); Gwaltney of Smithfield, Ltd. v. Chesapeake Bay 

Foundation, Inc. , 484 U.S. 49, 57 (1987) ("Congress could have phrased its requirement in language 

that looked to the past ... , but it did not choose this readily available option"); Barrett v. United States, 

423 U.S. 212, 216 (1976) (observing that Congress used the present perfect tense to "denot[e] an act that 

has been completed"). The Dictionary Act also ascribes significance to verb tense. It provides that, "[i]n 

determining the meaning of any Act of Congress, unless the context indicates otherwise [,] ... words 

used in the present tense include the future as well as the present." 1 U. S. C. §1. By implication, then, 

the Dictionary Act instructs that the present tense generally does not include the past. Accordingly, a 

statute that regulates a person who "travels" is not readily understood to encompass a person whose only 

travel occurred before the statute took effect.

Carr v. United States, 130 S. Ct. 2229, 2236 (2010). See also Johnson v. United States, 529 U.S. 694,

701 (2000) ("Absent a clear statement of intent, we do not give retroactive effect to statutes burdening 

private interests").

Since the manufacturing and importation of PCBs generally has been banned, and EPA can issue test 

orders only to current manufacturers and importers, there is no obvious candidate for a test order under 

Section 408(p) of the FFDCA. Although in theory EPA could issue a test order to entities that are 

inadvertently generating PCBs, the effort required to identify such entities could be substantial, and may 

not be justified given the existing body of literature and the fact that EPA already is assessing the 

noncancer risks of PCBs.

Conclusion

EPA currently is assessing the potential endocrine effects of PCBs in the context of the IRIS program. 

To the extent that PCBs do present risks to human health or the environment, the actions that can be 

taken to eliminate or reduce those risks are being taken - manufacturing has been banned; other activities 

are regulated; equipment has been, or is being, removed from service; and contaminated sites have been, 

and are being, remediated under the Comprehensive Environmental Response, Compensation and 

Liability Act, state laws and voluntary programs. There is little, if anything, to be gained by including 

PCBs in the EDSP program.

If you have any questions regarding these comments, please contact Patricia Kablach Casano at 202-

637-4228 or pat.casano@ge.com.

Sincerely,

Patricia Kablach Casano

Counsel, Government Affairs

Corporate Environmental Programs

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. Please also see general response to comment under EPA Comment Code: 2060 Chemicals 

with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 227

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 2

EPA Comment Code: 2020

Comment: Additional hazard screening studies on MTBE are unnecessary because of previous 

legislative action at the Federal and State level and recent EPA studies of MTBE’s prevalence in 

drinking water sources and environmental fate.

* Twenty three States have banned the use of MTBE as a gasoline oxygenate and the Federal 

requirement to have a certain concentration of oxygen in reformulated gasoline has been eliminated. 

These two actions have effectively eliminated the use of MTBE as a gasoline oxygenate throughout the 

United States. Repeated analysis of retail gasoline by the Alliance of Automobile Manufacturers has 

confirmed the absence of MTBE in the US fuel supply. It was use of MTBE as a gasoline oxygenate that 

resulted in surface and underground water contamination in previous years. Having already mitigated 

the future risk to drinking water, requiring additional hazard screening studies for endocrine effects is 

pointless.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Richard Becker

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0029

Comment Part: 12

EPA Comment Code: 2020

Comment: VII. EDSP Test Order Authority Applies to Current Manufacturers and Importers

The 1996 amendments to the SDWA provide EPA authority to include in the EDSP “substances that 

may be found in sources of drinking water” to which a “substantial population” may be exposed. The 

applicable wording in the EDSP Test Order authority section, FFDCA §408(p)(5) “Collection of 

Information,” uses the present tense and thus clearly focuses on current manufacturers and importers, 

not past:

“The Administrator shall issue an order to a registrant of a substance for which testing is required under 

this subsection, or to a person who manufactures or imports a substance for which testing is required 

under this subsection, to conduct testing in accordance with the screening program . . . .”

Therefore, ACC believes that for chemicals no longer manufactured or imported but which, in some 

instances, may be found as contaminants of drinking water, are not covered by the 1996 endocrine 

amendments to the SDWA.
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Page 228

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: James Lamb

Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0030

Comment Part: 1

EPA Comment Code: 2020

Comment: January 18, 2010 

Stephen A. Owens 

EPA Assistant Administrator 

Office of Chemical Safety and Pollution Prevention 

US EPA Headquarters Ariel Rios Building 

1200 Pennsylvania Ave., NW 

Washington, D.C. 20460

Dear Dr. Owens: 

RE: Hercules Inc. Comments on Inclusion of Toxaphene on the Second List of Chemicals Under the 

EDSP (Docket ID: EPA–HQ–OPPT–2009–0477); Addendum to an approved Information Collection 

Request by EPA to OMB Regarding the Second List of Chemicals under the EDSP (EPA ICR No. 

2249.02; OMB Control No. 2070-0176 (Docket ID: EPA-HQ-OPPT-2007-1081) and the Endocrine 

Disruptor Screening Program Draft Amended Policies and Procedures for Screening Safe Drinking 

Water Act Chemicals 

[EPA-HQ-OPPT-2007-1080; FLR-8848-9] 

The following comments are submitted by Exponent on behalf of Hercules, a wholly own subsidiary of 

Ashland Inc.

Within the Federal Register Vol. 75, No. 221 on Wednesday, November 17, 2010, EPA announced the 

second list of chemicals and substances for which EPA intends to issue test orders under the EDSP. EPA 

established the EDSP in response to section 408(p) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA). This second list of chemicals expands the EDSP in an effort to include more pesticides, and 

adds priority drinking water chemicals into the program for screening as authorized by Safe Drinking 

Water Act (SDWA) Section 1457. Hercules Incorporated (“Hercules”), a wholly owned subsidiary of 

Ashland Inc. is herein submitting its formal comments on the proposed inclusion of toxaphene in the 

second list of chemicals. (Docket ID: EPA–HQ–OPPT–2009–0477).

EPA has also published an Information Collection Request to OMB pertaining to List 2, and a Draft 

Amended Policies and Procedures for Screening Safe Water Drinking Act Chemicals, which provide 

additional information regarding the basis for such Screening Requirements. Therefore we are also 

submitting comments on these documents as they are relevant to the inclusion of toxaphene as a List 2 

chemical (Docket ID: EPA-HQ-OPPT-2007-1081).

Toxaphene is not a registered pesticide, nor are there existing import tolerances for toxaphene. All 

registrations for toxaphene were cancelled in -the 1980’s. To the best of our knowledge, toxaphene is no 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 229

longer manufactured in the US, except for gram quantities for research purposes. In fact, available 

sources of toxaphene are so limited that Hercules would be unlikely to be able to procure sufficient 

toxaphene to be able to perform the Tier 1 Screening Assays, particularly as the material has only 

moderate oral systemic toxicity.

In its Policies and Procedures, EPA states: 

“That is, EPA does not intend to issue orders to companies who manufacture or import a chemical for 

research and development purposes only, or who otherwise manufacture or import quantities of a 

chemical that are more appropriately measured in grams (as opposed to thousands of pounds). The 

rationale for this de minimis exemption is also based on the authority for listing an Other SDWA 

Chemical for EDSP screening (see Unit II.B.).” 

Therefore, using this criterion, EPA should not issue test orders for toxaphene. 

EPA Should Issue EDSP Orders Only To Current Manufacturers and Importers

• EPA states that it will rely on the authority granted the Agency by FFDCA section 408(p)(5)(A) to 

issue test orders requiring screening of substances identified in Phase 2 of the EDSP. The Act states: 

– “The Administrator shall issue an order to a registrant of a substance for which testing is required 

under this subsection, or to a person who manufactures or imports a substance for which testing is 

required under this subsection, to conduct testing in accordance with the screening program . . . .” 

• FFDCA §408(p)(5)(a). By its terms, FFDCA §408(p)(5)(a) refers to current registrants, manufacturers 

and importers. The FFDCA uses the present tense when referring to potential order recipients, and does 

not explicitly or implicitly grant EPA authority to issue testing orders to those who are no longer 

manufacturers of a chemical. 

• EPA recognized the limit of its authority to current manufacturers when it issued testing orders for the 

first phase of its EDSP. At that time, it issued orders only to current manufacturers of pesticide 

chemicals. Those who could demonstrate they no longer manufactured a chemical were exempt from the 

test orders. Further, those who agreed to discontinue sale of the chemical into the pesticide market were 

also exempt from the test orders. In its Draft Phase 2 Policies and Procedures, EPA generally continues 

to limit its order authority to current manufacturers of substances on the Phase 2 list. This is consistent 

with its policies and procedures issued for the initial EDSP screening [FN1: EPA. Endocrine Disruptor 

Screening Program; Policies and Procedures for Initial Screening: Notice. 72 Fed. Reg. 17560, April 15, 

2009 (“Phase 1 Policies and Procedures”).]

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: James Lamb

Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0030

Comment Part: 4

EPA Comment Code: 2020
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 230

Comment: It is important to note that in contrast to some other chlorinated hydrocarbons, toxaphene 

dechlorinates during weathering, generally reducing the toxicity. Environmental toxaphene is steadily 

being reduced and there are no new sources in the United States adding to potential human exposure. 

Testing is therefore unnecessary and wasteful of animals and resources.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 5

EPA Comment Code: 2020

Comment

5. HCFC-22 Production and Importation Are Subject to Phase-down and Phase-out 

HCFC-22 is a Class II ozone depleting chemical under the Montreal Protocol and EPA has developed 

regulations under the Clean Air Act, Section 605, to implement the phase down and elimination of US 

consumption (i.e. production+imports-exports) as required under the Protocol (74FR, 66412, December 

15, 2009). The Montreal Protocol required a 65% reduction in US baseline consumption beginning 

January 2010, a 90% phase down from January 2015, 99.5% reduction from 2020 and full phase-out by 

2030. Although the Protocol program is not chemical specific, US regulations are couched in terms of 

individual chemicals and company allowances have been allocated. The expenditure of allowances is 

rigorously monitored. The regulations are complex but a steady reduction in HCFC-22 allowances 

available to US companies is specified for the January 1, 2010 to December 31, 2014 period. As stated 

above, US regulations designed to prevent release of ozone depleting refrigerants are in place. All 

regulations implementing stratospheric ozone protection are rigorously enforced. The stratospheric 

ozone protection regulations under the Clean Air Act mean that releases of HCFC-22 are minimized and 

that the production and consumption of this material will diminish markedly in the foreseeable future. 

Eventual phase-out is guaranteed and EPA will seek opportunities to accelerate the phase-down and 

bring forward the phase-out.

6. Conclusion 

Taken together, the physical/chemical nature, biological properties, and the reduction of production and 

use provide strong evidence that it is not appropriate for HCFC-22 to be included in the list of materials 

to be screened under the EDSP. 

References: 

ECETOC (1989). Joint Assessment of Commodity Chemicals (JACC) No. 9, Chlorodifluoromethane, 

European Chemical Industry Ecology and Toxicology Centre, Brussels. 

EPA (2008). Chemical Expert Input and Review for the Third Contaminant Candidate List (CCL3). 

EPA 815-R-08-0009. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 231

EU RAR (2007). European Union Risk Assessment Report, Chlorodifluoromethane, CAS No, 75-45-6,

EINECS No. 200-871-9, November 2007, Italy. 

Longstaff E., Robinson M., Bradbrook C., Styles J. A., Purchase I. F. H. (1984). Genotoxicity and 

carcinogenicity of some fluorocarbons: assessment by short-term in vitro tests and chronic exposure in 

rats. Toxicol. Appl. Pharmacol. 72: 15-31.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 13

EPA Comment Code: 2020

Comment: EPA has developed regulations under the Clean Air Act, Section 605, to implement the 

phase down and elimination of US consumption of HCFC-22 (I .e. production+imports-exports)[FN18: : 

74FR, 66412, December 15 , 2009] because HCFC-22 is a Class II ozone depleting chemical under the 

Montreal Protocol. The stratospheric ozone protection regulations under the Clean Air Act mean that 

releases of HCFC-22 are minimized and that the production and consumption of this material will 

diminish markedly in the foreseeable future. The regulations are complex but a steady reduction in 

HCFC-22 allowances available to US companies is specified for the January 1, 2010 to December 31, 

2014 period.

Taken together, the physical/chemical properties of the material and the reduction of production and use 

further support that it is not appropriate for HCFC-22 to be included in the list of materials to be 

screened under the EDSP. The evidence clearly shows that HCFC-22 will not be found in "sources of 

drinking water" and therefore "substantial populations" will not be exposed to HCFC-22. The criteria for 

listing are not met.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: W. Caffey Norman

Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0037

Comment Part: 4

EPA Comment Code: 2020

Comment: E. The Phaseout of 1,1,1-Trichloroethane Makes Future Exposure Impossible

One reason that 1,1,1-trichloroethane drinking water exposure has declined effectively to
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 232

zero is that it may no longer be manufactured or imported into the United States. Under Clean

Air Act § 604(a), implementing the Montreal Protocol on Substances That Deplete the Ozone

Layer, 1,1,1-trichloroethane was phased out of production, except for feedstock use, effective

January 1, 2002.[FN14: 42 U.S.C. § 7671c(a). There would be no drinking water or other exposure 

resulting from manufacture for feedstock use, which is defined as "the manufacture of a substance that is 

used and entirely consumed (except for trace quantities) in the manufacture of other chemicals." CAA § 

601(11)(A), 42 U.S.C. § 7671(11)(A).]

In any case, inclusion of 1, 1, 1-trichloroethane in EDSP would serve no useful purpose: EPA recently 

determined that no change to the current MCL (200 ppb, the same as the MCLG) is warranted, based in 

part on the STORET and NAWQA data discussed above "show[ing] no to low occurrence at threshold 

levels of interest" and “indicat[ing] that any resulting NPDWR change would affect systems that rely on 

source water at none of the NAWQA locations and at less than 0.1 percent of the STORET 

locations.”[FN15: 75 Fed. Reg. 15500, 15562 (March 29, 2010).]

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. Also, please see general response to comment under EPA Comment Code: 2080 

Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 

1457 Requirements.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 5

EPA Comment Code: 2020

Comment: There is an additional reason to remove carbon tetrachloride from the second list. One 

reason that carbon tetrachloride drinking water exposure has declined effectively to zero is that it may 

no longer be manufactured or imported into the United States. Under Clean Air Act § 604(a), 

implementing the Montreal Protocol on Substances That Deplete the Ozone Layer, carbon tetrachloride 

was phased out of production, except for feedstock use, effective January 1, 2000. [FN11: 42 U.S.C. § 

7671c(a). There would be no drinking water or other exposure resulting from manufacture for feedstock 

use, which is defined as "the manufacture of a substance that is used and entirely consumed (except for 

trace quantities) in the manufacture of other chemicals." CAA § 601(11)(A), 42 U.S.C. § 7671(11)(A).] 

The phaseout of carbon tetrachloride means there will not be future drinking water exposure. 

These occurrence data demonstrate that a substantial population is not exposed to VDC, methylene 

chloride, or carbon tetrachloride for purposes of EDSP screening.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Robert Simon

Commenter Organization: American Chemistry Council
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Comment Response Document

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EPA Document ID: EPA-HQ-OPPT-2009-0477-0048

Comment Part: 2

EPA Comment Code: 2020

Comment: The unique history of PFOA at EPA distinguishes this chemical from the other 133 

chemicals listed in the Draft ESP List 2. The Agency has been working with the industry and other 

stakeholders for over a decade, through a series of information collection, risk assessment and risk 

management actions to reduce exposure to PFOA. Several of these actions that are likely to produce 

results within the next year are directly relevant to the objectives of the EDSP. Accordingly, we 

recommend that PFOA be ranked as a low priority for near-term action under the EDSP. The basis for 

this conclusion is outlined in the remainder of these comments:

1. Phase out of PFOA: Domestic production and use of PFOA have been steadily declining since 2000. 

In 2006, industry and EPA collaborated to establish the 2010/2015 PFOA Stewardship Program as an 

effort to make this phase-out more systematic and transparent. Under this program, the eight major 

fluoropolymer and fluorotelomer manufacturing companies have committed to reduce manufacturing 

emissions and product content of PFOA, precursor chemicals and related higher homologue chemicals. 

Goals of the program are:

* 95% global reduction in facility emissions and product content by 2010; and

* Work toward elimination by 2015.

EPA has publicly recognized the accomplishments of the PFOA Stewardship Program, stating that the 

participating companies are currently “on target” to meet the 2010 goals.[FN2: EPA, Office of Pollution 

Prevention Accomplishments Report January 2007-January 2009, at 20, see 

http://www.epa.gov/oppt/ar/oppt_ar_2009.pdf.]

2. EPA Chemical Action Plan: On December 30, 2009 EPA issued, as part of its new Toxic Substances 

Control Act (TSCA) chemicals management program, its Chemical Action Plan (CAP) for Long-Chain 

Perfluorinated Chemicals. This plan anticipates further regulatory action under Section 6 of TSCA that 

will “expand the reach” of the current PFOA Stewardship Program to address additional sources of 

PFOA. It is anticipated that the CAP for the Long-Chain Perfluorinated Chemicals will be consistent 

with the ambitious goals of the Stewardship Program but will transform the voluntary aspect of that 

program into specific regulatory obligations applicable to all relevant parties. It is expected that these 

steps will further reduce public exposure to PFOA.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Michael White

Commenter Organization: Chemical Producers and Distributors Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0049

Comment Part: 9

EPA Comment Code: 2020
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 234

Comment: EDSP Test Order Authority Applies to Currently Manufacturers and Importers 

Section 1457 of the SDWA authorizes EPA to include in the EDSP “any other substance that may be 

found in sources of drinking water” provided EPA determines a “substantial population may be exposed 

to such substance.” However, section §408(p)(5) of the FFDCA dealing with test orders states that: 

“The Administrator shall issue an order to a registrant of a substance for which testing is required under 

this subsection, or to a person who manufactures or imports a substance for which testing is required 

under this subsection, to conduct testing in accordance with the screening program . . . .”

CPDA believes this statutory use of the present tense in section 408(p)(5) precludes EPA from issuing 

EDSP test orders for SDWA chemicals that are no longer manufactured or imported, but which may be 

found in sources of drinking water. The Agency has provided no evidence of the practical utility of 

collecting the information on these chemicals. Thus, EPA should neither list nor issue test orders for 

chemicals that are not currently manufactured or imported.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America and Endocrine Policy Forum

EPA Document ID: EPA-HQ-OPPT-2009-0477-0050

Comment Part: 8

EPA Comment Code: 2020

Comment: Inclusion of legacy chemicals in List 2:

Like EPA, member companies and organizations of CLA and EPF share the common goal of protecting 

the environment. Given the importance of this goal, we question the Agency's inclusion of legacy 

chemicals in List 2. In our opinion the inclusion of legacy chemicals does not appear to be aligned with 

safeguarding the public. The EDSP is a resource and time-intensive program. Priority should be given to 

those chemicals in current use with the potential for substantial or potentially increasing environmental 

exposure. As the Agency is well aware there are several chemicals on the draft List 2 that are no longer 

in commercial use (either in general or for pesticide use). We would suggest that the Agency does not 

spend its limited resources on legacy chemicals. The Agency has in-house in vitro rapid screening 

programs, such as those used for the oil dispersants, that are better suited to activities with legacy 

chemical concerns.[FN12: 

http://www.epa.gov/ncct/download_files/factsheets/Technical%20Fact%20Sheet%20EST%20paper%20

In%20Vitro%20Tests%208%20Oil%20Dispersants%20 7-6-2010.pdf]

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 

Commenter Name: Frank Sanders

Commenter Organization: Bayer CropScience LP
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 235

EPA Document ID: EPA-HQ-OPPT-2009-0477-0066

Comment Part: 3

EPA Comment Code: 2020

Comment: Inclusion of legacy chemicals in List 2:

We question the Agency’s inclusion of legacy chemicals in List 2. In our opinion the inclusion of legacy 

chemicals does not appear to be aligned with safeguarding the public. The EDSP is not a rapid screening 

program, and because of this priority should be given to those chemicals in current use with the potential 

for substantial or potentially increasing environmental exposure. As the Agency is well aware there are 

several chemicals on the list that are no longer in commercial use (either in general or for pesticide use). 

Given that these chemicals are no longer in commerce, the environmental exposure of these chemicals 

will continue to decrease over time. We would suggest that the Agency does not spend its limited 

resources, nor waste animals, on chemicals for which potential environmental exposure is decreasing. 

The Agency has in-house in vitro rapid screening programs, such as those used for the oil dispersants, 

that are better suited to activities associated with legacy chemical concerns.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 2

EPA Comment Code: 2020

Comment: Velsicol believes, that hexachlorocyclopentadiene, endrin, heptachlor and chlordane are not 

found in drinking water to which a substantial population arc exposed and, therefore, should not have 

been included on the Draft EDSP List 2. Further, Velsicol believes endrin, heptachlor and chlordane 

should not be listed because they are no longer produced or used. EDSP testing for those substances 

would require EPA to order former manufacturers to conduct testing, which exceeds EPA's authority 

under the EDSP provisions of the FFDCA and, in any event, is bad policy. Velsicol, therefore, believes 

EPA's listing of hexachlorocyclopentadiene, endrin, heptachlor and chlordane was contrary to law and 

science. EPA should not include those substances on its final EDSP list 2.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 5

EPA Comment Code: 2020
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 236

Comment: Velsicol also believes endrin, heptachlor and chlordane should not be listed because they are 

no longer produced and used. EDSP testing for those substances would require EPA to order former 

manufacturers to conduct testing, which exceeds EPA’s authority under the EDSP provisions of the 

FFDCA and, in any event, is bad policy.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 10

EPA Comment Code: 2020

Comment: IV. EPA Should Not Include on the EDSP List 2 Substances that are No Longer 

Manufactured in the United States

EPA includes in its Draft EDSP List 2 substances that are no longer manufactured in the United States. 

Examples of those substances include endrin, heptachlor and chlordane, which are discussed in more 

detail below. EDSP testing of those substances would have to be conducted by former manufacturers of 

those substances. Velsicol believes that ordering testing by former manufacturers exceed Agency 

authority and, in any event, is bad policy. Because EPA may not and should not order former 

manufacturers to conduct EDSP testing, it should not list chemicals for which there are no current 

manufacturers.

EPA slates that it will rely on the authority granted the Agency by FFDCA section 408(p)(5)(A) to issue 

test orders requiring screening of substances identified in Phase 2 of the EDSP. The Act states:

"The Administrator shall issue an order to a registrant of a substance for which testing is required under 

this subsection, or to a person who manufactures or imports a substance for which testing is required 

under this subsection, to conduct testing in accordance with the screening program...." 

FFDCA §408(p)(5)(a) (emphasis added). By its terms, FFDCA §408(p)(5)(a) refers to current 

registrants, manufacturers and importers ("manufacturers” for purposes of this comment). The Act uses 

the present tense when referring to potential order recipients, and does not explicitly or implicitly grant 

EPA authority to issue testing orders to those who are no longer manufacturers of a chemical. 

EPA recognized the limit of its authority to current manufacturers when it issued testing orders for the 

first phase of its EDSP. At that time, it issued orders to current manufacturers of pesticide chemicals. 

Those who could demonstrate they no longer manufactured a chemical were exempt from the Phase 1 

orders. Further, those who agreed to discontinue sale of the chemical into the pesticide market were also 

exempt from the Phase 1 orders. In sum, EPA limited its order authority to current, continuing 

manufacturers of Phase 1 pesticide chemicals. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 237

In its Draft Phase 2 Policies and Procedures, EPA generally continues to limit its order authority to 

current manufacturers of substances on the Phase 2 list. [FN4: EPA, Endocrine Disruptor Screening 

Program: Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals, 75 Fed. Reg. 

70558, Nov. 17, 2010 ("Draft Phase 2 Policies and Procedures").] This is consistent with its policies and 

procedures issued for Phase 1 screening. [FN5: EPA. Endocrine Disruptor Screening Program; Policies 

and Procedures for Initial Screening: Notice. 72 Fed. Reg. 17560, April 15, 2009 ("Phase 1 Policies and 

Procedures").] In its Draft Phase 2 Policies and Procedures, EPA acknowledges "the Agency generally 

intends FFDCA section 408(p) as giving the Agency authority to issue orders to current registrants, 

manufacturers, and importers of a chemical." Draft Phase 2 Policies and Procedures at 70567, col. 2 

(emphasis added). Specifically, it proposes to exempt from Phase 2 screening those manufacturers who 

do not currently manufacture the chemical identified for testing (Test Order response option 4). See, 

Draft Phase 2 Policies and Procedures at 70564. Velsicol agrees with this approach for a number of legal 

and equitable reasons: 

• First, EPA's proposed approach is consistent with the operative provisions of the FFDCA that limit the 

Agency's authority to issue test orders to current manufacturers and importers. This provides a strong 

legal basis for limiting testing to current manufacturers.

• Second, as EPA concluded, only manufacturers who continue to manufacture a chemical will receive 

economic benefit from the sale of the chemical with which to defray the cost of testing. This provides a 

very strong equitable basis for limiting testing to current manufacturers.

• Third, EPA's proposed approach is consistent with EPA's past implementation of its EDSP. Only 

current manufacturers were subject to the first phase of the EDSP. Again, from an equitable perspective, 

there is no bas is for EPA to create different duties and burdens for different phases of the EDSP.

• Fourth, the proposed approach will make EDSP implementation easier and more equitable. For 

example, if EPA extended its authority beyond current manufacturers, it would have to find a legal and 

equitable way to identify and issue testing orders to all past manufacturers and importers (some of whom 

may not have manufactured or imported a chemical for decades). Where there exist current 

manufacturers, EPA would have to find a way to require cost sharing among current and past 

manufacturers (again, who may not have manufactured a substance for decades). Where there is no 

current manufacturer (as in the case of a highly persistent substance that is no longer manufactured), 

EPA would have to find an equitable way to identify and provide for cost sharing among former 

manufacturers who may not have manufactured the substance for decades. If EPA extends its EDSP 

beyond current manufacturers, the Agency should explain the legal basis for that decision, how it will 

identify past manufacturers and how it will provide for cost sharing. EPA should publish those policies 

and procedures and provide an opportunity for public comment. 

• Finally, extending its order authority to past manufacturers makes meaningless EPA's currently 

proposed option to exempt manufacturers who agree to discontinue manufacturing of the chemical. 

Little would be gained by a current manufacturer who agrees to cease manufacturing in order to be 

exempted from a test order if EPA could later require EDSP screening of that former manufacturer.

For all the above reasons, Velsicol believes EPA should limit EDSP testing for EDSP List 2 substances 

to current manufacturers. EPA should not, therefore, require EDSP testing of substances that are no 

longer manufactured. There would be no basis, then, to list substances on the EDSP List 2 that will not 

be tested within the EDSP. Rather than attempting to list those substances, EPA should direct its 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 238

resources to determining whether substances that might be tested are found in sources of drinking water 

to which a substantial population are exposed.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 15

EPA Comment Code: 2020

Comment: B. EPA Should Not Include Chlordane, Endrin, or Heptachlor on the EDSP List 2 Because 

They are No Longer Manufactured in the United States 

Chlordane, Endrin and Heptachlor are no longer manufactured in the United States. The manufacture of 

Heptachlor, Endrin and Chlordane ceased in 1989, 1980 and 1996, respectively. EDSP testing of those 

substances, therefore, would have to be conducted by a former manufacturer of those substances. As 

discussed in Comment IV above, Velsicol believes that ordering testing by former manufacturers exceed 

Agency authority and, in any event, is bad policy. Because EPA may not and should not order former 

manufacturers to conduct EDSP testing, it should not list Chlordane, Endrin and Heptachlor for EDSP 

testing. 

As discussed in Comment IV above, PFDCA section 408(p)(5)(A), the authority upon which EPA relies 

to issue EDSP testing orders does not explicitly or implicitly grant EPA authority to issue testing orders 

to those who are no longer manufacturers of a chemical. EPA recognized this limit to its authority when 

it issued testing orders for the first phase of its EDSP. EPA limited its order authority to current, 

continuing manufacturers of Phase 1 pesticide chemicals. In its Draft Phase 2 Policies and Procedures, 

EPA generally continues to limit its order authority to current manufacturers of substances on the Phase 

2 List. [FN21: EPA, Endocrine Disruptor Screening Program; Draft Policies and Procedures for 

Screening Safe Drinking Water Act Chemicals, 75 Fed. Reg. 70558, Nov. 17, 2010 ("Draft Phase 2 

Policies and Procedures”).] This is consistent with its policies and procedures issued for Phase 1 

screening.[FN22: EPA Endocrine Disruptor Screening Program; Policies and Procedures for Initial 

Screening: Notice. 72 Fed. Reg. 17560, April 15, 2009 ("Phase I Policies and Procedures").] As 

discussed above, Velsicol believes EPA should limit EDSP testing to current manufactures for a number 

of legal and equitable reasons:

• It is consistent with the operative provisions of the FFDCA that limit the Agency's authority to issue 

test orders to current manufacturers and importers. This provides a strong legal basis for limiting testing 

to current manufacturers. 

• Only manufacturers who continue to manufacture a chemical will receive economic benefit from the 

sale of the chemical with which to defray the cost of testing. This provides a very strong equitable basis 

for limiting testing to current manufacturers. 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

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• It is consistent with EPA's past implementation of its EDSP. There is no basis for EPA to create 

different duties and burdens for different phases of the EDSP. 

• It will make EDSP implementation easier and more equitable.

• Extending its order authority to past manufacturers makes meaningless EPA's currently proposed 

option to exempt manufacturers who agree to discontinue manufacturing of the chemical.

For all the above reasons and the reasons discussed in Comment IV, above, Velsicol believes EPA 

should limit EDSP testing for EDSP List 2 substances to current manufacturers. EPA should not, 

therefore, require EDSP testing of Chlordane, Endrin and Heptachlor. There would be no basis, then, to 

place those substances on the EDSP List 2.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 

Commenter Name: Terry F. Quill

Commenter Organization: Quill Law Group, LLC on behalf of Velsicol Chemical, LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0073

Comment Part: 2

EPA Comment Code: 2020

Comment: Additional Supplemental Information

In response to a recent discussion with EPA, Velsicol would like to reiterate that EDSP testing of 

chlordane, heptachlor and endrin, pesticide active ingredients that have not been manufactured for a 

number of years, would constitute a research program because EPA will not have a means to regulate 

these substances. Therefore, Velsicol believes, EPA should not list those substances on its EDSP List 2.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 

Commenter Name: Terry F. Quill

Commenter Organization: Quill Law Group, LLC on behalf of Velsicol Chemical, LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0073

Comment Part: 4

EPA Comment Code: 2020

Comment: In addition, EPA asked whether chlordane, heptachlor or endrin were manufactured for nonpesticide uses. Velsicol is certain that endrin, heptachlor and chlordane were manufactured for pesticide 

uses only, their use was limited to pesticide applications and there were no industrial chemical 

applications of the molecules. Velsicol believes that it was the sole manufacturer of the active 

ingredients of chlordane and heptachlor, and that the active ingredient of endrin was produced by only 
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Velsicol and, for a brief time, Shell Chemical in Denver. (While at one time Velsicol had heard from 

USEPA that chlordane was manufactured in China ten years ago, upon investigation that claim was 

found incorrect.) Therefore, Velsicol was the sole manufacturer of chlordane, heptachlor and endrin 

(with the exception of the limited Shell manufacturing) and it manufactured chlordane, heptachlor and 

endrin for pesticide uses only.

Finally, in response to EPA's inquiry, Velsicol would like to reiterate that chlordane, heptachlor and 

endrin are no longer manufactured or exported. Chlordane, heptachlor and endrin are listed on Annex A 

of the Stockholm Convention with no specific exemptions. Therefore, it would be a violation for any of 

the 172 Parties to the convention to manufacture or use these substances.

Velsicol appreciates this opportunity to provide the Agency supplemental information. Please do not 

hesitate to call me at 301-538-5048 if you have questions or require additional information.

Sincerely,

Terry F. Quill

Enc. (one CD)

Attachments 

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.2]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.3]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.4]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.5]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.6]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.7]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.8]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.9]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.10]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.11]

[See PDF Docket ID EPA-HQ-OPPT-2009-0477-0073.12]

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 
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EPA Comment Code: 2030 Contaminants Unlikely to Persist in Drinking Water

General Response: EPA received several comments requesting that chemicals be excluded from the 

second EDSP list based on information that the chemical was not persistent in the environment and 

therefore was unlikely to occur in sources of drinking water. EPA disagrees with these comments and 

after evaluation believes that most of the SDWA chemicals mentioned under this comment code should 

remain on the second EDSP list. A few of the contaminants mentioned in this section (e.g., benzyl 

choride, cumene hydroperoxide, oxirane, methyl (propylene oxide)) have been removed for other 

reasons. For additional information, please see general response to comment under EPA Code: 2010

Contaminants Identified by Commenters as Being or Potentially Incompatible with Test Assays.

EPA has identified and reviewed production and/or release data for these chemicals; EPA believes that 

these data are reliable for determining that these chemicals “may be found in sources of drinking water” 

to which a “substantial population may be exposed.” For more information, please see general response 

to comment under EPA Code: 1060 SDWA 1457.

In developing the CCL 3 process, the agency sought input from the National Academy of Sciences’ 

National Research Council (NRC), the National Drinking Water Advisory Council (NDWAC), and the 

Science Advisory Board on how to improve the CCL process. Each of these panels recommends that 

EPA should identify and retrieve data from sources that have information about occurrence of 

contaminants in drinking water or source water including sources that have a link (pathway) to drinking 

water. The Toxics Release Inventory (TRI) database, which includes information on releases to water, 

land and air, was specifically included as a data source that could be reviewed as one of the “sources that 

have a link (pathway) to drinking water.”

EPA believes that it is appropriate to use TRI data and production data to evaluate the potential of a 

contaminant to be found in sources of drinking water. EPA also recognizes that the persistence of some 

chemicals in ground water will likely differ from that of the same chemical in surface water. EPA is 

mindful that the rate and volume of chemical releases can be as much a factor as persistence in 

determining a chemical's likelihood of being found in sources of drinking water. For example, 

ubiquitous chemicals in such dispersive or down-the-drain uses as solvents and detergents are constantly 

being released into the environment. These chemicals can be present in water and result in potential 

exposure, even though the chemicals themselves may degrade with relative rapidity. 

Individual Comments

Commenter Name: Marcy Banton

Commenter Organization: LyondellBasell Industries

EPA Document ID: EPA-HQ-OPPT-2009-0477-0011

Comment Part: 2

EPA Comment Code: 2030

Comment: 2. Propylene oxide is not expected to be found or persist in water.

As noted above, propylene oxide is readily biodegradable in aquatic environments (MITI, 1988); hence 

it is not expected to be persistent in the environment. Furthermore, propylene oxide spontaneously 
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hydrolyses to propylene glycol in contact with water; hence any propylene oxide that may enter water is 

quickly broken down to non-toxic propylene glycol.

The proposed second list of chemicals are purportedly to be for examination of chemicals found in 

drinking water; however, there is insufficient evidence that propylene oxide meets the Safe Drinking 

Water Amendments requirements that this substance “may be found in sources of drinking water” and 

“that a substantial population may be exposed”. There is no Maximum Contaminant Level (MCL) or 

secondary drinking water standard for propylene oxide nor has this substance been included to the 

contaminant candidate list (CCL). Propylene oxide is therefore not subject to any proposed or 

promulgated national primary drinking water regulations. In addition, we are not aware of any reports of 

detectable concentrations of propylene oxide in sources of drinking water. Therefore, propylene oxide 

clearly does not meet the criteria for inclusion in the second list of chemicals for endocrine disruption 

screening.

Response: Please see general responses to comment under EPA Comment Codes: 2030 Contaminants 

Unlikely to Persist in Drinking Water and 1060 SDWA 1457.

Commenter Name: Terry Medley

Commenter Organization: E.I. du Pont de Nemours and Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0016

Comment Part: 1

EPA Comment Code: 2030

Comment: January 13, 2011

TO: Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency (EPA)

1200 Pennsylvania Ave., NW

Washington DC 20460-0001

RE: Comments on "Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 

Screening," Docket EPA-HQ-OPPT-2009-0477

To Whom It May Concern:

E.I. du Pont de Nemours and Company (DuPont) respectfully submits to the Environmental Protection 

Agency (EPA) comments and information in response to a Federal Register Notice issued on November 

17, 2010 "Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening" (75 

Fed. Reg. 70248) ("Draft EDSP List 2").

DuPont has a 208-year legacy of core values, rooted strongly in safety, health and environmental 

stewardship. DuPont is a science company with a history of innovation. This innovation includes 

experience and expertise in putting science to work to design in product attributes that help protect or 

enhance human health, safety and the environment. DuPont supports the objectives of the Endocrine 

Disruptor Screening Program (EDSP) in its continued screening of chemicals for their potential effects 

on the endocrine systems of humans, fish and wildlife.
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The subject of our comments is the chemical HCFC-22 (CAS #75-45-6; EINECS # 200-871-9; IUPAC 

name: chlorodifluoromethane), which is included on the Draft EDSP List 2 under the category of 

“Drinking water chemical based on CCL 3 List.” DuPont believes that HCFC-22 should not be included 

in the Agency's final EDSP Second List of Chemicals for Tier 1 Screening based on the following:

1. While the moderate water solubility (2.93 g/1 at 25 C) of HCFC-22 presents a theoretical possibility 

of exposure via drinking water, at ambient temperatures where exposure would be expected, HCFC-22 

would be a gas. Its low boiling point (-40.8 C), high Henry's Law constant (3,025 Pa-m3/mol. at 25 C), 

and high vapor pressure (1,045 KPa at 25 C) indicate that it will rapidly partition into the atmosphere, 

even if the primary vehicle for release was an aqueous solution. Therefore, there would be a low 

potential for exposure via drinking water.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 1

EPA Comment Code: 2030

Comment: Dow AgroSciences LLC is providing specific comments regarding inclusion of oxyfluorfen 

on "Draft Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening, 75 

Fed. Reg. 70248; 11/17/2010.

308/2E

January 18, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

U.S. Environmental Protection Agency

One Potomac Yard

2777 S. Crystal Drive

Arlington, VA 22202

Docket ID number EP A-HQ-OPPT-2009-0477

Endocrine Disrupter Screening Program (EDSP)

Dow AgroSciences, LLC (DAS) appreciates the opportunity to submit comments on the US

Environmental Protection Agency's (EPA or the Agency) “Endocrine Disrupter Screening Program:

Second List of Chemicals for Tier I Screening" (List 2).[FN1: "Endocrine Disruptor Screening Program; 

Second List of Chemicals for Tier 1 Screening." 75 Federal Register 70248 (November 17, 2010).] The 

compounds which comprise List 2 expand the EDSP in an effort by the Agency to include more active 

ingredients and to add priority drinking water chemicals as authorized by the Safe Drinking Water Act 

(SDWA) section 1457. Among the compounds on List 2 is oxyfluorfen, a selective pre- and postemergence herbicidal active ingredient.
EPA-OGWDW Final EDSP List 2 February 2013

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Pursuant to EPA's request for comments on List 2, DAS is providing specific remarks which underscore 

oxyfluorfen's low potential for dietary exposure through drinking water and minimal risk as an 

endocrine disrupter. In addition, DAS offers observations regarding the inclusion of oxyfluorfen on List 

2 which emphasize the following concerns: 1) absence of a full evaluation by the Agency of data sets 

submitted for List 1[FN2: "Final List of Initial Pesticide Active Ingredients and Pesticide Inert 

Ingredients to be Screened Under the Federal Food, Drug, and Cosmetic Act." 74 Federal Register 

17579 (April 15, 2009).] 

; 2) the increasing burden placed on laboratory testing capacity from test order issuance for List

I and now List 2; and 3) issuing test orders for this active ingredient ahead of its docket opening for 

Registration Review.

Probability of US population exposure to oxyfluorfen via drinking water is extremely low.The SDWA 

specifies that the Candidate Contaminant List (CCL) must include contaminants that are not subject to 

any proposed or promulgated National Primary Drinking Water Regulations, are known or anticipated to 

occur in public water systems, and may require regulation under the SDWA.[FN3: "Drinking Water 

Contaminant Candidate List 3- Draft." 73 Federal Register 9628 (February 21, 2008).]With a stated 

scope that includes anticipated presence in public water systems, DAS does not believe that CCL 3 is an 

appropriate selection for prioritization of a list 2 for the EDSP program which clearly specifies that the 

administrator needs to determine that a “... substantial population may be exposed to such a substance.” 

DAS believes that chemicals listed on CCL 3 do not a priori meet the SDWA requirement for testing 

under EDSP and therefore, List 2 is not a definitive, scientifically rigorous list of chemicals with a high 

potential for human exposure.

Environmental Fate The environmental fate profile of oxyfluorfen, as documented by the Agency in its 

Reregistration Eligibility Decision (RED)[FN4: US EPA “Reregistration Eligibility Decision (RED) 

Oxyfluorfen” (October 2002). US EPA Office of Prevention. Pesticides, and Toxic Substances; EPA 

738-R-02-014.] , is well understood and limits its exposure to sources of drinking water. Low solubility 

in water, low volatility, and strong adsorption to soil minimize the risk of oxyfluorfen moving from the 

soil surface to ground or surface water. Any oxyfluorfen that reaches surface water will be dissipated 

rapidly via a combination of microbial degradation, adsorption to sediment, and photodegradation.

Surface Water

Source water monitoring information is maintained in the Storage and Retrieval (STORET) Data 

Warehouse[FN5: http://www.epa.gov/storet/] although its reporting is voluntary for the States. 

Extracting information from STORET yielded at total of 80 surface water sites in 3 states (California, 

Kentucky and Tennessee) that were monitored for oxyfluorfen from 2003 to 2007. Within this 

timeframe, 331 samples were analyzed for oxyfluorfen, and no quantifiable residues were found while 4 

samples were reported as “present at less than quantification levels.” 

Additional directed surface water monitoring has also been performed by the US Geological Survey in 

its National Water Quality Assessment (NAWQA) program.[FN6: http://water.usgs.gov/nawqa/] This 

statistically-designed sampling program analyzed for oxyfluorfen in 191 surface water sites with 

detections found at 9 sites over the 2001-2010 period. The maximum detected concentration was 0.0875 

ug/L which is well below the level of concern for this molecule (HBSL 20 ug/L)[FN7: 

http//infotrek.er.usgs.gov/apex/f?p=HBSL:HOME:0]

Ground Water
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Furthermore, monitoring for oxyfluorfen has also been carried out in groundwater, most recently as part 

of NAWQA protocols. In these assessments, 2057 sites were monitored for oxyfluorfen, and no residues 

were detected.

Response: Please see general response to comment under EPA Code: 2030 Contaminants Unlikely to 

Persist in Drinking Water. Also, please see general responses to comment under EPA Codes: 1060 

SDWA 1457, 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do 

Not Meet SDWA 1457 Requirements, and 2100 Pesticide Registration Review Issues. In addition,

please see Response to Comments on the Public Review Draft of the Information Collection Request

(ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of Certain Chemicals 

Under the Endocrine Disruptor Screening Program (EDSP)” (USEPA, 2012d) that is being published 

simultaneously with this comment response document. 

Commenter Name: Marie Martinko

Commenter Organization: Society of the Plastics Industry, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0022

Comment Part: 2

EPA Comment Code: 2030

Comment: I. CHP Does Not Meet the Listing Criteria 

The EPA provides three criteria for this listing: 

- The material appears on the Candidate Contaminate List 3 (CCL 3) of the Safe Drinking Water Act 

(SDWA)[FN2: USEPA. 2009. Contaminant Candidate List 3 Chemicals: Classification of the PCCL to 

the CCL, EPA 815-R-09-008. August, 2009. Last accessed January 13, 2011 at: 

http://water.epa.gov/scitech/drinkingwater/dws/ccl/upload/CCL3_PCCLtoCCL_08-31-09_508.pdf.] and 

that “such substances may occur in sources of drinking water to which a substantial population may be 

exposed.” [75 FR 70250] 

- The material has potential to interact with the estrogen (E), androgen (A) or thyroid (T) hormonal 

systems. 

- The material is not strongly acidic or basic and therefore would not be incompatible with the testing 

assays.

CHP does not meet the first criterion for listing on the Second List of Chemicals for Tier 1 Screening for 

endocrine disruption. 

II. CHP Does Not Present Substantial Exposure via Drinking Water 

Although CHP is listed in the CCL 3, there are no data supporting the presence of the substance in 

drinking water. Further, the chemical properties of the material, the use patterns, and the data reported to 

EPA in the Toxics Release Inventory (TRI) all indicate that the material is not likely to be present in 

sources of drinking water. 

EPA was the sponsor country when CHP was presented in 2008 in the Screening Information Data Set 

(SIDS) program, operated under the Organization for Economic Cooperation and Development 

(OECD), for High Production Volume (HPV) substances. The SIDS Initial Assessment Report (SIAR) 
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indicates that hydroperoxides are oxidizing chemicals and therefore they are not stable in natural water 

containing metals and organic matter. The stability of hydroperoxides in pure water does not represent 

the situation under real-world conditions. In the presence of transition metals or other reducing agents, 

hydroperoxides rapidly decompose, forming alcohols, acids, or water depending on the starting 

peroxide. Thus, in natural waters containing transition metals and organic matter, CHP is not expected to 

be stable.

This degradation takes place at standard temperature and pressure (STP), so no hydroperoxide reaches 

the surface water.[FN3: Review of the Environmental Fate of Selected Chemicals (Final Report), SRI, 

1977 [NTIS PB-267 121].]

The equilibrium criterion (EQC) Level III Fugacity model (U.S. EPA, 2006; 2007) was used to evaluate 

the fate, transport and distribution of CHP between environmental matrices. Level III fugacity modeling, 

using loading rates for air, soil, and water of 1000 kg/h for each medium, shows the following percent 

distribution for CHP: air = 1.1%; soil = 64.9%; water = 33.9%; sediment = 1.47% (U.S. EPA, 2007). 

This indicates that soil, not water, is the primary medium for accumulation, if CHP were released to the 

environment.

The 2009 TRI listing shows that the total release to surface water of all facilities manufacturing or 

processing CHP was zero pounds. Further, over 97% of the CHP disposal was controlled on-site by 

manufacturers or processors, and of this approximately 68% was discharged to Class I injection wells, 

which are designed to prevent contamination of drinking water sources. Releases to landfill (from onsite and off-site sources) were less than 5% of the overall total. 

Finally, the use pattern also limits potential exposures outside of chemical manufacturing or processing 

operations and indicates that the material is not likely to be present in sources of drinking water. CHP is 

used as a modifier with certain resins, a polymerization initiator and as a raw material to make other 

organic peroxides and resins. Releases to the environment and potential industrial worker exposure can 

occur during handling in industrial settings, including manufacture (open vessel), use and spills. 

Consumer exposure is expected to be extremely low because only negligible amounts of hydroperoxide 

are expected to remain after its use in the processing of materials based on application of the Arrhenius 

equation. During manufacturing processes relying on temperature to decompose hydroperoxides, the 

process materials are typically held at a thermal decomposition temperature for many half-lives; 

therefore, only negligible amounts of the hydroperoxides are expected to remain. Manufacturers provide 

customers with data sheets showing half-lives as a function of temperature so they can select appropriate 

process temperatures and holding times. Hydroperoxides are also decomposed with metal salts acting as 

an accelerator for decomposition at lower temperatures. Either temperature or metal salts result in 

decomposition so that residuals are so low as to be negligible. In the case of metal salt acceleration any 

residuals are typically bound in a non-permeable thermoset plastic matrix. It is important to 

manufacturers of articles using hydroperoxides as free radical sources to ensure that the hydroperoxide 

is reacted, until only negligible amounts remain, to avoid post-processing changes in material properties 

and subsequent changes in product quality. 

Thus the chemical and physical properties and the fact that no CHP is reported to be released to surface 

water demonstrate that at most de minimis quantities of CHP could be present in drinking water, and 

demonstrate that the Agency will find it difficult to support the requirement that “such substances may 

occur in sources of drinking water to which a substantial population may be exposed.” [75 FR 70250]
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Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 3

EPA Comment Code: 2030

Comment: In addition, both compounds readily degrade in water from metabolism by organisms and 

from chemical reactions in the environment. In summary, not only does the USGS not monitor the 

nation’s water supplies for methanol or ethanol, such monitoring is technically very complex, and is not 

needed as both alcohols are naturally occurring substances that are readily biodegradable. 

In 1999, the Methanol Institute commissioned a study by Malcolm Pirnie, Inc. entitled “Evaluation of 

the Fate and Transport of Methanol in the Environment” See Attachment 2. This report summarized 

existing information from over 100 published studies, and employed computer modeling to determine 

the fate of methanol in the environment based on several spill/release scenarios. Given methanol’s half –

life of just one to seven days in both surface water and groundwater, the authors concluded that in both 

surface and ground waters, methanol would be rapidly biodegraded under a wide range of possible water 

quality conditions. In addition, in surface water, the infinite solubility of methanol also contributes to its 

rapid dilution to very low concentrations. Following any of the conceptual release scenarios presented, 

methanol is not likely to persist in soil or water due to its rapid biodegradation. 

While the methanol industry places a top priority on product stewardship and the safe handling of 

methanol, there have been isolated incidences of methanol spills, and in each case there was no 

environmental damage to water supplies: 

● In December, 1989, sabotage to three railroad tank cars in Fairbanks, Alaska resulted in the release of 

9,300 gallons of methanol. Samples taken from nearby drinking-water wells and groundwatermonitoring wells were below the analytical detection limit. [FN2: See, “Groundwater Issues Relating to 

Alaskan Methanol Spill,” Journal of Petroleum Technology vol. 44, no. 8 (August 1992), pp. 936-940.]

● On August 31, 2002, 40,000 gallons of methanol were released 100 feet from the Willamette River 

when a transfer pump failed at a Borden Chemical facility in Springfield, Oregon. On September 6th, 

methanol concentrations in the Willamette River immediately adjacent to the spill site were 300 mg/l, 

and soon dropped to below 20 mg/l. While methanol was initially detected in river water samples 

collected from the river bank below the spill area, samples collected downstream from the site 

consistently failed to detect any methanol. [FN3: Additional information regarding this release can be 

found on the Oregon Department of Environmental Quality website, at the following url: 

http://www.deq.state.or.us/lq/ecsi/ecsidetail.asp?seqnbr=827]

● On September 21, 2010, officials at a DuPont plant in Belle, West Virginia discovered that 160,000 

pounds of methanol had leaked from a heat exchanger over a 24-hour period. State officials found that 

the discharge into the Kanawha River did not result in any reports of fish kills or other environmental 

effects. 
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As these incidents demonstrate, even in cases where there have been significant accidental releases of 

methanol to water supplies there have been no risks that a substantial population had been exposed to 

methanol. 

These critical factors do not appear to have been taken into account by EPA in choosing to include 

methanol in the EDSP List, yet they are precisely the sort of factors that the Agency is required to 

consider under SDWA Section 1457.

Response: Please see general responses under EPA Comment Codes: 2040 Naturally Occurring 

contaminants. Also see general response to comment under EPA Comment Code: 2030 Contaminants

Unlikely to Persist in Drinking Water.

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 4

EPA Comment Code: 2030

Comment: * Available research has demonstrated the rapid elimination of MTBE from surface waters 

and the inherent biodegradation of MTBE in groundwater aquifers (EPA, 2005).

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0026

Comment Part: 1

EPA Comment Code: 2030

Comment: See attached file(s) in reference to comments on EDSP for isoxaben. 

January 18, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

U. S. Environmental Protection Agency

One Potomac Yard

2777 S. Crystal Drive

Arlington, VA 22202

Docket ID number EPA-HQ-OPPT-2009-0477 Endocrine Disruptor Screening Program (EDSP)

Dow AgroSciences, LLC (DAS) appreciates the opportunity to submit comments on the US 

Environmental Protection Agency’s (EPA or the Agency) “Endocrine Disruptor Screening Program: 

Second List of Chemicals for Tier 1 Screening” (List 2).[FN1: “Endocrine Disruptor Screening 

Program; Second List of Chemicals for Tier 1 Screening.” 75 Federal Register 70248 (November 17, 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 249

2010).] The compounds which comprise List 2 expand the EDSP in an effort by the Agency to include 

more active ingredients and to add priority drinking water chemicals as authorized by the Safe Drinking 

Water Act (SDWA) section 1457. Among the compounds on List 2 is isoxaben, a selective preemergence herbicidal active ingredient.

Pursuant to EPA’s request for comments on the Draft EDSP List 2, DAS is providing specific remarks 

which underscore isoxaben's low potential for dietary exposure through drinking water and minimal risk 

as an endocrine disruptor. In addition, DAS offers observations regarding the inclusion of isoxaben on 

List 2 which emphasize the following concerns: 1) absence of a full evaluation by the Agency of data 

sets submitted for List 1[FN2: “Final List of Initial Pesticide Active Ingredients and Pesticide Inert 

Ingredients to be Screened Under the Federal Food, Drug, and Cosmetic Act.” 74 Federal Register 

17579 (April15, 2009).]; and 2) the increasing burden placed on laboratory testing capacity from test 

order issuance for List 1 and now List 2.

Probability of US population exposure to isoxaben via drinking water is extremely low. 

The SDWA specifies that the Candidate Contaminant List (CCL) must include contaminants that are not 

subject to any proposed or promulgated National Primary Drinking Water Regulations, are known or 

anticipated to occur in public water systems, and may require regulation under the SDWA.[FN3: 

“Drinking Water Contaminant Candidate List 3 - Draft.” 73 Federal Register 9628 (February 21, 2008).] 

When describing the method for inclusion of chemicals on List 2, an emphasis is placed on potential 

contamination of drinking water. Notably, isoxaben is not identified as a concern based on the SDWA 

and does not appear on CCL 3.

Environmental Fate 

The environmental fate profile of isoxaben, as addressed in the EPA's document entitled “Isoxaben; 

Pesticide Tolerances[FN4: “Isoxaben; Pesticide Tolerances.” 75 Federal Register 69353 (November 12, 

2010).],” is well understood and limits its exposure to sources of drinking water. Low solubility in 

water, low volatility and strong adsorption to soil minimize the risk of isoxaben moving from the soil 

surface to ground or surface water. Any isoxaben that reaches surface water will be dissipated rapidly 

via a combination of microbial degradation, adsorption to sediment and photodegradation.

More importantly, isoxaben is not a target molecule of the Storage and Retrieval (STORET) Data 

Warehouse[FN5: http://www.epa.gov/storet/] or the National Water Quality Assessment 

(NAWQA)[FN6: http://water.usgs.gov/nawqa/] program and has no reported residue detections in 

groundwater or surface water.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code: 

2030 Contaminants Unlikely to Persist in Drinking Water.

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 2

EPA Comment Code: 2030
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Comment: Fundamental physical properties and release patterns indicate that HCFC-22 is unlikely to 

be detectable in sources of drinking water or in drinking water per se. No direct measurements of 

HCFC-22 in surface water, sources of drinking water or drinking water itself are identified in the public 

literature. It is not surprising that such measurements do not exist since there is little likelihood that 

HCFC-22 would be detectable and would certainly not reach significant levels. 

HCFC-22 is a gas under ambient conditions (boiling point -40.8oC, -41.4oF). Its aqueous solubility of 

approximately 2.8g/liter at 25oC (CCL3 information sheet) is often described as “slight” or even 

“moderate”. However, to achieve that level in water, the atmosphere of HCFC-22 would have to be 

maintained at saturation. The Henry’s law constant of 4.07 x 10-2 atm-m3/mol (CCL3 information 

sheet) indicates that HCFC-22 levels will fall substantially as the partial pressure in the atmosphere in 

contact with the aqueous phase is reduced. Since HCFC-22 is present only at very low levels in the 

general atmosphere (low parts per trillion), any water not sealed from ambient air would rapidly lose 

HCFC-22 to equilibrate at extremely low levels. These properties indicate HCFC-22 will not “rain out” 

to yield detectable contamination of surface waters.

The most recent summary of EPA’s Toxic Release Inventory (TRI) information, based on 2009 data, 

shows that release of HCFC-22 to surface water was only 2,798 pounds per year. This small amount is 

released in a single state. As explained above, HCFC-22 will be rapidly lost from surface water to 

equilibrate with very low levels in ambient air to leave vanishingly low concentrations in the surface 

water. This pattern does not meet the criteria for listing.

The use of HCFC-22 in refrigeration does not yield releases to water. The handling of HCFC-22 is 

controlled by regulations for stratospheric ozone protection under Section 608 of the Clean Air Act. 

These regulations mandate that equipment containing Class I and Class II ozone depleting chemicals 

(HCFC-22 is in Class II) can only be worked on by licensed technicians, that the refrigerant is not 

vented at any time, that reclamation is employed, and that leaks in large equipment are repaired. At the 

end of the life of refrigeration equipment, HCFC-22 must be recovered before disposal of the 

equipment. These regulations minimize releases to the atmosphere and prevent HCFC-22 from being 

placed in landfill in scrapped equipment. 

The evidence clearly shows that HCFC-22 will not be found in “sources of drinking water” and 

therefore “substantial populations” will not be exposed to HCFC-22. The criteria for listing are not met.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. 

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 5

EPA Comment Code: 2030

4. HCFC-22 Should not Have Been Included in the Third Candidate Contaminant List (CCL3) 

As described in the Federal Register notice of November 17, 2010 (75FR 70248), the reason that HCFC22 was included in the initial second list for EDSP Tier 1 testing was its place as an unregulated 

contaminant on the CCL3. In reality, HCFC-22 should not have been included in the CCL3. That it went 
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unnoticed is not surprising since none of the properties of HCFC-22 would lead to an expectation of 

finding it in water or the need for listing in the CCL3. 

The information sheet prepared by EPA that supports HCFC-22 being included on the CCL3 contains 

very little evidence and the data listed have been misinterpreted. For example, the “Health Effects Data: 

Non-cancer” includes a single Russian study of 1983 vintage that employed oral dosing for 26-weeks in 

rats. The stated result was a LOAEL of 13.5 mg/kg-day with effects on “brain and coverings” (“other 

degenerative changes”), altered blood cell counts (unspecified), weight loss and decreased weight gain. 

This LOAEL led to the derivation of a Health Reference Level (HRL) of 31.5μg/L. In turn, this evidence 

yielded maximum scores for “Potency” and “Severity.” However, the results of this study are 

completely at odds with multiple well conducted repeat dose inhalation studies that employed extremely 

high dose levels. The published results of an oral study in rats (Longstaff et al. 1984) also do not support 

the findings in the Russian study. Longstaff et al. (1984) administered a dose level of 300 mg/kg-day of 

HCFC-22 in corn oil 5 days per week for 52-weeks and the animals were observed until week 125 when 

full post mortem examinations were performed. HCFC-22 showed no effect on body weight gain or any 

evidence of other adverse effects. The Longstaff et al. (1984) study has been thoroughly reported and 

appears to have been well conducted. The weight of evidence for HCFC-22 (ECETOC, 1989; EU RAR, 

2007) clearly shows that this refrigerant is of extremely low toxicity.

The other component leading to HCFC-22 being included on the CCL3 is the EPA Toxic Release 

Inventory (TRI) data for 2004. Release to surface water is shown as 2,972 lbs/year, released in a single 

state. However, the maximal scores for “Prevalence” and “Magnitude” apparently have been based on 

total releases of more that 7 million pounds per year spread across 35 states. The overwhelming majority 

of the TRI releases at that time would have been to the atmosphere with no route to water 

contamination. 

The inappropriate scores achieved in the assessment process supported an EPA classification of “L? –

L” rating. Assuming this means “possible listing to listing” on the CCL3, it suggests that there was some 

uncertainty even with inappropriately inflated scores. A report of a “Chemical Expert Input Review for 

the Third Contaminant Candidate List” (EPA, 2008) did not recommend any chemicals for removal 

from the list but did recommend “...that the data for the compound HCFC-22 be evaluated to see if 

using data on release to surface water versus total release data would change its ranking and, therefore, 

inclusion on the list. This was recommended because the compound is a gas, and looking at the release 

to surface water data may indicate there is less likelihood it would occur in water”. We assume this 

recommendation was not followed since the removal of HCFC-22 from the CCL3 would certainly have 

resulted. 

We understand that this comment cannot lead directly to removal of HCFC-22 from the CCL3, but an 

inappropriate CCL3 listing should not be used to support inclusion in the EDSP second list of chemicals 

for Tier 1 screening.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA 

Comment Code: 1060 SDWA 1457. 

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 2

EPA Comment Code: 2030

Comment: 1. Hydrazine (CAS# 302-01-2)

a. Hydrazine Does Not Present Substantial Exposure via Drinking Water 

Hydrazine does appear on the CCL3, however, it clearly does not pose a risk to a substantial population 

because it is not a probable contaminant in drinking water and therefore does not pose a risk to human 

health by this route.

For all industrial purposes, hydrazine is manufactured and used entirely as hydrazine hydrate [FN3: 

Anhydrous hydrazine is not used primarily as a rocket propellant and has no industrial uses.] (CAS# 

7803-57-8 H2NNH2 • H20). The primary uses of hydrazine hydrate are as a chemical intermediate 

predicated on the fact that hydrazine hydrate is a very reactive molecule, which is entirely consumed in 

the selected application.

When used as a blowing agent in polyurethane applications, the material reacts and is released as 

nitrogen (N2) and water (H20). Similarly, when used as an anticorrosion additive to boiler water in 

power plants, it reacts with oxygen (02) and is released as nitrogen and water.

The small amount released into reservoirs from power plants is further diluted and has a very short halflife in surface water, again, reacting with dissolved oxygen to form nitrogen and water.

Government reports cite literature indicating "Hydrazine is rapidly removed from polluted waters, with 

less than one-third of the original concentration remaining in dirty river water after two hours. More 

than 90% of the hydrazine added to pond or chlorinated, filtered county water disappeared after 1 day". 

[FN4: Slonin AR, Gisclard JB. 1976. Hydrazine degradation in aquatic systems. Bull Environ Contam 

Toxicol 16 :301-309. taken from U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service Agency for Toxic Substances and Disease Registry September 1997]

In addition, the 2009 TRI listing shows that the total release to surface water of all facilities 

manufacturing or processing hydrazine was only 638 pounds, and that over 85% of the disposal of 

hydrazine is in Class I injection wells, designed to prevent contamination of drinking water sources.

Level III fugacity modeling shows that, when released into air, "a high amount of the substance is 

expected to remain in air."[FN5: Substance Profile for the Challenge Hydrazine. Environment Canada 

Health Canada June 2009 pl4.] Finally, in the extremely unlikely event any hydrazine were present, 

treatment of water for drinking by chlorination or ozonolysis would further degrade hydrazine as 

typified by reaction with sodium hypochlorite.

N2H4, H20 +2 NaOCl -> 2 NaCl +3 H2O +N2 

Thus the chemical and physical properties along with the fact that little hydrazine is released to surface 

water demonstrate that at most de minimis quantities of hydrazine could be present in drinking water. 

The Agency has not demonstrated that a substantial population would be exposed to hydrazine by this 

route.
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Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. 

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 5

EPA Comment Code: 2030

Comment: 2. Triethylamine (TEA) (CAS# 121-44-8)

a. Triethylamine Has Not Been Shown to Present a Substantial Exposure via Drinking Water

Triethylamine is used as a catalyst for polymerization reactions, a solvent and corrosion inhibitor, and an 

intermediate in the production of various chemicals including pesticides. Release of TEA to surface 

water is reported as 2,142 lbs in the Toxic Release Inventory of 2009, which is less than 1% of the total 

TEA releases reported in the TRI. TEA is readily biodegradable in water (92% in 14 days and 96% in 21 

days) [FN7: Monoethylamine ; Diethylamine ; Triethylamine ; Dimethylethylamine ; 

Monoisopropylamine ; Nheptylamine ; Diisopropylamine; N,N-Dimethylisopropylamine Et 

Diethylaminopropylamine: Biodegradabilite Ultime Selon La Norme ISO 7827, 1992 Arkema 

unpublished laboratory data ] and thus is expected to rapidly dissipate from surface water sources and is 

not expected to accumulate in the environment.

To date, there are no monitoring data available for TEA. Until actual monitoring data are available for 

drinking water, it is not established that TEA may occur in sources of drinking water to which a 

substantial population may be exposed.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 7

EPA Comment Code: 2030

Comment: 3. Triphenyltin Hydroxide (TPTH) (CAS# 76-87-9)

a. Triphenyltin Hydroxide Has Not been Shown to Present a Substantial Exposure via Drinking Water

Triphenyltin Hydroxide appears on Candidate Contaminate List 3, however, it has not been shown to 

pose a risk to a substantial population as a probable contaminant in drinking water. The total industrial 

releases reported in the 2009 TRI was 5 pounds and this amount was released to air. No releases to 

surface water were reported.
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TPTH is a restricted use pesticide, a non-systemic foliar fungicide. The EPA assessment for drinking 

water in the RED states "Based on environmental fate data, TPTH will partition to a high degree to soils 

and is not expected to leach to ground water at significant concentrations." [FN10: EPA 738-R-99-010 

Sept 1999]

Tolerances with amendments and changes specified in the RED document meet the FQP A safety 

standard for the general population. The EPA water modeling indicates potential dietary concerns from 

residues in drinking water (surface water source). However, because of soil binding and the buffer zones 

that are required on TPTH labels, the Agency does not believe TPTH will reach water at levels of 

dietary concern. The Agency is requiring additional data to verify its conclusion; based on these studies, 

EPA will determine whether water monitoring is required.

Triphenyltin is degraded in surface water. Outdoor irradiation (tested in June) of dilute aqueous 

solutions of TPTH indicated nearly complete photodegradation. The rate of photodegradation was 

reported to vary with seasonal light intensity (decreasing with decreasing light) and the pH ofthe 

aqueous solution (slightly more rapid at pH 9 than at neutral pH ~ 7.2).[FN11: Degradation 

oftriphenyltin hydroxide in water Charles J. Soderquist, Donald G. Crosby, J. Agric. Food Chern., 1980, 

28 (1), pp 111- 117]

There are no monitoring data available for TPTH. Because of the use of worst case and maximum 

allowable application rates, the estimated concentrations for water from modeling are, by design, 

conservative. Until actual monitoring data are available for drinking water, it is not established that 

TPTH may occur in sources of drinking water to which a substantial population may be exposed.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA 

Comment Code: 1060 SDWA 1457. 

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 10

EPA Comment Code: 2030

Comment: 4. Cumene Hydroperoxide (CHP) (CAS# 80-15-9)

Arkema supports the comments submitted by the Organic Peroxide Producers Safety Division (OPPSD) 

regarding CHP and reiterates the major elements below.

a. Curnene Hydroperoxide Has Not Been Shown to Present a Substantial Exposure via Drinking Water

Although CHP is listed in the EPA CCL3, there are no data supporting the presence of the substance in 

drinking water. Further, the chemical properties of the material, the use patterns, and the data reported to 

EPA in the TRI all indicate that the material is not likely to be present in sources of drinking water.

Hydroperoxides are oxidizing chemicals and therefore are not stable in natural water.[FN13: OECD 

SIDS Initial Assessment Profile, Hydroperoxides Category, SIAM 27, Oct 2008] In the presence of 
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transition metals or other reducing agents, hydroperoxides rapidly decompose. Hydroperoxides will 

react with metals and organic matter from natural waters, forming alcohols, acids, or water depending on 

the starting hydroperoxide. [FN14: Review Of The Environmental Fate Of Selected Chemicals (Final 

Report), SRJ, 1977 [NTIS PB 267- 121]] This degradation takes place at standard temperature and 

pressure (STP), so no hydroperoxide reaches the surface water.

The EQC Level III Fugacity model (U.S. EPA, 2006; 2007) was used to evaluate the fate, transport and 

distribution of CHP between environmental matrices. Level III Fugacity modeling, using loading rates 

for Air, Soil, and Water of 1 000 kglh for each media, shows the following percent distribution: CHP: 

Air = 1.1 %; Soil = 64.9%; Water = 33.9%; Sediment = 1.47% (U.S. EPA, 2007) This indicates that soil, 

not water, is the primary medium for accumulation, if CHP were released to the environment.

The 2009 TRI listing shows that the total release to surface water of all facilities manufacturing or 

processing CHP was 0 pounds. Further, over 97% of the CHP disposal of reported releases was 

controlled on-site by manufacturers or processors, and of this~68% was discharged to Class I injection 

wells, designed to prevent contamination of drinking water sources. Releases to landfill (from on-site

and off-site sources) are < 5% of the overall total.

Finally, the use pattern also limits potential exposures outside of chemical manufacturing or processing 

operations. CHP is used as a modifier with certain resins, a polymerization initiator and as a raw 

material to make other organic peroxides and resins. It is also used as a metal accelerator. Releases to 

the environment and potential industrial worker exposure can occur during handling in industrial 

settings, including manufacture (open vessel), use and spills. Exposure outside of manufacturing and 

processing operations is expected to be extremely low. During manufacturing processes in which 

hydroperoxides are used, the process materials are typically held at a thermal decomposition temperature 

for many half-lives, and therefore only negligible amounts of the hydroperoxides are expected to remain. 

It is important to manufacturers of articles using hydroperoxides to ensure the hydroperoxides are fully 

reacted to avoid post-processing changes in material properties and subsequent changes in product 

quality.

Thus the chemical and physical properties and the fact that no CHP is reported to be released to surface 

water demonstrate that at most de minimis quantities of CHP could be present in drinking water. This is 

insufficient to support a finding that CHP "may occur in sources of drinking water to which a substantial 

population may be exposed. [FN15: Federal Register I Vol. 75, No. 221 I Wednesday, November 17, 

2010 I Notices]

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. 

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 12

EPA Comment Code: 2030

Comment: 5. Chlorodifluoromethane (HCFC-22) (CAS Number 75-45-6)
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Arkema supports the comments submitted by PHD Consulting on behalf of certain 

manufacturers/importers of HCFC 22 and notes the major elements below.

a. HCFC-22 Does Not Present Substantial Exposure via Drinking Water

Fundamental physical properties and release patterns indicate that HCFC-22 is unlikely to be detectable 

in sources of drinking water or drinking water per se. HCFC-22 is a gas under ambient conditions 

(boiling point -40.8°C, -41.4°F). Although the aqueous solubility of approximately 2.8 g/liter at 

25°C[FN16: EPA CCL3 information sheet] is often described as "slight" or even "moderate", to achieve 

that level in water, the atmosphere of HCFC-22 would have to be maintained at saturation. The Henry's 

law constant of 4.07 x 10-2 atm-m3/mol [FN17: ibid] indicates that HCFC-22 levels will fall 

substantially as the partial pressure in the atmosphere in contact with the aqueous phase is reduced. 

Since HCFC-22 is present only at very low levels in the general atmosphere (low parts per trillion), any 

water not sealed from ambient air would rapidly lose HCFC-22 to equilibrate at extremely low levels. 

These properties indicate HCFC-22 will not "rain out" to yield detectable contamination of surface 

waters. 

The most recent summary of EPA's Toxic Release Inventory (TRI) information, based on 2009 data, 

shows that release ofHCFC-22 to surface water was only 2,798 pounds per year. This small amount is 

released in a single state. As explained above, HCFC-22 will be rapidly lost from surface water to 

equilibrate with very low levels in ambient air to leave vanishingly low concentrations in the surface 

water. This pattern does not meet the criteria for listing.

The use of HCFC-22 in refrigeration does not yield releases to water. At the end of the life of 

refrigeration equipment, HCFC-22 must be recovered before disposal of the equipment. These 

regulations minimize releases to the atmosphere and prevent HCFC-22 from being placed in landfill.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 1

EPA Comment Code: 2030

Comment: The American Chemistry Council Diisocyanates Panel herein submits comments relating to 

the inclusion of Toluene diisocyanate (“TDI,” CASRN 26471-62-5) among the substances included in 

EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening. These 

comments are submitted pursuant to EPA’s request for comments on the Draft EDSP List 2, 75 Fed. 

Reg. 70248; 11/17/2010. 

January 18, 2011 

OPPT Document Control Office (DCO) 

EPA East Building, Room 6428 

1201 Constitution Avenue, N.W. 

Washington, DC. 20460 
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Attention: Docket ID Number EPA-HQ-OPPT-2009-0477 

Submitted via Federal eRulemaking Portal: http://www.regulations.gov 

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] 

Dear Sir or Madam, 

The American Chemistry Council (“ACC”) [FN1; The American Chemistry Council (ACC) represents 

the leading companies engaged in the business of chemistry. ACC members apply the science of 

chemistry to make innovative products and services that make people's lives better, healthier and safer. 

ACC is committed to improved environmental, health and safety performance through Responsible 

Care®, common sense advocacy designed to address major public policy issues, and health and 

environmental research and product testing. The business of chemistry is a $674 billion enterprise and a 

key element of the nation's economy. It is one of the nation’s largest exporters, accounting for ten cents 

out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and 

development. Safety and security have always been primary concerns of ACC members, and they have 

intensified their efforts, working closely with government agencies to improve security and to defend 

against any threat to the nation’s critical infrastructure.], in a separate communication, has provided 

overarching comments related to EPA’s Draft EDSP List 2, Draft Policies and Procedures, and the 

EDSP Information Collection Request. The ACC Diisocyanates Panel (“Panel”) [FN2; The Panel 

includes U.S. manufacturers of TDI and/or MDI: BASF Corporation, Bayer Material Science, The Dow 

Chemical Company, and Huntsman Corporation.] herein submits specific comments relating to the 

inclusion of Toluene diisocyanate (“TDI,” CASRN 26471-62-5) among the substances included in 

EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the 

“Draft EDSP List 2”). These comments are submitted pursuant to EPA’s request for comments on the 

Draft EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010, (the “Listing Notice”). 

1. Although TDI occurs on the contaminant list (CCL3) of the Safe Drinking Water Act (SDWA), its 

occurrence as a drinking water contaminant is scientifically implausible by virtue of its 

physical/chemical properties. Therefore, there is no basis for relying on the CCL3 to assert that TDI 

“may be found in sources of drinking water” to which a “substantial population” may be exposed. 

* As is the case for all isocyanate substances, TDI hydrolyzes rapidly upon contact with water. The 

hydrolysis of the hydrophobic TDI substance is a heterogeneous reaction, which results in formation of 

insoluble polyurea solids. [FN3: Yakabe Y., Henderson, K. M., Thompson, W. C., Pemberton, D., Tury, 

B. and Bailey, R. E. (1999). Fate of methylenediphenyl diisocyanate and toluene diisocyanate in the 

aquatic environment. Environ. Sci. Technol. 33(15): 2579-2583.] The pseudo-first-order rate constant 

for hydrolysis of the water-soluble analog, phenyl isocyanate, in water is reported to be 3.39 x 10-2 sec.-

1 at 25°C, which corresponds to a half-life of 20 seconds at pH 7. [FN4: Castro, E. A., Moodie, R. B. 

and Sansom, P. J. (1985). The kinetics of hydrolysis of methyl and phenyl isocyanates, J. Chem. Soc. 

Perkin Trans. II, 737-742.] Therefore, it can be concluded that hydrolysis of TDI occurs promptly upon 

its dissolution in water; and as such, the substance cannot persist as a chemical meeting the criterion that 

a “substantial population” may be exposed.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. 
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Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 3

EPA Comment Code: 2030

Comment: 2. The production and use of TDI occurs in closed systems, where contact with water is 

carefully and strictly avoided. Therefore, its potential for emission to the aquatic environment is very 

low. Because of this, and its known reactivity in water, environmental monitoring programs typically 

have not included TDI as a target contaminant. 

* In contact with water or humid air, TDI forms insoluble polyurea which could cause abrasion 

problems and blockage of valves and pipes. Consequently releases of TDI to effluents are expected to be 

nonexistent at the production site. Since production is performed in closed systems, releases to soil and 

sediment are also expected to be negligible. The produced TDI is transported in road tankers, tank 

containers, rail tank cars or drums either from the production site or is conveyed in pipelines to loading 

or using sites. Road tankers and tanks are pressurized with dry air or nitrogen to eliminate contact of 

TDI with moisture present in ambient air. Cleaning of road tankers and tank containers with water is 

rarely performed. Drums which have contained TDI are decontaminated with polyethylene glycol and 

aqueous solutions containing surfactant. Wastewater resulting from these cleaning and decontamination 

procedures is strictly controlled and is not likely to contain TDI because TDI reacts with water to form 

polyureas which are insoluble and inert compounds. 

* Although TDI is a target analyte of U.S. EPA analytical methods for solid wastes and water (e.g., SW846, Method 8260), these methods may be susceptible to generating false-positive detections of TDI. It 

has been shown that polyurethane and polyurea derivatives of TDI (which may be components or 

contaminants of common laboratory equipment), could be thermally decomposed in the heated injection 

port of various gas chromatographic analyses, and thereby result in formation of trace amounts of TDI 

during such analyses. It is therefore cautioned that any environmental monitoring results showing 

positive detections of TDI in water, sediment, or soil, should be critically evaluated, and perhaps 

validated using methods which avoid thermal decomposition such as cool-on-column injection/gas 

chromatography-mass spectrometry (COC-GC-MS) or liquid chromatography-mass spectrometry (LCMS).

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0036

Comment Part: 6

EPA Comment Code: 2030

Comment: In conclusion, EPA should remove TDI from the Draft EDSP List 2 because TDI cannot 

plausibly occur in drinking water and the lack of a rational basis for determining that a substantial 

population may be exposed to TDI. The Panel appreciates the opportunity to provide comments to the 
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Page 259

Agency on implementation of the EDSP. Please do not hesitate to contact me at (202) 249-6721 or 

Sahar_Osman-Sypher@americanchemistry.com should you require additional information/clarification 

on any of the provided comments. 

Sincerely, 

Sahar Osman-Sypher 

Manager, Diisocyanates Panel

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA 

Comment Code: 1060 SDWA 1457. 

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 7

EPA Comment Code: 2030

Comment: Environmental fate of ethylene glycol

When released to the aquatic compartment ethylene glycol will not tend to partition to air because it has 

a relatively low vapor pressure (8.0 Pa at 20C). Furthermore, ethylene glycol is unlikely to partition

strongly to soils or sediments because it has a log Kow of-1.36 (ASTDR, 1997; Hansch, 1995). Ethylene 

glycol is unlikely to persist in the aquatic compartment because it is very rapidly biodegraded, showing 

90-100 % removal after 10 days in an OECD ready biodegradability study (BASF AG, 1996). Rapid 

biodegradation has also been observed in natural river water samples. In samples of river water dosed 

with ethylene glycol at up to 10 mg/L and incubated at 20 and 8 °C, Evans & David (1974) observed 

that primary biodegradation was complete after 3 and 14 days, respectively. The biodegradation of 

ethylene glycol in groundwater and soils is also comparably fast, with a half-life of 22 hours observed in 

groundwater, 16.5 hours in sandy loam soil and 6 hours in sandy silt (McGahey & Bouwer, 1992).

As previously stated, ethylene glycol will not be significantly removed through either volatilization or 

adsorption and could therefore be transported through the water table. However rapid biodegradation 

should curtail the distance that the substance will ultimately travel. Evidence that this occurs is 

illustrated by a monitoring study conducted on Truro Creek, a tributary of the Assiniboine River, which 

flows through Winnipeg International Airport. In this study, although concentrations of ethylene glycol 

as high as 83 mg/L occurred in the vicinity of the site, this could not be detected in any samples taken 2 

km downstream of the sampler (North/South Consultants Inc., 1998).

Ethylene glycol should not be included on the EPA’s Contaminant Candidate List 3.

The Panel submitted comments (attached) on the listing of ethylene glycol on EPA’s CCL 3 and 

maintains that ethylene glycol should not be included on the CCL 3. As outlined in the comments, 

ethylene glycol is not known to occur in drinking water, and indeed, neither the National Contaminant 

Occurrence Database (NCOD) that EPA is required to consider in its development of the CCL 3, nor any 

other source of finished water or ambient water occurrence data, reflected any detections of ethylene 

glycol in water. Further, in the penultimate stage of the Universe-to-Preliminary CCL (PCCL) screening 
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process, EPA erroneously used the total environmental releases from the TRI for 2004 of 10,076,483 

pounds to define ethylene glycol’s potential to occur in drinking water. Particularly given the absence of 

any water detections of ethylene glycol, EPA should have focused instead on the level of surface water 

releases of 576,990 pounds in 2004. As pointed out in the comments, proper reliance on surface water 

releases -- 576,990 pounds -- together with ethylene glycol’s proper toxicity categorization -- TC 

5 -- means that ethylene glycol, according to Exhibit 11 in the PCCL Screening Document, should have 

remained in the Universe and should not have moved to the PCCL.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. 

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 10

EPA Comment Code: 2030

Comment: The limited presence of acetaldehyde in drinking water is not unexpected, given its physical 

and chemical properties. As noted in EPA’s Chemical Summary for Acetaldehyde (prepared by EPA’s 

Office of Pollution Prevention and Toxics[FN4: http://www.epa.gov/chemfact/s_acetal.txt ] (EPA 749-

F-94-003a)) acetaldehyde, if released into water, will rapidly biodegrade or volatize. For a typical river, 

the half-life of acetaldehyde is 9.3 hours and the estimated half-life for the reaction of acetaldehyde with 

OH produced by UV light is 6.2 hours. EU notes very rapid hydrolysis (hrs) in environmental media. 

Additionally, the Chemical Summary for Acetaldehyde states that, according to laboratory tests, 

acetaldehyde is easily biodegraded by acclimated sludge and sewage with theoretical biological oxygen 

demand (BOD) values ranging from 28% in 24 hours to 100% in 5 hours and it is readily biodegraded 

by anaerobic treatment.

Response: Please see general responses to comment under EPA Comment Codes: 2030 Contaminants 

Unlikely to Persist in Drinking Water and 2040 Naturally Occurring Contaminants.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 1

EPA Comment Code: 2030

Comment: January 13, 2011

EPA Document Control Office (7407M)

Office of Pollution Prevention & Toxics

Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, D.C. 20460

RE: Comments of The Dow Chemical Company on "Endocrine Disruption Screening Program:
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Second List of Chemicals for Tier I Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-

0477; FRL-8848-7], specifically concerning Propylene Oxide.

Dear Sir, Madame,

The Dow Chemical Company (Dow) is a major producer of propylene oxide (PO; CASRN 75-569) 

globally, with significant production facilities operating in the US. Dow has a strong product 

stewardship program in place, which includes evaluation of potential risk from production, handling, 

and use of its products over their lifecycle. As a major producer of PO, Dow has participated in several 

efforts to gather, summarize, evaluate, and supplement available data to support development of risk 

assessments for chemicals such as PO. Thus, Dow has a long history of providing and reviewing data to 

determine the potential hazards and risks of PO.

EPA should remove PO from this rulemaking. Based on the weight-of-evidence, and particularly in 

keeping with Dow's and EPA's principle of reducing unnecessary testing, Dow strongly recommends 

that PO be removed from the list of proposed substances to be tested for Tier 1 screening under the 

Endocrine Disruption Screening Program (EDSP).

This recommendation is based on a variety of facts, including the following:

1) PO is unlikely to occur as a contaminant of water bodies used as drinking water sources in the United 

States. This conclusion is based on geographic locations of the reported surface water emissions, 

according to reporting year 2009 TRI data. Furthermore, because the substance is readily biodegradable 

and hydrolysable, it does not persist in surface water or groundwater environments.

Response: Please see general responses to comment under EPA Comment Codes: 2030 Contaminants 

Unlikely to Persist in Drinking Water and 1060 SDWA 1457.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 4

EPA Comment Code: 2030

Comment: 1) The second list of substances proposed for endocrine screening is presumed to be based 

on potential exposure to these substances as a result of their occurrence as drinking water contaminants. 

The potential for PO to occur as a drinking water contaminant can be indicated from the magnitude and 

spatial distribution of surface water emissions, as reported within the Toxics Release Inventory (TRI) 

program. Data for reporting year 2009 indicate a total of 1,415 lbs. was emitted to surface waters, with 

1,409 lbs. occurring at The Dow Chemical Company, Freeport, TX and 5lbs. occurring at The Dow 

Chemical Company, Midland, MI. The surface water outfall associated with the emissions at Freeport, 

TX occurs on the Brazos River, at a location where effluent is mixed with seawater prior to discharge, 

and also influenced by tidal influx of seawater from the Gulf of Mexico. Therefore, the surface water 

occurring at, or downstream of, this outfall would contain salinity and other water quality attributes 

which prevent its use as drinking water source. Similarly, the outfall at Midland, MI occurs to the 

Tittabawassee River which is not used as a drinking water source. Based on these reported emissions to 
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surface waters from TRI, it can be concluded that a significant human population is not exposed to PO 

as a contaminant in drinking water.

Response: Oxirane, methyl- (propylene oxide) has been removed from the second EDSP list. Please see 

general response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters as 

Being or Potentially Incompatible with Test Assays. Please see general response to comment under EPA 

Comment Code: 2030 Contaminants Unlikely to Persist in Drinking Water.

Commenter Name: Michael Boucher

Commenter Organization: McKenna Long & Aldridge LLP on behalf of Ferro Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0064

Comment Part: 1

EPA Comment Code: 2030

Comment: January 19, 2011

By Hand

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, NW

Washington, D.C. 20004

Attention: Docket ID No. EPA-HQ-OPPT-2009-0477

Re: Docket Identification Number EPA-HQ-OPPT-2009-0477

Comments of Ferro Corporation

Dear Sir or Madam:

On behalf of our client Ferro Corporation, we submit the enclosed comments regarding EPA's 

November 17, 2010 proposal (75 Fed. Reg. 70,248) to require screening of benzyl chloride (CAS 

Registry Number 100-44-7) under the Endocrine Disruptor Screening Program. We welcome any 

questions that EPA has about this submission and look forward to the Agency's response.

Very truly yours,

Michael Boucher

/mb

Enclosure (114 pp.)

DOCKET IDENTIFICATION NUMBER EPA-HO-OPPT-2009-0477

COMMENTS OF FERRO CORPORATION

January 18, 2011
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In the November 17, 2010 Federal Register, the U.S. Environmental Protection Agency ("EPA" or "the 

Agency") has proposed to require screening of benzyl chloride under the Endocrine Disruptor Screening 

Program ("EDSP").[FN1: 75 Fed. Reg. 70,248 (Nov. 17, 2010); see also 75 Fed. Reg. 77,869 (Dec. 14, 

2010) (extension of the initial public comment period from December 17, 2010 to January 18, 2011).] 

The sole basis for EPA's proposal is benzyl chloride's inclusion in the final Contaminant Candidate List 

3 ("CCL 3") compiled by EPA's Office of Water.[FN2: Drinking Water Contaminant Candidate List 3 -

Final, 74 Fed. Reg. 51,850 (Oct. 8, 2009).] In brief, EPA has tried to use benzyl chloride's listing on the 

CCL 3 to satisfy the Safe Drinking Water Act's ("SDWA's") criteria for screening a substance under the 

EDSP.[FN3: 75 Fed. Reg. at 70,251.] Specifically, based solely on benzyl chloride's CCL 3 listing, EPA 

has determined both that benzyl chloride "may be found in sources of drinking water" and "that a 

substantial population may be exposed to" benzyl chloride in drinking water.[FN4: 42 U.S .C . § 300j-17 

(section 1457 of the SDWA).]

Benzyl chloride's CCL 3 listing does not reasonably satisfy the SDWA criteria that EPA must satisfy to 

require screening of benzyl chloride under the EDSP. The administrative record underlying both the 

CCL 3 listing of benzyl chloride and the November 17, 2010 screening proposal for benzyl chloride 

lacks any evidence either that benzyl chloride "may be found in sources of drinking water" or "that a 

substantial population may be exposed to" benzyl chloride in drinking water. To the contrary, the factual 

record underlying the CCL 3 listing of benzyl chloride contains persuasive evidence that benzyl chloride 

is not "found in sources of drinking water."

Furthermore, benzyl chloride is hydrolyzed to benzyl alcohol relatively quickly in water, benzyl alcohol 

is readily biodegradable, and the toxicity of benzyl alcohol is low.[FN5: United Nations Env't 

Programme, Chemicals Branch, "OECD Screening Information Data Set for Benzyl Chloride" (June 

2002), available at http://www.chem.unep.ch/irptc/sids/OECDSIDS/100447.pdf (attached hereto as 

Exhibit 1); see also U.S. Nat'1 Library of Med., Toxicology Data Network, Hazardous Substances Data 

Bank, Environmental Fate Data Summary for Benzyl Chloride, CAS Registry Number 100-44-7, 

available at http://toxnet.nlm .nih.gov/cgi-bin/sis/htmlgen?HSDB (attached hereto as Exhibit 2) .

Also, benzyl chloride is subject to stringent controls at all times, from its original manufacture to its 

ultimate use as an intermediate to manufacture other substances. Accordingly, there is not likely to be 

any benzyl chloride in sources of drinking water or any substantial human population that is exposed to 

benzyl chloride in drinking water. For the foregoing reasons, Ferro Corporation ("Ferro") respectfully 

requests EPA to exclude benzyl chloride from any screening under the EDSP until the Agency can 

reasonably satisfy the SDWA's criteria for such screening.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water and general response to comment under EPA Comment Code: 

1060 SDWA 1457.

Commenter Name: Michael Boucher

Commenter Organization: McKenna Long & Aldridge LLP on behalf of Ferro Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0064

Comment Part: 4

EPA Comment Code: 2030
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Comment: Exhibit 3 attached hereto summarizes the information that EPA used to list benzyl chloride 

on the CCL 3. In Exhibit 3, EPA presented no "occurrence data" for benzyl chloride in either "finished 

water" or "ambient water." Although the IUR reported that between 50 and 100 million pounds of 

benzyl chloride were manufactured or imported in both 1998 and 2002, the TRI reported that a mere 259 

pounds of benzyl chloride were released to surface water in 2004, and this miniscule quantity was 

divided between three States . The TRI also reported that a total of 18,750 pounds of benzyl chloride 

were "released" in 2004, and this comparatively small quantity was divided between ten different States. 

Furthermore, 18,491 of the 18,750 pounds of benzyl chloride "released" in 2004 other than to surface 

water must have been releases to air and/or lawful hazardous waste disposal or treatment, based on the 

specific release data collected by the TRI. In Exhibit 3, however, EPA did not characterize the vast 

majority of the 2004 TRI "releases" that were not releases to surface water. Lastly, and most 

importantly, Exhibit 3 cited Krasner et al. (2006) as "supplemental water data." [FN14: Stuart W. 

Krasner et al., "Occurrence of a New Generation of Disinfection Byproducts," 40 Envtl. Sci. Tech . 7175 

(2006) (attached hereto as Exhibit 4).] In such study, 12 public water treatment plants were tested for 

benzyl chloride, and none was detected.

In addition, EPA acknowledged that many of the substances on the CCL 3 have substantial data gaps 

that the Agency would have to fill before regulating such substances under the SDWA. [FN15: 74 Fed. 

Reg. at 51,851. ] Benzyl chloride is a substance with significant data gaps. Specifically, EPA stated (1) 

that no comprehensive drinking water occurrence data exist for benzyl chloride and (2) that no method 

suitable for a national drinking water occurrence study exists for benzyl chloride. [FN16: 74 Fed. Reg. at 

51,851.]

Furthermore, benzyl chloride is hydrolyzed to benzyl alcohol in water, benzyl alcohol is readily 

biodegradable, and the toxicity of benzyl alcohol is low. [FN17: United Nations Env't Programme, supra 

note 5; see also U.S. Nat'1 Library of Med., supra note 5.] Although the rate of hydrolysis depends on 

both temperature and concentration, the hydrolysis of benzyl chloride to benzyl alcohol is a relatively 

fast reaction. [FN18: See United Nations Env't Programme, supra note 5, at 86 tb1.3, 96.] Accordingly, 

as a technical matter, there is not likely to be any benzyl chloride in sources of drinking water or any 

substantial human population that is exposed to benzyl chloride in drinking water.

Lastly, benzyl chloride is subject to stringent engineering controls and regulatory requirements for 

transportation, storage, handling, and use throughout the supply chain and by the ultimate users. For 

Ferro's part, all primary containment equipment meets industry standards (i.e. American Society of 

Mechanical Engineers, American Petroleum Institute) for closed manufacturing systems. Storage tanks 

have conservation vents and vapor balancing systems to minimize emissions to air. Secondary 

containment drains to an industrial sewer or has containment dikes. Loading areas have vapor balancing 

system to minimize emissions, and the drum-loading process uses a local exhaust system to minimize 

vapors as drums are filled. Operators are qualified under well-established training and qualification 

programs. The foregoing controls make it unlikely that benzyl chloride will be released to a source of 

drinking water at any time.

DISCUSSION

EPA claims that the listing of benzyl chloride on the CCL 3 alone satisfies the EDSP screening criteria 

in section 1457 of the SDWA. Specifically, EPA claims that the inclusion of benzyl chloride on the CCL 

3 originally required a determination that benzyl chloride may be found in sources of drinking water. 

The Agency did not investigate, however, whether such a determination was actually made (it was not) 
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or was reasonably based on evidence in the administrative record (again, it was not). Then, EPA 

summarily concludes without further explanation or any apparent factual basis that benzyl chloride's 

CCL 3 listing also means that a substantial population may be exposed to benzyl chloride in drinking 

water.

Based on the evidence currently in the administrative record, EPA cannot satisfy the SDWA's criteria for

requiring the screening of benzyl chloride under the EDSP. Specifically, the evidence in the 

administrative record does not reasonably support a determination either that benzyl chloride "may be 

found in sources of drinking water" or that "a significant population may be exposed" to benzyl chloride 

in drinking water. Ferro addresses each of the foregoing factual determinations in turn below.

Benzyl chloride is not found, or likely to be found, in sources of drinking water.

The data underlying the CCL 3 listing of benzyl chloride, namely, Exhibits 3 and 4 hereto, do not 

reasonably support a conclusion that benzyl chloride may be found in sources of drinking water. Krasner 

et al. (2006) recently tested 12 carefully selected, "challenged" public water treatment plants, looked for 

benzyl chloride, and found none. EPA funded and collaborated in the study, which was reviewed in 

accordance with the Agency's peer and administrative review policies.[FN19: Krasner et al., supra note 

14, at 7184.] If benzyl chloride were likely to be in any sources of drinking water, the study should have 

detected benzyl chloride in at least one of the 12 public water systems included in the study, but this did 

not happen.

There are no occurrence data for benzyl chloride in either finished water or ambient water. There also 

are no comprehensive drinking water occurrence data for benzyl chloride, and there is no method 

suitable to conduct a national drinking water occurrence study of benzyl chloride.

An insignificant quantity (259 pounds) of benzyl chloride was released to surface water in 2004, and this 

amount was divided between three States. In addition, any individual release of benzyl chloride to 

surface water in 2004 would have hydrolyzed to benzyl alcohol reasonably quickly, and benzyl alcohol 

not only has low toxicity but also is readily biodegradable. Thus, the miniscule releases of benzyl 

chloride to surface water in 2004 would have disappeared quickly and not have existed long enough, or 

in sufficient quantity, to contaminate any typical sources of drinking water.

A total of 18,750 pounds of benzyl chloride were "released" in 2004, but this comparatively small 

quantity was divided between ten different States. In addition, based on the specific release data actually 

collected by the TRI, 18,491 of the 18,750 pounds of "releases" reported for the TRI in 2004 must have 

been releases to air, lawful hazardous waste management activities, or a combination of the two. 

However, EPA did not characterize the 18,491 pounds of "releases" in 2004 that were not releases to 

surface water. Accordingly, there is no way to know from the record created by EPA whether any of the 

18,491 pounds of benzyl chloride "released" in 2004 had a potential to contact any sources of drinking 

water, but we can infer that such contact was highly unlikely.

If some or all of the 18,491 pounds "released" in 2004 actually represented lawful hazardous waste 

management activities, then such quantity would not have been available to contaminate any sources of 

drinking water. On the other hand, if some or all of the 18,941 pounds were actual releases to air in 

2004, then such releases took place to air over ten different States. Even in such a case, however, one 

would have reasonably expected at most limited, sporadic, and widely distributed precipitation of benzyl 

chloride from the atmosphere to surface water in 2004, where any precipitation would have hydrolyzed 
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to benzyl alcohol relatively quickly and not have contaminated any typical sources of drinking water -

assuming, of course, that hydrolyzation to benzyl alcohol had not already taken place in the atmosphere.

Although 50 to 100 million pounds of benzyl chloride were reported for the IUR in 1998 and 2002, such 

manufacture and import volumes do not automatically equate to any expected release to any specific 

environmental medium. Indeed, the "releases" of benzyl chloride reported for the 2004 TRI and 

reflected in Exhibit 3 are insignificant in comparison to the quantity of benzyl chloride reported for the 

IUR in 1998 and 2002. This reflects the stringent controls under which industry manages benzyl 

chloride at all times from its initial manufacture to its later use as an intermediate in the manufacture of 

other substances. Moreover, to the extent that benzyl chloride was imported in 1998 and 2002, any 

environmental releases from manufacturing of the imported material would have taken place outside the 

United States and not have been available to contaminate any sources of drinking water in the United 

States.

No significant population is exposed, or likely to be exposed, to benzyl chloride in drinking water.

EPA baldly asserts that the inclusion of benzyl chloride in the CCL 3 is evidence that a significant 

population may be exposed to benzyl chloride in drinking water. Ferro finds no evidence in the record 

for EPA's assertion. For the reasons explained above, benzyl chloride is not found, or likely to be found, 

in sources of drinking water. Furthermore, EPA has offered no factual evidence of any kind to support 

its claim that a significant population may be exposed to benzyl chloride in drinking water. Accordingly, 

Ferro concludes that EPA has not reasonably demonstrated the likelihood of any such exposure, as 

required by section 1457 of the SDWA.

In conclusion, EPA has not presented any evidence to reasonably support its claims that benzyl chloride 

may be present in sources of drinking water and that a significant population may be exposed to benzyl 

chloride in drinking water. Thus, EPA has so far failed to reasonably satisfy the criteria in section 1457 

of the SDWA for requiring the screening of benzyl chloride under the EDSP. Accordingly, Ferro 

respectfully requests that EPA exclude benzyl chloride from any screening under the EDSP until the 

Agency can reasonably satisfy the SDWA's requirements for such screening.

[See Attachment PDF Docket ID: EPA-HQ-OPPT-2009-0477-0064]

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water and please see general response to comment under EPA Comment 

Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not 

Meet SDWA 1457 Requirements

Commenter Name: Jack Snyder

Commenter Organization: Styrene Information and Research Center (SIRC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0067

Comment Part: 4

EPA Comment Code: 2030

Comment: 4. Justification for mitigating the prescribed ecotoxicity screening assays of styrene for 

endocrine disrupting effects.
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The screening of styrene for endocrine disrupting properties under the EDSP should be reconsidered 

based on a lack of exposure demonstrated by environmental monitoring data as well as known 

environmental fate data. To be specific:

1. Styrene has a strong tendency to volatilize from water and furthermore is rapidly degraded in the 

environment through both biotic and abiotic processes. 

2. Styrene concentrations in the environment are well monitored. They are variable, but generally low. 

Any transient high values are attributed to being in the vicinity of point sources, and evidence of rapid 

removal is demonstrated in cases with multiple sampling.

As a result of the rapid elimination from environmental spheres, supported by monitoring data, it may be 

concluded that sufficient concentrations to cause endocrine disrupting effects are unlikely to be reached. 

In the rare cases that higher concentrations do occur they will not be sustained in the environment and as 

such it is considered unlikely that they would cause significant endocrine related effects in aquatic 

species.

Properties

Styrene, though having many applications, is not commonly detected at high levels in the environment. 

This can be attributed to its environmental fate properties. For example, it has been shown to be rapidly 

biodegraded in the environment. In a standard ready biodegradability study 70.9% styrene was found to 

have been degraded in 28 days (BASF AG, 1988). The substance was also found to be susceptible to 

biodegradation in river water, with > 50% removal being observed in 33 days (Fu, 1992). Adsorption 

(Koc = 352) and volatilisation (HLC = 232 Pa m3 mol) are also important removal processes for this 

compartment (ECB, 2002). Mackay Level I modelling of styrene predicts that 98.6 % of the substance 

will partition to air (BASF SE, 2009). Atmospheric degradation half-lives for styrene have been 

calculated, both for the reaction with hydroxyl radicals (7.4 hours) and with ozone (9.2 hours), which 

combined estimate an overall atmospheric half-life of 4 hours. These data support the rapid removal of 

styrene from aquatic and atmospheric compartments. Therefore it should be expected that in general 

environmental concentrations and hence exposures are low. This hypothesis is confirmed by the 

available monitoring data below.

Occurrence

Surface water concentrations of styrene have been measured in a number of countries. In the UK in 1995 

and 1996, a monitoring operation was conducted choosing sampling sites close to potential point 

sources. This operation found that in most cases styrene was not detected and concluded that it could be 

said with confidence that the majority of values were below 10 μg/L, with many being below 0.1 μg/L. 

However there were some transient high values. The removal of styrene in the environment may be

demonstrated in a study of a river receiving effluent from a WWTP treating water from a plastics 

manufacturer. The river water was sampled upstream of the outlet (7.9 μg/L), at the outlet (0.0465 μg/L) 

and 6.5 km downstream of it (0.0191 μg/L). This is a clear indicator of the rapid rate at which styrene is 

removed from the water compartment. Samples taken from the River Mersey and River Thames were 

below 1 μg/L indicating that styrene, while common, is not a ubiquitous contaminant and unlikely to be 

present at concentrations which would cause endocrine related effects on aquatic populations. Levels of 

styrene in groundwater also have been found to be very low.

Summary
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The environmental fate properties of styrene are well documented, and indicate an overall lack of 

persistence in the environment. The available monitoring data for surface waters confirms this, with 

overall levels being measured as extremely low. There are some transient higher levels in the vicinity of 

point sources, however it has also been demonstrated that these are rapidly reduced in time. Therefore, 

based on exposure considerations, it is our opinion that the overall level of concern warranted for 

styrene as an endocrine disruptor is low, and that screening for these properties under the EDSP should 

not be required.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA 

Comment Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore 

Do Not Meet SDWA 1457 Requirements.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 12

EPA Comment Code: 2030

Comment: B. Hex Is Not Expected to be Found in Sources of Drinking Water to Which a Substantial 

Population is Exposed 

Velsicol believes the chemical and physical properties of Hex support the conclusion that Hex is not 

expected to be found in drinking water to which a substantial population is exposed and, therefore, 

should not be listed on the EDSP List 2. Hex is a highly reactive chemical intermediate used to produce 

a number of chemical products. It has low water solubility and a short half- life, especially in the 

presence of light. For these reasons, Hex is unlikely to be found unbound to particulate matter in surface

water is unlikely to persist in surface water, and unlikely to move readily in ground water. Hex, 

therefore, would not be expected to be found in drinking water to which a substantial population is 

exposed. 

Hex is both rapidly and extensively photodegraded in the environment. The half-life of Hex in sunlight 

is less than 10 minutes.[FN6: Zepp R.G.) Baughman G.L., Schlotzhauer P.F. (1979): Dynamics of 

processes influencing the behaviour of hexachlorocyclopentadiene in the aquatic environment. Paper 

presented at the 178th National Meeting of the American Chemical Society, Washington, 9- 14 

September.] Reported half-life values ranged from less than 2 minutes [FN7: Wolfe N.L., Zepp R.G .. 

Schlotzhauer P., Sink M. (1982): Transformation pathways of hexachlorocyclopentadiene in the aquatic 

environment. Chemosphere 11, 9 1-101.] to 4 minutes in natural sunlight [FN8: Chou S.F., Griffin R.A., 

Chou M.I. (1987): Products of hexnchlorocyclopcntadiene (C-56) in aqueous solution. Environ. 

Toxicology and Chemistry 6, 371-376.] and less than l minute when irradiated with a mercury-vapor 

light source.[FN9: Butz R.G. , Yu C.C., Atallah Y.H. (1982): Photolysis of hexachlorocyclopentadiene 

in

water. Ecotoxicol. Environ. Safety 6, 347-357. ] Researchers have demonstrated the complete loss of 

14C-hex from an aqueous 2 ppm solution irradiated with light of wavelengths greater than 290 nm after 

one-half hour. [FN10: Yu C.C. & Atallah, Y.H, (1977b). Photolysis of hexachlorocyclopentadiene, 

Chicago, Velsicol Chemical Corporation Project No. 482428, Report No.4 Laboratory Report.]
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The photomineralization of hex adsorbed to silica gel has also been demonstrated after 4 days irradiation 

with light of wavelengths of greater than 290 nm. [FN11: Korte ( 1978). Photomineralization of 

hexachlorocyclopentadience and ecotoxological profile analysis of hexachlorocyclopentadiene. 

Unpublished report prepared for Velsicol Chemical Corporation, Chicao, IL] In this case, chloride and 

carbon dioxide were the major photodegradation products. 

Hex also undergoes hydrolysis, although the rate of hydrolysis is much slower than the rate of 

photolysis. The reported average hydrolysis rate constant over a pH range of 3-10 was 1.5 x 10-6 at 

30°C, [FN12: Wolfe ( 1982), ibid.] which corresponds to a half-life of 5.35 days. [FN13: US-EPA 

(1984): Health Assessment Document for HCCP. Final Report No. EPA-600/8- 84- 001F. U.S. 

Environmental Protection Agency, Cincinnati, OH, order No. PB 85-12491 S, National Technical 

Information Service (NTIS), Springfie ld, VA, 1-1- 9-20, A- 1-A-12 (IUCLID).] At pH 7 and 30°C a 

hydrolytic half- life or 3.3 days was found. [FN14: Wolfe ( 1982), ibid.] The addition of natural 

sediments sufficient to adsorb up to 92% of the compound caused the rate constant to vary by less than a 

factor of 2. It was therefore concluded that sorption to sediments would not significantly affect the rate 

of hydrolysis. Biodegradation of Hex also occurs in water under laboratory conditions. In a static 

laboratory culture, 100% of Hex was lost within 7 days from both 5 mg/l and LO mg/1 solutions. [FN15: 

Tabak H.H., Quave S.A., Mashni C.I. et al. (1981): Biodegradability studies with organic priority 

pollutant compounds. J. Water Pollut. Control. Fed. l0, 1503-1518] Volatilization was not reported to 

occur under the test conditions. 

In sum, Hex is rapidly and extensively photodegraded and, to a lesser extent, hydrolyzed and 

biodegraded in aquatic environments. All of these degradation processes would be expected to occur for 

hex in surface waters. For ground water, hydrolyzation would be expected to be the primary degradation 

process for Hex. Velsicol believes that the rapid and extensive photodegradation of Hex as well as the 

biodegradation and hydrolysis of Hex in sources of drinking water make it unlikely to be found in 

sources of drinking water to which a substantial population may be exposed. 

Hex also has a low solubility in water. Its partition coefficient (log Kow) is 3.99 [FN 16: Callahan, 

M.A., W.M. Slimak, N.W. Gabel, et al. Water-Related Environmental Fate of 129 Priority Pollutants. 

Volume II. EPA-440/4-79-029b. Washington, D.C.: US Environmental Protection Agency. December 

19979, p 57-2. ] and it has a water solubility of 2 ppm at 25 degrees C. [FN 17: American Conference of 

Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological 

Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 

1986. 300.] The measured Koc for Hex is 4265. [FN18: Chou, S.F.J., Griffin, R.A. (1983): Report, 

IL/SGS/BGN-104; Order No. PB84-1 16060, National Technical Information Service (NTIS), 

Springfield, VA, .1-54 ] Substances with Koc values greater than 1000 arc tightly bound to soil 

components and are immobile in soils. Hex, therefore, is expected to bind to sediments and particulates 

in surface waters. To the extent Hex in surface water reaches public water systems, it would likely be 

bound to particulate matter and, therefore, filtered out of finished water. Because Hex binds to 

particulates such as soil and clay, it would be expected not to migrate in ground water. It would, 

however, hydrolyze in groundwater. For these reasons, Velsicol believes Hex is unlikely to be found in 

sources of drinking water in any meaningful amounts. Further, Velsicol believes any Hex bound to 

particulates in treated water would be filtered out of the water supply to the extent that significant 

populations would not be exposed.
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Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 16

EPA Comment Code: 2030

Comment: C. Chlordane, Endrin, and Heptachlor are Not Expected to be Found in Sources of Drinking 

Water to Which a Substantial Population is Exposed 

Velsicol believes the chemical and physical properties of Chlordane, Endrin and Heptachlor support the 

conclusion that those substances are not expected to be found in drinking water und that a substantial 

population is not exposed to those substances. It is well known that these substances have low water 

solubility and adsorb to organic matter. While the substances are persistent, they bind tightly to soil and 

sediment. Therefore, Chlordane, Endrin and Heptachlor do not move readily in ground water and are 

mostly bound up in sediments in surface waters. To the extent these substances are in the water column 

in surface waters, they are tightly bound to particulates that are removed in water treatment. Importantly, 

these substances have not been produced or used in the US for some time. Therefore, all environmental 

levels of these substances are expected to decrease. EPA should take these factors into consideration 

when it makes a determination as to whether, at this time, Chlordane, Endrin and Heptachlor are found 

in drinking water and whether a substantial population are exposed. 

EPA's recent review of existing drinking water standards demonstrated Chlordane, Endrin and 

Heptachlor are not found in sources of drinking water to which a substantial population is 

exposcd.[FN23: EPA, National Primary Drinking Water Regulations; Announcement of the Results of 

EPA's Review of Existing Drinking Water Standards and Request for Public Comment and/or 

Information on Related Issues. 75 Fed. Reg. 15500, March, 29, 2010 (the "DWS Review"). The DWS 

Review repo1ts 2009 EPA Occurrence Data reported at: EPA, Office of Water, The Analysis of 

Regulated Contaminant Occurrence Data from Public Water Systems in Support of the Second Six-Year 

Review of National Primary Drinking Water Regulation, October 2009, EPA- 815-B-09-006 

("Occurrence Data Report"). ] For Chlordane, EPA reported in the DWS Review that only one water 

system (0.003% of the reporting systems) repotted a Chlordane concentration exceeding the MCL 

of2ppb when the nondetect levels were set at the MRL (.2ppb) or 1/2 the MRL. The estimate of 

population served by that system was 80, or only 0.00004% of the total population served by reporting 

systems. EPA cot1cludecl,"[t]aking into consideration the low occurrence of this contaminant, EPA has 

decided than any revision to the MPDWR would be a low priority activity for the Agency..." DWS 

Review at 15530. For Heptachlor, EPA reported in the DWS Review that only one water system 

(0.003% of the reporting systems) reported a Heptachlor concentration exceeding the one-half the MCL 

of .2ppb. The estimate of population served by that system was 325, or only 0.0002% of the total 

population served by reporting systems. EPA concluded, “[t]aking into consideration the low occurrence 

of this contaminant, EPA has decided that any revision to the MPDWR would be a low priority activity 

for the Agency .. . " DWS Review at 15546. EPA did not review the occurrence data for Endrin in the 

DWS Review. 
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The Occurrence Data Report, upon which EPA's DWS Review is based, summarizes the results of wel1 

over 100,000 analyses for reported by drinking water systems serving over 180 million people. For 

Endrin, only one water system (0.003%) reported a concentration exceeding the MCL of 2.0ppb. The 

population served by that system was 300 (0.000%). Occurrence Data Report, Table A34. It is also 

important to note that the Occurrence Data Report indicates the percent of systems with Chlordane 

detections above the MRL has decreased from 1.19% to 0.21% from the first to the latest Six Year 

Review. This may indicate a decrease of Chlordane in the environment, in which case levels are 

expected to decrease further over time. 

As Velsicol comments above concerning Hex, EPA should carefully consider available data when 

determining whether Chlordane, Endrin and Heptachlor are found in sources of drinking water to which 

a substantial population is exposed. When assessing the Occurrence Data Report, however, EPA should 

consider the limitations of that data source. As discussed above, EPA's treatment of non-detects presents 

a problem for understanding whether substances are actually present in drinking water. It is also 

important to consider that a typical problem in the analyses for Chlordane, Endrin and Heptachlor r is 

the choice of analytical equipment. Many water suppliers use electron capture gas chromatography 

(ECGC) to analyze water samples. While ECGC is very sensitive and can generate data in the sub-ppb 

range, it is not specific and typically fails to identify the actual concentrations of individual substances. 

Therefore, ECGC often results in false positive results for particular substances. Other water suppliers 

my utilize mass spectrometer gas chromatography (MSGC) which is very specific but not very sensitive. 

Because of the cost of MSGC, analyses are likely more often conducted with ECGS, resulting in high 

rate of false positives. For this reason, Velsicol believes it is likely the few positive results for 

Chlordane, Endrin and Heptachlor may be false positives. Again, because EPA did not critically review 

the reported data and consider the likelihood of false positive results, and because it has not provided the 

underlying data for outside review, it is not possible to fully assess the quality of the data to determine 

whether the few values reported to exceed the MDL are analytical artifacts. In any event, even if the few 

reported values exceeding the MOL are not artifacts, which they likely are, they would not demonstrate 

Chlordane, Endrin and Heptachlor may be found in sources of drinking water to which a substantial 

population are exposed. 

VII. Conclusion

Velsicol appreciates this opportunity to provide comments on EPA's Draft Phase 2 Policies and 

Procedures. For the reasons discussed above, Velsicol believes EPA improperly listed 

hexachlorocyclopentadiene, endrin, heptachlor and chlordane on its Draft EDSP List 2. It should 

removes these chemicals when it finalizes its list. 

Please contact Sherman Friedman at Sfricdman@velsicol.com if you have questions.

Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. Also, please see general response to comment under EPA Comment Code: 2030 

Contaminants Unlikely to Persist in Drinking Water.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0069
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Comment Part: 1

EPA Comment Code: 2030

Comment:

Comments on inclusion of epichlorohydrin on second list for EDSP.

January 17, 2011

EPA Document Control Office (7407M)

Office of Pollution Prevention & Toxics

Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, D.C. 20460

RE: Comments of The Dow Chemical Company on "Endocrine Disruption Screening Program:

Second List of Chemicals for Tier I Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-0477; FRL-8848-7], specifically concerning Epichlorohydrin.

Dear Sir or Madame,

The Dow Chemical Company (Dow) is a major producer of Epichlorohydrin (ECH; CASRN 106- 89-8) 

globally, with significant production facilities operating in the US. Dow has a strong product 

stewardship program in place, which includes evaluation of potential risk from production, handling, 

and use of its products over their lifecycle. As a major producer of ECH, Dow has participated in several 

efforts to gather, summarize, evaluate, and supplement available data to support development of risk 

assessments for chemicals such as ECH. Thus, Dow has a long history of providing and reviewing data 

to determine the potential hazards and risks of ECH.

EPA should remove ECH from this rulemaking. Based on the weight-of-evidence, and particularly in 

keeping with Dow's and EPA's principle of reducing unnecessary testing, Dow strongly recommends 

that ECH be removed from the list of proposed substances to be tested for Tier l screening under the 

Endocrine Disruption Screening Program (EDSP).

This recommendation is based on a variety of facts, including the following:

1) ECH is unlikely to occur as a contaminant of water bodies used as drinking water sources in the 

United States. This conclusion is based on geographic locations of the reported surface water emissions, 

according to reporting year 2009 TRI data. Furthermore, because the substance is readily biodegradable 

and hydrolysable, it does not persist in surface water or groundwater environments.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA 

Comment Code: 1060 SDWA 1457.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0069
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Comment Part: 3

EPA Comment Code: 2030

Comment:

3) ECH is rapidly hydrolyzed, especially under acidic conditions such as those associated with gastric 

fluid, the contact with which would occur as a result of any oral exposure via a drinking water route.

Details supporting each of these lines of evidence are provided below:

1) The second list of substances proposed for endocrine screening is presumed to be based on potential 

exposure to these substances as a result of their occurrence as drinking water contaminants. The 

potential for ECH to occur as a drinking water contaminant can be indicated from the magnitude and 

spatial distribution of surface water emissions, as reported within the Toxics Release Inventory (TRI) 

program. Data for reporting year 2009 indicate a total of 6,345 lbs. was emitted to surface waters, with 

6,095 lbs. occurring at The Dow Chemical Company, Freeport, TX and 250 lbs. occurring at Clariant 

Corp., Martin, SC. The surface water outfall associated with the emissions at Freeport, TX occurs on the 

Brazos River, at a location where effluent is mixed with seawater prior to discharge, and also influenced 

by tidal influx of seawater from the Gulf of Mexico. Therefore, the surface water occurring at, or 

downstream of, this outfall would contain salinity and other water quality attributes which prevent its 

use as a drinking water source. Additionally, the amount reported as released in 2009 is higher than that 

reported from the facility in previous years, due to a one-time incident. Consequently, estimates of 

future annual releases would likely be smaller.

No epichlorohydrin has been detected in water kept in containers coated with epoxy resins

(detection limit 3 μg/litre) (van Lierop, 1978).

Following the setting of the drinking water standard for the EU of 0.1 μg/L, a series of analytical 

methods were published and used in testing: Epichlorohydrin was not detected in any of the samples 

tested by regulatory agencies (see Table l). Although the samples analyzed were not from the U.S., the 

suspected sources of contamination of drinking water (by coagulants or from storage tank and drinking 

and waste water pipe lining) are relevant also in other geographies.

Table [See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0069]

Based on these reported emissions to surface waters from TRI and the lack of detected quantities in 

drinking water in similar geographies, it can be concluded that a significant human population is not 

exposed to ECH as a contaminant in drinking water in the US.

These data, along with mammalian toxicity chronic data demonstrating no targeting of endocrine organs, 

indicate that Tier 1 screening is not necessary for ECH, since similar Tier 2-type studies were negative. 

Certainly, the available data render ECH a low priority for any further endocrine toxicity screening.

Based on data relating to ECH production by several producers in the United States which account for 

42 percent of the global production and relating to the use pattern primarily in the United States, risk 

management measures are being applied (engineering controls, occupational standards, drinking water 

standards, Material Safety Data Sheets, and other US regulations).
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The above stated evidence indicates that systemic effects noted from exposure to ECH show no 

indication of hormonal effects and are simply reflective of generalized toxicity.

3) If in contact with water, Epichlorohydrin will rapidly hydrolyze. The half-life for this reaction has 

been determined in an OECD Ill study at three different pH values with half-lives ranging from 4 to 7 

days at 20 o C (Solvay Pharmaceuticals Int., 2001 in draft US-HPV IUCLID). Similar half-lives (2.5-3.3 

days) were reported in other studies (Pringer, V.O. (1 980); Krijgsheld, K.R., and van der Gen, A. 

(1986) both in draft US-HPV IUCLID).

The hydrolysis reaction is significantly attenuated by nucleophiles commonly present in waste water or 

natural waters (Thiols, Phenols, Alcohols).

The product formed from hydrolysis is readily biodegradable (MITI). The Japanese Institute of

Technology and Evaluation concludes Epichlorohydrin to be readily biodegradable based on this result.

--------

Therefore, removing ECH from the Endocrine Disrupter Screening Program is supported by the weightof-evidence of available data, as indicated by the details and references discussed above and provided 

below.

Sincerely,

Jean Kasakevich

Associate EH&S Product Stewardship Director

The Dow Chemical Company

Midland, Ml48674

References

Bridges, B.A. ( 1978). On the detection of volatile liquid with bacteria: experiments with dichlorvos and 

epichlorohydrin. Mutation Research, 54:367-371.

Cassidy, S.L., Dix, K.M., Jenkins, T. (1983). Evaluation of a testicular sperm head counting technique 

using rats exposed to dimethoxyethyl phthalate (DMEP), glycerol amonochlorohydrin (GMCH), 

epichlorohydrin (ECH), formaldehyde (FA), or methyl methanesulphonate (MMS). Archives of 

Toxicology 53:71-78.

Enterline, P.E., Henderson, V., Marsh, G. (1990). Mortality of workers potentially exposed to 

epichlorohydrin. British Journal of Industrial Medicine 47:269-276.

Epstein, S.S., et al. ( 1972). Detection of chemical mutagens by the dominant lethal assay in the mouse. 

Toxicology and Applied Pharmacology 23:288-325.

IPCS (1984). Epichlorohydrin. Geneva, World Health Organization, International Programme on 

Chemical Safety (Environmental Health Criteria 33).

John, J.A., et al. (1983a). Inhalation toxicity of epichlorohydrin: effects on fertility in rats and rabbits. 

Toxicology and Applied Pharmacology 68:415-423.
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John, J.A., et al. (1983b). Teratologic evaluation of inhaled epichlorohydrin and allylchloride in rats and 

rabbits. Fundamental and Applied Toxicology 3:437-442.

Kirkhart, B. (1981). Micronucleus test on 21 compounds. In: deSerres FJ, Ashby J, eds. Evaluation of 

short-term tests for carcinogens. Amsterdam, Elsevier/North Holland, pp. 698-704.

Laskin, S., Sellakumar, A.R., Kuschner, M. ( 1980). Inhalation carcinogenicity of epichlorohydrin in 

noninbred Sprague-Dawley rats. Journal of the National Cancer Institute 65(4):751-758.

Schultz, V.C. ( 1964). Fettleber und chronisch-asthmoide Bronchitis nach Inhalation eines 

Farbenlosungsmittels (Epichlorohydrin). [Fatty liver and chronic asthmoid bronchitis following 

inhalation of a paint solvent (epichlorohydrin).] Deutsche mediziniche Wochenschrift 89:1342-

1344.

Sram, R.J ., Zudova, Z., Kuleshov, N.P. ( 1980). Cytogenetic analysis of peripheral lymphocytes in 

workers occupationally exposed to epichlorohydrin. Mutation Research 70: 115-120.

Sram, R.J ., et al. (1981). An evaluation of the genetic toxicology of epichlorohydrin. Mutation Research 

87(3):299-319.

Van Duuren, B.L., Goldschmidt, B.M, Paul, J.S. (1974). Carcinogenic activity of alkylating agents. 

Journal of the National Cancer Institute 53:695-700.

Van Esch, G.J., Wester, P.W. (1982). Induction of preneoplastic lesions in the forestomach of rats after 

oral administration of 1-chloro-2,3-epoxypropane. II. Carcinogenicity study. Bilthoven, National 

Institute of Public Health and Environmental Protection.

van Lierop, J.B.H. ( 1978). Simple and rapid determination of epichlorohydrin at the lower parts per 

billion level by gas chromatography-mass fragmentography. Journal of Chromatography 166:609-610.

Venable, J .R., et al. ( 1980). A fertility study of male employees engaged in the manufacture of 

glycerine. Journal of Occupational Medicine 22:87-91.

Wester, P.W., Vander Heijden, C.A., Van Esch, G.J. (1985). Carcinogenicity study with epichlorohydrin 

(CEP) by gavage in rats. Toxicology 36:325-339.

WHO (2004). Epichlorohydrin in Drinking-water. Background document for development of WHO 

Guidelines for Drinking-water Quality.

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants 

Unlikely to Persist in Drinking Water. Also, please see general responses to comment under EPA 

Comment Codes: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore 

Do Not Meet SDWA 1457 Requirements and 1060 SDWA 1457.
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EPA Comment Code: 2040 Naturally Occurring Contaminants

General Response: EPA sought and used the best available information regarding all substances on the 

second EDSP list, including those that have the potential to naturally occur. Although EPA 

acknowledges that acetaldehyde, acrylamide, methanol, and perchlorate have the possibility to occur 

naturally in the environment, this is not the only known pathway of occurrence for these chemicals to 

enter into the environment. Anthropogenic pathways for these chemicals to enter the environment are 

shown through data from the Toxic Release Inventory (TRI), Chemical Update System/Inventory 

Update Rule (CUS/IUR), and chemical manufacturing information. TRI contains information on toxic 

chemical releases from facilities that meet reporting criteria (for most chemicals the thresholds are 

25,000 pounds for manufacturing and processing and 10,000 pounds for use). CUS/IUR contains site 

and manufacturing information for chemicals manufactured (including imported) in amounts of 25,000 

pounds or greater at a single site. These chemicals will not be excluded from the Second List of 

Chemicals for Tier 1 Screening based on their ability to occur naturally in the environment. Specific 

data used for acetaldehyde, acrylamide, methanol, and perchlorate on CCL 3 can be found at 

http://water.epa.gov/scitech/drinkingwater/dws/ccl/upload/Final-CCL-3-Contaminant-InformationSheets.pdf.

Individual Comments

Commenter Name: Linda Ferguson

Commenter Organization: American Pacific Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0021

Comment Part: 1

EPA Comment Code: 2040

Comment: January 17, 2011

Document Control Office

Office of Pollution Prevention and Toxics (7407M)

U. S. Environmental Protection Agency

1200 Pennsylvania Ave., NW.

Washington, DC 20460-0001

DOCKET ID NUMBER EPA-HQ-OPPT-2009-0477 ENDOCRINE DISRUPTOR

SCREENING PROGRAM (EDSP)

American Pacific Corporation (AMPAC) appreciates the opportunity to submit comments to EPA’s 

Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the “Draft 

EDSP List 2”). On November 17, 2010, EPA announced the second list of chemicals and substances for 

which EPA intends to issue test orders under the EDSP [US EPA, 2010a; EPA-HQ-OPPT-2009-0477; 

FRL-8848-7]. Perchlorate was included on the second list for Tier 1 testing. 

American Pacific Corporation is the sole domestic manufacturer of ammonium perchlorate and one of 

three manufacturers of perchlorates in the United States. The other manufacturers focus on perchlorates 

based on aluminum, magnesium, potassium, sodium and lithium for a variety of industrial applications. 
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It is our understanding that US EPA is interested in receiving information and comments that may 

influence the exclusion or inclusion of chemicals on the second EDSP list. American Pacific 

Corporation, founded in 1955 and headquartered in Las Vegas, Nevada is submitting these comments to 

present our rationale, based on the criteria outlined by EPA as to why the chemical perchlorate should be 

excluded from the second EDSP list.

AMPAC Perchlorate Manufacturing

Perchlorates are oxidizers produced by the electrochemical oxidation of salt. They occur both naturally 

and through manufacturing.

AMPAC’s perchlorate business is a worldwide leader in the production of ammonium perchlorate (AP) 

and other perchlorate chemicals and derivatives. We have supplied AP for use in aerospace, national 

defense programs and commercial applications for more than 40 years. American Pacific Corporation 

has been the exclusive manufacturer of AP in North America since 1998, when Kerr-McGee Chemical 

Corporation decided to exit the business of perchlorate manufacturing.

EPA Criteria for Tier 1 Testing

In some instances, perchlorate has been detected because of contamination from industrial sites that use 

or manufacture it. In other instances, there is no clear source of perchlorate contamination. In those areas 

it may be naturally occurring, or could be present because of the use of Chilean fertilizers, which were 

imported to the U.S. by the hundreds of tons in the early 19th century. Recent areas of research have 

suggested that perchlorate can be created by non-anthropogenic atmospheric conditions. Perchlorates are 

also created as a byproduct of chlorine generators used in swimming pool chlorination systems. 

In establishing its basis for selection in the EDSP Tier 1 Screening program, EPA indicates that is has 

focused on a subset of chemicals and substances that have been listed as priorities within EPA's drinking 

water and pesticides programs.

“First, the Agency identified candidate chemicals that are either contaminants regulated with a national 

primary drinking water regulation (NPDWR) or are unregulated contaminants that are listed on the third 

Contaminant Candidate List (CCL 3). EPA began with the 85 regulated drinking water contaminants 

with existing NPDWRs and the 116 unregulated contaminants listed on CCL 3 because these represent 

many of the priority contaminants for the drinking water program.”

There are literally hundreds of chemicals listed as candidate contaminants on the national primary 

drinking water regulation (NPDWR) list (40 CPR part 141) or that were listed as unregulated 

contaminants on the Contaminant Candidate List (CCL 3). Perchlorate is listed in CCL 3; therefore it 

was automatically included on the second list for Tier 1 testing.

In an attempt to prioritize the chemicals that were captured in EPA's initial screening, criteria were 

developed to consolidate the list of chemicals developed by the Office of Water (OW) and the Office of 

Pesticide Programs (OPP) to exclude any chemical that fell into one or more of the following categories 

according to EPA: 

1. Biological agent and naturally occurring chemicals (e.g., microbials, microbial toxins, inorganics, 

radionuclides). 
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2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

disinfection byproducts or DBP's, microbes, microbial toxins, degradate compounds with more than one 

possible source etc.). 

3. Chemicals already included on the first EDSP list. 

4. Chemicals that are hormones with confirmed endocrine effects. 

5. Chemicals that are not likely to be biologically active or which are incompatible with testing assays 

for various reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or 

basic, solubility, vapor pressure molecular weight).

6. Pesticides that are scheduled for registration review after FY 2008.

The basis for AMPAC’s comments arguing that perchlorate merits exclusion from the second list of 

chemicals included for Tier 1 screening are confined to the first two criteria. We address those two 

exclusionary criteria below.

I. Exclusion for biological agents that are also naturally occurring chemicals

The possibility that perchlorate contamination of surface and groundwater may have multiple origins 

(military, industrial, agricultural, or natural) has long complicated site characterization and efforts to 

assign responsibility for remediation.

Perchlorate is composed of one chlorine and four oxygen atoms. Chlorine and oxygen, like most 

chemical elements, can have different isotopes, meaning they have variable numbers of neutrons. 

Because of the unique chemical structure, scientists can use isotopic “fingerprinting” to analyze the 

stable isotope ratio of chlorine and oxygen in perchlorate and distinguish the perchlorate from fertilizer, 

anthropogenic sources, and naturally formed perchlorate. For example, isotopic studies indicate that 

natural perchlorate is produced on Earth in arid environments by the oxidation of chlorine species 

through pathways involving ozone or its photochemical products (Journal of Geophysical Research, Vol. 

115, EOOEII, I5 PP., 2010 doi: 10.1029/2009JE003425).

Other examples of the science related to naturally occurring perchlorate include:

• Data from isotopic analysis demonstrate that natural perchlorate found in the US Southwest and Chile 

were formed in the upper atmosphere from ozone and an isotope of chlorine commonly found in the 

atmosphere (Jackson et al., 2010).

• The average perchlorate in rainwater was 15 ppt with maximum values of 102 ppt (Rajagopalan et al., 

2009). The amount distributed via precipitation in the continental US was estimated to be 51,000 kg (56 

tons) of perchlorate (Rajagopalan et al., 2009). The mass flux due to precipitation was comparable to 

other known environmental release sources (Rajagopalan et al., 2009).

• Lightning was reported to cause sufficient energy to bond atmospheric chlorine together with oxygen 

(Jackson et al., 2010; Dasgupta et al., 2005).

• Perchlorate is found in the US from natural deposition. For example USGS has detected perchlorate in 

Western US soils as well as groundwater sources, none of which are close to any industrial sources. In 

has been detected in groundwater from the Holocene and Pleistocene age in the Rio Grande Basin (New 

Mexico), and in groundwater from the Holocene age throughout the arid Southwest (Jackson et al.,

2010).
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• Perchlorate is found in groundwater from non-industrial sources. In a survey of wells that had with 

minimal human impact, more than 55% of wells had perchlorate levels greater than 40 parts per trillion 

(ppt) (Jackson et al., 2010). Other reports groundwater perchlorate concentrations in 54 Texas counties 

and two New Mexico counties reported detection of perchlorate in 51 of 56 samples with over 22% of 

the samples having greater than 4 ppb (Dasgupta et al., 2005). This area was also reported to have no 

readily ascertainable anthropogenic source. Some samples were reported to have nearly 60 ppb of 

perchlorate (Dasgupta et al., 2005).

• Perchlorate is found consistently in Chilean nitrate fertilizer at concentrations of approximately 0.5 to 

2 mg/g (Urban sky et al., 2001). The source of Chilean perchlorate is atmospheric and, as nitrate ions 

have been found to accumulate in subsoil zones beneath deserts and warm scrublands, it is possible that 

the same is true of perchlorate (Dasgupta et al., 2005).

The extent to which perchlorate is documented to occur naturally merits exclusion based on the criteria 

established by EPA.

Response: Please see general responses to comment under EPA Comment Codes: 2040 Naturally 

Occurring Contaminants and 1050 Evaluation Criteria Review.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 2

EPA Comment Code: 2040

Comment: According to the U.S. Geological Survey, both methanol and ethanol are not included as 

analytes under the analytical methods employed by the USGS National Water Quality Laboratory, and, 

as such, the USGS does NOT compile monitoring data for the nation’s ambient waters and water 

supplies with respect to methanol or ethanol. Although, according to the USGS, it is possible to 

determine methanol and ethanol concentrations in water by separating the alcohols from water using gas 

chromatography with mass spectral flame ionization and thermal conductivity detection, there are 

several problems that would make monitoring for point sources problematic. Both methanol and ethanol 

are produced naturally in the environment.

Response: The agency has not included ethanol on the Second List of Chemicals for Tier 1 Screening. 

Please see general response to comment under EPA Comment Code: 2040 Naturally Occurring 

Contaminants.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 2

EPA Comment Code: 2040
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Comment: The purpose of this document is to examine the Agency’s inclusion of perchlorate on the 

November 17th list. The following are comments for the Agency to consider. 

• It is understood that with sufficient dose and duration of exposure perchlorate, exerts its effect on the 

thyroid gland. It is also likely that almost any chemical, given sufficient dose and duration, will affect 

the endocrine system. However, perchlroate’s action is fundamentally different than chemicals US EPA 

has been considering as endocrine disruptors. As noted in the EDSP, US EPA aims to evaluate 

chemicals that mimic endogenous sex hormones. The concern is that hormone mimetics may add to or 

negate endogenous effects. However, the chemical structure, function, and action of perchlorate do not 

mimic any of the thyroid hormones or the pituitary hormones, such as thyroid stimulating hormone 

(TSH).

• In addition to not mimicking hormonal effects, perchlorate is excludable based on two of US EPA’s 

criteria: 

1. Biological agents and naturally occurring chemicals. Perchlorate is a naturally occurring chemical. It 

is formed atmospherically and deposited in precipitation. 

2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

degradate compounds with more than one possible source). The sources of perchlorate are diverse; for 

example, it is found naturally as a byproduct of some types of municipal water chlorination processes, 

and it is used in organic farming and fireworks produced abroad.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants. Also, please see general response to comment under EPA Comment Code: 

2020 Contaminants No Longer Manufactured or Imported, or Used in the US, also Includes Pesticides 

with Cancelled Registrations.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 7

EPA Comment Code: 2040

Comment: Criterion 1. Biological agents and naturally occurring chemicals (e.g., microbials, microbial 

toxins, inorganics, radionuclides).

Perchlorate is composed of one chlorine and four oxygen atoms. Chlorine and oxygen, like most 

chemical elements, can have different isotopes, meaning they have variable numbers of neutrons 

(neutrally charged particles). Scientists can analyze the stable isotope ratio of chlorine and oxygen in 

perchlorate to distinguish the perchlorate from fertilizer, anthropogenic sources, and naturally formed 

perchlorate. The following are some publicly available literature related to naturally occurring 

perchlorate.

• Data from isotopic analysis demonstrate that natural perchlorate found in the US Southwest and Chile 

were formed in the upper atmosphere from ozone and an isotope of chlorine commonly found in the 

atmosphere (Jackson et al., 2010).
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• The average perchlorate in rain water was 15 ppt with maximum values of 102 ppt (Rajagopalan et al., 

2009). The amount distributed via precipitation in the continental US was estimated to be 51,000 kg (56 

tons) of perchlorate (Rajagopalan et al., 2009). The mass flux due to precipitation was comparable to 

other known environmental release sources (Rajagopalan et al., 2009).

• Lightning was reported to cause sufficient energy to bond atmospheric chlorine together with oxygen 

(Jackson et al., 2010; Dasgupta et al., 2005).

• Perchlorate is found in the US from natural deposition. For example USGS has detected perchlorate in 

Western US soils as well as groundwater sources, none of which are close to any industrial sources. In 

has been detected in groundwater from the Holocene and Pleistocene age in the Rio Grande Basin (New 

Mexico), and in groundwater from the Holocene age throughout the arid Southwest (Jackson et al., 

2010).

• Perchlorate is found in groundwater from non-industrial sources. In a survey of wells that had minimal 

human impact, more than 55% of wells had perchlorate levels greater than 40 parts per trillion (ppt) 

(Jackson et al., 2010). Other reports document groundwater perchlorate concentrations in 54 Texas 

counties and two New Mexico counties in 51 of 56 samples with over 22% of the samples having 

greater than 4 ppb (Dasgupta et al., 2005). This area was also reported to have no readily ascertainable 

anthropogenic source. Some samples were reported to have nearly 60 ppb of perchlorate (Dasgupta et 

al., 2005).

• Perchlorate is found consistently in Chilean nitrate fertilizer at concentrations of approximately 0.5 to 

2 mg/g (Urbansky et al., 2001). The source of Chilean perchlorate is atmospheric and, as nitrate ions 

have been found to accumulate in subsoil zones beneath deserts and warm shrublands, it is possible that 

the same is true of perchlorate (Dasgupta et al., 2005).

Given the source of this perchlorate in the upper atmosphere, world wide distribution could occur. Rain 

water is a source of perchlorate globally. In summary, perchlorate is a naturally occurring chemical and 

meets this criterion.

Criterion 2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified 

(e.g., disinfection byproducts or DBPs, microbes, microbial toxins, degradate compounds with more 

than one possible source).

The sources of perchlorate for which the manufacturer, importer, or registrant cannot be clearly 

identified are both natural and anthropogenic. Over the past 50 years, perchlorate salts have been 

produced commercially by several manufacturers. As noted above, it is possible to distinguish between 

natural and anthropogenic sources through isotopic fingerprinting, but it is more difficult to distinguish 

between different anthropogenic sources (i.e., fireworks versus road flares). There are currently three 

manufacturers of perchlorate in the US (American Pacific Corporation, GFS Chemicals, and Barium and 

Chemicals, Inc.), however, the sources of perchlorate found environmentally are diverse, and fall into 

one or more categories: (1) natural, (2) import from outside the US, (3) a byproduct in Chilean nitrate 

fertilizer, and (4) a byproduct of some municipal water treatments (e.g., hypochlorite). Although the 

source of perchlorate in Chilean fertilizer is natural, it can be distinguished from perchlorate deposited in 

the US. Some examples from publicly available literature include:
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• One significant source of perchlorate in ground water is from agricultural use of imported Chilean 

nitrate fertilizer that contains perchlorate. This type of fertilizer is used in organic farming. The amount 

of perchlorate in typical Chilean nitrate fertilizer is approximately 0.1% by weight (Dasgupta et al., 

2005). One study estimated that over the past 60 years, the source strength from Chilean nitrate fertilizer 

in food was an average 0.75 Gg per year (approximately 800 tons per year) and natural sources 

contributed 0.13 – 0.64 Gg per year (approximately 150 - 700 tons per year) (Dasgupta et al., 2006).

• Perchlorate is as a contaminant of hypochlorite used to disinfect drinking water. Hypochlorite is also 

used agriculturally as a preservative and to control microbial risks. Perchlorate is an oxidation product of 

hypochlorite and is found in concentrations of up to 8,000 ppb in household bleach (MA DEP, 2006), 

6,750 ppb in water treatment plant hypochlorite solutions (MA DEP, 2006), and 23,400 ppb in 

agricultural hypochlorite solutions (Sanchez et al., 2009). Perchlorate was detectable in over 90% of 

hypochlorite used in water treatment plants (Sanchez et al., 2009).

• While there are clear instances were industrial practices of the past have led to industrial 

contamination, the attribution of source of perchlorate at these sites is different than previously thought 

in some cases. In the US Southwest, groundwater and desert soil samples had isotopic fingerprints that 

were distinct from Chilean and industrial sources suggesting the source was neither agricultural nor 

industrial (Sturchio et al., 2009).

• Kelp fertilizer, like Chilean nitrate fertilizer, is often used in organic farming. Kelp has been reported 

to contain up to 885,000 ppb perchlorate (Orris et al., 2003).

As detailed, perchlorate could be excluded based on either of the first two criteria. The remaining 

exclusion criteria are for chemicals that were on the 2005 EDSP list, hormones with confirmed 

endocrine effects, chemicals which are incompatible with testing assays, and pesticides that are pending 

review. Perchlorate was not on the 2005 EDSP list, is not a hormone, is not incompatible with testing, or 

a pesticide. Therefore, these exclusion criteria do not apply to perchlorate. As US EPA stated, “any 

chemical that fell into one or more” of the categories should be excluded.

Response: Please see general responses to comment under EPA Comment Codes: 2040 Naturally 

Occurring Contaminants and 2020 Contaminants No Longer Manufactured or Imported, or Used in the 

US, also Includes Pesticides with Cancelled Registrations.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 9

EPA Comment Code: 2040

Comment: First, like perchlorate, nitrate satisfies the first criteria for exclusion: it is naturally occurring. 

Nitrate can be formed atmospherically (Dasgupta et al., 2005; Jackson et al., 2010). Nitrate can also be 

produced environmentally by bacteria.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants.
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Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 11

EPA Comment Code: 2040

Comment: 7.0 CONCLUSIONS

The goal of the EDSP—to screen many chemicals for potential endocrine activity—is ambitious, and 

any attempt to streamline the process is commendable. In summary, we make several comments for US 

EPA to consider.

• US EPA should streamline its list and exclude perchlorate. This is based on a number of scientific 

evaluations along with the criteria established by US EPA:

1. Biological agents and naturally occurring chemicals. Perchlorate is a naturally occurring chemical. It 

is formed atmospherically and deposited in precipitation.

2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

degradate compounds with more than one possible source). The sources of perchlorate are diverse; for 

example, it is found naturally as a byproduct of some types of municipal water chlorination processes, 

used in organic farming, and used in fireworks and road flares produced abroad.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants. Also, please see general response to comment under EPA Comment Code: 

2020 Contaminants No Longer Manufactured or Imported, or Used in the US, also Includes Pesticides 

with Cancelled Registrations.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 3

EPA Comment Code: 2040

Comment: Finally, EPA should consider the extensive ongoing toxicology research program that the 

US Food and Drug Administration (FDA) is conducting on acrylamide. This research program is 

targeted at addressing acrylamide in food, which is well established as a more important exposure source 

for the general public than drinking water or other environmental sources. In addition, acrylamide’s 

natural presence in a wide variety of foods suggests that it should be excluded from EDSP (based on 

EPA’s exclusion criteria) as it is a naturally occurring chemical. 

If you have any questions regarding these comments, please contact me at (202) 419-1500 or 

ajaques@regnet.com. 

Sincerely, 

Andrew M. Jaques 

Deputy Director
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NORTH AMERICAN POLYELECTROLYTE PRODUCERS ASSOCIATION

COMMENTS ON THE INCLUSION OF ACRYLAMIDE (CAS NO. 79-06-1) IN “ENDOCRINE 

DISRUPTOR SCREENING PROGRAM: SECOND LIST OF CHEMICALS FOR TIER 1 

SCREENING”

75 FR 70248; NOVEMBER 17, 2010; EPA-HQ-OPPT-2009-0477

January 18, 2011 

I. Introduction and Overview 

The North American Polyelectrolyte Producers Association (NAPPA)[FN1: Current members of 

NAPPA include Ashland Inc., BASF, Kemira Water Solutions, Inc., and Nalco Company.] submits the 

following comments on the US Environmental Protection Agency’s (EPA) announcement of a second 

list of chemicals and substances for which EPA intends to issue test orders under the Endocrine 

Disruptor Screening Program (EDSP). The members of NAPPA are major North American 

manufacturers and importers of synthetically produced coagulants and flocculants, which are generically 

referred to as polyelectrolytes. Polyacrylamides are a significant class of these polyelectrolytes. NAPPA 

members produce polyacrylamides and also the acrylamide monomer and have been very active in the 

assessment of the toxicology of acrylamide.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 5

EPA Comment Code: 2040

Comment: NAPPA also notes that EPA’s own exclusion criteria present a basis for removing 

acrylamide from this test rule because acrylamide is created naturally in the process of cooking food and 

also present in some uncooked foods. EPA specifically notes that it intends to exclude “naturallyoccurring chemicals” from the EDSP list. Food has, in fact, been determined to be a much more 

significant source of exposure than drinking water to acrylamide. The formation of acrylamide in food is 

not due to artificial ingredients or environmental contamination but from the conversion of natural 

amino acids present in food. This source of acrylamide is outside of the control of EPA or 

acrylamide/polyacrylamide industry and occurs through the normal course of living and, as such, 

acrylamide could be considered a naturally-occurring chemical. Moreover, the role of acrylamide in 

food is currently be evaluated by the FDA, including an extensive toxicology research program at the 

National Center for Toxicological Research (NCTR). Further testing of acrylamide under EDSP Tier 1 

is unlikely to contribute meaningfully to this assessment.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants.
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Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 11

EPA Comment Code: 2040

Comment: VI. Acrylamide Should be Excluded Based on EPA’s Criteria for the EDSP List 

EPA states on its EDSP website that it streamlined the list for EDSP Group 2 by excluding any chemical 

that fell into one or more of the following categories: 

1. Biological agent and naturally-occurring chemicals (e.g., microbials, microbial toxins, inorganics, 

radionuclides). 

2. Chemicals for which the manufacturer, importer or registrant cannot be clearly identified (e.g., 

disinfection byproducts or DBPs, microbes, microbial toxins, degradate compounds with more than one 

possible source etc.). 

3. Chemicals already included on the first EDSP list. 

4. Chemicals that are hormones with confirmed endocrine effects. 

5. Chemicals that are not likely to be biologically active or which are incompatible with testing assays 

for various reasons due to one or more of their physiochemical properties (e.g., gases, strongly acidic or 

basic, solubility, vapor pressure molecular weight). 

6. Pesticides that are scheduled for registration review after FY 2008. 

NAPPA believes that EPA’s exclusion criterion for “naturally-occurring chemicals” is appropriately 

applied to acrylamide given the natural formation of acrylamide in the process of cooking food and also 

its presence in some uncooked foods (see FDA survey of U.S. foods[FN6: FDA survey of Acrylamide in 

food: 

http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/ChemicalContaminants/Acrylami

de/ucm053549.htm] and WHO summary of acrylamide in food in Attachment 1). 

EPA specifically notes that it intends to exclude “naturally-occurring chemicals” from the EDSP list. 

The formation of acrylamide in food is not due to artificial ingredients or environmental contamination 

but from the conversion of natural amino acids present in food. This source of acrylamide is outside of 

the control of EPA or the acrylamide/ polyacrylamide industry and occurs through the normal course of 

living. As such, NAPPA believes that EPA would be correct in considering it a naturally-occurring 

chemical. 

Food is a much more significant source of exposure than drinking water to acrylamide. Exposure to 

acrylamide has been evaluated previously by a number of organizations (e.g., NTP/CERHR, Canada, 

WHO, EU) and the most regularly identified sources for exposure to the general population are smoking 

and food. For the non-smoker, the US National Toxicology Program (NTP) Center for the Evaluation of 

Risks to Human Reproduction (CERHR) concluded that food is the most significant source of general 

population (non-occupational) exposure. Another important conclusion from this CERHR assessment is 

that drinking water exposure is anticipated to be negligible (<0.01 μg/kg bw/day). A similar conclusion 

was also reached recently in an assessment by Canada (Environment Canada and Health Canada 2009), 

which stated: 
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The greatest source of exposure of the general population to acrylamide is from its formation from 

naturally occurring components of certain foods when cooked at high temperatures, such as french fries 

and potato chips[FN7: Acrylamide is actually food in a wide variety of foods, most cooked, but some 

raw. See FDA and WHO surveys.]. Intake from environmental media such as drinking water or air and 

exposures during use of consumer products are very low in comparison. 

The role of acrylamide in food is currently being evaluated by the FDA, including an extensive

toxicology research program at the National Center for Toxicological Research (NCTR), which is 

discussed in the next section. Further testing of acrylamide under EDSP Tier 1 is unlikely to contribute 

meaningfully to this assessment.

Response: Please see general responses to comment under EPA Comment Codes: 2040 Naturally 

Occurring Contaminants and 1050 Evaluate Criteria Review.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 4

EPA Comment Code: 2040

Comment: EPA has included acetaldehyde on its second list of chemicals to be included in the EDSP 

program (EDSP List 2), given the Agency’s determination that acetaldehyde meets the statutory 

authority of §1457 SDWA, which authorizes EPA to require testing of drinking water contaminants if a 

substantial population may be exposed. As these comments explain, any acetaldehyde exposure that may 

occur from drinking water is de minimis in comparison to other sources of exposure. Acetaldehyde is an 

endogenously formed substance that results from metabolism of biomolecular processes (amino acid and 

carbohydrate metabolism, lipid peroxidation, etc.) and is naturally present in many foods and beverages. 

Indeed, the primary source of exposure to acetaldehyde is exogenous, as a natural component of the food 

and drink the public consumes; the intake of acetaldehyde from these sources is significantly greater 

than any exposure from drinking water. Additionally, while acetaldehyde has expressed some effects on 

reproductive endpoints, these must be considered in the context of the bioavailability of acetaldehyde 

from exogenous sources of exposure versus endogenous acetaldehyde levels from normal cell function.

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants. Also, please see general response to comment under EPA Comment Code: 

1060 SDWA 1457.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 8

EPA Comment Code: 2040

Comment: II. Drinking Water is a De Minimis Contributor to the Public Exposure to Acetaldehyde 
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As the Agency is well aware, acetaldehyde is ubiquitous; it occurs naturally in the environment and 

forms readily in the human body as well as in most species of animals and plants. Acetaldehyde is a 

natural component in many common foods including pears, apples, bananas, bread, yogurt and peas. An 

important pathway, is the production of acetaldehyde in the human body as a byproduct of alcohol 

metabolism during which ethanol is metabolized into acetaldehyde, which is then converted into acetic 

acid, and finally into CO2. 

Acetaldehyde is formed as a product of incomplete wood burning in fireplaces and woodstoves, coffee 

roasting, burning of tobacco, vehicle exhaust fumes, and coal refining and waste production, with 

residential fireplaces and woodstoves being the two highest sources of acetaldehyde emissions (EPA, 

2000). 

Acetaldehyde is generally recognized as safe (GRAS) in the United States and it is used in Canada and 

the United States as a synthetic flavoring substance and adjuvant in various foods (including dairy and 

meat products, fruit juices, baked goods, alcoholic and non-alcoholic beverages, gelatin desserts and 

candy). Reported concentrations of acetaldehyde in these products have ranged from 3.9 mg/L in 

beverages to 2000 μg/g in frostings (U.S. FDA, 1982; U.S. NRC, 1985; Burdock, 1995; Feeley, 1996).

Acetaldehyde is considered one of the most important sensory carbonyl compounds in wine and makes 

up roughly 90% of the total aldehyde in wine. At low levels, acetaldehyde provides the fruity aroma 

associated with wine and at high levels, acetaldehyde adds what is considered the unique feature to 

sherry (Thomas, 2004).

Response: Please see general response to comment under EPA Comment Code: 2040 Naturally 

Occurring Contaminants.
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EPA Comment Code: 2060 Chemicals with Toxicity Data Indicating Endocrine 

Disruption or Other Reproductive Developmental Endpoints

General Response: EPA acknowledges that for some of the chemicals listed on the second EDSP list 

there may be existing data relevant to the Tier 1 screening assays. However, EPA disagrees with 

removing these chemicals from the second EDSP list at this time. Order recipients will have an 

opportunity to submit any relevant data to the Tier 1 assays or Other Scientifically Relevant Information 

(OSRI) as part of their initial response to receiving an order. For specific information on submitting or 

citing existing data or OSRI, please see the existing EDSP policies and procedures that were published 

in 74 FR 17560, April 15, 2009 (USEPA, 2009b) and the Endocrine Disruptor Screening Program; Draft 

Policies and Procedures for Screening Safe Drinking Water Act Chemicals 75 FR 70558, November 17, 

2010 (USEPA, 2010a). Please also see Endocrine Disruptor Screening Program; Final Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document. EPA supports the idea of conserving resources 

and preventing redundancy in testing by using OSRI data.

Please see general response to comment under EPA Code: 2020 Contaminants No Longer Manufactured 

or Imported, or Used in the US, also Include Pesticides with Cancelled Registrations. Several 

contaminants mentioned in this section have been removed from the second EDSP list (dinoseb, 

fenarimol, and methoxychlor).

Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria 

Review for information on ToxCast.

Individual Comments

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 11

EPA Comment Code: 2060

Comment: In addition, considerable data have already been collected on the endocrine disrupting 

potential of lindane, its isomers and its byproducts. The organoclorines, the chemical class to which 

lindane belongs, are a particularly data rich class of compounds that have been shown to act as 

competitive inhibitors of androgen receptors and to induce conversion of androgen to oestrogen in a 

variety of systems (Sonnenschein and Soto 1998; Daxenberger 2002; Lemaire, Terouanne et al. 2004; 

Scippo, Argiris et al. 2004; Storrs and Kiesecker 2004; McKinlay, Plant et al. 2008).

A large number of experiments on animals have shown that lindane exposure can lead to reproductive 

toxicity in animals through a variety of mechanisms including disruption of steroid hormone 

homeostasis, hormone receptor binding and disruption of spermatogenesis (McKinlay, Plant et al. 2008; 

Di Consiglio, De Angelis et al. 2009). Tests on animals have also indicated that lindane exposure can 

shorten oestrous cycles, lower luteal progesterone concentrations, increase blood serum concentrations 

of insulin and oestradiol and alter thyroid hormone levels in the animals used (Rawlings, Cook et al. 

1998; Beard and Rawlings 1999; Alvarez-Pedrerol, Ribas-Fito et al. 2008). Evidence for lindane's 

estrogenic (Raizada, Misra et al. 1980; La Sala, Farini et al. 2010) and anti-estrogenic activities 
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(Chadwick, Cooper et al. 1988; Cooper, Chadwick et al. 1989) is so widely accepted that it has been 

used as a control to validate in vitro estrogenic assays (Scippo, Argiris et al. 2004; La Sala, Farini et al. 

2010). In addition, several epidemiological studies have linked lindane to infertility and premature births 

in humans (Colborn, vom Saal et al. 1993; Cioroiu, Tarcau et al. 2010). 

Summary and conclusions: Lindane is a regulated drinking water contaminant that has been banned 

from use as a pesticide and as a result, exposure is decreasing rapidly. Lindane has already been shown 

to have endocrine-disrupting activity that results in reproductive toxicity; therefore additional testing 

would be redundant and is not warranted.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints and 

general response to comment under EPA Comment Code: 2020 Contaminants No Longer Manufactured 

or Imported, or Used in the US, also Includes Pesticides with Cancelled Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 13

EPA Comment Code: 2060

Comment: F. Dinoseb 

Due to several poisoning cases and deaths of manufacturing workers attributed to this herbicide, it was 

banned by the EPA in 1986. Despite significant use, well water contamination at the time was found to 

be limited to two low-use wells. The ban was partially due to substantial evidence for this herbicide's 

endocrine disrupting properties, although there is currently very little potential for human exposure to 

dinoseb. Studies have reported birth defects in animals born to females fed comparatively low doses as 

well as abnormal sperm and decreased weight of the thyroid gland in males at doses close to calculated 

occupational exposures at the time (Felsot 1998). 

Summary and conclusions: There is clear indication that dinoseb interferes with reproduction and 

development there is currently very little chance of exposure, therefore Tier 1 information would not be 

useful in regulation of this substance and it should be removed from the second list of chemicals for 

screening.

G. Carbon tetrachloride 

Carbon tetrachloride (CCl4) is an established human hepatotoxin and nephrotoxin whose metabolites 

cause oxidative tissue damage that leads to the development of steatosis, necrosis and cirrhosis of the 

liver in rats (Ruprah, Mant et al. 1985; Abraham, Wilfred et al. 1999; Bruckner, Ramanathan et al. 2002; 

Dang, Wang et al. 2007). Specifically, the chemical is activated by CYP2E1 to form the trichloromethyl 

radical (CCl3*), which can variously bind to cellular molecules leading to the fatty depositions 

characteristic of steatosis or, in the case of CCl3*-DNA adducts, hepatic cancer (Weber, Boll et al. 

2003). As a result, toxicity due to CCl4 exposure can be interrupted with the use of antioxidants and 

mitogens (Weber, Boll et al. 2003). As outlined in Title 40 of the Code of Federal Regulations part 82, 
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CCl4 production and importation has been banned in the United States since 1996 because of its 

documented toxicity. 

Because of the enzyme’s role in mediating metabolic activation, tissues with high relative expression of 

CYP2E1, including the liver and kidneys, are especially vulnerable to CCl4-induced toxicity (ATSDR 

2003). Because CYP2E1 is also present in testicular tissues, the chemical impacts the spermatogenic 

cycle in rats, ultimately leading to hypogonadism similar to that seen in human patients with alcoholinduced cirrhosis (Van Thiel, Gavaler et al. 1980; Sundari, Wilfred et al. 1997; Abraham, Wilfred et al. 

1999; Horn, Ramos et al. 2006). Rats exposed to 2 ml CCl4 / kg / week for 16 weeks showed decreased 

testicular weights relative to controls, in addition to abnormal testicular histopathologies including 

complete atrophy of seminiferous tubules and germ cell degeneration (Khan and Ahmed 2009). In the 

same animals, CCl4 exposure was associated with a dose-dependent decrease in serum testosterone, 

follicle stimulating hormone and luteinizing hormone, likely due to oxidative damage to Leydig cells 

(Santos, Ferraz et al. 2004; Khan and Ahmed 2009).

Summary and conclusions: The mechanism of action of this chemical is clearly defined and the toxicity 

has been well characterized; further testing in EDSP assays would add no regulatory value and is not 

warranted and CCl4 should be removed from the second list of chemicals to be tested.

H. Polychlorinated biphenyls (PCBs) 

PCBs were used extensively in the manufacture of transformers, capacitors, and other heat transfer 

devices through the late 1970's. In 1979, their manufacture and importation was banned in the United 

States, based on mounting evidence that they were toxic to humans and the environment. Extensive 

exposure and toxicological information is available from the Agency for Toxic Substances and Disease 

Registry’s (ATSDR) database (Agency for Toxic Substances and Disease Registry (ATSDR) 2000).

PCBs are found throughout the environment. They do not easily break down and bioaccumulate in the 

fatty tissues of fish and mammals. The major route of human exposure is consumption of fish. Exposure 

to PCBs is regulated to extremely low levels by several federal agencies. EPA’s standard for PCBs in 

drinking water is 0.5 parts per billion (ppb) and 0.17 parts per trillion in lakes and streams. FDA’s 

residue limits for PCBs ranging from 0.2 ppm (parts per million) in infant foods to 3 ppm in poultry and 

red meat. OSHA regulates worker exposure by inhalation to less than 1 milligram per cubic meter 

(mg/m3) over a 40-hour work week for 42% chlorine PCBs and to less than 0.5 mg/m3 for 54% chlorine 

PCBs. PCB levels in tissues from the US population are now declining. In addition, storage and disposal 

of PCB waste are regulated under the Toxic Substances Control Act (TSCA). 

ATSDR reviews existing data on the endocrine effects of PCB exposure and concludes that PCBs can 

affect a wide variety of endocrine systems. PCBs generally have much lower estrogenic potency than the 

endogenous hormone, 17β-estradiol. PCB mixtures can produce weak estrogenic responses and PCB 

congeners with multiple ortho-chlorines may be at least partly responsible for these responses. 

Estrogenicity in vivo, as measured by increased uterine wet weight, has been observed for Aroclor 1242, 

PCB 47, PCB 52 and a hydroxylated derivative – but not for the coplanar congener PCB 77. PCB 47 and 

a hydroxylated derivative also display estrogenic activity in vitro in a cell proliferation assay. In 

addition, anti-estrogenic effects in vivo have been reported for PCB 77 and in vitro for other congeners 

with no or single ortho-chlorines. 
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In humans, PCB exposure may be associated with menstrual disturbances, repeated miscarriages and 

effects on male fertility. In female rats, reproductive effects of Aroclor 1254 include reduction in 

preweaning weight gain, delayed puberty, reduced mating rate, reduced implantation rate and mean 

number of embryos, reduced uterine weight during proestrus, and reduced uterine response to exogenous 

17β-estradiol in ovariectomized offspring. Effects in females of various other species have also been 

described, including decreased conception in mice, partial or total reproductive inhibition in minks, and 

prolonged menstruation and decreased fertility in monkeys. Female minks and monkeys are particularly 

sensitive to reproductive effects of PCBs. In male rats, decreases in numbers of normal fertilized eggs, 

blastocytes, implants and embryos as well as decreases in seminal vesicle and ventral prostate weights 

have been observed, and gestational and lactational exposure to PCBs can adversely affect morphology 

and production of sperm and fertility in the male offspring of rats and mice. These data address 

endpoints evaluated in the ER binding, uterotrophic and Hershberger assays used to identify estrogen 

and androgen agonists and antagonists in EDSP Tier 1, specifically body weight, uterine weight, vaginal 

histopathology, ventral prostate and seminal vesicle weights. 

Data from animal studies indicate that exposure to PCBs affects thyroid histology, disrupts the 

production and transport of thyroid hormones and accelerates their metabolic clearance. In particular, 

neurobehavioral deficits in rat pups exposed to Aroclor 1254 in utero and during nursing were 

significantly attenuated by subcutaneous injections of T4. Similarly, increased testis weight and sperm 

production in rats that were administered Aroclor 1254 were attenuated by injections of T4. Similar 

effects to those produced by PCBs can be produced by other hypothyroid-inducing agents.

These data address endpoints evaluated in the pubertal male and female assays used to identify antithyroid activity in EDSP Tier 1. In addition, other effects of PCBs on endocrine function are noted in 

animal studies including effects on the adrenal glands and serum adrenal steroid levels. 

PCBs have induced endocrine-related effects in a variety of other taxa. For example, fish in early life 

stages were more vulnerable than adults to PCB toxicity. Avian reproduction was impaired due to 

decreased egg hatchability and increased embryotoxicity. A suite of developmental effects observed 

repeatedly in Great Lakes wildlife has been characterized as the Great Lakes embryo mortality, edema, 

and deformity syndrome (GLEMEDs syndrome). 

Summary and Conclusions: PCBs are an extremely well-studied chemical class; their endocrine 

disrupting potential has been demonstrated in rodents, birds, fish and other wildlife as well as in 

epidemiologic studies, including information for several of the Tier 1 assay endpoints. Considering this 

toxicological information as well as the fact that the production and use of PCBs in nearly all 

circumstances have been banned for over thirty years, that exposure to remaining PCBs is already tightly 

controlled by existing regulations and that remediation of PCB contaminated sites is also subject to 

TSCA regulation and EPA guidance, it is highly unlikely that any new information would be gained 

from further testing in the EDSP Tier 1 assays or that any such information would result in additional 

regulatory action. It is more likely that risk reduction will be achieved through continued emphasis on 

clean-up and revitalization. 

III. Substances used in Tier 1 assay validation 

Three of the Phase II chemicals (methoxychlor, fenarimol and vinclozolin) were used in validation 

studies for Tier 1 assays. Together with the abundance of other information regarding the endocrine 
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activity of these chemicals, these data render further testing redundant and there is therefore no reason 

for including these chemicals in the second list for screening.

A. Methoxychlor 

Methoxychlor has weak ER agonist and AR antagonist activity and was used as a reference chemical in 

validation studies for the AR binding, female pubertal, male pubertal, and uterotrophic assays (EPA 

2007f). In the female pubertal experiment, methoxychlor advanced the onset of vaginal opening, 

affected estrous cyclicity “as expected” and decreased serum levels of TSH and T4 hormones (EPA 

2007g). In the uterotrophic validation studies, methoxychlor weakly affected uterine weight gains 

(Organisation for Economic Co-operation and Development (OECD) 2003). In an analysis of ToxCast 

information with particular focus on endocrine activity, methoxychlor and its more active metabolite, 

2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were used as reference chemicals, based on 

their well-characterized estrogenic activity (Reif, Martin et al. 2010). Both chemicals showed expected 

high activity in multiple estrogen binding and transcriptional activation assays. These chemicals both 

have estrogenic effects (Miller, Gupta et al. 2006), and in ToxCast data, the daughter metabolite (HPTE) 

demonstrated higher potency across more assays than its parent, consistent with evidence showing that 

the metabolism of methoxychlor to HPTE results in higher ER affinity (Nimrod and Benson 1997). In 

contrast, when tested in a male pubertal assay, methoxychlor did not effect preputial separation or 

thyroid levels, and no treatment-related histopathology was noted (EPA 2007h).

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Dinoseb and methoxychlor have been removed from the second EDSP list. Please also see EPA 

Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or Used in the US, also 

Includes Pesticides with Cancelled Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 15

EPA Comment Code: 2060

Comment: B. Fenarimol 

In validation studies for the female pubertal and aromatase assays, fenarimol was used as a weak 

aromatase inhibitor control (Battelle, Brueggemeier et al. 2007; EPA 2007g). Fenarimol has also 

demonstrated estrogenic activity in an uterotrophic assay (Andersen, Bonefeld-Jorgensen et al. 2006) 

and anti-androgenic activity in a Hershberger assay (Vinggaard, Jacobsen et al. 2005). In addition to in 

vitro and mammalian studies, fenarimol has been tested in echinoderms (Sugni, Tremolada et al. 2010), 

shrimp (Kumar, Correll et al. 2010), and daphnia (Hassold and Backhaus 2009). In fathead minnows, 

fenarimol reduces plasma vitellogenin and egg numbers in female fish (Thorpe, Benstead et al. 2007). 

C. Vinclozolin 

Vinclozolin is a well characterized anti-androgenic fungicide known to inhibit testosterone binding 

(Kelce, Monosson et al. 1994) and was used as a control in validation of the fish short-term 
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reproduction, Hershberger, steroidogenesis, and male pubertal assays. In validation studies for the fish 

short term reproductive assay, vinclozolin caused significant decreases in fecundity at high doses 

(900μg/L). Male secondary sex characteristics, testicular degeneration, and male gonad weight were the 

most sensitive endpoints (EPA 2007i). In validation studies of the Hershberger assay, vinclozolin caused 

decreased weights of all five male sex accessory tissues (Organisation for Economic Co-operation and 

Development (OECD) 2004). In validation studies of the steroidogenesis assay, vinclozolin increased 

estradiol and decreased progesterone (M.H., M.M. et al. 2005). In validation studies of the male pubertal 

assay, vinclozolin caused delayed preputial separation and increased body weight at puberty (EPA 

2007h). Vinclozolin also binds to recombinant fathead minnow androgen receptor (Wilson, Cardon et al. 

2004) and has been found to interfere with mating behavior in male frogs (Hoffmann and Kloas 2010).

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Fenarimol has been removed from the second EDSP list. Please also see EPA Comment Code: 2020 

Contaminants No Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with 

Cancelled Registrations.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 17

EPA Comment Code: 2060

Comment: V. Industrial chemicals 

For many industrial chemicals, especially those that have been manufactured for decades and/or to 

which humans have a history of exposure (e.g. widely used organic solvents or manufacturing 

intermediates), a wide range of toxicological information exists that should be considered prior to any 

further testing for these chemicals. Here we present five examples.

A. Acrylamide 

“The genotoxic, mutagenic and carcinogenic potentials of acrylamide have been studied extensively,” 

and several mechanisms of these toxicities have been described and NOAELs established (Erkekoglu 

and Baydar 2010). Biotransformation of acrylamide by CYP2E1 to glycidamide accounts for a 

significant proportion of its toxicity, particularly with regard to its “potent” neurotoxicological effects as 

evaluated in experimentally dosed rats and mice by measuring hind- and forelimb grip strength 

(Ghanayem, Bai et al. 2010). Metabolism of acrylamide to glycidamide is also required for exposureinduced mutagenicity (Ghanayem, Bai et al. 2010). Consequently, obesity-induced upregulation of 

CYP2E1 expression exacerbates the reproductive toxicity resulting from acrylamide exposure 

(Ghanayem, Bai et al. 2010). 

Current hypotheses on mechanisms of action for acrylamide’s neurotoxicity suggest that the compound 

inhibits kinesin-based fast axonal transport and/or directly inhibits neurotransmission (LoPachin, Jones 

et al. 2003; LoPachin 2004). While its glycidamide-mediated neurotoxicity may account for some of 

acrylamide’s observed reproductive impacts (which predominantly affect males), multigenerational 

studies in rats have identified additional mechanisms that contribute to the chemical’s cumulative 
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toxicity profile. Acrylamide increases Leydig cell death and perturbs gene expression levels related to 

testicular function, including genes involved in apoptosis, cell cycle control, and nucleic acid binding in 

rats administered 60 mg/kg/day, contributing to sperm defects and abnormal histopathological testicular 

lesions along with a dose-dependent decrease in serum testosterone (Yang, Lee et al. 2005). Regarding 

the frequent appearance of thyroid tumors in rats chronically administered acrylamide, acute in vivo 

studies found a slight increase in serum T4 and some decrease in TSH, “which could suggest a direct 

stimulation of the thyroid rather than an indirect effect on thyroid regulators” (Khan, Davis et al. 1999; 

Chico Galdo, Massart et al. 2006). In vitro, acrylamide impacts DNA integrity but shows little influence 

on “the specific biochemical growth and functional variables of thyroid cells in vitro” (Chico Galdo, 

Massart et al. 2006).

From these observations, a neuropathy NOAEL has been established at 0.5 mg/kg/d and a fertility 

NOAEL at 2 mg/kg/d, the latter of which is 2,000-fold greater than the estimated dietary exposure 

(WHO 2002; Dybing and Sanner 2003; Konings, Baars et al. 2003; Erkekoglu and Baydar 2010). 

Clearly defined mechanisms of toxicity have been determined for acrylamide and NOAELs have been 

established for the most potent of those toxicities; again, further testing in EDSP assays would add no 

regulatory value and is not warranted and acrylamide should be removed from the second list of 

chemicals for testing.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Linda Ferguson

Commenter Organization: American Pacific Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0021

Comment Part: 3

EPA Comment Code: 2060

Comment: Additional Reasons for Exclusion

In the supplementary information EPA posted online, EPA was careful to emphasize that not being 

included on the second list should not be interpreted to mean the EPA has no interest in the potential for 

endocrine disruption activity. Conversely, some chemicals were specifically excluded because 

information on their endocrine effect is already available and widely known:

“Although these chemicals have been excluded from the second EDSP list for one or more of these 

reasons, it is important to note that these exclusions do not imply that the Agency has no interest in the 

potential for endocrine disruption activity for these chemicals. In some instances, the Agency recognizes 

that information on endocrine effects is already available (e.g., for the hormones) or the Agency is 

currently collecting information (e.g., through the first EDSP list.” (Endocrine Disruptor Screening 

Program; Second List of Chemicals for Tier 1 Screening at page 70251)

Perchlorate is an extremely well studied chemical due its history of pharmacological use. It is not a 

chemical that can either bind to thyroid receptors or mimic thyroid hormones. Rather, given sufficient 

dose and duration, perchlorate inhibits iodide uptake to the thyroid, which will eventually act to decrease 

hormone production of the two hormones the thyroid produces, thyroxine (T4) and triiodothyronine 

(T3).
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According to the research reviewed, perchlorate is not a carcinogen, does not accumulate in the body 

and is excreted within hours. The effects on the thyroid appear to be not significant in an iodine 

sufficient population such as is found in the United States. According to the National Academy of 

Sciences (NAS), the first observed effect, the inhibition of iodide uptake by the thyroid gland occurs at 

245 ppb. The first “adverse” effect, the decrease in thyroid hormones T3 and T4 occurs at 14,000 ppb. 

The low levels of perchlorate found in some wells and public water systems are unlikely to cause 

adverse effects in humans and are predominantly the result of natural occurrence.

Given the sheer volume of the perchlorate data set and what is known about its mode of action, it is 

unclear what else EPA could possibly determine under the guidance and criteria that establish the EDSP.

Conclusions

Based on the criteria established by EPA, perchlorate should not be listed amongst the chemicals 

identified for further testing pursuant to EDSP [US EPA, 2010a; EPA-HQ-OPPT-2009-0477; FRL8848-7]. As US EPA stated, “any chemical that fell into one or more” of the exclusionary criteria should 

not be included on the second Tier 1 list. Because both of the first two criteria apply to perchlorate, it 

should be excluded from the second list of chemicals being considered for Tier 1 screening.

Few chemicals have been the subject of such extensive research and so many peer-reviewed published 

studies as perchlorate. One of the unique scientific aspects of perchlorate is that we have a 

comprehensive understanding of how it affects the body. Perchlorate’s previous medical use and 

knowledge of the mechanism of action reduces uncertainty compared to most environmental chemicals. 

Several studies, draft risk assessments, guidance document revisions as well as an extensive and 

comprehensive review by the National Academy of Sciences (NAS), Agency for Toxic Substances and 

Disease Registry (ATSDR), and subsequent studies have confirmed the NAS panel’s conclusions 

concerning the current state of the science regarding perchlorate.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 1

EPA Comment Code: 2060

Comment: January 18, 2011 

Mr. Steve A. Owens 

Assistant Administrator 

Office of Chemical Safety and Pollution Prevention 

U.S. Environmental Protection Agency 

1200 Pennsylvania Ave., N.W. 

Washington, D.C. 20460-0001 
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Re: Comments on Specific Chemicals (Benzene and MTBE) for the “Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-0477; FRL-8848-7] 

Dear Mr. Owens: 

The American Petroleum Institute (API) appreciates the opportunity to submit comments on the 

Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the “draft 

EDSP List 2”). API is a national trade association representing more than 450 member companies 

involved in all aspects of the oil and gas industry, including exploration, production, refining, 

transportation, distribution, and marketing of petroleum and petroleum products. 

API is providing comments on two of the substances on EPA’s draft EDSP List 2, specifically methyl 

tertiary butyl ether (MTBE) and benzene. API has sponsored extensive health effects research on these 

two chemicals in the past. We believe the available data are sufficient to characterize the risk of these 

chemicals for endocrine effects and that the studies required under EDSP Tier 1 are an unnecessary and 

costly waste of resources.

Specific Comments on Methyl Tertiary Butyl Ether (MTBE): 

EPA already has extensive data available on MTBE from which to characterize the risk of endocrine 

effects. For example; 

* EPA issued an enforceable testing consent order under TSCA Section 4 on MTBE (FR Vol 53. No. 62, 

March 31, 1988). The required studies included a 90-day repeat dose study in rats, developmental 

toxicity studies in rats and rabbits, a 2-generation rat reproduction study, and a chronic study in rats. All 

those studies have been completed, submitted to EPA, and published in the peer-reviewed literature. 

* EPA issued a rulemaking under the Fuels and Fuel Additives Health Effects Testing Regulation 

pursuant to Section 211(b) (2) and 211(e) of the Clean Air Act (59 FR 33042 and 33081, June 27, 1994). 

The rule required testing of gasoline containing the maximum allowable concentration of MTBE. 

Required studies included a 90-day repeat dose study in rats, developmental toxicity studies in rats and 

mice, a 2-generation rat reproduction study, and a chronic study in rats. All of those studies have been 

completed and submitted to EPA. 

* EPA, on October 29, 1999 (64 FR 58409) announced its intent to develop aquatic life criteria for 

several chemicals including MTBE. In a follow-up announcement in March, 2006, EPA said that since 

1999, they had “conducted a careful review of 33 toxicity studies and a national survey of MTBE 

occurrence in surface waters. EPA has determined that MTBE typically is found in the aquatic 

environment at levels far below those that are toxic to aquatic life. Consequently, EPA does not intend at 

this time to publish new ambient water quality criteria for MTBE under Section 304(a) of the Clean 

Water Act.” These determinations, and the methods used, were published in 2002 in the scientific 

journal Environmental Science and Technology. Among the studies conducted and reviewed was Earlylife stage toxicity of methyl tertiary-butyl ether (MTBE) to the fathead minnow (Pimephales promelas) 

under flow-through test conditions (ENSR, 1999). That study found no evidence of altered growth and 

development of fish embryos. Another one of the studies, Methyl tertiary-Butyl Ether - A flow-through 

life-cycle toxicity test with the cladoceran (Daphnia magna), is proposed for EDSP Tier 2. EPA should 
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recognize that studies already exist that can inform them about the likelihood of endocrine effects from 

MTBE. 

* The European Union (EU) Risk Assessment Report on MTBE (Third Priority List, Volume 19, 2002) 

summarized the available data on the aquatic compartment, reproductive effects, developmental effects, 

and other effects on the endocrine and reproductive system. The EU Risk Assessment Report began the 

Risk Characterization on MTBE (Section 4.1.3) by stating, “Extensive data are available for MTBE’s 

health based evaluation. Because MTBE has been of great public interest, abundant information is 

available on occupational and consumer exposure, toxicokinetics and the toxicological effects’ endpoints. The numerous case reports of MTBE’s use in cholecystolithotripsy have given valuable 

information in the assessment of acute effects in humans. There are also a number of reports with 

controlled MTBE exposure and epidemiological data. Although not all reports formally concur with EU 

or OECD guidelines, most of them are well-conducted studies from the ‘80s and ‘90s providing for a 

sound data set.”

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Leslie Berry

Commenter Organization: American Chemistry Council Oxo Process Panel

EPA Document ID: EPA-HQ-OPPT-2009-0477-0027

Comment Part: 2

EPA Comment Code: 2060

Comment: Additionally, 1-butanol in the environment is readily biodegraded, almost non-toxic to 

aquatic life, and is not likely to cause environmental harm at levels normally found in the environment 

(USEPA, 1994). The 2005 Organization for Economic Cooperation and Development Screening 

Information Data Set (OECD SIDS) Program’s evaluation of 1-butanol showed that1-butanol is only 

slightly toxic following acute oral, dermal, or inhalation exposure and is not a genotoxicant. 

Neurotoxicity and developmental toxicity are observed only after acute exposure to very high dose 

levels (6,000 – 8,000 ppm) of 1-butanol; levels rarely experienced within occupational settings or the 

environment. 1-Butanol is readily metabolized by enzymes present in all organisms to n-butyraldehyde 

and n-butyric acid; two chemicals that are also present within all environmental species and mammalian 

organisms due to endogenous metabolism of foodstuffs and cellular components (Barton et al., 2000).

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 9

EPA Comment Code: 2060

Comment: c. TPTH Has Already Been Tested in Higher Tier Studies
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In the course of registration as a fungicide, TPTH has been evaluated in many of the higher tier studies. 

Information from registrants and information from the literature indicate that developmental toxicity has 

been evaluated in the rat, mouse, and rabbit. Further there are reproduction studies available in several 

species including rat, mallard duck, and bobwhite quail. Chronic (2 year) feeding studies are also 

available for this material. Tier 1 screening studies do not appear to be necessary to aid in the 

assessment of this material, based on the body of data already available from studies that are considered 

Tier 2 in vivo studies.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0035

Comment Part: 2

EPA Comment Code: 2060

Comment: 2. The International Isocyanate Institute has initiated in-vitro screening tests to investigate 

the estrogen- and androgen-receptor binding potential of MDA, as part of its ongoing product 

stewardship efforts for the global isocyanates industry. The results of these studies will be forwarded to 

the Agency in the first quarter of 2011. The results of these studies are expected to supplement the 

reported findings by Tullner (1960) where an uterotrophic response as well as hypertrophy of the 

adrenal and thyroid were observed in ovariectomized rats. Secretion of 17-hydroxycorticoid was 

transiently inhibited in dogs. [FN5: Tullner, W.W., Endocrine effects of methylenedianiline in the rat, 

rabbit and dog. Endocrinology 66: 470-474, 1960]

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 10

EPA Comment Code: 2060

Comment: B. Ecological Effects of Acrylamide Have Been Well Studied and Do Not Suggest a Need 

for Further Testing 

There are adequate data to show that acrylamide has moderate to low toxicity in aquatic organism and is 

not anticipated to cause significant adverse environmental effects. A wide range of aquatic plants, 

invertebrates (daphnids, midge larvae, opossum shrimp, oyster larvae) and fish (goldfish, stinging 

catfish, rainbow trout, fathead minnow, bluegill) have been tested with acrylamide. 

In a recent environmental assessment of acrylamide, Canada noted that “experimental ecotoxicological 

data indicate that acrylamide does not cause significant harm to aquatic organisms at low 

concentrations” (Environment Canada 2009) and concluded that: 
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[A]crylamide is not entering the environment in a quantity or concentration or under conditions that 

have or may have an immediate or long-term harmful effect on the environment or its biological 

diversity or that constitute or may constitute a danger to the environment upon which life depends. In 

addition, acrylamide does not meet the criteria for persistence or bioaccumulation. 

A full review of the available acrylamide environmental data can be found in the 2009 Canadian 

assessment and also in the earlier EU RAR. 

V. Existing Toxicology Data on Acrylamide Addresses EPA Data Needs 

There have been numerous toxicity studies conducted on acrylamide in a number of animal species. As 

EPA concluded in its recent IRIS assessment (2010), “The animal database is robust.” EPA and other 

assessments have generally found the nervous system, specifically degenerative peripheral nerve 

changes, to be the principal site of the toxic actions of acrylamide (EPA 2010, EU 2002, WHO 2002). 

In regards to reproductive and developmental effects, which is a primary focus of EDSP, EPA 

concluded in 2010 (IRIS) that, “there is a large database for reproductive effects from oral exposure to 

acrylamide.” A thorough review of the reproductive and development data is available in the recent IRIS 

assessment; therefore, NAPPA will not summarize the information again in these comments except to 

note that there are multiple well-documented 2-generation reproductive effects and developmental 

toxicity studies on acrylamide in multiple species. These are the types of studies that EPA is considering 

for Tier 2 of EDSP. 

With such a “robust” and “large database” of higher-tier toxicology studies available on acrylamide, 

NAPPA sees no real risk assessment value to EPA in conducting Tier 1 EDSP studies. Further, EPA 

notes that it has high confidence in its conclusion that neurological effects are the most sensitive 

endpoint for acrylamide. EDSP Tier 1 is unlikely to provide any great insight to the Agency on this 

critical effect; however, as discussed in Section VII, FDA has an extensive testing program to further 

evaluate possible health risks of acrylamide.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 12

EPA Comment Code: 2060

Comment: VII. Significant New Toxicology Data on Acrylamide Being Developed by the FDA NCTR 

and NTP 

There are significant toxicological studies underway on acrylamide through the US Food and Drug 

Administration’s (FDA) National Center for Toxicological Research (NCTR) in conjunction with the 

National Toxicology Program (NTP). NCTR’s Fiscal Year 2009-2010 document[FN8: FDA NCTR FY 

2009-2010 report: 

http://www.fda.gov/downloads/AboutFDA/CentersOffices/NCTR/ResearchAccomplishmentsPlans/UC
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M200349.pdf] outlines its research accomplishments and ongoing work on acrylamide (this is 

summarized in Attachment 2). The NCTR is evaluating both the chronic and neurological effects of 

acrylamide and glycidamide, the primary metabolite of acrylamide, in adult and developing animals. 

Additionally, NCTR is conducting a series of mechanistic studies and developing a PBPK/PD model for 

acrylamide. 

Testing and pathology reviews have been completed for the chronic two-year bioassays on acrylamide 

and glycidamide and also for the newborn-mouse assay comparing the carcinogenicity of acrylamide 

and glycidamide. Final reports for these studies are expected in the near future. Several of the 

neurological studies are complete and have been published (references listed in Attachment 2). When 

the NCTR/NTP overall program is complete, it will represent an enormous toxicological data set for 

acrylamide, well beyond what EPA is currently contemplating for acrylamide under EDSP Tier 1. 

VIII. Conclusion 

In summary, NAPPA believes that EPA should remove acrylamide from the list of substances to be 

included in the EDSP program because: 

* A “substantial population” is not exposed to acrylamide from drinking water. In fact, US and other 

health agencies have specifically concluded that drinking water is not a significant source of exposure to 

acrylamide. 

* Acrylamide has a drinking water PHG of zero (0). Additional testing under the EDSP program will not 

change this standard or improve EPA’s regulation of acrylamide in drinking water. Further, EPA 

regulation of free acrylamide in polyacrylamide water treatment technologies, which have 

environmental and public health benefits, ensures that potential acrylamide contamination must be <0.5 

ppb. The resulting exposure from even this contamination is exceedingly small (<0.01 μg/kg bw/day) 

and in most cases it will be much less. 

*Acrylamide has an extensive toxicology database which the EPA IRIS assessment considers “robust,” 

including “a large database for reproductive effects from oral exposure to acrylamide.” This available 

higher-tier in vivo data on acrylamide obviates the need to conduct EDSP Tier 1 testing. 

* EPA does not have the authority under the SDWA to require testing of ecological organisms as 

envisioned in the EDSP. More significantly, there is no indication from the considerable testing of 

acrylamide in aquatic organism that it poses a significant risk to the environment. 

* Acrylamide’s natural presence in a wide variety of foods suggests that it should be excluded from 

EDSP (based on EPA’s exclusion criteria) and best addressed by the extensive research program 

underway by the FDA/NTP. 

NAPPA trusts that once EPA reviews the available information provided in these comments, it will 

remove acrylamide from the list of EDSP candidate substances and not issue EDSP test orders on 

acrylamide. 

REFERENCES 

Environment Canada and Health Canada 2009. Screening Assessment for the Challenge Program: 2-

Propenamide (Acrylamide) CAS 79-06-1. August 2009 
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EU RAR 2002. European Union Risk Assessment Report – Acrylamide (CAS No. 79-06-1; EINECS 

No: 201-173-7). EUR 19835 EN. http://ecb.jrc.it/DOCUMENTS/ExistingChemicals/RISK_ASSESSMENT/REPORT/acrylamidereport011.pdf. 

NSF 2000. Review of Contaminant Occurrences in Drinking Water Treatment Chemicals: A Summary 

Report of NSF International Results (1991 to 1999). Prepared for Health Canada, Health Protection 

Branch, by NSF International, Ann Arbor, MI. March 31, 2000.

Attachment 1: Summary of the Distribution Weighted Concentration of Acrylamide in Several 

Commodities from 2002 to 2004 (FAO/WHO 2005, Table 4)

[See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0042.2]

Attachment 2: Summary of U.S. FDA National Center for Toxicological Research on Acrylamide

[See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0042.2]

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints. Also, 

see general responses to comment under EPA Comment Codes: 2090 Contaminants with MCLG of zero

and 1065 EPA’s Authority to Require Testing.

Commenter Name: Robert Simon

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0048

Comment Part: 3

EPA Comment Code: 2060

Comment: 3. Current Database on Endocrine-Modulating Capability: PFOA is one of the most 

thoroughly studied industrial chemicals. PFOA and ammonium perfluorooctanoate (APFO), the form of 

PFOA typically used in fluoropolymer manufacturing, have already been subject to multiple tests that 

inform the potential of these substances to modulate the endocrine system. This testing has been 

conducted by a wide spectrum of researchers, including governmental, academic and industry scientists.

PFOA has been well characterized in multiple test systems using experimental animals, including nonhuman primate species. Additional human health and environmental data are also available as noted 

below. These tests have primarily been designed to detect health hazards caused by any mode of action, 

including endocrine modes. In addition, some of the existing research has directly addressed the 

relationship between PFOA and endocrine-related biomarkers. Specific citations for some of the most 

relevant studies are provided at the end of these comments. The data from these studies provide a strong 

basis for evaluating several of the endpoints of interest to the EDSP program. By way of summary, the 

relevant research includes the following categories of studies:

a. Two-Generation Reproduction Study in Rats: A guideline two-generation reproduction study with 

APFO has been performed.
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b. Chronic Toxicity Studies in Rats: The chronic toxicity and oncogenicity of APFO has been 

investigated in two 2-year feeding studies in rats.

c. Developmental Toxicity Studies in Rats, Rabbits, and Mice: Available studies include developmental 

toxicity testing of APFO in fetal rats, rabbits and mice.

d. Mechanistic Studies Evaluating Potential Endocrine Activity: Several studies have examined 

endpoints relevant to the potential endocrine-modulating activity of APFO. These studies have included 

examination of APFO effects on testosterone and estradiol levels, as well as hepatic aromatase activity, 

in rats.

e. Studies in Non-Human Primates: The available data include results from a 26-week oral toxicity study 

in cynomolgus monkeys that examined effects on reproductive organs as well as correlative 

histopathology (including adrenal, epidiymis, mammary gland, pancreas, pituitary, prostate, seminal 

vesicles, testes, and thyroid) and serum hormone parameters (cortisol, testosterone, estradiol, estrone, 

estriol, free and total triiodothyronine, and free and total thyroxine.)

f. Human Data: The existing literature provides substantial data from studies of worker populations 

engaged in the production and use of APFO as well as of populations living in an area surrounding a 

fluoropolymer manufacturing facility.

g. Ecological Studies: There are several existing aquatic studies that are pertinent to the assessment of 

endocrine effects of APFO and PFOA, including tests in the rare minnow, Gobiocypris rarus, as well as 

fathead minnows, Pimephales promelas. These studies have included examinations of gene expression, 

hormone levels, enzyme activity, reproductive health and developmental effects.

These studies, which are part of a well-established toxicology database on PFOA, have provided the 

basis for EPA and industry actions on this chemical over the last several years.

4. On-Going Studies: PFOA is the subject of a number of on-going health studies. Several of these 

studies are expected to be completed later this year or next year.

a. The National Toxicology Program (NTP) has an on-going testing program on PFOA including a longterm (2-year) bioassay with in utero exposure. This study was undertaken in response to EPA-OPPT’s 

specific nomination of such a study in 2003 as a high priority information need for the Agency’s 

evaluation of PFOA. OPPT should evaluate the results of the studies that it requested, which we 

understand are moving toward completion, before initiating additional tests in mammalian species.[FN3: 

http://ntp.niehs.nih.gov/index.cfm?objectid=BDA0E838-123F-7908-7B489F914405394E]

b. The C8 Science Panel, an independent panel of scientists, is conducting a series of community 

epidemiology studies and worker epidemiology studies that will address a number of these endpoints. 

The results are expected in 2011 and 2012.[FN4: http://www.c8sciencepanel.org/timeline.html]

5. EPA Drinking Water Health Advisory Development: In 2009, EPA issued a Provisional Health 

Advisory to provide communities with a protective limit on exposure to PFOA through drinking water. 

EPA’s Office of Water (OW), with support from the Office of Chemical Safety and Pollution 

Prevention, is currently developing a Permanent Health Advisory, which is expected to be completed in 

2011. The Advisory will reflect EPA’s evaluation of the extensive set of data noted above.
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The Permanent Health Advisory is intended to be comprehensive in scope. It will be protective for 

chronic exposure and will reflect EPA’s consideration of the effects of PFOA on all health endpoints, 

including those effects related to any endocrine-related mechanism of action that has been identified in 

the large body of existing toxicology data.

Thus, the OW Advisory will, sometime in 2011, provide EPA with the appropriate risk-based context 

for further information needs about PFOA. As a matter of sound policy and minimization of unnecessary 

animal testing, it would be prudent for EPA to evaluate the results of its own risk assessment and 

drinking water protection guideline before launching a new information collection initiative on a 

chemical that has been as extensively tested as PFOA.

Conclusion

As described above, PFOA has been the subject of substantial information collection, toxicity testing, 

risk assessment and exposure reduction activities for over a decade. Those activities provide the 

framework for how the EDSP program should address this chemical.

The existing scientific literature provides an extensive database on how APFO and PFOA may affect 

health and the environment. The database includes significant information on how PFOA may interact 

with the endocrine system. This literature provides a robust scientific foundation for EPA to set a 

Permanent Health Advisory on PFOA for the protection of drinking water, the primary exposure 

pathway of concern for Phase 2 of the EDSP. In addition, through a series of voluntary and regulatory 

program actions, EPA is on a course that is expected to reduce current public exposures to PFOA even 

further than has been achieved to date. Few other chemicals identified in the Draft EDSP List 2 are the 

subject of a comparable scientific understanding and a set of systematic risk reduction actions by the 

Agency.

Importantly, EPA should consider the fact that key developments related to PFOA will be occurring in 

2011. These include the further development of EPA’s plan for the Chemical Action Plan on LongChain Perfluorinated Chemicals and the Permanent Health Advisory. These developments will provide 

important insights about the overall and specific needs for further information about PFOA. 

Accordingly, we strongly urge EPA to await the results of these strategic actions and ongoing studies on 

PFOA over the next year before pursuing any EDSP Tier 1 Screening. 

We appreciate the opportunity to provide information and comment on the Agency’s approach to PFOA 

under the EDSP. If you have any questions or would like additional information, please contact Robert 

J. Simon at 202-249-6700 or robert_simon@americanchemistry.com.

Sincerely,

Robert J. Simon

Vice President

Chemical Products & Technology Divisions

Attachment: References

References
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Biegel, L. B., Hurtt, M. E., Frame, S. R., O'Connor, J. C., and Cook, J. C. (2001). Mechanisms of 

extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol. Sci. 60, 44-55.

Biegel, L. B., Liu, R. C. M., Hurtt, M. E., and Cook, J. C. (1995). Effects of ammonium 

perfluorooctanoate on Leydig cell function: in vitro, in vivo, and ex vivo studies. Toxicol. Appl. 

Pharmacol. 134, 18-25.

Butenhoff, J., Costa, G., Elcombe, C., Farrar, D., Hansen, K., Iwai, H., Jung, R., Kennedy, G., Lieder, 

P., Olsen, G., and Thomford, P. (2002). Toxicity of ammonium perfluorooctanoate in male 

cynomologous monkeys after oral dosing for 6 months. Toxicol. Sci. 69, 244-257.

Cook, J. C., Murray, S. M., Frame, S. R., and Hurtt, M. E. (1992). Induction of Leydig cell adenomas by 

ammonium perfluoroctanoate: a possible endocrine-related mechanism. Toxicol. Appl. Pharmacol. 113, 

209-217.

Liu, R. C. M., Hahn, C., and Hurtt, M. E. (1996a). The direct effect of hepatic peroxisome proliferators 

on rat Leydig cell function in vitro. Fundam. Appl. Toxicol. 30, 102-108.

Liu, R. C. M., Hurtt, M. E., Cook, J. C., and Biegel, L. B. (1996b). Effect of the peroxisome proliferator, 

ammonium perfluorooctanoate (C8), on hepatic aromatase activity in adult male Crl:CD BR (CD) rats. 

Fundam. Appl. Pharmacol. 30, 220-228.

Oakes, K.D., P.K. Sibley, K.R. Solomon, S.A. Mabury and G.J. van der Kraak. 2004. Impact of 

perfluorooctanoic acid on fathead minnow (Pimephales promelas) fatty acyl-COA oxidase activity, 

circulating steroids, and reproduction in outdoor mesocosms. Environ. Toxicol. Chem. 23, 1912-1919.

Sibinski LJ, Allen JL, Erickson,EE. 1987. Two year oral (diet) toxicity/carcinogenicity study of 

fluorochemical FC-143 in rats. Expt. No. 0281CR0012. St. Paul, MN USA: Riker Laboratories, Inc., 

U.S. Environmental Protection Agency Administrative Record 226-0437, 226-0438, 226-0439, 226-

0440.

Wei, Y., Y. Liu, J. Wang, Y Tao and J. Dai. 2008. Toxicogenomic analyses of the hepatic effects of 

perfluorooctanoic acid on rare minnows (Gobiocypris rarus). Toxicol. Appl. Pharmacol. 226, 285-297.

Wei, Y., J. Dai, M. Liu, J. Wang, M. Xu, J. Zha and Z. Wang. 2007. Estrogen-like properties of 

perfluorooctanoic acid as revealed by expressing hepatic estrogenresponsive genes in rare minnows 

(Gobiocypris rarus). Environ. Toxicol. Chem. 26, 2440-2447.

York RG, Kennedy GL Jr., Olsen GW, Butenhoff JL. 2010. Male reproductive system parameters in a 

two-generation reproduction study of ammonium perfluorooctanoate in rats and human relevance. 

Toxicology 271 (1-2), 64-72.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints. 

Please also see Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published simultaneously with this 

comment response document.
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Commenter Name: Kathleen Roberts

Commenter Organization: Methyl Tertiary Butyl Ether (MTBE) Consortium

EPA Document ID: EPA-HQ-OPPT-2009-0477-0053

Comment Part: 2

EPA Comment Code: 2060

Comment: The MTBE Consortium’s comments are intended to provide EPA an awareness of the 

existence and key findings of available relevant information on endocrine effects for MTBE. The 

following comments are not intended to be an exhaustive review and analysis of all studies that could 

pertain to the potential for MTBE to interact with the estrogen, androgen, or thyroid hormonal systems; 

EPA is referred to other existing reviews for this information (European Commission, 2002; McGregor, 

2006; Cruzan, 2007). Instead, these comments focus on the Tier 1 screening battery and MTBE 

information that is available that have addressed these endpoints. The MTBE Consortium believes that 

because of the wealth of available information available and being developed on MTBE that 

characterize endocrine effects, EPA’s EDSP would be better served by excluding MTBE from the 

second list of substances under consideration for EDSP Tier 1 screening.

As discussed below, the MTBE Consortium respectfully urges EPA to remove MTBE from the list of 

chemicals slated for Tier 1 screening. MTBE has been well-studied and there is ample data in the 

literature. Further testing is unlikely to better inform the issues. The following describes much of the 

existing literature on MTBE toxicology testing in greater detail.

EPA Should Consider the Availability and Results of Existing Data before Selecting Chemicals for 

EDSP Screening

In its Federal Register notice announcing the second EDSP list of substance candidates, EPA notes that 

it focused on substances that have been listed as priorities within EPA’s drinking water and pesticide 

programs.[FN3: 75 Fed. Reg. at 70250.] EPA states in its Federal Register notice on its draft policies 

and procedures for screening Safe Drinking Water Act (SDWA) chemicals that “[a]s part of the EDSP, 

EPA issues orders to collect certain test data on selected chemical substances.”[FN4: 75 Fed. Reg. 

70558, 70560 (Nov. 17, 2010).] This implies that if there is little or no need to collect certain test data, 

there would be no reason to include a substance on the EDSP candidate list.

Table 1 lists the screening test recommended in the EDSP Tier 1 battery, studies that are available that 

address these endpoints, and their references. Following Table 1 is a more detailed explanation of the 

data available for each endpoint.

Table 1: Endocrine Disruption Screening Program Tier 1 tests related to similar prior studies

[See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0053.2]

*Selected key details summarized below.

In Vitro Tests Recommended in the EDSP Tier 1 Battery Already Exist for MTBE

ER Binding -- Rat Uterine Cytosol
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The ability of MTBE and two major metabolites, tertiary butyl alcohol (TBA) and formaldehyde, to 

displace 17β-[3H] estradiol binding has been examined in recombinant human ER from baculovirusinfected insect cells (Moser et al., 1998). After an overnight incubation with labeled estradiol and a wide 

range of concentrations of MTBE, TBA or formaldehyde, or estradiol (positive control), the receptor 

complex was precipitated and washed, and the radioactivity of the pellet indicated whether labeled 

estradiol binding had been altered by the presence of MTBE/TBA/formaldehyde or the positive control. 

Figure 5a in this report shows the DPM of 5 nM (5 x 10-6 mM) labeled estradiol-ER complex 

unchanged by the presence of MTBE over the range of what appears to be 11 different concentrations 

examined with ten-fold difference between these concentrations (Figure 5a) ranging from 10-11 M to 

10-4 M (10-8 mM- 0.1 mM). Estradiol concentrations of 10-7 M and higher completely inhibited 5 x 10-

6 mM labeled estradiol binding, which would be expected. Moser et al. also reported no alteration in 

estradiol binding by TBA and formaldehyde at concentrations up to 0.1 mM, which is presumably why 

data for metabolite binding assays were not shown.

Estrogen Receptor α (hERα) Transcriptional Activation -- Human Cell Line (HeLa-9903)

Moser et al. (1998) also describes having tested the ability of MTBE to activate the ER in a mammalianbased transfection assay using human liver HepG2 cells. Changes in activation of the ER and 

translocation of the ER complex to the response element on the DNA can be detected using this assay. 

The MTBE dose range tested (shown in Figure 5b as the average of three separate experiments and 

expressed as log (M)) ranged from -8 to -4 (i.e, 10-8 to 10-4 M or 10-5 mM to 0.1 mM). MTBE neither 

induced ER activity nor antagonized a maximally inducing dose of estradiol.

The Interagency Center for the Evaluation of Alternative Toxicological Methods 

(ICCVAM)/Interagency Coordinating Committee on the Validation of Alternative Methods 

(NICEATM) Expert Panel (2002) has made a number of recommendations for testing compounds of 

interest to satisfy Tier 1 testing in in vitro ER binding and ER transcriptional activation (TA) assays. 

One of these is an upper limit test concentration of 1 mM for the ER binding assay (one panel member 

felt 1 mM was excessive for the TA assay and 0.1 mM should suffice). Other considerations should be 

taken into account, however, including solubility and denaturation of the receptor at high test substance 

concentrations. Although Tier 1 ER TA test guidelines specify rat cytosol ER receptor for the ER 

binding assay and HeLa cells for the ER TA assay, discussions among review panel members 

considering earlier drafts of the test battery indicate that alternative cell types may be suitable. 

Performance following good laboratory practice (GLP) guidelines is another recommendation.

These were not intended to be GLP studies. Careful examination of all experimental details, findings, 

and documentation of these assays already reported by Moser et al. (1998) may show that there is no 

need for further testing of MTBE in other competitive ER binding or ER transcriptional activation 

assays. The fact that Moser et al. included MTBE metabolites in their ER competition studies and also 

found these to be negative is additional evidence to support their conclusion that MTBE’s effects in vivo 

are not mediated through the ER. Several endpoints related to androgen hormone modulation have been 

the focus of prior studies in rodent model systems, but AR binding per se is not among those reported in 

the open peer-reviewed literature.

AR Binding -- Rat Prostate Cytosol

No MTBE studies were found specifically measuring AR binding. Several laboratories have 

independently conducted 28-day gavage studies of MTBE and looked at effects on male rat prostate and 
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other accessory sex organ weights. If MTBE were binding to ARs on these organs, then it seems 

reasonable to expect to see some effect on these androgen-dependent weights. None have found any 

consistent effects (discussed in more detail later).

Several endpoints related to androgen hormone modulation have been the focus of prior studies in 

rodent model systems, but AR binding per se is not among those reported in the open peer-reviewed 

literature.

Steroidogenesis -- Human Cell Line (H295R)

One published report of testing MTBE and TBA in freshly isolated male Sprague- Dawley rat Leydig 

cells shows that high concentrations of MTBE or TBA (50-100 mM) are capable of suppressing basal 

and hCG-stimulated testosterone production (de Peyster et al., 2003). High MTBE concentrations were 

used in that experiment with the objective of exploring how doses of MTBE could have increased 

Leydig cell tumors in rodent cancer bioassays. Based on assumptions explained in that paper, the 50 mM 

concentration in cells could be roughly 2.5 times the maximum experienced in testicular tissues of rats 

in the inhalation cancer bioassays showing increased Leydig cells (Bird et al., 1997).

The freshly isolated rat Leydig cell experiment focused on testosterone and was not designed to be a 

screening assay for any type of effect on steroidogenesis or to identify any no observed adverse effect 

concentration (NOEAC), both of which would have required a much greater range of concentrations and 

analysis of more endpoints in addition to testosterone in the supernatant. EDSP Tier 1 screening 

specifies a human female adrenal carcinoma cell line. Two of the reasons for selection are that these 

cells are commercially available and cells have evidently been shown to express enzymes of 

steroidogenesis that are considered key (or expresses “most” but not necessarily known that it expresses 

all). Effects on the several sex steroids can be screened using these cells, including progesterone, 

testosterone, androstenedione, estrone, and 17β-estradiol.

Aromatase -- Human Recombinant Microsomes

In a 14-day exploratory experiment involving adult male Sprague-Dawley rats, mean aromatase catalytic 

activity (measured by the tritiated-water release assay) in the group gavaged with 1200 mg/kg BW/day 

MTBE showed aromatase activity in liver and testicular microsomes to be reduced by approximately 50 

percent relative to corn oil vehicle controls (de Peyster et al., 2003). On the other hand, decreased serum 

testosterone and increased serum estradiol was also observed in the same animals -- the opposite of what 

might be expected if decreased aromatase activity were the only effect. A possible explanation was that 

elevated estradiol in the MTBE group detected in that experiment could have been causing competitive 

product inhibition (Shimizu et al., 1993), which would then decrease aromatase activity; however, even 

if that were the case, then the cause of the serum estradiol increase in that experiment still eluded 

explanation. High doses are being used in these experiments to be comparable to doses experienced by 

rats reported to have a higher Leydig cell tumor incidence in high dose long-term MTBE cancer 

bioassays.

Attempting to understand any MTBE effect on aromatase as a possible explanation for the rat Leydig 

cell increase, follow-up experiments in Sprague-Dawley male rats using additional gavage dose levels 

have been conducted (de Peyster et al., in progress). Although analysis of data is not quite complete, it is 

clear that liver and testicular microsomal aromatase activity continue to show dose-related decreasing 
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trends in this high-dose MTBE in vivo rat model. Final results for other related endpoints are expected 

soon.

The Tier 1 aromatase screening assay specifies measurement of aromatase activity using the same 

tritiated-water release assay used above but using human recombinant microsomes expressing aromatase 

(CYP19) that are commercially available.

It seems clear that MTBE (or a metabolite) is able to alter CYP19 activity when administered to male 

rats by gavage daily for 14 days at doses in the range of 1200-1500 mg/kg BW/day--doses far exceeding 

any levels a human would ever tolerate. The physiological implications of this, including exactly how 

this might translate to altered testicular or circulating steroid hormone levels in the whole organism, has 

been more difficult to pin down with consistent results. While it is true that these authors and others 

have often seen statistically significant reductions in serum testosterone levels in male rats given high 

doses of MTBE, this has been difficult to detect unless blood is sampled within an hour after the gavage 

dose is administered. A secondary effect of altered activity of MTBE-inducible P450 enzymes could be 

contributing to this finding. Although often MTBE dose-response trends are observed, these are not 

always highly significant (or are not statistically significant), and involvement of the stress hormone 

corticosterone could not be ruled out. Elevated corticosterone has also been observed in several studies 

of MTBE.

In Vivo Tests Recommended in the EDSP Tier 1

Battery Already Exist for MTBE

Uterotrophic (Rat)

This in vivo assay can detect both estrogenic and antiestrogenic effects of test substances. The main 

endpoint in the standard uterotrophic assay is uterine weight. Comments accompanying the Tier 1 

battery (Table 1) state a preference for using ovariectomized females exposed by subcutaneous injection, 

avoiding first-pass metabolism. Uterine weights are compared among groups exposed to estradiol, test 

chemical(s), estradiol+test chemical(s), and vehicle alone.

Interested in following up on the lack of evidence for MTBE interaction with the ER -- as reported by 

Moser et al. (1998) and described above -- Okahara et al. (1998) conducted a uterotrophic assay to test 

MTBE in an immature mouse system. The authors chose the mouse because of interest in its response to 

MTBE in other studies; that is, higher incidence of hepatocellular adenomas concurrent with reduced 

incidence of uterine cystic hyperplasia at the highest concentration (8000 ppm) (Bird et al., 1997)

That study was completed before establishment of EDSP test guidelines. For various reasons that were 

easily justified at that time, their laboratory chose the gavage route (vs. subcutaneous injection) and use 

of immature (vs. ovariectomized) mice. MTBE was administered for five days by gavage. The young 

CD-1 mice used in that experiment tolerated repeated doses of 1,500 mg/kg MTBE, which is slightly 

less than one-half of the adult mouse oral LD50 (4,000 mg/kg, ATSDR, 1996), without experiencing 

any reduction in body weight gain. The treatment regimen used in this study produced little if any

reproducible effect on immature mouse uterus and no effect on ovaries. The Society of Toxicology 

(SOT) abstract/poster presentation elaborates further that uteri from mice treated with MTBE alone had 

a distinct, translucent appearance even when weights were no different from comparable controls and 

mean uterine: BW ratio of the MTBE+E2 group was slightly higher than the E2 control (p<0.05). 

Uterine weights in MTBE only animals were not significantly different from corn oil controls, however. 
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No clear, consistent effect of MTBE was observed on uterine peroxidase activity or ovarian, liver, or 

kidney weights in that experiment.

It seems logical, however, to take a few recommendations into consideration before conducting another 

uterotrophic assay: (1) mice may be the more interesting if not the more relevant test species to use in 

this case given the lack of any significant effects even hinting of an endocrine-related effect reported in 

female rats exposed to MTBE; (2) understanding the rationale for subcutaneous route (avoid first-pass 

metabolism), even still why not administer the test substance by a route more likely to reflect normal 

human exposures; and (3) given the additional lack of evidence pointing to mechanism involving 

interaction with ERs, and the limited number of endpoints typically observed in this standard assay (just 

uterine weights), time, effort, and animal resources might be better spent on some completely different 

approaches to include more endpoints and elucidate other possible endocrine effects that have not 

received as much attention.

Hershberger (Rat)

This assay uses gonadectomized adult male rats and is designed to detect androgenic and antiandrogenic effects. Weights of male accessory sex organs are compared among groups exposed to 

testosterone propionate (TP), test chemical(s), TP+test chemical(s), and vehicle alone.

Experiment 3 reported in de Peyster et al. (2003) was essentially a Hershberger assay although with a 

limited number of accessory sex organs weighed because of its slightly different focus. The main 

purpose of that experiment was to determine the effect of MTBE on the pituitary secretion of LH when 

androgen stimulation was controlled by silastic capsule implants containing TP. Organ weights are not 

reported in the publication, but prostate and seminal vesicles were among the weights recorded at 

necropsy. Although actual data were not shown, the results section of this publication states that “overall 

there was no clear indication from pituitary or accessory organ weights that these organs had been 

affected directly by MTBE under the conditions of this experiment.”

The standard Hershberger assay conducted now includes reporting of weights of more accessory sex 

organs (bulbocavernosus/levator ani muscle, glans penis, and Cowpers gland) that were not observed in 

this experiment. Several laboratories have independently conducted gavage studies lasting up to 28 days 

of daily dosing with MTBE and observed no consistent effects on male rat prostate and other accessory 

sex organ weights, although none of the investigators appear to have weighed all five organs expected 

now in the Hershberger.

If MTBE were binding to ARs on these organs, it seems reasonable to expect to see at least some effect 

on the androgen-dependent accessory sex organ weights in multiple studies conducted. None have found 

any consistent effects.

The full 1992 report of the chronic inhalation cancer bioassay conducted in F344 rats (Chun et al., 

summarized in Bird et al., 1997) includes some brief notations in the necropsy report about 

epididymides and seminal vesicle sizes being decreased (e.g., p. 105) in high dose animals sacrificed at 

week 82, however, there are no weights of these organs in that report or other quantitative, objective 

measurements made to support that.

Pubertal Female (Rat)
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This assay assesses pubertal development and thyroid function in intact female rats. The recommended 

standard assay is capable of detecting anti-thyroid, estrogenic, or antiestrogenic effects or agents that 

alter pubertal development. No generally comparable studies have been reported to date. Endocrinerelated effects have been the focus of studies only in adult female mice (Moser et al., 1998). 

Furthermore, no non-endocrine-focused studies at all have been conducted in pubertal female animals. A 

close look at everything already known about the estrogenic/antiestrogenic potential (or lack thereof) in 

adult female rats (no findings of endocrine activity concern in any study) and mice (Moser et al., 1998) 

should be carefully scrutinized before deciding whether a pubertal female rat test is necessary and, if so, 

how it should be designed.

Pubertal Male (Rat)

Pubertal development and thyroid function in intact male rats is the focus of this study using weanling 

male rats, and a 30-day gavage dosing period. This test is included in the Tier 1 battery specifically to 

detect anti-thyroid, androgenic, or anti-androgenic chemicals or agents that alter pubertal development.

Only two studies appear to have used male pubertal animals, one of which is reported only as an 

abstract. Almeida et al. (2004) exposed male BALB/c mice through drinking water containing 80, 800, 

or 8000 μg/L (ppb) MTBE for 28 days. An abstract of this 28-day drinking water study had reported an 

increase in abnormal seminiferous tubules, increased tubular diameters, decreased testosterone, 

increased testis and seminal vesicle weights, and decreased epididymal weights in young male mice 

exposed to MTBE. Full details of this study apparently have yet to be published, and the study findings 

were not replicated in a 51-day drinking water experiment conducted by de Peyster et al. (2008) using 

the same water concentrations and starting with 22-23 day old male mice exposed through 76-77 days of 

age. Essentially no MTBE effects were found in this follow up study. The study focused on the 

endpoints used by Almeida et al., not on screening for any endocrine effects in pubertal animals, so it 

did not include everything called for in the EDSP Tier 1 pubertal rat assay.

Amphibian Metamorphosis (Frog)

An amphibian metamorphosis study is reported by Paulov (1987). Tadpoles (Rana temporaria) were 

exposed to nominal concentrations of MTBE in the range 100 to 10,000 mg/l. The 48-h LC50 under 

these conditions was 2500 mg/l, with concentrations of up to 2000 mg/l without any lethal effect. 

Exposure to lower levels (100 mg/l) led to a marked weight increase of tadpoles and frogs that had 

undergone metamorphosis. At this concentration, metamorphosis was stimulated, occurring two days 

earlier than in controls. The normal time from hatching to metamorphosis of R. temporaria is commonly 

30-45 days (Loman, 1999), but may show even more plasticity, e.g., 20-60 days, temperature being the 

most important variable (Merilä et al., 2000).

Although any deviation from the normal is usually considered adverse, this is not so in this case. Larvae 

tend to concentrate into large schools in shallow water where their density sometimes reaches 100 

individuals per liter. Crowding effect is typical for such tadpole aggregations, and the sizes of 

metamorphosed juveniles are variable. Larger juveniles usually metamorphosed first. These have higher 

survival rates during their first over-wintering, which emphasizes an advantage of early metamorphosis.

Fish Short-Term Re-Production

MTBE has been thoroughly tested in freshwater and marine aquatic organisms and the results support a 

low concern for aquatic toxicity (EU Commission, 2002; FERC, 2010). A significant database is 
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available of acute and chronic tests performed in three trophic levels of aquatic species. The findings in 

standard protocol tests indicate generalized toxicity at high exposure concentrations, but did not find 

specific adverse effects on the apical endpoints of reproductive toxicity indicative of endocrine 

dysfunction. Developmental effects in medaka (Oryzias latipes) were not observed at concentrations up 

to 480 mg/L, and all fish hatched, fed and swam normally (Werner et al., 2001). A guideline Early Life 

Stage test with eggs and larvae/fry of fathead minnow (Pimephales promelas) is available that concluded 

effects only at high water concentrations (31-d NOEC is 299 mg/l.) (ENSR, 1999).

Moreels et al. (2006) investigated the effects of short-term and long-term exposure of adult zebrafish 

(Danio rerio) to MTBE in flow-through systems. The study examined: survival, vitellogenin 

concentration, gonadosomatic index (GSI), fecundity, fertilization rate, hatch rate, and sperm motility. 

The study found that chronic exposure over three weeks to effective MTBE concentrations of 0.11 mg/L 

induced a significant increase in the vitellogenin concentration of male fish. The impact of a chronic, 

eight-week exposure at effective concentrations ranging from 0.44 to 220 mg/L had no significant effect 

on fecundity, fertilization, or hatch rate, but highly significant impacts on sperm motility. Spermatozoa 

of all MTBE-exposure groups showed significantly lower straight-line velocity and lower average path 

velocity compared to those of the non-exposed group. The authors concluded that the results suggest that 

chronic exposure to MTBE negatively affects fish sperm motility at concentrations that are 

environmentally relevant and several orders of magnitude lower than concentrations inducing acute 

effects.

There are a number of weaknesses in the study and resulting publication, including:

* The flow-through system used in the study is inadequately described. This precludes a definitive 

evaluation of the adequacy of the system. In addition, water quality measures (e.g., dissolved oxygen, 

pH, ammonia) are not reported which, again, precludes assessment of the adequacy of the exposure 

system.

* The data were statistically analyzed for outliers; however, there is no mention of how many outliers 

were identified, where they existed, and how these values were treated.

* The MTBE concentrations used in experiment 1 are peculiar. The range consists of five extremely 

tight concentrations with non-geometric spacing and one significantly lower concentration. Such a 

concentration range could provide an inadequate concentration-response curve from which the LC50 

was derived. The data from this experiment should have been provided for evaluation of adequacy.

* The deduced LC50 from the above experiment is accompanied by a “standard deviation throughout” 

and it is unclear what this means. LC50 values are typically accompanied by a 95 percent confidence 

interval from which variability associated with the measure can be evaluated.

* Measured MTBE concentrations are poorly defined. In experiment 1, concentrations of MTBE were 

measured twice. It is unclear if the values reported in Table 1 are the average of these two measures or 

the level of variability associated with the measures. MTBE concentrations in experiment 2 were 

apparently measured four times and the same issues exist as with experiment 1. MTBE concentrations 

were not measured in experiment 3, but rather values are reported based upon extrapolating results from 

experiment 1. This is misleading. If only limited analyses of MTBE concentrations were going to be 

performed, then the authors should have made some general statements about the observed relationships 
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between nominal and measured concentrations and reported all results based upon nominal 

concentrations.

* The authors provide no information on the precision and accuracy of the radioimmunoassay (RIA) 

methods used to assess vitellogenin induction. Values such as coefficient of variation, limit of 

sensitivity, and results of standard curves should have been provided. 

Regarding the study findings, below is a description and comments of the major observations made in 

the study.

* Gonadal-Somatic Index (GSI). The GSI, a measure of reproductive tract maturation, was not affected 

in either male or female fish at MTBE exposure concentrations as high as 37 mg/l. Thus, MTBE had no 

discernible effect on reproductive tract development.

* Vitellogenin. Plasma vitellogenin levels were significantly elevated among male fish exposed to 0.11 

and 37 mg/l MTBE. Vitellogenin protein is produced in the liver of oviparous vertebrates in response to 

estrogenic stimulation. The detection of significant vitellogenin levels in male fish is commonly used as 

a biomarker of exposure to estrogenic substances. Results from this experiment suggest that MTBE is 

estrogenic. Vitellogenin levels measured in MTBE-exposed males (~2 mg/ml), as well as in control 

females (~4 mg/l) are quite low. Plasma vitellogenin levels in induced males or mature females typically 

in excess of 10 mg/ml (e.g., Korte et al., 2000). These low numbers may reflect some deficiency in the 

assay.

* Fecundity. Fecundity was quantified as the average number of eggs produced by female fish per week. 

Egg production was not affected by exposure to MTBE concentrations as high as 220 mg/l.

* Fertilization Rate. The authors do not describe how fertilization rate was determined, but presumably, 

these values were based upon the percentage of eggs in which embryos were observed. Fertilization rate 

was not affected by MTBE exposure concentrations as high as 220 mg/l.

* Hatch Rate. Hatch rate was measured as the percentage of eggs from which larvae emerged. The 

authors describe some differences between hatch rates of eggs from MTBE treatments versus controls, 

but ascribe no significance to these observations. In addition, no concentration-response relationship was 

observed in hatch rate among the MTBE treatments. It would appear that MTBE had no effect on hatch 

rate of eggs at exposure concentrations as high as 220 mg/l.

* Sperm Motility. The percentage of mobile sperm was not affected by exposure to MTBE 

concentrations as high as 220 mg/l. Various subindices of sperm motility (straight line velocity, average 

path velocity, curvilinear velocity) were significantly affected by MTBE concentrations as low as 0.44 

mg/l. These results suggest that MTBE, at exposure concentrations approaching environmental 

relevance, impact sperm mobility characteristics. Noteworthy, is that no concentration-response 

relationships were discerned in these experiments. This suggests that either: a) maximal effects were 

observed at the lowest MTBE concentration evaluated (0.44 mg/l) and a concentration-response 

relationship would have been observed at lower exposure concentrations; or b) the values measured 

among the MTBE treatments reflect “normal” motility and the control values are abnormally high. This 

is an important issue and the investigators should have pursued this observation with additional 

exposures at lower MTBE concentrations. These sperm velocity measures are highly susceptible to 

timing with significant losses in velocity occurring within seconds after activation of the sperm (Kime et 
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al. 1996). Accordingly, differences in the timing of the velocity measurements between control and 

treatment groups can falsely indicate a treatment effect.

In summary, the Moreels et al. (2006) study provides some observations regarding the potential effects 

of MTBE on reproductive function in fish. Both the title of the article and the major conclusion drawn, 

however, are inaccurate as MTBE was not shown to cause significant reproductive dysfunction even at 

very high exposure concentrations. By most measures reported, MTBE had no discernible effect on 

various reproductive parameters at exposure concentrations as high as 220 mg/l. Results do suggest that 

MTBE is estrogenic and has the potential to alter sperm quality at exposure concentrations as low as 

0.44 mg/l, however. Experiments from which both of these conclusions are drawn are, at best, 

preliminary observations. The potential estrogenicity of MTBE should be pursued with analyses of 

vitellogenin mRNA levels in exposed fish, as well as the direct assessment of MTBE’s ability to activate 

the ER using a reporter assay system (e.g., Arnold et al., 1996). Effects of MTBE on sperm motility 

should be re-evaluated under tightly controlled experimental conditions to eliminate possible impacts of 

experimental design on outcome. Both vitellogenin induction and sperm motility should be evaluated at 

lower MTBE exposure concentrations to discern whether a concentration-response relationship exists 

for these apparent effects. Should these effects be substantiated in more definitive experiments, then 

further evaluation is warranted to establish whether these effects impact reproductive success of the fish 

(see Mills et al., 2003).

To address questions raised by the Moreels et al. (2006) study, the European Fuel Oxgenates 

Association (EFOA) sponsored LeBlanc (2010) to undertake a further investigation. This study 

objective was to test the hypothesis that MTBE elicits estrogenic activity and employed both in vitro and 

in vivo. In vitro analysis was conducted with the yeast estrogen screen (YES). YES is a sensitive assay 

that has been employed by numerous laboratories to assess estrogenic activity of both pure compound 

and environmental samples. The YES assay measures the ability of a single or mixture of compounds to 

initiate transcriptional activation of a recombinant ER-reporter gene in engineered yeast cells. A human 

estrogen receptor (hER) and estrogen response elements (ERE) coupled to the lac-Z reporter gene are 

integrated into yeasts (Saccharomyces cerevisae). The protein product of the lac-Z reporter gene is the 

enzyme galactosidase, which is secreted into the medium. In vivo analysis of the estrogenicity of MTBE 

was determined using the medaka fish vitellogenin assay. As a positive reference substance 17βestradiol with a strong estrogenic action was used.

The study found that MTBE did not show:

* Estrogenic activity in the in vitro YES;

* Increase of vitellogenin in plasma of Medaka fish exposed to MTBE; or

* Increase of vitellogenin mRNA in the liver, except at the highest dose level (significant increase (26x) 

compared to control at nominal 500 mg MTBE per liter) after one week of exposure, but not after two 

weeks of exposure.

The full report of the study is attached.

The positive control 17β-estradiol was active in the in vitro YES at a level of 1E- 9 Mol/l, while MTBE 

did not show any activity at 0.1 Mol/l. In addition, vitellogenin in plasma and vitellogenin mRNA in 

liver of Medaka fish was increased 100,000 times compared to the control at a concentration of 250 
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nanogram 17β-estradiol per liter. This last level was a nominal level and was not checked by chemical 

analysis.

The level of aromatase m-RNA in the liver did not change by exposure to MTBE or exposure to 17βestradiol. It is concluded, that aromatase in the liver is probably not affected by estrogens and cannot be 

used as an endpoint for estrogens.

The in vivo study is considered preliminary as the exposure conditions were not strictly controlled or 

maintained. The test media were renewed for 50 percent every 24 hours, but at the highest dose levels 

most of the MTBE appeared to be evaporated just before the renewal. In addition, also in the control 

medium MTBE was found.

On the basis of the average estimated levels of MTBE, these preliminary findings indicate that 

estrogenic effects are not to be expected at an average MTBE level of 35 mg/liter for 14 days in Medaka 

(Oryzias latipes). This level is very close to the NOAEL of 26 mg MTBE per liter in a 28 day lifecycle 

test with the very sensitive marine mysid shrimp Americamysis bahia (Rausina et al. 2002). In fresh 

water the no observable adverse effect level (NOAEL) for reproduction effects in Medaka (Oryzias 

latipes) was observed to be greater than 480 mg/l (Werner et al., 2001).

In summary, the LeBlanc study shows strong qualitative or semi-quantitative evidence that MTBE is not 

an estrogen. This was demonstrated in an in vitro YES. In addition, in a preliminary study Medaka, 

exposed in vivo to MTBE, did not show specific effects of estrogens like increased synthesis of 

vitellogenin and vitellogenin mRNA in the liver.

Further work to confirm the in vivo results of the LeBlanc study is on-going. An Organization for 

Economic Cooperation and Development (OECD) Guideline 229 study under GLP conditions will be 

conducted on MTBE in 2011 and the results of this study will be published and made available to 

regulatory bodies interested in MTBE.

The available information for MTBE aquatic and endocrine effects do not indicate concerns for 

endocrine modulation at relevant exposure concentrations. There is a significant body of standard 

guideline studies in three trophic levels in freshwater and marine organisms that show MTBE is a low 

order of toxicity to aquatic organisms. Although there are a couple of reports of MTBE association with 

effects on endocrine parameters in frogs and fish, these findings are not convincing and follow up work 

do not support their conclusions. A further OECD guideline study is on-going to assess fish reproductive 

toxicity and is expected to lend additional support that MTBE is not an endocrine modulator in aquatic 

organisms.

Tier 2 Testing Requirements Are Already Available for MTBE

Following the reporting of the results from the Tier 1 screening effort, EPA may decide to order Tier 2 

assays to be conducted. As stated by EPA, the three goals of Tier 2 assays include: (1) determining 

whether a substance may cause endocrine-mediated effects through or involving estrogen, androgen, or 

thyroid hormone systems; (2) determining the consequences to the organism of the activities observed in 

Tier 1; and (3) establishing the relationship between doses of an endocrine-active substance 

administered in the test and the effects observed.
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EPA indicates on its website that the Tier 2 tests will be longer in duration than Tier 1 tests as they will 

be designed to encompass critical life stages and processes as well as a broad range of dose levels. These 

tests will be administrated by the relevant route of exposure to fully integrate toxicokinetic and 

metabolic processes into the experimental design. Results from these tests will provide a more 

comprehensive profile of the toxicity resulting from a chemical exposure and provide a dose response 

relationship for the adverse effects. Adverse effects may be delayed until the age that fertility is typically 

achieved. As stated on EPA’s website, the Tier 2 tests will encompass exposure over two generations 

and include effects on fertility and mating, embryonic development, postnatal growth and development, 

and attainment of sexual maturity.

MTBE was tested for reproductive toxicity in both a single generation study (Biles et al., 1987) and a 

two-generation study (Bevan et al., 1997a). Both studies were conducted using the inhalation route of 

exposure. Although not expressly stated, it appears that both studies were conducted according to test 

guidelines commonly used at that time.

The Biles et al. (1987) study contained many endpoints related to the normal function of estrogenic, 

androgenic, and thyroid hormonal systems. Endpoints affected by the estrogenic and androgenic systems 

include mating and fertility assessments, histopathological exam of the male and female gonads and 

accessory sex organs, and organ weight data for male and female gonads and male accessory sex organs 

for adult animals. The Bevan et al. (1997a) study contained much of the same endpoints and the 

collection period was expanded to cover two generations. MTBE has been tested for developmental 

toxicity in both rats and mice (Conaway, et al., 1985) and mice and rabbits (Bevan et al., 1997b). Both 

studies were conducted using the inhalation route of exposure. It appears that both studies were 

conducted according to test guidelines commonly used at that time.

Comparison of the Tier 1 screening results currently available with the Tier 2 tests already conducted 

indicates that much of the information that would be requested by EPA for MTBE in the proposed 

EDSP initiative already exists. EPA should focus its EDSP on requiring testing (with concomitant cost 

and animal use) for substances that do not already have available data under Tier 1 or Tier 2 and/or have 

shown some potential to affect the endocrine system.

Conclusion

MTBE’s potential to interact with estrogen and androgen hormone function has been the subject of 

significant scientific review. Thyroid has not received specific attention as available repeated exposure 

and reproductive and developmental toxicity studies have not indicated a concern for thyroid effects.

Interest in elucidating mechanisms of certain types of tumors reported to occur with very high MTBE 

doses in rodent cancer bioassays have prompted investigators to continue to use very high doses in many 

of the relevant studies conducted so far -- often pushing the models and the physiology of the endocrine 

system to the limit -- to see if the effect(s) hypothesized would occur under extreme dose conditions 

used in the cancer bioassays. When the main effects of interest have been observed (e.g., statistical 

reduction in circulating testosterone), although sometimes statistically significant, none of the effects has 

been dramatic and some are not always seen consistently, which could mean the effects are secondary 

(e.g., altered hormone metabolism due to liver P450 induction), or the effects could be confounded by 

generalized toxicity at those high doses. The objective of those mechanistically-oriented studies are 

often focused on more specific hypotheses or research questions, and thus were a little different from 

screening for all endocrine effects and were non-GLP. Nevertheless, the results of those experiments 
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should be taken into account when deciding how much more time, effort, and other resources should be 

devoted to basic Tier 1 screening.

Based on the information provided in Table 1 and the foregoing discussion, it is readily apparent that 

MTBE has been thoroughly tested in standard toxicology studies (chronic, reproductive toxicity) and a 

number of mechanistic studies in mammalian and aquatic species providing significant information on 

potential endocrine activity. Moreover, there is a large body of research that has been conducted and is 

on-going or planned to understand findings that have been observed on endocrine parameters. Therefore, 

further screening tests are not likely to inform on endocrine effects beyond what is already known or 

being developed.

For all of the reasons noted above, the MTBE Consortium respectfully urges EPA to remove MTBE 

from the list of chemicals slated for Tier 1 screening. MTBE has been well studied and there is ample 

data in the literature. Further testing is unlikely to better inform the issues. If EPA does not delete 

MTBE from the list, it should require only those endocrine studies that have not already been tested.

Sincerely,

Kathleen M. Roberts

Manager, MTBE Consortium

Attachment

[See PDF Docket ID# EPA-HQ-OPPT-2009-0477-0053.2]

REFERENCES

Almeida L, Pascale C and Hall E. (2004). The effects of methyl tertiary-butyl ether on mouse testis. 

Toxicologist. 78(S-1):188 (abstract #914).

Agency for Toxic Substances and Disease Registry (ATSDR). (1996). Toxicological Profile for MTBE. 

U.S. Department of Health and Human Services, Public Health Service.

Arnold SF, Robinson MK, Notides AC, Guillette Jr LJ and McLachlan JA. (1996).. A yeast estrogen 

screen for examining the relative exposure of cells to natural and xenoestrogens. Environ. Health 

Perspect. 104:544-548.

Bevan C, Neeper-Bradley TL, Tyl RW, Fisher LC, Panson RD, Kneiss JJ and Andrews LS. (1997a). 

Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats. Journal of 

Applied Toxicology. 17(Suppl 1):S13-9.

Bevan, C., Tyl, R.W., Neeper-Bradley, T.L., Fisher, L.C., Panson, R.D., Douglas, J.F. and Andrews, 

L.S. (1997b). Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in 

mice and rabbits. Journal of Applied Toxicology. 17, S21-9.

Biles RW, Schroeder RE and Holdsworth CE. (1987). Methyl tertiary butyl ether inhalation in rats: A 

single generation reproduction study. Toxicol. Ind. Health. 3:519–533.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 317

Bird MG, Burleigh-Flayer HD, Chun JS, Douglas JF, Kneiss JJ and Andrews LS. (1997). Oncogenicity 

studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice and F-344 rats. Fundamental and 

Applied Toxicology. 30:264-275.

Conaway CC, Schroeder RE and Snyder NK (1985). Teratology evaluation of methyl tertiary butyl ether 

in rats and mice. Journal of Toxicology and Environmental Health. 16: 797-809.

Cruzan G, Borghoff SJ, de Peyster A, Hard GC, McClain M, McGregor DB and Thomas MG. (2007). 

Methyl tertiary-butyl ether mode of action for cancer endpoints in rodents. Regulatory Toxicology and 

Pharmacology. 47:156-165.

de Peyster A, MacLean K, Ahern L, Westover C and Rozenshteyn D. (2003). Subchronic oral studies of 

MTBE in male Sprague-Dawley rats to investigate mechanisms of Leydig cell tumors. Toxicol Sci. 

72:31-42.

de Peyster A, Rodriguez Y, Shuto R, Goldberg B, Gonzales F, Pu X and Klaunig JE. (2008). Effect of 

oral methyl-t-butyl ether (MTBE) on the male mouse reproductive tract and oxidative stress in liver. 

Reproductive Toxicology. 26:246-253.

ENSR. (1999). Early-life stage toxicity of methyl tertiary-butyl ether (MTBE) to the fathead minnow 

(Pimephales promelas)under flow-through test conditions. Testing laboratory: ENSR Environmental 

Toxicology Laboratory. Report no.: 0300-036-041-002. Report date: 1999-10-04.

FERC (Fuel Ethers REACH Consortium). (2010). Chemical Safety Report. Methyl Tertiary Butyl Ether.

ICCVAM/NICEATM Expert Panel (2002). Expert Panel Evaluation of the Validation Status of the In 

Vitro Test Methods for Detecting Endocrine Disruptors: Estrogen Receptor and Androgen Receptor 

Binding and Transcriptional Activation Assays.

European Commission. (2002). EUR 20417 EN - European Union Risk Assessment Report Tertbutyl

methyl ether, Volume 19.282. Joint Research Centre, Ispra.

Korte JJ, Kahl MD, Jensen KM, Pasha MS, Parks LG, LeBlanc GA and Ankley GT. (2000). Fathead 

minnow vitellogenin: complementary DNA sequence and messenger RNA and protein expression after 

17b-estradiol treatment. Environ. Toxicol. Chem. 19:972-981.

Kime DE, Ebrahimi M, Nysten K, Roelants I, Rurangwa E, Moore HDM and Ollevier F. (1996). Use of 

computer assisted sperm analysis (CASA) for monitoring the effects of pollution on sperm quality of 

fish; application to the effects of heavy metals. Aquatic Toxicol. 36:223-237.

LeBlanc GA. (2009). An evaluation of the estrogenicity of methyl-tert-butyl ether. North Carolina State 

University, Raleigh, North Carolina. Report for European Fuel Oxygenates Association, Brussels, 

Belgium.

Li D, Yuan C, Gong Y, Huang Y, Han X. Dongmei L, Chuntao Y, Yi G, Yufeng H, Xiaodong H. 

(2008). The effects of methyl t-butyl ether (MTBE) on the male rat reproductive system. Food Chem 

Toxicol. 46:2402-2408.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 318

Loman J. (1999). Early metamorphosis in common frog Rana temporaria tadpoles at risk of drying: an 

experimental demonstration. Amphibia-Reptilia. 20: 421-430.

McGregor D. (2006). Methyl tertiary-butyl ether: Studies for potential human health hazards. Critical 

Reviews in Toxicology. 36:319-358.

Merilä J., Laurila A., Timenes Laugen A., Räsänen K. and Pahkala M. (2000.) Plasticity in age and size 

at metamorphosis in Rana temporaria – comparison of high and low latitude populations. Ecography. 23: 

457–465.

Mills LJ, Gutjahr-Gobell RE, Horowitz DB, Denslow ND, Chow MC, and Zaroogian GE. (2003). 

Relationship between reproductive success and male plasma vitellogenin concentrations in cunner, 

Tautogolabrus adspersus. Environ. Health Perspect. 111:93-99.

Moreels D, Van Cauwenberghe K, Debaere B, Rurangwa E, Vromant N, Bastiaens L, Diels L, Springael 

D, Merckx R and Ollevier F.( 2006). Long-term exposure to environmentally relevant doses of methyltert-butyl ether causes significant reproductive dysfunction in the zebrafish (Danio rerio). Environ. 

Toxicol. Chem. 25:2388-2393.

Moser G, Wolf DC, Sar M, Gaido KW, Janszen D and Goldsworthy T. (1998). Methyl tertiary butyl 

ether-induced endocrine alterations are not mediated through the estrogen receptor. Toxicol. Sci. 41:77-

87.

Okahara N, de Peyster A, McPherson SE and MacGregor JA. (1998). Effect on MTBE on estrogensensitive tissues of immature female CD-1 mice. Toxicologist 42:174.

Paulov S. (1987). Action of the anti-detonation preparation methyl tert-butyl ether on the model species 

Rana temporaria. Biologia. 42:185-189.

Shimizu, Y., Yarborough, C., and Osawa, Y. (1993) Competitive product inhibition of aromatase by 

natural estrogens. J Steroid. Biochem. Molec. Biol. 44:651-656.

Werner I., Koger C.S., Deanovic L.A. and Hinton D.E. (2001). Toxicity of methyl-tert-butyl ether to 

freshwater organisms. Environ. Pollution 111:83-88.

Williams TM, Cattley RC and Borghoff SJ. (2000). Alterations in endocrine responses in male SpragueDawley rats following oral administration of methyl tert-butyl ether. Tox Sci. 54:168-176.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.
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EPA Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like 

Effect

General Response: EPA acknowledges that for some of the chemicals listed on the second EDSP list 

there may be existing data relevant to the Tier 1 screening assays. However, EPA disagrees with 

removing these chemicals from the second EDSP list at this time. Order recipients will have an 

opportunity to submit any relevant data to the Tier 1 assays or Other Scientifically Relevant Information 

(OSRI) as part of their initial response to receiving an order. For specific information on submitting or 

citing existing data or OSRI, please see the existing EDSP policies and procedures that were published 

in 74 FR 17560, April 15, 2009 (USEPA, 2009b) and the Endocrine Disruptor Screening Program; Draft 

Policies and Procedures for Screening Safe Drinking Water Act Chemicals, 75 FR 70248, November 17, 

2010 (USEPA, 2010a). Please also see Endocrine Disruptor Screening Program; Final Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document. EPA supports conserving resources and 

preventing redundancy in testing by using OSRI data.

Individual Comments

Commenter Name: Peter Voytek

Commenter Organization: The HAP Task Force (HAP)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0010

Comment Part: 2

EPA Comment Code: 2070

Comment: The notice indicates that inclusion of a chemical in the second list does not reflect any 

presumption by EPA that the chemical or substance does in fact interfere with the endocrine systems of 

humans or other species. In the case of 1,1,2-trichloroethane, a mammalian reproductive toxicity study 

conducted by the Task Force and submitted to EPA pursuant to the ECA meets the principal Tier 2 

requirement and indicates that 1,1,2-trichloroethane is not likely to affect the endocrine system.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Marcy Banton

Commenter Organization: LyondellBasell Industries

EPA Document ID: EPA-HQ-OPPT-2009-0477-0011

Comment Part: 1

EPA Comment Code: 2070

Comment: December 16, 2010

Document Control Office (7407M)

Office of Pollution Prevention & Toxics

Environmental Protection Agency

1200 Pennsylvania Avenue, NW
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Washington, DC 20460

RE: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier

1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7]

To Whom It May Concern:

LyondellBasell Industries (LyondellBasell) appreciates the opportunity to provide comment on the U.S. 

Environmental Protection Agency’s (EPA) announcement of a second list of chemicals and substances 

for which EPA intends to issue test orders under the Endocrine Disruptor Screening Program (EDSP) 75 

Federal Register, Number 221, November 17, 2010 70248-70254.

LyondellBasell supports the identification, assessment and management of substances that may pose a 

risk to human health or the environment due to disruption of the endocrine system. The EPA tiered 

screening program is an important first step but must be coupled with review of other available 

scientifically relevant information to assure that appropriate substances are selected and evaluated in this

screening program. Where relevant information exists, the results should be taken into account when 

deciding how much more time, effort and other resources should be devoted to basic Tier 1 screening.

Based on weight of evidence and in keeping with EPA’s principle of reducing unnecessary testing, 

propylene oxide should be removed from the second list of proposed substances to be tested for Tier 1 

screening. This is based on the fact propylene oxide has a substantial body of existing relevant 

information which exceeds the intent of the screening tests for Tier 1 and hence this substance does not 

merit the need to undergo less stringent tests under the Tier 1 battery. Also propylene oxide is not 

expected to be present in sources of drinking water and therefore does not meet the criteria for inclusion 

in the second list of chemicals. Additionally, as propylene oxide hydrolyzes to propylene glycol in 

aqueous systems and propylene glycol is used in a number of the Tier 1 screening test systems, 

propylene oxide may not be compatible with testing in the Tier 1 in vitro and in vivo aquatic organism’s 

tests.

1. Propylene oxide has been tested in higher order animal studies for reproductive and developmental 

toxicity, and results indicate that propylene oxide does not cause effects suggestive of endocrine 

disruption. There is no reason to include propylene oxide in endocrine disruption screening assays, 

because any suggestive or positive findings would be superseded by the negative results of the whole 

animal studies.

An extensive database of toxicity studies in mammalian species already exists for propylene oxide that 

contains data relevant to evaluation of the endocrine system. Propylene oxide has been thoroughly tested 

in numerous sub-chronic toxicity studies, teratology studies, a two-generation reproduction study and 

chronic/carcinogenicity studies and none of these studies indicate any targeted effects on the endocrine 

system. Reviews and risk assessments of the available toxicity information for propylene oxide are 

provided by European Union (2002) and Sweeney et al. (2009).

Propylene oxide has been tested for reproductive toxicity in a two-generation study (Hayes, et al., 1988). 

This study was conducted using the inhalation route of exposure and used Fischer-344 rats as test 

subjects. Although not expressly stated, it appears that this study was conducted according to test 

guidelines in use at the time.
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The Hayes study contained many endpoints related to the normal function of estrogenic, androgenic and 

thyroid hormonal systems. Endpoints affected by the estrogenic and androgenic systems include mating 

and fertility assessments, histopathological exam of the male and female gonads and accessory sex 

organs, and organ weight data for male and female gonads and male accessory sex organs for adult 

animals. There were no reported adverse effects for any of these parameters from exposure of up to 300 

ppm propylene oxide. Endpoints dependent on the thyroid hormonal system included growth rates and 

viability of the parental generation and offspring. Decreased body weights/body weight gain of the 

parental F0 and F1 animals were noted with the 300 ppm PO exposure. No effects on pup viability were 

noted. Therefore, there is no evidence of altered thyroid function in this study. The no-observed-effectlevel (NOEL) for reproductive toxicity in this study was 300 ppm while the NOEL for systemic toxicity 

was 100 ppm (based on decreased body weights/body weight gain).

Propylene oxide has been tested for developmental toxicity in rats (Harris et al., 1989) and rabbits 

(Hardin et al., 1983). Both studies were conducted using the inhalation route of exposure. The rat study 

was conducted according to test guidelines used at that time while the rabbit study used only one 

exposure concentration (500 ppm) and a control group. The no-observed-adverse-effect-concentration 

(NOAEC) for the rat study was 300 ppm based on decreased maternal feed consumption and body 

weight gain and the increased incidence of fetuses and litters with a rib of variable length on the seventh 

cervical vertebra at the 500 ppm exposure concentration. The authors concluded that the rib variations 

were related to the maternal toxicity.

Likewise repeated exposure studies for propylene oxide do not indicate effects on the endocrine system. 

Propylene oxide effects are limited to local site-of-contact and there are no indications of systemic 

toxicity or effects to distant endocrine tissues (Sweeney et al., 2009).

There is also a wealth of health effects information available on propylene glycol, the microsomal 

epoxide hydrolase hydrolysis metabolite of propylene oxide. This extensive database of studies has been 

reviewed by the NIEHS National Toxicology Program (NTP) Center for Evaluation of Risks to Human 

Reproduction (CERHR) and concluded “current estimated exposures to propylene glycol are of 

negligible concern for adverse developmental and reproductive toxicity in humans” (NTP CERHR, 

2004).

The database for environmental effects and ecotoxicology of propylene oxide is also extensive, allowing 

for a robust evaluation of its aquatic hazard properties. The log Kow value of propylene oxide is low (< 

1) (Hansch and Leo, 1979; Deneer et al., 1988; Shell Research Ltd., 1986) suggesting a low tendency to 

partition to organic phases and therefore a low potential for bioaccumulation. Propylene oxide is readily 

biodegradable in aquatic environments (MITI, 1988); hence it is not expected to be persistent in the 

environment. Propylene oxide also was not found to present an ecotoxicity hazard based on the results 

of acute studies (Crews, 1974; Shell Research Ltd., 1986).

Response: Oxirane, methyl- (propylene oxide) has been removed from the second EDSP list. Please see 

general response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters 

as Being Potentially Incompatible with Test Assays. Also, please see general response to comment 

under EPA Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like Effect.

Commenter Name: John Jachetta

Commenter Organization: Dow AgroSciences LLC
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0014

Comment Part: 4

EPA Comment Code: 2070

Comment: Mammalian toxicology of picloram: no indication of endocrine-related effects: 

The toxicological database for picloram is extensive. The low toxicity of the material on both an acute 

and chronic basis is well-documented and accepted by a wide range of regulatory authorities. Endocrinerelated effects have never been found in any study.

In short-term dietary repeat-dose rat studies (6, 7, 8, 9), picloram (the acid, isooctyl ester, and 

triisopropanolamine salt) showed no endocrine-related effects. The primary target organ was the liver, 

with increased weight and minimal microscopic changes (hepatocellular hypertrophy), and a NOEL for 

these effects (and the additional effect of increased kidney weight) of 50-90 mg a.e./kg bw/day. The 

liver was also the target organ in dogs: a 6-month dietary study showed increased liver weights (NOEL 

was 35 mg a.e./kg bw/day).

In chronic dietary repeat dose/carcinogenicity studies (10,11, 12), picloram (the acid) was noncarcinogenic and showed no endocrine-related effects. The primary target organs were the liver and 

kidney, with NOELs for these effects ranging from 20-500 mg a.e./kg bw/day.

In developmental toxicity studies (13, 14, 15, 16), picloram (the acid, potassium salt, isooctyl ester, and 

triisopropanolamine salt) showed no endocrine-related effects. In rabbits, decreased maternal weight 

gain, feed consumption and feces, and excessive salivation were seen, driving maternal NOELs of 20-

200 mg a.e./kg bw/day and developmental NOELs of 400-500 mg a.e./kg bw/day. In rats, decreased 

body weight gain, decreased food consumption and excessive maternal salivation were seen, driving 

maternal NOELs of 68-280 mg a.e./kg bw/day and developmental NOELs of 298-560 mg a.e./kg 

bw/day.

In a reproduction toxicity study (17), the definitive test for endocrine disruption, picloram (the acid) 

showed no endocrine-related effects. In rats, histopathological lesions in the kidney of males of both 

generations and some females and blood in the urine, decreased urine specific gravity, increased 

absolute and relative kidney weights, and increased body weight gain in males of both generations were 

seen, driving a parental NOEL of 200 mg a.e./kg bw/day and a reproductive NOEL of 1000 mg a.e./kg 

bw/day. The negative results for endocrine disruption, from this study in particular, make any 

requirements for lower tier screening studies unnecessary.

In conclusion, picloram has shown no endocrine-related effects in the extensive toxicological database 

conducted in support of its registration and uses.

Ecotoxicology of picloram: no indication of endocrine-related effects

Picloram has been tested in several ecotoxicological studies in support of its registrations and has been 

shown to generally be of low toxicity in chronic studies. The following chronic animal studies are 

available for picloram:

* Bobwhite quail, reproduction NOEC = 1500 ppm (picloram acid; Dow AgroSciences Study no. 

011172 (18);

* Rainbow trout, 70-d ELS NOEC = 0.55 ppm (picloram acid) (19);

* Fathead minnow, 32-d ELS NOEC = 7.19 ppm (picloram TIPA salt) (20);
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* Daphnid, 21-d NOEC = 6.79 ppm (picloram acid) (21);

* Daphnid, 21-d NOEC = 11.8 ppm (picloram acid) (22);

* Midge, 28-d NOEC = 100 ppm (picloram acid) (23);

* Earthworm, 56-d NOEC = 125 g/ha or 0.167 mg/kg dry soil (picloram acid) (24)

Additionally, as discussed previously, an extensive mammalian toxicity data package is available for 

picloram and/or its salts and ester. In conclusion, available toxicology and ecotoxicology results for 

picloram are not indicative of any potentially endocrine-related sublethal or reproduction effects at 

environmentally relevant concentrations. Picloram should therefore not be considered a priority for 

endocrine screening under the 2nd EDSP list.

The available information on picloram has been deemed sufficient to register this active substance in the 

United States. The risk assessment conclusions indicated, with ample safety margins, that the proposed 

uses of picloram are not expected to pose any adverse sublethal effects on animal populations. Similar 

conclusions of low risk were reached also in other geographies, such as the European Union.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 4

EPA Comment Code: 2070

Comment: As an alternative, if flumetsulam is not removed from List 2, DAS respectfully requests 

flumetsulam not to be considered a priority for the EDSP. This is based upon the extensive toxicology 

database for flumetsulam that clearly demonstrates very low toxicity with no indications of endocrine 

disruption at doses up to and including the US EPA and OECD limit dose of 1000 mg/kg/day, and the 

minimal potential for human exposure to flumetsulam.

Flumetsulam is non-toxic following acute exposure (Billington and Gehen, 2010). In subchronic and 

chronic repeat dose studies in rats, the only effects were on the kidney and the cecum. These studies of 

varying duration (28-day to two-year) also indicate very low toxicity, with NOAEL levels being at or 

near the limit dose. For instance, in a 28-day study, 1000 mg/kg/day was identified as the NOAEL based 

upon histopathological changes in the kidney that occurred only at 2500 mg/kg/day, and were 

accompanied by the presence of amorphous crystals in the urine, likely representing precipitate of the 

test material (Yano et al. 1988). Similar kidney effects were observed in a two-year chronic 

toxicity/oncogenicity study at the limit dose of 1000 mg/kg/day, but not at lower dose levels, with no 

evidence for carcinogenicity (Stott et al. 1991). The developmental toxicity study and the 2-generation 

reproduction study, designed to detect health hazards caused by any mode of action, including endocrine 

modes, did not detect any developmental or reproductive effects at the limit dose of 1000 mg/kg/day 

(Zielke et al. 1988; Zempel et al. 1990). There are no indications of adverse effects that could be 

attributed to modulation of the endocrine system at doses at or well above the limit dose in any of the 

existing studies.
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Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Terry Medley

Commenter Organization: E.I. du Pont de Nemours and Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0016

Comment Part: 3

EPA Comment Code: 2070

Comment: 3. Testing that has previously been conducted on HCFC-22 does not suggest potential 

effects on reproductive target organs or measures of reproduction and fertility. Repeated dose toxicity 

studies in rabbits, rats, guinea pigs, dogs, and cats, including carcinogenicity studies in rats and mice, all 

show low-level target organ toxicity with no effects indicative of endocrine modulation. Reproductive 

toxicity studies in rats and mice showed no effects indicative of endocrine-mediated effects, and did not 

compromise the reproductive success (i.e., mating and fertility) of the animals. Furthermore, in rat and 

rabbit developmental toxicity studies, no effects indicative of endocrine-mediated effects were observed.

As described above, due to the physical nature of the test substance and the low potential for exposure to 

the general population and environment, DuPont believes that HCFC-22 should not be included in the 

final EDSP Second List of Chemicals for Tier 1 Screening. The current EDSP Tier 1 battery of 

screening assays has not been validated for use with inhalation exposures, and several of these assays 

would not be practical for inhalation exposures given the nature of the assays. Furthermore, there are 

numerous guideline toxicity studies available that evaluate potential endocrine target organs that 

illustrate that HCFC-22 has low target organ toxicity, and would therefore be expected to have a low 

potential for endocrine activity.

Thank you for the opportunity to comment on this very important matter. If you have any questions or 

would like additional information, please contact John O'Connor at 302-996-8120.

Sincerely,

Terry Medley

Global Director

DuPont Corporate Regulatory Affairs

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 5

EPA Comment Code: 2070

Comment: EPA reports short-term exposure to alachlor can lead to eye and skin irritation, while longterm exposure may result in damage to liver, kidney, spleen, the lining of the nose and eyelids, and 

cause cancer (EPA 2010c). Studies to determine actions on the endocrine system have produced results 

that are variable and inconclusive.
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In an ER competitive-binding assay using rat uterine cytosol, alachlor did not exhibit any effect on 

[3H]17ß-estradiol at a 50% inhibition concentration (IC50) >1000 μM (Blair, Fang et al. 2000). Klotz et 

al. (1996) utilized three assays, yeast estrogen screen (YES), competition binding with the human 

estrogen receptor (hER), and activation of an estrogen-responsive reporter gene in MCR-7 human breast 

cancer cells, to test a variety of chemicals (Klotz, Beckman et al. 1996). They reported weak activity by 

alachlor in the YES at a concentration of 10 μM, weak binding inhibition of [3H]17ß-estradiol (E2) to 

(hER) at relatively high concentrations of >100 μM, and moderate induction of luciferase activity in 

breast cancer cells at 1 μM, which did not further increase at 10 μM, indicating that alachlor may be 

only a partial agonist of hER. However, Soto et al. (1995) showed that alachlor in similar concentrations 

was not estrogenic in the E-SCREEN assay, a sensitive test that evaluates proliferation of MCF-7 human 

breast cancer cells under the influence of estrogens (Soto, Sonnenschein et al. 1995). Nor did alachlor 

show activity in trout reporter gene and vitellogenin production assays (Petit, Le Goff et al. 1997). In a 

study to determine the ability of chemicals to bind the alligator estrogen receptor (aER) and 

progesterone receptor (aPR) using a protein extract prepared from the oviduct of the alligator, Vonier et 

al. (1996) reported an IC50 of 27 μM for alachlor as compared to 0.0078 μM for 17ß-estradiol, but no 

interaction by alachlor with the aPR (Vonier, Crain et al. 1996). Jin et al. (1997) demonstrated neither 

agonist nor antagonist activity of alachlor in a recombinant human progesterone receptor (hPR) 

expressed in yeast cells (Jin, Tran et al. 1997). Kojima et al. (2004) tested 200 pesticides for both 

agonism and antagonism to two hER subtypes, hERα and hERβ, and a human androgen receptor (hAR), 

via transactivation assays using Chinese hamster ovary cells (Kojima, Katsura et al. 2004). Alachlor 

showed antiestrogenic properties in the hERα transactivation assay with 10–10 M E2, but at a 

significantly higher dose (10–5 M) than the well-known ER antagonist tamoxifen at 10–8 and 10–7 M. 

Assessment by Kojima et al. (2004) of these same pesticides for their inhibitory effect on androgenic 

activity showed alachlor to be a weak inhibitor, with an RIC20 (concentration of the test compound 

showing 20% inhibition of the androgenic activity induced by 10–10 M DHT) of 9.6 X 10-6 M, a 

considerably higher concentration than the RIC20 of 4.3 X 10-8 M for the diphenyl ether herbicide 

Chlornitrofen, a potent androgenic inhibitor. Cheek et al. (1999) examined the ability of alachlor to bind 

a recombinant human thyroid receptor (hTRβ1) and to interact with the serum transport proteins, 

transthyretin and thyroid-binding globulin (TBG), and found no action at doses as high as 100 μM 

(Cheek, Kow et al. 1999).

In vivo studies include a three-generation toxicity study in which rats were administered alachlor at dose 

levels up to 30 mg/kg bw/day (Schroeder and Hogan 1981). No treatment-related effects on mating, 

fertility, male-female sex ratios, pup survival, testicular weight, or histopathology of the reproductive 

organs were noted. Developmental toxicity studies conducted by Monsanto in rats and rabbits (Rodwell 

1980; Schroeder 1988) revealed no statistically significant differences in the mean numbers of viable 

fetuses, resorptions, post-implantation losses, total implantations, corpora lutea, sex distribution of pups, 

or mean fetal body weights between the treated groups and controls. In a rodent carcinogenicity study, 

male rats developed benign tumors in the thyroid follicular cells at 126 mg/kg/day, but not at 42 

mg/kg/day or lower (Wilson, Thake et al. 1996) and the authors concluded that these tumors were 

produced by way of a non-genotoxic mode of action that includes UDPGT induction, increased TSH, 

alterations in T3/T4 hormone production and thyroid hyperplasia. Based on excessive body weight loss 

(>30%), hepatocellular necrosis, and slightly decreased survival, the authors also concluded 126 

mg/kg/day was above the MTD. In a risk assessment of the chloroacetanilides alachlor, acetochlor and 

butachlor, development of thyroid tumors was not a recommended endpoint because, again, toxic effects 

were noted only at doses above the MTD, and, in addition, humans were more refractory to the 

induction of thyroid follicular cell tumors than rats (EPA 2006a). An epidemiological study that 
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evaluated >1000 alachlor manufacturing-plant employees showed no evidence of increased incidence of 

thyroid tumors or any other hormonally-mediated cancer (breast, testicular, ovarian, uterine or prostate) 

over the 25-year period of record (Acquavella, Riordan et al. 1996). A study of the relationship of 

hypospadias (a defect of the male reproductive system that has been produced experimentally in animals 

by prenatal and perinatal administration of pesticides with estrogenic and/or antiandrogenic properties) 

and proximity to agricultural pesticide use in eastern Arkansas, indicated that alachlor was negatively 

associated with hypospadias (Meyer, Reif et al. 2006).

In two avian reproductive studies (Gallagher, Beavers et al. 1999a; Gallagher, Beavers et al. 1999b) and 

a fish reproductive study (Rhodes and Muckerman 1984) any noted effects were generally produced 

only at the highest doses of alachlor used.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2060 Chemicals with Toxicity Data Indicating 

Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 7

EPA Comment Code: 2070

Comment: Alachlor appears to have minimal potential to interfere with estrogen-estrogen receptor 

binding or alter transcriptional activity of estrogen receptor responsive genes. Alachlor does not bind or 

alter transcriptional activity of the progesterone receptor. Alachlor does not bind to human thyroid 

receptor, thyroid binding globulin or transthyretin. Production of thyroid tumors in rats occurs only at 

very high dose levels through a secondary mode of action, i.e., induction of hepatic UDPGT, which has 

little relevance to humans. Evidence of endocrine disruption was not noted in mammalian toxicity and 

chronic developmental tests. An epidemiological study of alachlor manufacturing plant employees 

showed no increase in the incidence of thyroid or any other hormonally mediated cancers. A casecontrol study relating hypospadias to exposure to agricultural pesticides indicated a negative association 

for alachlor. No consistent indication of endocrine activity was noted in several bird, fish, and 

amphibian studies. The lack of likely exposure combined with proven lack of endocrine activity should 

exempt alachlor from further testing.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 9

EPA Comment Code: 2070

Comment: Two studies are available that evaluated pyridate along with other pesticides as potential 

endocrine disruptors. Okubo et al. (2004) examined the estrogenic and antiestrogenic activities of 
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pesticides with suspected residues in vegetables and fruits by using the cell proliferation of estrogendependent human breast cancer MCF-7 cells in vitro (Okubo, Yokoyama et al. 2004). Pyridate did not 

affect cell proliferation at non-cytotoxic concentrations, and was therefore interpreted as having no 

estrogenic activity. Results of competition by pyridate for binding hER and hAR showed weak affinities 

(RBA value for ERα of 0.069% as compared to 100% for positive control diethystilbestrol; and RBA 

value for AR of 0.011% as compared to 100% for positive control mibolerone). The authors concluded 

that any activity by pyridate was relatively low. 

Using a microtiter plate receptor assay with recombinant hAR to evaluate the androgen receptor binding 

affinity of a number of pesticides, Bauer et al. (2002) reported minimal displacement of [3H]-DHT 

binding by pyridate at an RBA of 0.007% as compared to DHT at 100% (Bauer, Bitsch et al. 2002). This 

binding was demonstrated to be reversible in exchange assays. 

Summary and conclusions: Pyridate binds weakly to hAR, and hER, but there was no evidence for 

estrogenic or antiestrogenic properties in cell proliferation assays.

Response: Pyridate has been removed from the second EDSP list. Please see general response to 

comment under this EPA Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or 

used in the US, also Includes Pesticides with Cancelled Registrations. Also, please see general response 

to comment under EPA Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like 

Effect.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 18

EPA Comment Code: 2070

Comment: B. Benzene 

“The primary target for adverse systemic effects of benzene following chronic exposure is the 

hematological system,” and additionally the chemical has been classified by the United States 

Department of Health and Human Services, the Environmental Protection Agency (EPA) and the 

International Agency for Research on Cancer as a confirmed human carcinogen based on sufficient data 

from epidemiological studies and animal evidence (ATSDR 2007). 

While essentially all known metabolites of benzene have been shown to decrease erythropoiesis, 

numerous mechanistic studies have established the central role played by the rapid metabolism of 

benzene by CYP2E1 (Snyder and Hedli 1996; Smith 1996a; Smith 1996b). CYP2E1 oxidizes benzene to 

benzene oxide before rearranging to form phenol, benzene’s major initial metabolic product (Vogel and 

Günther 1967; Jerina, Daly et al. 1968; Lindstrom, Yeowell-O'Connell et al. 1997; Ross 2000). CYP2E1 

subsequently oxidizes phenol to catechol or hydroquinone, compounds that are further oxidized by 

myeloperoxidase (MPO) to 1,2- and 1,4-benzoquinone and other highly reactive quinines that stimulate 

production of reactive oxygen species and culminate in protein and DNA damage in stem or early 

progenitor cells (Smith 1996a; Smith 1996b; Nebert, Roe et al. 2002). This damage manifests as 

hematopoietic and leukemogenic effects (ATSDR 2007). Inhibition of benzene’s metabolism 

consequently reduces benzene’s toxicity (Andrews, Lee et al. 1977).
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Epidemiological case studies consistently “provide clear evidence of a causal relationship between 

occupational exposure to benzene and benzene-containing solvents and the occurrence of acute 

nonlymphocytic leukemia, particularly the myeloid cell type (acute myelogenous leukemia)” (Rinsky, 

Hornung et al. 2002; ATSDR 2007; Integrated Risk Information System (IRIS) 2007). Based on human

leukemia data, EPA derived a range of inhalation unit risk values of 2.2x10-6–7.8x10-6 (μg/m3)-1 for 

benzene (Integrated Risk Information System (IRIS) 2007); for risks ranging from 1x10-4 to 1x10-7, the 

corresponding air concentrations for lifetime exposure range from 13.0–45.0 μg/m3 (4–14 ppb) to 

0.013–0.045 μg/m3 (0.004–0.014 ppb), respectively (Rinsky, Young et al. 1981; Rinsky, Smith et al. 

1987). ATSDR notes that benzene is typically in drinking water at concentrations less than 0.1 ppb and 

it is typically at the lower end of the observed range of 0.02—34 ppb found in ambient air samples 

(ATSDR 2007). 

As a confirmed human carcinogen, there can be no added regulatory value in determining whether 

benzene also has endocrine disrupting potential and further testing in the EDSP assays is not warranted 

and benzene should be removed from the second list of chemicals to be tested.

C. Nitrobenzene 

Many of the toxic effects of nitrobenzene (NB) are dependent on enzymatic activation by intestinal flora 

(following oral exposure); similar activation can be accomplished by various redox reactions in 

erythrocyte or hepatic microsomes (Levin and Dent 1982; Rickert 1987; Bryant and DeLuca 1991). 

Principal metabolites include p-nitrophenol, p-nitroaniline and p-aminophenol, with the remaining 

chemical oxidized to additional nitrophenols or reduced to aniline and other aminophenols (Wang, 

Zhang et al. 2010a). In this regard, NB shares structure-activity relationships with other aromatic nitroand amino- compounds that produce common reactive nitroxide intermediates that relate to shared 

mutagenic and metabolic impacts (Verna, Whysner et al. 1996). These reactive intermediates include the 

superoxide anion and hydrogen peroxide, which may disturb the redox balance of target cells leading to 

oxidative stress and ultimately account for many of NB’s toxicological effects (Gutteridge 1995). 

Acute, subacute and chronic exposure to NB consistently leads to damage to blood products, the spleen, 

liver and testes (Bond, Chism et al. 1981; Burns, Bradley et al. 1994; Mitsumori, Kodama et al. 1994; 

Shimo, Onodera et al. 1994; WHO 2003b; Wang, Zhang et al. 2010a; Wang, Zhang et al. 2010b). 

Exposure in humans and other animals over a wide range of concentrations leads to the immediate 

development of methemoglobenemia, a pathological overabundance of oxidized hemoglobin (Goldstein 

and al 1983; WHO 1986; Maples, Eyer et al. 1990). Abundant evidence suggests that NB’s reactive 

metabolites accelerate oxidation of hemoglobin to methemoglobin, causing the metalloprotein to lose its 

ability to reversibly bind oxygen (Smith 1996c; Percy, McFerran et al. 2005; EPA 2009c). 

At relatively low subacute doses (30 mg/kg/d in mice exposed for two weeks), a marginal dose-related 

increase in alanine- and aspartate aminotransferase suggests liver toxicity (Burns, Bradley et al. 1994). 

In rats, acute administration of relatively high doses of NB has led to the development of hepatocellular 

nucleolar enlargement at 110 mg/kg, centrilobar hepatocytic necrosis at 200 mg/kg, and decreasing 

numbers of spermatozoa in the epididymis accompanied by necrotic debris at 300 mg/kg (Bond, Chism 

et al. 1981). At 125 mg/kg/day for 28 days in rats, liver, spleen and kidney weights increase while 

testicular weights decrease with concurrent degeneration of seminiferous tubule epithelium, although 

these effects tended to abate after a two-week recovery period (Shimo, Onodera et al. 1994). Significant 

dose-related increases in the incidence of both sperm abnormality and positive micronucleus tests have 

been observed at approximately 100 mg/kg, or 1/5 LD50 (Wang, Zhang et al. 2010a).
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Although no human epidemiological data have been analyzed for evidence of potential carcinogenic 

impacts, two-year inhalational studies exposing mice and rats to up to 50ppm NB have noted an 

increased incidence of multiple dispersed tumor types which may be related to NB’s oxidation and 

reduction mechanisms (Maples, Eyer et al. 1990; Cattley, Everitt et al. 1994; Dreher and Junod 1996; 

Holder 1999). “The distribution of carcinogenicity involves four singular organ sites—lung, mammary 

gland, kidney, and endometrium: two concordant thyroid responses in male B6C3F1 mice and male 

F344/N rats, and two concordant liver responses in male F344/N and CD rats. These distributed organ 

responses present a spectrum of mixed malignancy, species/strain, and sex responses. Altogether, the 

evidence is 'sufficient' for the determination of NB carcinogenicity in animals (two species, three strains, 

eight sites) by the inhalation route” (Holder 1999). It is expected that activated NB would bind DNA and 

protein like other carcinogenic nitroarenes, although either this binding is insufficient for carcinogenesis 

in all organs or the binding was metabolically reduced at these sites (Holder 1999). “Anticarcinogenic 

mechanisms in these organs remain unknown, but it is plausible that specific antioxidants were either 

already present or induced, quenched the nitroxides, prevented binding, and thus protected these tissues” 

(Netke and al. 1997; Primiano, Sutter et al. 1997; Holder 1999). 

Nitrobenzene has demonstrated hemato-, nephro- and hepatotoxicity and is a rodent carcinogen with 

described mechanisms of action; there can be little added regulatory value in determining whether 

nitrobenzene also has endocrine disrupting potential and further testing in EDSP assays is not warranted 

and nitrobenzene should be removed from the second list of chemicals to be tested.

D. Trichloroethylene 

In humans and in experimental animals, trichloroethylene (TCE) exposure leads to an extensively 

documented array of cancer and non-cancer effects including biochemical, cellular and target organ 

alterations. TCE toxicity is most evident in the kidneys, liver and nervous system, although the greatest 

concordance between animal and human data suggests that nephrotoxicity is of greatest concern as most 

other effects are rarely observed in multiple species (Barton and Clewell 2000; Wartenberg, Reyner et 

al. 2000; National Research Council (NRC) 2006). Lifetime TCE exposure studies of high doses (GE 

500 mg/kg/d for rats and GE 1,000 mg/kg/d in mice) consistently report non-cancer kidney toxicity in 

both species (National Cancer Institute (NCI) 1976; National Toxicology Program (NTP) 1983; NTP 

1988). 

Metabolic activation of TCE can occur through a variety of pathways, most importantly via cytochrome 

P450 oxidation and glutathione conjugation (Pahler, Parker et al. 1999; Lash, Fisher et al. 2000a; Lash, 

Parker et al. 2000b). The latter pathway is implicated in the generation of reactive metabolites, S-(1,2-

dichlorovinyl)-glutathione (DCVG) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC), associated with 

various cytotoxic and carcinogenic responses (Lash, Parker et al. 2000b). DCVC has been specifically 

described as a nephrotoxin (Lash, Parker et al. 2000b). 

No reproductive effects have been documented from epidemiologic studies of human populations 

exposed to TCE, and two-generation studies in mice and rats have generally been negative for a wide 

range of reproductive endpoints except at very high doses of approximately 1,000 mg/kg/d (Manson, 

Murphy et al. 1984; Zenick, Blackburn et al. 1984; Cosby and Dukelow 1992; Dawson, Johnson et al. 

1993; Agency for Toxic Substances and Disease Registry (ATSDR) 2000). The ability of rat oocytes to 

be fertilized decreases after exposure to 0.66 g TCE/kg/day for up to 5 days and may be related to 

observed alterations in oocyte plasma membrane composition, although these changes are not 
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accompanied by any modifications in ovarian gene expression (Berger and Horner 2003; Wu and Berger 

2007; Wu and Berger 2008). 

A lack of reproductive effects in humans and animals suggests low or no endocrine disrupting potential 

of trichloroethylene. Other toxicities are well documented however, including neuro, nephro- and 

hepatotoxicity, and further testing in EDSP assays is not warranted and TCE should be removed from 

the second list of chemicals to be tested. 

E. Nitroglycerin (glyceryl trinitrate) 

Nitroglycerin (glceryl trinitrate, GTN), like other organic nitrites, has been extensively studied clinically 

due to its wide application in the chemotherapeutic treatment of cardiovascular disease. In addition to 

human data from more than 150 years of clinical use, data from experimental exposure in several 

species includes information on many of the chronic, developmental and reproductive endpoints sought 

in EDSP Tier 1 in vivo tests. Most animal toxicity studies on GTN are not readily available in the open 

literature but are reviewed in a EPA Health Advisory, from which the following information is taken 

unless otherwise indicated (EPA 1987; Bingham, Cohrssen et al. 2001). 

Standard therapeutic doses in humans range between 0.2 to 10 mg/day (Einert, Adams et al. 1963). 

Requiring only minutes to exert therapeutic effects, GTN is rapidly metabolized to several dinitrite 

compounds in a variety of tissues and organs, especially in the liver by multiple cytochrome P450 and 

glutathione S-transferases and elsewhere by mitochondrial aldehyde dehydrogenase (Needleman, Blehm 

et al. 1971; Bustard, Ryan et al. 2003; Badejo, Hodnette et al. 2010). In the process, nitric oxide (NO) is 

produced and activates soluble guanylate cyclase to exert GTN’s vasodilatory effects (Bustard, Ryan et 

al. 2003; Badejo, Hodnette et al. 2010). The principle dinitrate metabolites, glyceryl-1,2-dinitrate and 

glyceryl-1,3-dinitrate, have a half-life of approximately 15 minutes in humans. 

GTN is not highly toxic following acute exposure, with oral LD50s for male rats and mice of 822 and 

1,188 mg/kg, respectively. At these doses, indication of toxicity is marked by development of 

methemoglobinemia and ataxia progressing to death within one to six hours of exposure. In long-term 

studies, chronic exposure at lower GTP concentrations causes qualitatively and quantitatively different 

effects among rats, mice, dogs and other mammalian species. Ninety-day studies in rats showed only 

body weight effects up to 234 mg/kg/day. Anemia and testicular degeneration are also seen at higher 

doses up to 1,416 mg/kg. Two-year feeding studies were conducted in both rats and mice (Ellis, Hong et 

al. 1984). When treated for one year at doses up to 25 mg/kg/day, no effects were observed in rats 

beyond transient methemoglobinemia (Ellis, Hong et al. 1984). Transient damage to tissues and organs 

in male NZW rabbits following 26 week dermal GTN exposures of up to 240 mg/kg/day included an 

increase in kidney and heart weights in the highest dose group. These effects had resolved within five 

weeks of the final administration (Imoto, Kuramoto et al. 1986a). Rats fed between 363 and 434 

mg/kg/day showed decreased body weight gain, methemoglobinemia, and associated effects on 

erythropoiesis, liver pathology, including cholangiofibrosis, and hepatocellular carcinoma and interstitial 

cell tumors of the testes. At dietary doses of 31.5 and 38.1 mg/kg/day, the only phenotype observed was 

a lower incidence of liver lesions than that seen at the higher doses, and no effects were observed at 

doses about an order of magnitude lower. Mice were less sensitive to chronic GTN exposure, with the 

high dose of approximately 1000 mg/kg/day leading only to body weight changes and 

methemoglobinemia with its associated hematologic effects (Ellis, Hong et al. 1984). 
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Although GTN has not been examined for its capacity to bind estrogen, androgen or thyroid hormone 

receptors in in vitro assays, reproductive and developmental effects have been observed only following 

chronic experimental exposure to concentrations significantly greater than that needed to induce a 

therapeutic effect. A three-generation study in rats exposed to between 408 and 452 mg/kg/day for six 

months before F0 matings and throughout F1 and F2 generations found a systematic decrease in food 

consumption and body weight gain, but no clear indication of more extensive impacts in the F0 cohort. 

Infertility seen in F1 and F2 cohorts was attributed to an increase in interstitial cell tissue and 

consequently decreased spermatogenesis in males (NovaDel Pharma Inc. 2004). An additional threegeneration reproductive toxicity study in rats showed no effects on fertility, viability, growth, or 

development of offspring at doses up to 38 mg/kg/day. Adverse fertility effects were seen at doses above 

363 mg/kg/day which were secondary to malnutrition and testicular tumors. Developmental toxicity 

studies have been conducted in rats and rabbits given injection doses of up to 20 and 4 mg/kg/day, 

respectively, during typical gestation administration periods. No teratogenic, embryo toxic, or fetotoxic 

effects were observed. Aside from transient erythema at site of dermal application, pregnant NZW 

rabbits administered up to 240 mg/kg/day during days 6 through 18 of gestation showed no signs of 

decreased or abnormal reproductive performance or fetal development (Imoto, Nakao et al. 1986b). 

GTN has produced mixed results in the Ames test but was not mutagenic in a Chinese hamster ovary 

cell assay without metabolic activation. Chromosomal aberrations were not found in dogs given up to 5 

mg/kg/day for nine weeks or in rats given up to 234 mg/kg/day for eight weeks. A dominant lethal test 

in rats given 3, 32, or 363 mg/kg/day in the diet for 13 weeks also showed no effect on male fertility and 

no genotoxic activity. 

In humans, fatalities from industrial intoxication are uncommon. Medical studies of explosives workers 

with combined GTN have not found evidence of chronic intoxication or injury despite transient 

symptoms. An extensive epidemiologic study of 276 factory employees with long exposure to GTN and 

a related compound, ethylene glycol dinitrate, gave no evidence of permanent deterioration in health 

(Bingham, Cohrssen et al. 2001). Preliminary examination of data from a randomized, double-blind, 

placebo-controlled study of early childhood development of children exposed in utero to GTN found no 

impact (Guo, Xie et al. 2010). Summary and conclusions: Extensive studies, including studies in 

humans, have demonstrated that developmental and reproductive effects are not among the major 

toxicities of GTN, with the possible exception of testicular degeneration and interstitial cell tumors of 

the testes. If necessary, information regarding whether GTN is capable of interacting with the EAT 

pathways could be obtained by estrogen, androgen or thyroid hormone receptor binding studies or other 

in vitro assessment of GTN’s possible impact on these systems. Additional in vivo tests will be unlikely 

to provide data that haven’t already been gathered from existing toxicological, pharmacological and 

epidemiological sources. 

VI. Overall Summary and Conclusions

Consideration of exposure is a fundamental element of prioritization of chemicals for risk assessment. In 

the creation of the second list of chemicals for screening in the EDSP, EPA attempts to consider 

exposure by focusing not only on pesticides but also on chemicals that may be found in drinking. 

However, in order to reduce redundant testing, further considerations are necessary, including a first step 

of evaluating existing toxicological and exposure information for each chemical to determine whether 

any further testing is warranted, and to streamline any additional testing. 
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Abundant information exists for many, if not most, of the chemicals on the second list. For many of 

these chemicals (especially pesticides and industrial chemicals no longer manufactured or imported into 

the US) it is questionable whether “a substantial population may be exposed...” – an important 

consideration for prioritization, and also an essential stipulation that allows EPA to request information 

under SDWA. In addition, there is abundant existing toxicological information for many of these 

chemicals that renders further testing for endocrine effects moot, either by addressing endocrine-related 

activity or by characterizing the prevalent toxicity of a given chemical. We have provided such 

arguments for several chemicals that would warrant their removal from the second list.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect. Please also see general responses to comment under EPA 

Comment Codes: 2090 Contaminants with MCLG of Zero and 2060 Chemicals with Toxicity Data 

Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 2

EPA Comment Code: 2070

Comment: Mammalian toxicology of oxyfluorfen has no indication of endocrine - related effects.

A comprehensive package of regulatory toxicology studies has been conducted with oxyfluorfen and 

reviewed globally (e.g. USEPA, EU). Based on findings in all studies, no concerns are noted for primary 

endocrine disruption leading to adverse effects on the endocrine system. Assessment of human exposure 

via product application, food intake and especially water intake also demonstrates that potential for 

exposure to oxyfluorfen is low and therefore would not result in any adverse effects to human health.

Oxyfluorfen should therefore not be considered a priority for endocrine screening.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 5

EPA Comment Code: 2070

Comment: Specific Comments on Benzene: 

There is already an extensive database of human epidemiology data on benzene as well as numerous 

animal toxicology studies including data on reproductive and developmental toxicity endpoints.

* EPA’s Voluntary Children's Chemical Evaluation Program (VCCEP) asked companies to voluntarily 

provide information on health effects, exposure, risk, and data needs for various chemicals. On March 

30, 2006 the American Chemistry Council Benzene, Toluene and Xylene (BTX) VCCEP Consortium 
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submitted data for several chemicals, including benzene. That submission included an exposure 

assessment as well as data on reproductive and developmental toxicity. 

- In the VCCEP submission, the environmental background/ambient sources of benzene exposure 

included indoor air, outdoor air, diet, and water. The exposure assessment indicated that the inhalation 

pathway is the primary route of exposure with systemic (absorbed) doses at least one order of magnitude 

higher than those received via oral ingestion or dermal pathways, except for infant ingestion of human 

milk from an occupationally exposed mother. Of the ambient background sources, inhalation of indoor 

air contributed approximately 95% of the overall dose to children and prospective parents. Food and 

water accounted for 5%. EPA chose to include chemicals on the second EDSP list based only “on their 

pesticide registration status and/or because such substances may occur in sources of drinking water to 

which a substantial population may be exposed.” As noted above food/water accounted for just 5% of 

benzene exposure and currently benzene is not listed as a registered pesticide. 

- Based on a review of the available human data, included in the VCCEP submission, the existing data 

on male and female reproductive toxicity or developmental effects did not establish a causal relationship 

with benzene exposure. The VCCEP submission also included a review of animal toxicity studies of 

benzene via the oral, inhalation, and dermal route. The submission stated “A fertility study in female rats 

exposed to benzene at vapor concentrations up to 300 ppm (960 mg/m3) for 10 weeks prior to mating, 

and daily during gestation days (GD) 0-20 and lactation days (LD) 5-20 did not demonstrate any effect 

on female fertility or maternal performance.” As well, “No effects on male reproductive capabilities 

were observed in a study of the performance of male mice exposed up to 300 ppm (960 mg/m3) benzene 

for 10 weeks (one spermatogenic cycle) then mated with untreated females. However, some effects on 

testicular weight, testicular atrophy and abnormal sperm have been reported in a 90-day subchronic 

study in mice at similar doses; whereas male rats were unaffected.” Subsequently, after a review of the 

VCCEP submission EPA concluded in its July 1, 2007 response to the consortium that “All Tier 1 

toxicity studies and most of Tier 2 toxicity studies had been conducted. For Tier 1, acute toxicity studies, 

mutagenicity studies and numerous repeat-dose toxicity studies have been conducted.”.....” For Tier 2, 

numerous repeat-dose toxicity studies, adequate developmental studies by the inhalation route in several 

species, mutagenicity studies, immunotoxicity studies and metabolism and pharmacokinetic studies have 

been conducted” 

* The Agency for Toxic Substances and Disease Registry’s (ATSDR) 2007 Toxicology Profile of 

benzene noted that the “major effect of benzene from long-term exposure is on the blood” and a review 

of the developmental animal toxicity database indicates that benzene at high exposure concentrations 

typically causes maternal toxicity or stress, and can affect mammalian development processes. However, 

the majority of the reported effects suggest a nonspecific, generalized toxicity to the embryo, rather than 

toxicity to a specific developmental process, because there is no specific pattern of malformations 

associated with exposure. These effects were frequently associated with maternal toxicity or stress, such 

as maternal weight-gain effects and diet effects and suggest a general toxicity leading to growth 

retardation and delayed maturation. However, the conclusion of the ATSDR profile was that the 

available data was unable to link benzene to developmental or reproductive effects. 

* The EPA, the EU and the International Agency for Research on Cancer (IARC) have all conducted 

human health risk assessments on benzene, based primarily on human data. The extensive human health 

effects database of peer-reviewed publications supports that hematological endpoints and cancer are the 

critical health effects for benzene. Consequently, the conclusions reached by these regulatory bodies 

have led to extensive occupational and environmental regulations and risk management programs. These 
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programs have resulted in significant reductions in benzene emissions and exposure levels under 

numerous statutes, including the Clean Air Act, the Clean Water Act, the Safe Drinking Water Act, the 

Resource Conservation and Recovery Act (RCRA); the Comprehensive Environmental Response, 

Compensation, and Liability Act and the Pollution Prevention Act. 

API feels there is limited value in including benzene in the second EDSP chemical list for screening for 

endocrine activity. The expansiveness of the benzene database and the robust human dose response data 

currently available provide a wealth of hazard identification information that cover all modes of action, 

including endocrine pathways. As well, there are already effective occupational, environmental and risk 

management programs in place. It is highly unlikely that any additional data acquired from EDSP would 

provide any meaningful contribution to the overall risk characterization or risk management of benzene.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints. Also, 

please see general response to comment under EPA Comment Code: 2070 Contaminants Not Expected 

to Produce Estrogen-like Effect.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0026

Comment Part: 2

EPA Comment Code: 2070

Comment: Mammalian toxicology of isoxaben has no indication of endocrine - related effects. 

A comprehensive package of regulatory toxicology studies has been conducted with isoxaben and 

reviewed globally (e.g. USEPA, EU). Based on findings in all studies, no concerns are noted for primary 

endocrine disruption leading to any adverse effects on the endocrine system. Assessment of human 

exposure via product application, food intake and especially water intake also demonstrates that 

potential for exposure to isoxaben is low, and therefore would not result in any adverse effects to human 

health. Isoxaben should therefore not be considered a priority for endocrine screening.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Paul Dugard

Commenter Organization: Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0032

Comment Part: 4

EPA Comment Code: 2070

Comment: 3. HCFC-22 Does not Display Endocrine Disrupting Properties

Section 408(p) of the FFDCA provides that EPA may exempt a chemical from testing in the EDSP if 

EPA determines that “the substance is anticipated not to produce any effect in humans similar to an 

effect produced by a naturally occurring estrogen.” One of the criteria for excluding a chemical in the 

“streamlining” process is if a chemical is “not likely to be biologically active”. In the case of HCFC-22 

there are both structural reasons and extensive evidence to show that it is not an active endocrine 
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disruptor. Rather than attempt to list all the relevant toxicity studies, the reader is encouraged to consult 

the reviews in the Joint Assessment of Commodity Chemicals (JACC) published by the European 

Chemical Industry Ecology and Toxicology Centre (ECETOC, 1989) and the European Union Risk 

Assessment (EU RAR, 2007). 

HCFC-22 is a small, simple molecule that would not be expected to interact directly with endocrine 

receptors, and metabolism in rats was found to be minimal. Thus there is no reason to anticipate 

classical endocrine disruption based on chemical structure. 

Inhalation is the relevant route of exposure to HCFC for humans. It follows that the majority of HCFC22 toxicity studies have been conducted using the inhalation route of administration. Many repeat dose 

studies have been conducted including a number of long term studies in both rats and mice. Typically, 

the top dose level in many studies has been 50,000 ppm (6 hours per day, 5 days per week) and the 

absence of generalized toxicity at this high dose level is striking. There were no indications of effects on 

thyroid function or on male or female reproductive organs in any study. As an adjunct to a dominant 

lethal study in the rat, male reproductive structure and function (including fertility) were studied in 

detail. A slight reduction in prostate weight was recorded, possibly due to HCFC-22 at a dose level of 

50,000 ppm (5hr/day for 8 weeks), but there were no histopathological changes in any organ or in 

biochemical parameters relevant to reproduction. A number of teratology studies have been conducted in 

rats and rabbits without evidence of endocrine disruption. 

There have been no ecotoxicological studies, terrestrial or aquatic, performed on HCFC-22. Presumably 

this is because the absence of exposures make the testing unnecessary and also the difficulty of 

conducting such tests on a gas where there are no alerts to suggest testing is necessary.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033

Comment Part: 3

EPA Comment Code: 2070

Comment: b. The Hydrazine Structure is Unlikely to Interact with Endocrine Receptors

Hydrazine is a small inorganic molecule without any structural similarity to known estrogenic, 

androgenic or steroidal compounds. The Tier 1 in vitro screening tests are dependent on binding or 

interaction of test substances with endocrine receptors. These tests have been validated with structural 

hormone analogs. Hydrazine does not in any way fit into a scheme that would test materials of this type.

Response: Please see the general response to comment under this EPA Comment Code: 2070

Contaminants Not Expected to Produce Estrogen-like Effect.

Commenter Name: Rebecca Bernstein

Commenter Organization: Arkema Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0033
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Comment Part: 15

EPA Comment Code: 2070

Comment: c. HCFC-22 Has Already Been Tested in Higher Tier Studies

In the case of HCFC-22 there are both structural reasons and extensive evidence to show that it is not an 

active endocrine disrupter. Reviews of the relevant toxicity studies are available. [FN19: Joint 

Assessment of Commodity Chemicals (JACC) published by the European Chemical Industry Ecology 

and Toxicology Centre (ECETOC), 1989] [FN20: European Union Risk Assessment Report, 

Chloroditluoromethane, EINECS No: 200-871-9, November 2007]

HCFC-22 is a small, simple molecule that would not be expected to interact directly with endocrine 

receptors. Thus there is no reason to anticipate classical endocrine disruption based on chemical 

structure.

Many repeat dose studies have been conducted including a number of long term studies in both rats and 

mice. Typically, the top dose level in many studies has been 50,000 ppm (6 hours per day, 5 days per 

week) and the absence of generalized toxicity at this high dose level is striking. There were no 

indications of effects on thyroid function or on male or female reproductive organs in any study. As an 

adjunct to a dominant lethal study in the rat, male reproductive structure and function (including 

fertility) were studied in detail. Teratology studies conducted in rats and rabbits are adequate for hazard 

assessment.

Due to its high vapor pressure, it is very difficult to test HCFC 22 in water meaningfully. This likely 

explains why no drinking water studies and few experimental aquatic toxicity tests have been carried 

out.

There is one well documented, oral study in rats [FN21: Genotoxicity and Carcinogenicity of 

Fluorocarbons: Assessment by Short-Term in vitro tests and chronic exposure in rats, Longstaff Et al. 

Toxicology and Applied Pharmacology 72: 15-31 , 1984]. in which HCFC 22 was administered at a 

dose level of 300 mg/kg-day in corn oil 5 days per week for 52-weeks. The animals were observed until 

week 125 when full post mortem examinations were performed. Despite the limitation of a single dose 

of HCFC-22 in this study, this study showed no effect on body weight gain or any evidence of other 

adverse effects.

Inhalation, not drinking water, is the relevant route of exposure for humans and HCFC 22 has been well 

characterized using this route of exposure. Tier 1 screening studies do not appear to be necessary to aid 

in the assessment of this material, based on the body of data already available from studies that are 

considered Tier 2 in vivo studies.

In conclusion, for the reasons stated herein, the above referenced chemicals do not meet the criteria for 

listing under the Draft EDSP List 2.

Thank you for the opportunity to provide these comments.

Sincerely,

Rebecca J. Bernstein

Senior Director, Product Safety & Regulatory Affairs

Arkema Inc.
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Phone: (215-419-5415)

Email: rebecca.bemstein@arkema.com

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2030 Contaminants Unlikely to Persist in Drinking 

Water.

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 2

EPA Comment Code: 2070

Comment: Section 408(p) of the FFDCA also provides that EPA may exempt a chemical from 

endocrine testing if EPA determines that "the substance is anticipated not to produce any effect in 

humans similar to an effect produced by a naturally occurring estrogen."[FN5: 21 U.S.C. § 346a(p)(4).]

As discussed below, the testing conducted by the HAP Task Force for 1,1,2-trichloroethane, along with 

available data for EDC (to be supplemented by further required testing), meets the statutory criterion for 

EPA to conclude that these are substances unlikely to produce any effect in humans similar to the effect 

of a naturally occurring estrogen.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 6

EPA Comment Code: 2070

Comment: 1. 1,1,2-Trichloroethane

Pursuant to an ECA executed with EPA in 1999, [FN12: 65 Fed. Reg. 37550 (June 15, 2000).] the HAP 

Task Force conducted and reported on November 30, 2004 a multigeneration reproductive toxicity study 

in rats. Significantly, a mammalian multigeneration reproductive toxicity study is the primary Tier 2 

study for which the Tier 1 studies are a screen:

"Chemicals that go through Tier 1 screening and are found to have the potential to interact with the 

estrogen, androgen, or thyroid hormone systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing 

is designed to identify any adverse endocrine-related effects caused by the substance, and establish a 

quantitative relationship between the dose and that endocrine effect."[FN13: 75 Fed. Reg. 70558, 70563 

(November 17, 2010).] 

The reproductive toxicity study sponsored by the Task Force, conducted under EPA TSCA Guidelines, 

exposed rats to drinking water concentrations of 170, 570, and 1350 ppm of 1,1,2-trichloroethane. At 
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1350 ppm, reductions in body weights, weight gain, food efficiency and water consumption during 

gestation and lactation, and reductions in food consumption during lactation, were observed in P1 and 

F1 rats. Reduced pup weights were also observed on days 4-21 of lactation at the 1350 ppm exposure 

level. However, no reproductive effects were observed at any concentration level.

In addition, several aquatic toxicity studies have been conducted with 1,1,2-trichloroethane. One of 

those studies reported a no-observed-effect level of 10 mg/L (10 ppm) based on morphological changes 

and hatchability when molluscs (Lymnaea stagmalis) were exposed during the first cleavage division. 

[FN14: Adema and Vink, A Comparative Study of the Toxicity of 1,1,2-Trichloroethane, Dieldrin, 

Pentachlorophenol, and 3,4-Dichloroaniline for Marine and Fresh Water Organisms, Chemosphere 10: 

555-554 (1981).] There were no effects on reproduction when larvae of crustaceans (Artemia salina) 

were exposed to 10 mg/L or Daphnia magna were exposed to 18 mg/L. In fish (Pleuronectes platessa) no 

growth effects or malformations were found at 3 mg/L.

Therefore, the no-observed-effect level for reproductive effects in several aquatic species is many orders 

of magnitude higher than the 5 ppb MCL. [FN15: To the same effect, EPA's unit risk estimate for 1,1,2-

trichloroethane in drinking water is 1.6 x 10-6(ug/L).]

Based on the mammalian reproductive toxicity study and several aquatic reproductive toxicity studies, 1, 

1,2-trichloroethane is not likely to have any appreciable endocrine disruptor activity and should be 

considered as a low priority for further testing.

2. EDC

Pursuant to an ECA executed with EPA in 2003,[FN16: 68 Fed. Reg. 33125 (June 3, 2003).] the HAP 

Task Force agreed to conduct a multigeneration reproductive toxicity study in rats, currently scheduled 

to begin in 2011. As noted above, this is the primary Tier 2 study for which the Tier 1 studies are a 

screen, and should fully satisfy the EDSP Tier 2 test requirement for determining EDC's potential to be 

an endocrine disruptor. There is also a great deal of existing relevant data. In a study of EDC's effects on 

developmental and reproductive endpoints, drinking water concentrations ranging from 30 mg/L to 290 

mg/L were administered to mice. There were no dose-dependent effects on fertility, gestation, viability, 

or lactation, pup survival or weight gain. Based on these results the authors concluded that EDC posed 

little hazard to human development and reproduction. [FN17: Lane et al., Effects of 1,2-Dichloroethane 

and 1,1,1-Trichloroethane in Drinking Water on Reproduction and Development in Mice, Toxicol. 

Applied Pharmacol. 63:409-421 (1982).]

A subsequent study examined the development toxicity of EDC in rats. The animals were given 0 to 2.4 

mmoles of EDC per kg per day by gavage, equivalent to drinking water concentrations of about 1.99, 

2.65, 3.31 and 3.97 g/L. There were no differences in the number of implantation sites per litter or 

number of live fetuses per litter or mean fetal body weight at any of the doses compared to control 

values. There was no difference in the mean number of percent resorptions at the two lower exposure 

levels, but there was a significant increase in resorptions at 3.31 mg/ml which may have been attributed 

to mild maternal toxicity. No increases in fetal anomalies were observed at any of the dose levels. 

[FN18: Payan et al., Assessment of the Developmental Toxicity and Placental Transfer of 1,2-

Dichloroethane in

Rats, Fund. Applied Toxicol. 28:187-198 (1995).]
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An aquatic study examined the effects ofEDC on the early life stage of the fathead minnow (Pimephales 

promelas).[FN19: Benoit et al., A Fathead Minnow Pimephales Promelas Early Life Stage Toxicity Test 

Method Evaluation and Exposure to Four Organic Chemicals, Environmental Pollution (Series A) 28: 

189-197 (1982).] Concentrations ranging from 4 mg/L to 59 mg/L had no effect on the percent of 

hatchable embryos, percent normal larvae produced, or percent survivability at 28 days when compared 

to controls. The no-observed-effect level in several aquatic species was 4000-fold higher than the 5 ppb 

MCL. [FN20: Similarly, for comparison purposes, EPA's unit risk estimate for EDC in drinking water is 

2.6 x 10-6 (ug/L).]

EDC is not likely to have any appreciable endocrine disrupter activity and should be considered as a low 

priority for further testing.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: W. Caffey Norman

Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0037

Comment Part: 5

EPA Comment Code: 2070

Comment: F. Lack of Endocrine Effects Expected Based on Mammalian Data

Section 408(p) of the FFDCA provides that EPA may exempt a chemical from endocrine testing if EPA 

determines that "the substance is anticipated not to produce any effect in humans similar to an effect 

produced by a naturally occurring estrogen.”[FN16: 21 U.S.C. § 346a(p)(4).] As discussed below, 

available data for trans-1,2-dichloroethylene and 1,1,1-trichloroethane, meet the statutory criterion for 

EPA to conclude that these are substances unlikely to produce any effect in humans similar to the effect 

of a naturally occurring estrogen. Moreover, trans-l,2-dichloroethylene went through the EPA High 

Production Volume (HPV) Program and 1,1,1-trichloroethane went through the ICCA HPV program. 

EPA had no comment on the conclusion that trans-l,2-dichloroethylene did not present a reproductive or 

developmental concern. As part of the ICCA HPV process, all OECD member countries agreed that 

1,1,1-trichloroethane did not present a hazard for reproductive or developmental effects.

1. Trans-1,2-Dichloroethylene

Data from a developmental toxicity in rats show that trans-1,2-dichloroethylene is not a developmental 

toxicant. The NOEL was less than 2000 ppm for the dam and was determined to be 6000 ppm for the 

conceptus.[FN17: Hurtt, M.E., R. Valentine, and L. Alvarez, Fundamental and Applied Toxicology 20, 

225-230 (1993).] In a repeated exposure study, no effects on reproductive organs, sperm motility, and 

vaginal cytology parameters of rats or mice were noted when the animals were fed diets containing up to 

50,000 ppm microencapsulated test substance for 14 weeks.[FN18: National Toxicology Program (NTP) 

(2002) Toxicity Studies of Trans-l,2-Dichloroethylene (CAS No. 156-60-5) Administered in 

Microcapsules in Feed to F344/N Rats and B6C3Fl Mice. Toxicity Report Series No. 55. NIH 

Publication No. 02-4410.]

2. 1,1,1-Trichloroethane
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As shown in the enclosed summary table, the reproductive toxicity of 1,1,1- trichloroethane has been 

well investigated in several studies. In a two-generation study in ICR Swiss mice, 1, 1,1-trichloroethane 

was administered via drinking water to 30 female and 10 male animals/dose at 0, 100,300, or 1000 

mg/kg bw/day, for 5 weeks prior to mating and throughout gestation and lactation of the F1a litters. At 2 

weeks post-weaning of the F1b litters, the F0 adults were re-mated to produce F1b litters. At 2 weeks 

post-weaning of the F1b litters, the F0 adults were re-mated for teratology screening of the F1c pups. 

The F1b litters were culled to 30 males at weaning and placed on test solutions until age 14 weeks when 

they mated to produce the F2a litters. At 2 weeks post-weaning of the F2a pups, the F1b adults were remated for teratology screening of F2b pups. Adult mortality among the treated and control F0 and F1b 

generations was sporadic. Among the naïve controls, there was 20% mortality in both sexes in the F0 

generation. For the vehicle control, there was 10% and 3.3% mortality among the males and females, 

respectively, in the F0 generation. Mortality in the F0 generations was 0%, 10%, and 20% among males 

and 10%, 6.7%, and 13.3% among females exposed at 0.58, 1.75, and 5.83 mg/L, respectively. With the 

exception of 7.4% rate mortality in the females dosed at 0.58 mg/L, no mortality was observed in the 

F1b generation. The reason for the sporadic incidences of increased mortality could not be discerned at 

necropsy. No adverse reproductive effects were observed up to the highest dose tested. There were no 

effects on reproductive function and there was no increase in the incidence of skeletal or visceral 

malformations in either generation, indicating the NOAEL for reproductive toxicity was 1000 mg/kg 

bW/day, the highest dose tested.

In 13-week dietary studies, epididymal sperm counts were decreased 10-20% but only at high doses 

(4,800 mg/kg bw/day) and no other male reproductive parameters were affected or reproductive 

histopathology was observed.

The developmental toxicity of 1,1,1-trichloroethane has also been investigated in several studies. In a 

standard one generation study in rats, 1, 1,1-trichloroethane was administered via inhalation to 30 

animals/sex/ concentration at 0, 1000,3000 or 6000 ppm (corresponding to 0, 5.4, 16.4 or 32.8 mg/L), 

for 6 hours/day on GD 6-15. No deaths were observed. Maternal effects were seen at 32.8 mg/L 

(hypoactivity, reductions in food consumption, body weight gain, body weight, and gravid uterine 

weight) and at the two lower doses (reduced body weight gain and reduced food consumption); the 

NOAEL for maternal toxicity was < 5.4 mg/L. Fetal body weight was significantly reduced only for 

female fetuses in the 32.8 mg/L group; decreases for male fetuses and all fetuses combined were not 

statistically significant. No increases in fetal malformations were observed. Effects suggesting slight 

developmental delay (poorly or unossified cervical centrum) were observed at the high dose. A NOAEL 

of 16.4 mg/L for mild fetotoxicity demonstrated by developmental delay and decreased body weights of 

female fetuses was identified in this study. In other inhalation studies, neurobehavioural effects were 

observed; across studies, effects occurred at doses of 10.9 mg/L or higher. The developmental toxicity of 

1,1,1,-trichloroethane has been well investigated in oral studies in rats and mice; no toxicologically 

significant effects have been observed.

Finally, in humans, epidemiological studies failed to find statistically-significant associations between 

1,1,1-trichloroethane and adverse reproductive outcomes.

G Conclusion

Occurrence data clearly do not support the conclusion that a substantial population are or could be 

exposed to trans-1,2-dichloroethylene and 1,1,1-trichloroethane in drinking water. In fact, these data 
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show virtually no occurrence of these compounds in sources of drinking water at their respective MCLs. 

Available test data compel the conclusion that trans-1,2-dichloroethylene and 1,1,1-trichloroethane are 

unlikely to produce any effect in humans similar to the effect of a naturally occurring estrogen. In the 

circumstances, EPA cannot justify the considerable expense of screening/testing and the needless 

suffering and death of test animals for substances that do not meet the statutory criterion for inclusion in 

the testing program.

Very truly yours,

W. Caffey Norman

Enclosure

“1,1,1-Trichloroethane Summary of Effects on Fertility and Developmental Toxicity” [See PDF Docket 

ID: EPA-HQ-OPPT-2009-0477-0037.1]

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 2

EPA Comment Code: 2070

Comment: Section 408(p) of the FFDCA also provides that EPA may exempt a chemical from 

endocrine testing if EPA determines that "the substance is anticipated not to produce any effect in 

humans similar to an effect produced by a naturally occurring estrogen." [FN5 21 U.S.C. § 346a(p)(4).] 

As discussed below, available data meet the statutory criterion for EPA to conclude that these substances 

are unlikely to produce any effect in humans similar to the effect of a naturally occurring estrogen.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 7

EPA Comment Code: 2070

Comment: 1. VDC

VDC has been the subject of a great deal of testing and assessment, including an exhaustive Peer 

Consultation under EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). The Report of 

the Peer Consultation Meeting on Vinylidene Chloride [FN14: Held January 29-30, 2003, at the 

University of Cincinnati, http://www. tera.org/peer/vccep/vdc/vdcmeetingreport.pdf.] essentially 

supports the summary of the data presented: 
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"The potential toxicity of VDC has been extensively studied in a variety of assays and in a number of 

different species of test animals; a substantial hazard database has been accumulated during the past few 

decades. Data has been generated on categories listed in all three tiers of the VCCEP, and the database 

includes studies of varying sophistication and range. In many cases, multiple studies are available that 

individually or collectively provide a complete assessment of a particular VCCEP hazard category for 

VDC. Conversely, numerous studies have provided data that is applicable to more than one VCCEP 

category, for example the evaluation of gonads and nervous and immune system tissues in repeated-dose 

toxicity studies providing assessments of potential reproductive toxicity, neurotoxicity and 

immunotoxicity, respectively. Further testing to provide comprehensive evaluations of those few 

remaining categories of tests listed in VCCEP specifically targeted for evaluation in young animals 

would be dependent upon evidence of significant potential exposure of children. Since significant 

exposures to children do not occur from existing uses and applications of VDC, further hazard testing is 

unwarranted." 

Significantly, a mammalian multigeneration reproductive toxicity study, the primary Tier

2 study for which the Tier 1 studies are a screen, [FN15: "Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with the estrogen, androgen, or thyroid hormone systems 

will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrinerelated effects caused by the substance, and establish a quantitative relationship between the dose and 

that endocrine effect." 75 Fed. Reg. 70558,70563 (November 17, 2010).] has been conducted for VDC: 

there were no treatment-related effects upon reproduction, gonads, or secondary sex organs.

Based on the mammalian reproductive toxicity study and other data reviewed in the enclosed VCCEP 

Hazard Assessment, VDC is not likely to have any appreciable endocrine disrupter activity and should 

be considered as a low priority for further testing.

2. Methylene Chloride

Comprehensive reviews of toxicological information for methylene chloride are available in the WHO 

Environmental Health Criteria Document [FN16: World Health Organization International Programme 

on Chemical Safety, Environmental Health Criteria No. 164, Methylene Chloride, 2nd Ed. (1996).] and 

EPA's draft health assessment in support of the IRIS database. [FN#17: EPA, Draft Toxicological 

Review ofDichloromethane (Methylene Chloride) in Support of Summary Information on the Integrated 

Risk Information Service (IRIS) (2009).] Methylene chloride has been extensively tested and found to 

be of low general toxicity. In rodent repeat dose studies for general toxicity and carcinogenicity (from 

14-day to lifetime duration, inhalation or oral administration), the primary target organ has been shown 

to be the liver. Adverse effects in the mouse lung observed in some inhalation studies are considered to 

be a species-specific response. In none of these many studies employing dose levels up to 1,000 mg/kgday and above was there an indication that endocrine disruption had occurred or that reproductive 

organs had been affected. Despite high dose levels, effects on growth and body weight were minimal, if 

present at all, indicating that thyroid function was unaffected.

A limited number of studies designed specifically to address reproductive and developmental endpoints 

have been conducted using the oral route. In a study in which male and female rats were dosed from 90 

days before mating (dosing halted 10 days before mating) by gavage at dose levels of 0, 25, 75, and 225 

mg/kg-day, there were no effects on fertility, pregnancy outcome, litter parameters, or pup weight or 
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survival. [FN18: General Electric Company, Dichloromethane and ninety day oral toxicity study in rats, 

Submission under TSCA § 8(d), EPA Document No. 86-878210707 (1976).] In this study, pups were 

followed to postnatal day 90 without any adverse effects on multiple parameters. Methylene chloride 

was administered in another stud~ to male mice by subcutaneous injection 3 days per week at dose 

levels of 0, 250, 500 mg/kg. [FN19: 19 Raje R., Basso M., Tolen T., et al., Evaluation of in vivo 

mutagenicity oflow-dose methylene chloride in mice, J. Am. Coll. Toxicol. 7(5): 699-703 (1988).] 

Dosing began 4 weeks before mating with a 1-week break immediately before mating. Fertility was 

unaffected, there were no testicular effects and pregnancy, litter and pup parameters were all unaffected. 

In a more recent study, no adverse developmental effects were observed following dosing by gavage 

from gestational day 6 to 19. [FN20 Narotsky M.G., Kavlock R. J., A multidisciplinary approach to 

toxicological screening: II.

Developmental toxicity, J. Toxicol. Environ. Hlth. 45: 145-171 (1995).] The dose levels were 337.5 and 

450 mg/kg-day. 

For inhalation administration, in five developmental toxicity studies there were no results indicative of 

endocrine disruption despite exposure levels up to 4,500 ppm. In a well-designed and conducted twogeneration reproductive toxicity study, rats were exposed to 0, 100, 500, and 1500 ppm 6 hours per day 

from 14 weeks before mating (male and female), and throughout pregnancy, and the F1 pups were 

exposed from postnatal day 4 with mating at 17 weeks. [FN21: Nitschke K. D., Eisenbrandt D. L., 

Lomax L. G., et al., Methylene chloride: two-generation inhalation reproductive study in rats, Fundam. 

Appl. Toxicol. 11: 60-67 (1988).] There were no effects on fertility, pregnancy outcome, litter 

parameters, pup weight or survival. There were no histopathological effects seen in reproductive organs 

in any of the groups of rats. 

It can be concluded that methylene chloride has been shown not to possess endocrine disrupting 

potential in a range of studies employing high dose levels. A mammalian two generation reproductive 

toxicity study, the point of the Tier 1 screening, has already been conducted for this substance. 

Methylene chloride is not likely to have any appreciable endocrine disruptor activity and should be 

considered as a low priority for further testing.

Response: Please see general response to comment under EPA Comment Code: 2060 Chemicals with 

Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints. Also, 

please see general response to comment under EPA Comment Code: 2070 Contaminants Not Expected 

to Produce Estrogen-like Effect.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 11

EPA Comment Code: 2070

Comment: • Available data for VDC and methylene chloride are sufficient to conclude that they are 

unlikely to produce any effect in humans similar to those produced by a naturally occurring estrogen, 

thus they are exempt from testing. 

• The only Tier 2 study that EPA may lawfully require, mammalian reproductive toxicity, has already 

been done for the chemicals of concern. It is inconsistent with EPA's animal welfare policies and 
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common sense for EPA to impose expensive and animal-intensive Tier 1 screening when the study 

requirement for which the screening is done has already been filled.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 6

EPA Comment Code: 2070

4.2 Perchlorate is not consistent with the type of chemical US EPA has historically examined

We agree with the Agency that public health is benefited by scientific understanding of chemicals that 

mimic endogenous hormones. But some presented in the November 17th list, such as perchlorate, do not 

meet the Agency’s criteria. There are a few anthropogenic chemicals that are suggested to mimic thyroid 

hormone, similar to estrogen-like compounds. Although the potency of environmental chemicals to 

activate hormone receptors is often lower than that of endogenous hormones, there are some reports of 

thyroid hormone mimetics. For example, one study reports an in vitro study that demonstrates bisphenol 

A could displace T3 at the thyroid hormone receptor and suppress gene expression (Moriyama et al., 

2002). Dibutyl phthalate has also been reported to be thyroid receptor antagonist in vitro (Li et al., 

2010). We expect more research to further identify thyroid hormone agonists or antagonists in the 

future.

4.3 Perchlorate’s mechanism of action

Perchlorate is not an example of a chemical that can either bind to thyroid receptors or mimic thyroid 

hormones. Rather, given sufficient dose and duration, perchlorate inhibits iodide uptake to the thyroid 

which will eventually act to decrease thyroid hormone production. Iodide is taken up by the thyroid 

follicular cells via the sodium iodide symporter (NIS). The chemical structure, function, and action of 

perchlorate do not mimic thyroid hormones or pituitary hormones, such as TSH (Figure 1). Given 

sufficient dose and exposure, it is likely that almost any chemical will affect the endocrine system in 

some way.

In 2005, the National Academy of Sciences National Research Council (NRC) conducted a thorough 

and comprehensive review of the science of oral exposures to perchlorate. Of the many assessment 

made, the NRC reported that the science clearly demonstrates that perchlorate affects this target organ as 

any other chemical would effect a target organ. Thus, the weight of evidence demonstrates strongly that 

perchlorate does not exert its effect by mimicking a thyroid (or any other endocrine gland) hormone.

A second scientific conclusion by the NRC was that the mechanism of action for perchlorate is known 

and well characterized. This demonstrates that perchlorate does not mimic thyroid hormone action. The 

mechanism of action is inhibition of iodide uptake to the thyroid follicular cell. Further, the mechanism 

of action is reversible and is not adverse:
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• Regarding the mechanism of action, there is a threshold dose, called the No Observable Effect Level 

(NOEL), 0.007 mg/kg-day (equivalent to 245 ppb, assuming 70 kg and 2 Liters of water per day). Below 

this dose no effect of iodide uptake inhibition (IUI) has been reported in the scientific literature.

• Perchlorate has a short half-life of about eight hours, is not metabolized, and does not bioaccumulate.

• Other chemicals, such as nitrate and thiocyanate have the same mechanism of action as perchlorate.

Figure 1 Structures of Thyroxine (T4), Triiodithyronine (T3), Thyroid Stimulating Hormone (TSH), 

Perchlorate, Nitrate, Bromate, and Chlorate

T4 and T3 are secreted by the thyroid gland and interact with thyroid hormone receptors. TSH is 

secreted

by the anterior pituitary gland. The active subunit of TSH is composed of 138 amino acids. It is clear 

that

perchlorate, nitrate, bromate, and chlorate are structurally dissimilar to T4, T3, and TSH. Perchlorate,

nitrate, bromate, and chlorate are either listed on the CCL3 or have a NPDWR.

[Figure 1: See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0039.1]

a Source: Wikimedia Commons

b Source: thyroidmanager.org 

5.0 PERCHLORATE EXCLUSION FROM THE ENDOCRINE DISRUPTOR SCREENING

PROGRAM LIST

As mentioned previously, the Notice reports a chemical was considered for the November 17th EDSP 

list if it has a NPDWR or is on the CCL3 list. This list was streamlined from over 200 to 134 chemicals 

based on six exclusion criteria. US EPA (2010a) states that it streamlined the list

...by excluding any chemical that fell into one or more of the following categories.

The six criteria are listed on pages two and three. Perchlorate can be excluded based on two of the 

criteria listed.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 12

EPA Comment Code: 2070

Comment: • Additionally, US EPA is justified as other chemicals, such as nitrate, that do not mimic 

hormones and qualify for the same exclusion criteria above, are not on the EDSP list. The same 

exclusion criteria for nitrate apply to perchlorate; therefore, perchlorate should similarly be excluded.
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Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Intertox, Inc.

Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0039

Comment Part: 8

EPA Comment Code: 2070

Comment: 6.0 CHEMICALS SIMILAR TO PERCHLORATE WERE EXCLUDED FROM 

ANALYSIS

While perchlorate is listed on the November 17th EDSP list, other chemicals that have the same 

mechanism of action on the thyroid gland were listed on the “Initial compilation of chemicals and 

substances considered for the second endocrine disruptor screening program list,” but were excluded 

from the EDSP list. These include nitrate, bromate, and chlorate. All are regulated or on the CCL3 list. 

The Agency has not provided information on why each of these analytes was culled from the November 

17th list.

Nitrate is particularly suitable to compare to perchlorate as it affects the thyroid with an identical 

mechanism of action. As with perchlorate, nitrate does not mimic thyroid hormone. Although less 

potent, nitrate also causes IUI (Tonacchera et al, 2005; US EPA, 2010b). Nitrate has a NPDWR in the 

form of a Maximum Contaminant Level (MCL) [FN1 The MCL for nitrate is not based on thyroid 

effects, but on methemoglobinemia (i.e., “blue baby syndrome”) in infants under six months of age. This 

effect is due to the ability of both nitrite and nitrate to reduce the ability of hemoglobin to carry oxygen. 

This is not a thyroid-mediated effect.] and was listed by US EPA and then excluded from the November 

17th list.

The same two criteria listed by the Agency that would exclude perchlorate, would also exclude nitrate.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Stephen Longacre

Commenter Organization: FMC Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0040

Comment Part: 2

EPA Comment Code: 2070

Comment: 3) EPA Has Concluded That Clomazone's Toxicity Database is Complete and That No 

Further Human Health Risk Work is Needed

EPA's Clomazone Summary Document Registration Review: Initial Docket January 2007 [Docket 

Number: EPA-HQ-OPP-2006-0113-0017] indicates EPA HED has concluded that clomazone's toxicity 

database is completed and that no further human health risk work is needed based on the following 

sections of the review:
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Page 4: "The Agency believes that previously completed human health assessments are adequate and 

there is no dietary risk that exceeds the Agency's level of concern."

Page 7: “The acute dietary exposure estimates (females 13-50 years old) represented <1% of the a PAD 

(acute Population Adjusted Dose)."

Page 7: " The chronic dietary exposure estimates for the most highly exposed population subgroup 

(infants less than 1 year old) represented <1% of the cPAD (chronic Population Adjusted Dose)

Page 29: "HED has considered recent clomazone risk assessments, updates to toxicity, exposure and 

usage databases, open literature data, poisoning incident data, and changes in science policy in its 

review. HED has determined that recent risk assessments meet current standards for science, that 

toxicity or exposure databases for clomazone are complete and that there are no material changes in 

science policy that would warrant the submission of new data or a revision of risk assessments."

Page 30: "Toxicity database. The toxicity database for clomazone is generally complete."

Page 31: "The toxicity database required to perform an FQPA assessment is complete. Acceptable 

developmental studies in rats and rabbits and a two-generation reproduction study in rats are available."

Page 31: "FQPA factor. The FQPA factor was removed (1 x) by the old FQPA Committee in September, 

2000 based on the completeness of the data, no indication of susceptibility or sensitivity in 

developmental and reproduction studies and no residual concerns for pre-or postnatal toxicity to infants 

and children."

Page 32: "Conclusion: HED does not need any additional data to confirm our earlier conclusions 

regarding the exposure and resultant risks from the use of clomazone. The risk assessments on file are 

up to current standards and no further human health risk work is needed."

These collective comments indicate that EPA has no concerns that clomazone is a possible endocrine 

disruptor, and give comfort for scheduling clomazone for endocrine disruption screening at some point 

in the future, and for not including clomazone on the proposed second list for endocrine disruption 

screening.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 2

EPA Comment Code: 2070

Comment: Based on the weight of evidence of both the hazard and exposure assessments on 

ethylbenzene, and in keeping with our industry’s objective of reducing duplicative, unnecessary testing, 

the Panel strongly urges EPA to remove ethylbenzene from the list of proposed substances to be subject 

to Tier 1 screening under the EDSP. Ethylbenzene has already been subject to a full range of toxicity 
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testing that is relevant to endocrine mediated pathways, including a 2-generation reproductive effects 

study.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2060 Chemicals with Toxicity Data Indicating 

Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 4

EPA Comment Code: 2070

Comment: The Panel submitted extensive hazard and exposure information on ethylbenzene to EPA, 

under the Voluntary Children’s Chemical Evaluation Program (VCCEP) Pilot Program [(“Voluntary 

Children’s Chemical Evaluation Program (VCCEP): Tier 1 Pilot Submission for Ethylbenzene (CAS 

No. 100-41-4),” dated August 10, 2007 and attached]. In developing the VCCEP assessment, the Panel 

conducted a number of toxicology studies including a screening level immunotoxicity study, a 2-

generation reproductive effects study, a developmental neurotoxicity study, an adult neurotoxicity study 

and several metabolism studies. In addition, developmental toxicity studies, subchronic toxicity studies 

and a 2-year cancer bioassay study were available and are referenced in the VCCEP assessment. The 

Panel’s assessment was reviewed by an Expert Panel convened by Toxicology Excellence for Risk 

Assessment (TERA) under contract to EPA. 

A full EDSP Tier 2 mammalian toxicity assessment, therefore, has been completed for ethylbenzene and 

is sufficient to support a robust human risk assessment inclusive of endocrine considerations. 

Importantly, as summarized in the VCCEP report, the mammalian Tier 2 tests indicate ethylbenzene has 

minimal, if any, potential to induce toxicity responses consistent with alterations of endocrine-mediated 

pathways. Since ethylbenzene’s distribution in water is not widespread and concentrations are very low 

due to its high volatility, ethylbenzene also would not be expected to impact environmental species by 

endocrine-mediated mechanisms. Thus, conduct of EDSP Tier 1 studies is highly unlikely to identify 

endocrine-mediated responses of concern for health evaluations of either human or environmental 

species.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2030 Contaminants Unlikely to Persist in Drinking 

Water.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 14

EPA Comment Code: 2070

Comment: Adequate data are already available for Acetochlor and its degradates:
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Acetochlor was allowed to enter the market under the Federal Insecticide, Fungicide, and Rodenticide 

Act (FIFRA). As mandated under FIFRA, the process of developing and registering crop protection 

products for commercial use is comprehensive. Therefore, screening pesticide active ingredients, such as 

Acetochlor, for endocrine disruption is redundant given FIFRA pesticide requirements. FIFRA already 

requires that pesticides undergo a comprehensive battery of toxicology testing covering a broad 

spectrum of endocrine endpoints that are sufficient to detect endocrine disruption.

Acetochlor has undergone extensive testing, including a tiered battery of sub-chronic and chronic tests 

including a number of developmental and reproductive studies capable of detecting effects on endocrine 

mediated events. Data on endpoints pertaining to endocrine-mediated effects are also available from the 

studies performed on representative wildlife species, including fish and birds. Collectively, sub-chronic 

and chronic toxicity studies in rats, mice and dogs, developmental toxicity studies in rats and rabbits, as 

well as reproduction studies in rats evaluate a wide array of estrogen-, androgen- and/or thyroidsensitive tissues. Data were obtained on potential endocrine-mediated responses such as reproductive 

parameters (e.g. mating, fertility, and gestational indices), estrous cyclicity, sperm parameters, and 

histological alterations in a variety of endocrine controlled tissues, (e.g. epididymides, testes, ovaries, 

uteri, thyroid, adrenals, pituitary). The development of fetuses and offspring was also assessed by 

measuring endpoints related to growth, survival, and sexual development. Often additional endpoints 

such as hormone levels were included in study designs to better understand the toxicity profile of a 

compound. Metabolism studies in rats, poultry, ruminant animals and fish demonstrate the extent of 

absorption and excretion of Acetochlor over time as an indication of potential exposure and can help to 

identify any metabolites of concern. These repeat-dose studies have a robust experimental design and 

the results are highly reproducible. Data generated from these regulatory guideline studies have a long 

history of use in hazard assessment and risk assessment. The ARP believes that results from these 

studies can provide reliable and functionally equivalent information to the Tier 1 screening assays. 

Therefore, all three should be removed from List 2. In addition, the Office of Pesticide Programs has 

indicated that the EDSP will be implemented in the Registration Review process, which is to begin for 

Acetochlor in 2016. Therefore, it is unnecessary to place Acetochlor on List 2.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect. Also, please see general responses to comment under EPA 

Comment Codes: 2100 Pesticide Registration Review Issues and 2060 Chemicals with Toxicity Data 

Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 17

EPA Comment Code: 2070

Comment: Independent peer expert review panel finding on Acetochlor degradates should be utilized:

In May 2009, the Alliance for Risk Assessment assembled an independent peer expert review panel to 

review the toxicological profiles for the soil degradates of acetochlor and a closely-related herbicide, 

alachlor. In addition to staff from "Toxicology Excellence for Risk Assessment" (TERA), the panel 

included the following experts:
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* John P. Christopher, Department of Toxic Substances Control, California Environmental Protection 

Agency

* Lebelle Hicks, Maine Board of Pesticides, Department of Agriculture

* Santhini Ramasamy, Office of Water, U.S. Environmental Protection Agency

* Stephen M. Roberts, Center for Environmental and Human Toxicology, University of Florida

These highly respected State and Federal regulatory scientists reached firm conclusions on acceptable 

levels of human exposure to the acetochlor degradates in drinking water, which have now been 

published in the peer reviewed scientific literature.[FN6: Gadagbui, B., Maier, M., Dourson, M., Parker, 

A., Willis, A., Christopher, J.P., Hicks, L., Ramasany, S., Roberts, S.M. 2010. Derived Reference Doses 

(RIDs) for the Environmental Degradates of the Herbicides Alachlor and Acetochlor: Results of an 

Independent Expert Panel Deliberation. Regulatory Toxicology and Pharmacology 57:220-234.] In 

determining the critical endpoints for establishment of reference doses, the expert panel 

comprehensively evaluated the available data on Acetochlor ESA and Acetochlor OA related to 

potential effects on multiple endocrine-sensitive tissues and parameters and did not indicate any concern 

for endocrine-mediated toxicity. When this finding is considered in light of the previously noted absence 

of any on-going human exposure, it is clear that EDSP testing for Acetochlor degradates is unnecessary.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 2

EPA Comment Code: 2070

Comment: Based on weight of evidence and in keeping with our industry’s objective of reducing 

duplicative, unnecessary testing, the Panel strongly urges EPA to remove ethylene glycol from the list of 

proposed substances to be subject to Tier 1 screening under the EDSP. This is based on the fact that the 

National Toxicology Program (“NTP”) conducted a three-generation reproductive rat study of ethylene 

glycol that produced no compound-related adverse effects indicative of reproductive toxicity. This data, 

along with other mentioned below, suggest that Tier 1 screening is not necessary for ethylene glycol, 

since it is already known from similar Tier 2 type studies that the results will be negative.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 5

EPA Comment Code: 2070

Comment: The Center for the Evaluation of Risks to Human Reproduction (“CERHR”), a division of 

the National Institute of Environmental Health Sciences (“NIEHS”), reviewed the 
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reproductive/developmental effects of ethylene glycol in 2004; NTP reviewed CERHR’s conclusions, 

and agreed that ethylene glycol is “of negligible concern for repro/developmental effects.” NTP 

recognized that ethylene glycol can cause renal toxicity in animals under conditions where high doses 

are given by bolus administration, but not when lower doses are administered in drinking water or diet. 

Ethylene glycol has been tested in several higher order animal studies for reproductive, developmental, 

and chronic toxicity, by incorporation in food or water, and results indicate that ethylene glycol does not 

cause adverse effects suggestive of endocrine disruption. This data was recently reviewed by ATSDR 

[2010], which concluded “No histopathological changes occurred in endocrine organs of rats or mice in 

acute-, intermediate- and chronic-duration oral studies of ethylene glycol..... histological examinations 

included the adrenals, pancreas, pituitary, thyroid, and/or parathyroids.”

Moreover, ethylene glycol is readily biodegraded, and does not usually persist in ground water. EPA 

[2006] has established drinking water advisory levels for ethylene glycol based on definitive studies: 

lifetime exposure to 14 mg/l is “not expected to cause any adverse effects.”

A. EPA has established drinking water health advisory levels for ethylene glycol.

“The EPA has determined that exposure to ethylene glycol in drinking water at concentrations of 20 

milligrams per liter (mg/L) for 1 day or 6 mg/L for 10 days is not expected to cause any adverse effects 

in a child.

The EPA has determined that lifetime exposure to 14 mg/L ethylene glycol in drinking water is not 

expected to cause any adverse effects.”

Cited in ATSDR 2010 Toxicological Profile for Ethylene Glycol:

http://www.atsdr.cdc.gov/ToxProfiles/TP.asp?id=86&tid=21

See also

http://water.epa.gov/action/advisories/drinking/dwstandards.cfm#organics

B. Preliminary report of ethylene glycol as an endocrine disruptor was interpreted incorrectly.

A preliminary report seemed to have suggested that ethylene glycol may have endocrine activity because 

it reportedly induced production of vitellogen mRNA in male rainbow trout [Ren et al., 1996]. However, 

the study was not designed to determine whether or not ethylene glycol is an endocrine disrupter, and 

the senior author subsequently asserted that the study design was not appropriate to conclude that 

ethylene glycol is an endocrine disrupter: “We suggest that it is inappropriate to include ... EG on lists

of endocrine disrupters since the relationship of the vitellogenin mRNA induction we observed could be 

unrelated to endocrine activity of these materials and occurred only at very high doses” [Lech, 1997]. 

Furthermore, it should be noted that while substances of concern in the environment induced the levels 

of vitellogenin protein in male fish, ethylene glycol was shown only to induce the transcription stage.

C. NTP review of CERHR report agrees that ethylene glycol is of negligible concern for 

reproductive/developmental effects.
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An expert panel of the CERHR, a branch of the NIEHS, in 2004 reviewed the potential reproductive and 

developmental toxicity of ethylene glycol and effects which might be expected if ethylene glycol were 

an endocrine disruptor. The Panel’s conclusions were reviewed by NTP, which agreed that ethylene 

glycol is of negligible concern:

1. “The NTP concurs with the CERHR EG/PG Expert Panel that there is negligible concern of adverse 

developmental toxicity from EG at exposures below 125 mg/kg bw.”

2. “The NTP concurs with the CERHR EG/PG Expert Panel that there is negligible concern of adverse 

reproductive toxicity from EG”.

http://cerhr.niehs.nih.gov/evals/egpg/ethylene/EG_Monograph.pdf

D. Ethylene glycol has been tested in higher order animal studies for reproductive and developmental 

toxicity, and results indicate that ethylene glycol does not cause adverse effects suggestive of endocrine 

disruption. Ethylene glycol should not be included in EDSP, because any suggestive or positive findings 

in the screening assays would be superseded by the negative results of the whole animal studies.

1. Ethylene glycol has been tested by in a mouse three-generation reproductive toxicity study [De Pass 

et al, 1986]. There were no reproductive effects reported at concentrations up to 1% in the diet.

2. Ethylene glycol has been tested in a mouse continuous breeding study and showed no reproductive 

effects at drinking water concentrations up to 0.5%. At 1% it caused general toxicity [Lamb et al, 1985].

3. Ethylene glycol has been tested in rat and mouse developmental toxicity studies by various routes, 

and caused effects only when administered in bolus doses via the oral route. Extensive research has 

indicated that there is a threshold phenomenon due to saturation of metabolism resulting in an increase 

in the levels of the proximate toxicant, glycolic acid, at high bolus doses, which is not seen at lower dose 

rate conditions [Carney et al, 2010].

E. Based on the low octanol water partition coefficient of ethylene glycol it will have a low 

bioaccumulation potential.

If ethylene glycol is ingested (e.g. via drinking water) it has a rapid rate of metabolism. For example, in 

studies with rats, dogs and monkeys, at doses of 1-1000 mg/kg, half-lives of ethylene glycol in blood 

plasma were between 1 and 4 hours (WHO, 2002). The combination of low bioaccumulation potential 

and rapid metabolism provide strong evidence that internal concentrations and residence times in 

organisms will be low. Consequently, it is considered unlikely that ethylene glycol will occur in higher 

organisms for duration sufficient to enable it to induce endocrine disrupting effects.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2030 Contaminants Unlikely to Persist in Drinking 

Water.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046
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Comment Part: 8

EPA Comment Code: 2070

Comment: Conclusion

The Panel strongly urges EPA to remove ethylene glycol from the list of proposed substances to be 

subject to Tier 1 screening under the EDSP. This is based on the fact that the NTP conducted a threegeneration reproductive rat study of ethylene glycol that produced no adverse effects indicative of 

reproductive toxicity. This data, along with other mentioned above, suggest that Tier 1 screening is not 

necessary for ethylene glycol, since it is already known from definitive Tier 2 type studies that the 

results will be negative. Additionally, there is sufficient evidence from both the occurrence of ethylene 

glycol in the environment and its intrinsic properties to mitigate concern that ethylene glycol requires 

screening for its endocrine disrupting properties. Moreover, based on the available data, EPA cannot 

conclude that a substantial population may be exposed to ethylene glycol from drinking water sources, 

as required by Section 1457 of the SDWA for inclusion of a substance in the EDSP. Lastly, ethylene 

glycol should not be included on EPA’s CCL 3. Consequently, EPA should remove ethylene glycol 

from the Draft EDSP List 2.

However, if the Agency does not delete ethylene glycol from the list, it should require only those 

endocrine studies that are relevant to endpoints other than reproductive/developmental, such as thyroid 

effects and effects on non-mammalian species.

The Ethylene Glycols Panel appreciates the opportunity to comment on the Listing Notice. If you have 

any questions, please contact me, at (202) 249-6708, or by email 

Anthony_wagner@americanchemistry.com.

Sincerely,

Anthony D. Wagner

Manager, Ethylene Glycols Panel

REFERENCES [and abstracts]

Ren L, Meldahl A, Lech JJ.Dimethyl formamide (DMFA) and ethylene glycol (EG) are estrogenic in 

rainbow trout.

Chem Biol Interact. 1996 Sep 27;102(1):63-7. Review.

During our studies on the effects of environmental estrogenic chemicals on vitellogenin gene expression 

in fish, dimethyl formamide (DMFA) and ethylene glycol (EG) were used as solvents to dissolve and 

deliver hydrophobic beta-estradiol or nonylphenol. Control groups were injected with water only. It was 

surprising to find that in certain doses, Vg mRNA from control fish can be induced by DMFA or EG 

alone. This suggested that DMFA and EG are weak estrogens.

Lech J.Two solvents, dimethyl formamide (DMFA) and ethylene glycol (EG), induced the mRNA of 

vitellogenin in rainbow trout.

Chem Biol Interact. 1997 Dec 12;108(1-2):135. No abstract available.
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Carney EW, Tornesi B, Liberacki AB, Markham DA, Weitz KK, Luders TM, Studniski KG, Blessing 

JC, Gies RA, Corley RA. The Impact of Dose-Rate on Ethylene Glycol Developmental Toxicity and 

Pharmacokinetics in Pregnant CD Rats.

Toxicol Sci. 2010 Oct 15. [Epub ahead of print]PMID: 20952502 [PubMed - as supplied by publisher] 

Related citations

High-dose bolus exposure of rats to ethylene glycol (EG) causes developmental toxicity mediated by a 

metabolite, glycolic acid (GA), whose levels increase disproportionately when its metabolism is 

saturated. However, low level exposures which do not saturate GA metabolism have a low potential for 

developmental effects. Towards the goal of developing EG risk assessments based on internal dose 

metrics, this study examined the differences between fast (bolus) and slow (continuous infusion) doserate exposures to EG on developmental outcome and pharmacokinetics. Time-mated female CD rats 

received subcutaneous (SC) bolus injections of 0, 1000, or 2000 mg/kg/day of EG on gestation day (GD) 

6-15 once daily, while three corresponding groups were given the same daily doses as an infusion 

administered continuously from GD 6-15 via an SC implantable pump. In the SC bolus groups, 

increases in 11 fetal malformations (major defects) and 12 variations (minor alterations) were seen at the 

2000 mg/kg/day dose level, while increases in two malformations and two variations occurred at 1000 

mg/kg/day. In contrast, equivalent daily doses of EG given slowly via infusion did not cause any 

developmental effects. A pharmacokinetics time-course was then conducted to compare GD 11-12 

kinetics from oral bolus (gavage) exposure vs. SC infusion of EG. While dose-rate had a modest impact 

(8- to 11-fold difference) on peak EG levels, peak levels of GA in maternal blood, kidney, embryo, and 

exocoelomic fluid were 59, 100, 49, and 56 times higher, respectively, following gavage vs. the same 

dose given by infusion. These data illustrate how high dose bolus exposure to EG causes a dramatic shift 

to non-linear GA kinetics, an event which is highly unlikely to occur following exposures to humans 

associated with consumer and worker uses.

Lamb JC 4th, Maronpot RR, Gulati DK, Russell VS, Hommel-Barnes L, Sabharwal PS. Reproductive 

and developmental toxicity of ethylene glycol in the mouse.

Toxicol Appl Pharmacol. 1985 Oct;81(1):100-12.

The effects of ethylene glycol on reproduction of CD-1 mice were tested in a protocol which permitted 

continuous breeding during a specified interval. The dosage amounts of 0, 0.25, 0.5, or 1% ethylene 

glycol by continuous administration in drinking water for male and female mice were selected from the 

general toxic responses observed in a 14-day pilot study. After the first week of administration, begun at 

11 weeks of age, the animals were housed one male and one female per cage for 14 weeks during which 

time any offspring were examined, sexed, weighted, and killed to allow continuous mating of the first 

generation. At the end of the 14-week cohabitation period, the males and females were separated and 

any litters delivered after that time were kept until weaning. Those second-generation animals were 

mated at about 70 days of age. Slight, but statistically significant, decreases were found in the numbers 

of litters per fertile pair and live pups per litter in the 1% dose group and live pup weight at the 1% dose 

groups compared to control F0 mice. Facial anomalies were noted in a number of offspring of highdose-treated mice and an examination for skeletal defects demonstrated a pattern including reduction in 

the size of bones in the skull, fused ribs, and abnormally shaped sternebrae and vertebrae in the highdose-treated, but not the untreated, mice. Neither the 0.25 nor 0.5% dose groups were significantly 

affected. No clinical signs of toxicity or significant adverse effects on body weight or water 
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consumption were seen at the doses used, but two deaths occurred at the 0.5% quantity which may have 

been related to oxalate crystal deposition in the kidney.

DePass LR, Woodside MD, Maronpot RR, Weil CS. Three-generation reproduction and dominant lethal 

mutagenesis studies of ethylene glycol in the rat.

Fundam Appl Toxicol. 1986 Nov;7(4):566-72.

To assess the possible effects of ethylene glycol (EG) on reproductive performance and mutagenesis, 

three-generation reproduction and dominant lethal mutagenesis studies were performed in the Fischer 

344 rat. EG was included in the diet at approximate dosages of 1.0, 0.2, and 0.04 g/kg/day during three 

generations of reproduction. Each generation was bred once. In a dominant lethal mutagenesis study, the 

F2 males from the reproduction study were bred to three consecutive lots of untreated females at weekly 

intervals. Concomitantly, another group of untreated F2 males that received a single ip injection of 0.50 

mg/kg triethylenemelamine (TEM) were bred similarly to serve as a positive control group. No evidence 

of reduced fertility or increased fetal death was observed in any of the groups receiving EG. Dominant 

lethal effects in the TEM group confirmed the susceptibility of the rats to a known mutagen. In 

conclusion, there were no reproductive or dominant lethal effects associated with the inclusion of as 

much as 1.0 g/kg/day of EG in the diet.

The Tier 1 screening tests include:

Amphibian Metamorphosis; Fish Short-term Reproduction (Fish Assay);

Androgen Receptor Binding; Aromatase (Recombinant); Estrogen Receptor Binding; Hershberger; 

Pubertal Male; Pubertal Female; Steroidogenesis (Sliced Testes); Steroidogenesis (H295R); 

Uterotrophic; Adult Male Rat

ATSDR 2010 Inhalation Endocrine Effects. No gross or histological effects occurred in the adrenals in 

dogs (2/concentration) or monkeys (2–3/concentration), or thyroid in dogs (2/concentration), following 

whole-body exposure to apparently aerosolized ethylene glycol in concentrations of 10 or 57 mg/m3 for 

8 hours/day, 5 days/week for 6 weeks, or 12 mg/m3 continuously for 90 days (Coon et al. 1970). 

Additional endocrine end points were not evaluated. The relevance of these NOAELs is unclear because 

intake of ethylene glycol from ingestion of aerosol deposited on the fur likely significantly contributed 

to total dose (Tyl et al. 1995a, 1995b).

WHO (2000). Ethylene Glycol: Environmental Aspects. Concise International Chemical Assessment 

Document 22. World Health Organisation. Geneva. 2000.

EC (2000). State of the Science Report for Ethylene Glycol. Environment Canada, Health Canada, 2000.

ATSDR (1997). Toxicological profile for ethylene glycol and propylene glycol. Atlanta, GA, US 

Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and 

Disease Registry. 249 pp.

Hansch (1995). Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and 

Steric Constants. Washington, DC: American Chemical Society., 1995., p. 5
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BASF AG (1996). Pruefung der biologischen Abbaubarkeit von Ethylenglykol im DOC-Abnahme (DieAway) Test. unpublished data. Testing laboratory: Department of Ecology. Report no.: 96/0109/21/1. 

Owner company: BASF SE. Report date: 1996-03-15.

Evans WH, David EJ (1974) Biodegradation of mono-, di-, and triethylene glycols in river waters under 

controlled laboratory conditions. Water research, 8(2):97–100.

McGahey C, Bouwer EJ (1992) Biodegradation of ethylene glycol in simulated subsurface 

environments. Water science and technology, 26:41–49.

North/South Consultants Inc. 1998. An investigation of water quality in Truro Creek, 1998. Prepared by 

C. Bezte and D.S. MacDonell for Winnipeg Airports Authority Inc. Winnipeg, Manitoba.

WHO (2000). Ethylene Glycol: Human Health Aspects. Concise International Chemical Assessment 

Document 45. World Health Organisation. Geneva. 2002.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 1060 SDWA 1457.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 14

EPA Comment Code: 2070

Comment: Adequate data are already available for Alachlor and its degradates: 

Alachlor was allowed to enter the market under the Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA). As mandated under FIFRA, the process of developing and registering crop protection products 

for commercial use is comprehensive. Therefore, screening pesticide active ingredients, such as 

Alachlor, for endocrine disruption is redundant given FIFRA pesticide requirements. FIFRA already 

requires that pesticides undergo a comprehensive battery of toxicology testing covering a broad 

spectrum of endocrine endpoints that are sufficient to detect endocrine disruption. 

Alachlor has undergone extensive testing, including a tiered battery of sub-chronic and chronic tests 

including a number of developmental and reproductive studies capable of detecting effects on endocrine 

mediated events. Data on endpoints pertaining to endocrine-mediated effects are also available from the 

studies performed on representative wildlife species, including fish and birds. Collectively, sub-chronic 

and chronic toxicity studies in rats, mice and dogs, developmental toxicity studies in rats and rabbits, as 

well as reproduction studies in rats evaluate a wide array of estrogen-, androgen- and/or thyroidsensitive tissues. Data were obtained on potential endocrine-mediated responses such as reproductive 

parameters (e.g. mating, fertility, and gestational indices), estrous cyclicity, sperm parameters, and 

histological alterations in a variety of endocrine controlled tissues, (e.g. epididymides, testes, ovaries, 

uteri, thyroid, adrenals, pituitary). The development of fetuses and offspring was also assessed by 

measuring endpoints related to growth, survival, and sexual development. Often additional endpoints 

such as hormone levels were included in study designs to better understand the toxicity profile of a 

compound. Metabolism studies in rats, poultry, ruminant animals and fish demonstrate the extent of 

absorption and excretion of Alachlor over time as an indication of potential exposure and can help to 
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identify any metabolites of concern. These repeat-dose studies have a robust experimental design and 

the results are highly reproducible. Data generated from these regulatory guideline studies have a long 

history of use in hazard assessment and risk assessment. Monsanto believes that results from these 

studies can provide reliable and functionally equivalent information to the Tier 1 screening assays. 

Therefore, all three should be removed from List 2. In addition, the Office of Pesticide Programs has 

indicated that the EDSP will be implemented in the Registration Review process, which is to begin for 

Alachlor in 2016. Therefore, it is unnecessary to place Alachlor on List 2. 

The EPA itself has indicated that existing data are sufficient to address endocrine issues for alachlor 

In an order denying the petition to revoke tolerances of alachlor (and 4 other pesticides), issued in 

response to the petition by several states, [FN2: Federal Register August 2, 2006, Volume 71, Number 

148, pages 43905-43924] the EPA stated that “the RED indicated that alachlor does have effects on the 

endocrine system in that it disrupts the hormone balance leading to the formation of thyroid tumors”, but 

that “these effects only occurred at high doses which were well above any exposure levels humans 

would face from pesticidal use of alachlor.” This FR later states, “Monsanto also disputes the States’ 

assertion that alachlor is an endocrine disruptor ... Monsanto submitted a report that discussed in more 

detail alachlor’s potential for endocrine disruption (Ref. 17).” No MRID is given for Monsanto’s “Ref 

17.” Instead, it is cited as “Monsanto Company, Alachlor: Evaluation of the Potential for Endocrine 

Disruption (December 20, 2002).” 

Some of the other statements made by the Agency in this same FR notice are highly relevant to the 

question of whether additional EDSP screening is necessary for Alachlor: 

“EPA already has substantial information on the degree to which pesticides cause such [endocrine 

disruption] effects. These available data allow EPA to make weight-of-the-evidence assessments of a 

pesticide’s ability to cause adverse effects due to endocrine disruption.” ... “Although the 2-generation 

rat reproduction study currently is considered the definitive mammalian study to evaluate the adverse 

outcomes of endocrine disruptors for the endocrine disruptor screening program, it is not the only study 

routinely required or submitted for pesticides that provides information on potential endocrine effects” 

... [followed by discussion of subchronic, chronic, dev tox data] ... “For food-use pesticides, therefore, 

EPA generally has an [sic.] substantial database bearing on potential adverse endocrine effects. Not only 

does EPA require a 2-generation reproduction study in rats for such pesticides, but also requires multiple 

data in multiple species on subchronic and chronic toxicity and developmental toxicity which bear on, 

among other things, potential endocrine effects, including effects beyond those examined in the 2-

generation reproduction study. Thus, EPA believes that in many instances the totality of the information 

gleaned from current data required for pesticides on food will make it is [sic.] possible to develop a 

meaningful weight-of-the-evidence determination on the potential of the pesticide to adversely effect 

[sic.] the endocrine system.” 

The EPA went on to devote several pages (43919-43921) indicating that sufficient data already exist on 

pesticides to address endocrine disruption. It is clear from the language the Agency used in its response 

to the petition from the States that no additional data are required for Alachlor.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2100 Pesticide Registration Review Issues.

Commenter Name: Stephen Risotto
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Commenter Organization: American Chemistry Council (ACC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0056

Comment Part: 3

EPA Comment Code: 2070

Comment: DEHA is Not Anticipated to Produce Endocrine Effects in Humans

FFDCA Section 408(p)(4) provides for an exemption from the EDSP testing if a substance “is 

anticipated not to produce any effect in humans similar to an effect produced by a naturally occurring 

estrogen.” EPA has proposed [FN:4 Endocrine Disruptor Screening Program: Draft Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals, 75 Federal Register 70588 (November 

17, 2010).] that recipients of test orders for the second list of EDPS chemicals may ask EPA to 

reconsider some or all of the testing specified in the order if the recipient can “demonstrate (supported 

by appropriate data) that the chemical meets the standard for an exemption under Section 408(p)(4).” It 

is in appropriate and unnecessary for EPA to issue test orders and require a recipient response when 

sufficient data are already available to make a determination under Section 408(p)(4). [FN5: Contrary to 

the Agency’s current draft policy for SDWA chemicals, moreover, EPA has previously indicated that an 

exemption under Section 408(p) “is a waiver of all testing obligations” (63 Federal Register71564, 

December 28, 1998)] 

As discussed below, several studies, both in vitro and in vivo, have been conducted that demonstrate that 

DEHA is anticipated not to produce estrogenic (or other endocrine) effects in humans. In vitro studies 

last year include a yeast two-hybrid assay, AhR-CALUX assays in mouse hepotoma and Chinese 

hamster ovary cells, a T- screen assay in a rat pituitary tumor cell line, and estrogen receptor (ER) 

transactivation and 17β- estradiol receptor binding assays in human breast cell lines. In vivo studies 

include an ER- mediated luciferase (luc) reporter assay in mice, an Utherotrophic assay in SpragueDawley rats, and a study of antiandrogenic effects in Wistar rats. The results of all but the T-screen 

assay were negative (i.e., no treatment related effects).

DEHA did not bind to estrogen receptors with coactivator (TIF2) in S. cerevisiae Y190 up to the 

concentration of 1mM in the two year hybrid assay study conducted by Nishihara et al. (2000) [FN6: 

Nishihara T et al. Estrogenic activities of 517 chemicals by yeast two hybrid assay. J of Health Sci 46 

(4): 282-298 (2000).] Krugar et al. (2008) [FN7: Krϋger T et al. 2008. Plastic components affect the 

activation of the aryl hydrocarbon and the androgen receptor. Toxicology Apr 18; 246(2-3): 112-23

(2008).] reported a negative finding in a AhR-CALUX assay in mouse hepatoma (Hepal.12cR) cells at 

concentrations ranging up to 10-4 M DEHA in DMSO alone and with co-treatment at 60 pM TCDD. 

Kruger et al also did not observe an effect in AhR-CALUX assay conducted with Chinese hamster ovary 

(CHO-K1) cells at concentrations ranging up to 10-4 M DEHA in DMSO with and without co-treatment 

in 25pM R1881. DEHA administered at concentration up to 5x10-5 M in a rat pituitary tumor cell line 

(GH3) was found to stimulate cell proliferation, but at low potency, by Ghisari and Bonefield-Jorgenson 

(2009) [FN9: Ghisari M and Bonefield-Jorgenson EC. Effects of plasticizers and their mixtures on 

estrogen recptor and thyroid hormone functions. Toxicol Lett Aug 25; 189(1):67-77 (2009).]

Two studies in human breast cell lines have been conducted with DEHA. Ghisari and BonefieldJorgenson did not observe activity in MVLN cells (MCF-7 human breast cell line transfected with the 

firefly luciferase gene) and after the administration up to 5x10-5 M concentration of EHA. Although 

DEHA bound to 17β- estradiol receptor in two human breast cell lines (ZR-75 and MCF-7), it did not 

activate the receptor, in a study by Jobling et al. (1995). [FN9: Jobling S et al. A variety of 
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environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic.

Environ Health Perspect 103: 582-587 (1995).] The concentration used in the study (up to 1 mM 

DEHA) approached the solubility limit, however, and the authors were unable to determine DEHA’s 

affinity for the receptor.

In an ER- mediated luc receptor assay conducted in mice, Ter Veld et al. (2008) [FN10: Ter Veld MG et 

al Estrogenicity of food-associated estrogenic compounds in fetuses of female transgenic mice upon oral 

and IP maternal exposure. Reprod Toxicol 27(2) 133-9 (2009).] did not observe induction of luc activity 

after administration of DEHA both orally or intraperitoneally at single doses up to 100 milligrams per 

kilogram body weight (mg/kg-bw). No increase in uterine weight was observed ovariectomized 

Sprague- Dawley rats administered 1000 mg/kg-bw DEHA by intubation for 3 days (JPIA 1998) [FN 

11: Japan Plasticizer Industry Association (JPIA). Evaluation of adipic acid esters on estrogenicity by in 

vivo uterotrophy in ovariectomized rats. Mitsubishi Chemical Safety Institute Ltd. Unpublished report 

8L306 (1998). Cited in OECD 2005.]

Although Dalgaard et al (2003) [FN 12: Dalgaard et al. Di(2- ethylhexyl) adipate (DEHA) inducted 

developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats. 

Reprod Toxicol 17 (2): 163-170 (2003).] did observe a dose- related increase in postnatal death in 

Wistar rats following pre- and postnatal administration of doses of DEHA up to 800 mg/kg-body weight, 

they observed no effects of endocrine- related endpoints including “anogenital distance, nipple retention, 

sexual maturation, hormone levels, sperm parameters, organ weights, or histopathology of the 

reproductive system.” The authors noted that the results of their study indicate that DEHA does not 

constitute a risk for androgenic effects.

These data provide further support for the conclusion of an export report to the European Commission in 

200 that there is no basis for inclusion of DEHA on the candidate list of substances for further 

evaluation of their role in endocrine disruption. [FN13: European Commission DG ENV. Towards the 

establishment of a priority list of substances for further evaluation of their role in endocrine disruption –

preparation of a candidate list of substances as a basis for priority setting. Final Report. Prepared by 

BKH Consulting Engineers in association with TNO Nutrition and Food Research (November 10, 

2000). Available at http://ec.europa.eu/environment/endocrine/strategy/substances_en.htm.] The report 

was prepared to assist in implementation of the Commission’s Community Strategy for Endocrine 

Disrupters adopted in 1999 (COM(1999)706).

Summary

Based on the available data, EPA cannot conclude that a substantial population may be exposed to 

DEHA from drinking water sources, as required by Section 1457 of the SDWA for inclusion of a 

substance in the EDSP. Sufficient data exist, moreover, to support the conclusion that exposure to 

DEHA is not anticipated to disrupt estrogenic or androgenic activity in in vitro and in vivo systems. 

Consequently, EPA should remove DEHA from the second list of substances for which the Agency 

plans to issue test orders under the EDSP.

Please feel free to contact me if you have any questions about the above information. I will plan to 

follow up with the appropriate EPA staff in the coming weeks to discuss this information further.

Sincerely

Stephen P Risotto
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Senior Director, Phthalate Esters

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 2

EPA Comment Code: 2070

Comment: 2) There is a significant database already available on mammalian toxicity endpoints related 

to reproductive and developmental toxicity potential of PDC that basically replaces any Tier 1-type data 

that would be collected under EDSP, and which demonstrates no specific targeted effects on 

reproductive or developmental endpoints, along with additional chronic data that support this 

conclusion.

3) PDC has no structural alerts for estrogen- or androgen-receptor binding activity (Serfimova et al., 

2007).

4) PDC has extensive environmental toxicity testing data, including chronic reproductive studies in 

freshwater and seawater invertebrates, and an Early Life Stage study in freshwater fish, which include 

endpoints similar to the EDSP-required Tier 1-type data, none of which have indicated any effects 

relating to endocrine disruption.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 4

EPA Comment Code: 2070

Comment: 2) Based on weight-of-evidence available for mammalian toxicity and in keeping with 

EPA's principle of reducing unnecessary animal testing, Dow recommends that PDC be removed from 

the list of proposed substances to be tested for Tier 1 screening. This is based on the significant database 

available on mammalian toxicity endpoints related to reproductive and developmental toxicity, including 

a two-generation reproductive drinking water rat study on PDC that demonstrates no specific targeted 

effects on reproductive or developmental endpoints (Kirk et al., 1990), and a guideline developmental 

toxicity gavage rat study on PDC that did not demonstrate any specific targeted effects on 

developmental endpoints (Kirk et al., 1995). PDC was not considered to be a reproductive toxin 

following exposure of Sprague-Dawley rats to drinking water concentrations of 0.024%, 0.10%, or 

0.24%, with a NOAEL for adults and neonatal effects of 0.1 % PDC, while the reproductive NOEL was 

0.24% PDC, the limit of solubility (Kirk et al., 1990). Based on the results of the guideline, GLP, 

developmental toxicity study in rats, PDC was not teratogenic at a dose level which produced obvious 
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maternal toxicity (125 mg PDC/kg body weight/day) and 30 mg PDC/kg body weight/day was 

considered the NOAEL for maternal and fetal effects (Kirk et al., 1995). The conclusion on repro/dev 

tox from the OECD SIAR stated "Overall these studies provide no evidence that PDC selectively targets 

the male or female reproductive systems or the developing embryo/fetus." (OECD, 2006). These data, 

along with other mammalian toxicity chronic data demonstrating no targeting of endocrine organs, 

indicate that Tier I screening is not necessary for PDC, since it similar Tier 2-type studies were negative. 

Certainly, the available data render PDC a low priority for any further endocrine toxicity screening.

3) PDC does not possess any structural alerts or predicted activity for estrogen- or androgen-receptor 

binding, as indicated by the OASIS TIMES models (v2.25 .7C) (Serfimova et al., 2007).

4) PDC has extensive environmental toxicity testing data, including chronic reproductive studies with 

freshwater and marine invertebrates (Boeri, 1988 ; Ward et al., 1989), and an Early Life Stage study in 

freshwater fish (Benoit et al., 1982) . These studies include endpoints relating to reproductive success 

and survival of these aquatic organisms at various life-stages, which are similar to endpoints covered in 

the EDSP-required Tier 1 studies. The results of these studies generally indicate that no-observed-effect 

concentrations (NOEC) for these endocrine-linked endpoints are of similar magnitude to NOEC values 

for lethality. Therefore, existing data indicate that PDC does not have adverse effects on reproduction or 

development of aquatic organisms at concentrations below those that cause mortality.

Thus, there is a rich database available for PDC, one which evaluates most of the Tier 2 endpoints, to 

indicate that PDC does not demonstrate endocrine disruption effects.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 6

EPA Comment Code: 2070

Comment: Therefore, removing PDC from the Endocrine Disruptor Screening Program is supported by 

the weight-of-evidence of available data, as indicated by the details and references discussed above and 

provided below.

Sincerely,

Jean Kasakevich

Associate EH&S Product Stewardship Director

The Dow Chemical Company

Midland, MI 48674

References

Benoit, DA, Puglisi, FA and Olson, DL (1982) . A Fathead Minnow (Pimephales Promeles) Early Life 

Stage Toxicity Test Method Evaluation And Exposure To Four Organic Chemicals. Environmental 

Pollution (series A) 28, 189 - 197.
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Boeri RL 1988. Flow-through Chronic Toxicity of 1,2-Dichloropane to the Daphnid, Daphnia magna. 

Unpublished report of The Dow Chemical Company, Midland, MI.

IPCS (1993) Environmental Health Criteria 146: 1,3- Dichloropropene, 1,2- Dichloropropane, and 

mixtures, World Health Organization, Geneva, Switzerland.

Kirk, HD, Berdasco, NM, Breslin, WJ and Hanley, TR. 1995. Developmental toxicity of 1,2-

dichloropropane (PDC) in rats and rabbits following oral gavage. Fundamentals of Applied Toxicology 

28: 18-26.

Kirk, HD, Hanley, TR, Bond, DM, Firchau, HM, Peck, CN, Stebbins, KE and Johnson, KA. 1990. TwoGeneration Reproduction Study in Sprague-Dawley Rats. Unpublished report from The Dow Chemical 

Company, Midland, MI.

Moran, MJ, Lapham, WW, Rowe, BL and Zogorski, JS. 2002. Occurrence and status of volatile organic 

compounds in ground water from rural, untreated, self-supplied domestic wells in the United States, 

1986-99. Water Resources Investigations Report 02-4085, US Department of the Interior/US Geological 

Survey, pp 51 .

OECD SIDS. 2006 . SIDS Initial Assessment Report (SIAR) on 1,2-dichloropropane (propylene 

dichloride) .

Serafimova, R., Todorov, M., Nedelcheva, D., Pavlov, T., Akahori, Y., Nakai, M., and Mekenyan, O. 

2007. QSAR and mechnistic interpretation of estrogen receptor binding. SAR and QSAR in Environ. 

Research, 18 (3-4), 389-421

Ward GS, Rabe BA, Greer DH (1989) . 1,2-Dichloropropane : Chronic Toxicity to the Mysid 

(Mysidopsis bahia) under flow-through conditions. Unpublished report of The Dow Chemical Company, 

Midland, MI.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 2

EPA Comment Code: 2070

Comment: 2) There is a significant database already available on mammalian toxicity endpoints related 

to reproductive and developmental toxicity potential of PO, supplemented with chronic data, that 

basically replaces any Tier I-type data that would be collected under EDSP and does not support 

endocrine-related effects.
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3) PO is rapidly hydrolyzed to propylene glycol (PG), especially under acidic conditions such as that 

associated with gastric fluid, the contact with which would occur as a result of any oral exposure via a 

drinking water route.

4) PG is a substance that the FDA considers "Generally Recognized as Safe" (GRAS), and which is 

therefore acceptable for use in foods, drugs, and food applications. It has been extensively tested for 

reproductive/developmental toxicity without demonstrating any effects; it is ready biodegradable thus 

will not be present in the environment for long.

Response: Oxirane, methyl- (propylene oxide) has been removed from the second EDSP list. Please see 

general response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters as 

Being or Potentially Incompatible with Test Assays. Please also see general response to comment under EPA 

Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0060

Comment Part: 5

EPA Comment Code: 2070

Comment: 2) There is a significant amount of guideline reproductive/developmental toxicity data, 

representing Tier 2-type information, available on PO already. PO has been tested in several higher 

order animal studies for reproductive, developmental, and chronic toxicity by inhalation exposure (with 

clear demonstration of distribution to all tissues), and all the results indicate that PO does not cause 

effects suggestive of endocrine disruption. A well-conducted, guideline, inhalation two-generation rat 

study (Hayes et al., 1985; 1988) demonstrated inhalation exposure to levels up to 300 ppm over two 

generations did not produce any adverse effects on reproductive function. A well-conducted, guideline, 

inhalation developmental toxicity study in rats (Harris et aI., 1989) did not demonstrate any 

embryotoxicity, fetotoxicity, or teratogenicity related to repeated inhalation exposures to PO up to 500 

ppm. Several chronic inhalation bioassays in rats and mice demonstrate no specific, treatment-related 

effects (histopathological or general toxicity) on endocrine-related organs (NTP, 1985; Lynch et al., 

1984; Kuper et aI., 1988). These data, along with other mammalian toxicity subchronic and chronic data 

demonstrating no targeting of endocrine organs (Hackett et aI., 1982; Hardin et al., 1983; Hansen et al., 

2002), indicate that Tier I screening is not necessary or useful for PO, since existing, published Tier 2-

type studies show little or no potential for endocrine effects. Certainly the available data render PO a 

low priority for any further endocrine toxicity screening.

3) PO demonstrates ready biodegradability, and undergoes hydrolysis in water (t1/2 = 12.9 d in water; 

2.4 d in seawater) (Meylan et al., 1986). In fact, PO is rapidly hydrolyzed to PG under acidic conditions, 

such as exists for oral, drinking water route exposure to humans. The very low pH of human gastric 

juice (pH 1.46) has been shown to result in rapid hydrolysis of PO to PG (t 1/2 = 1.9 min; from Patil, 

1999 as described in EPA, 2006); thus if there were any human exposure to PO via drinking water, it 

would actually result in internal exposure to the hydrolysis product, PG a GRAS substance allowed for 

on-purpose exposure to humans via a multitude of uses in foods and drugs, as mentioned above.

4) PG, a substance that is also ready biodegradable, is non-toxic to aquatic organisms, does not persist in 

water, is determined to be Generally Recognized As Safe (GRAS), and has been extensively tested in 
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Tier 2-equivalent tests such as two-generation reproductive toxicity and developmental toxicity 

guideline studies (CERHR, 2(04). The Center for the Evaluation of Risks to Human Reproduction 

(CERHR), a division of the National Institute of Environmental Health Sciences (NIEHS), reviewed the 

risks for reproductive/developmental effects of PG in 2004, and concluded that PG is "of negligible 

concern for repro/developmental effects." (CERHR, 2004).

Response: Oxirane, methyl- (propylene oxide) has been removed from the second EDSP list. Please see 

general response to comment under EPA Comment Code: 2010 Contaminants Identified by Commenters as 

Being or Potentially Incompatible with Test Assays. Please also see general response to comment under EPA 

Comment Code: 2070 Contaminants Not Expected to Produce Estrogen-like Effect.

Commenter Name: Jack Snyder

Commenter Organization: Styrene Information and Research Center (SIRC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0067

Comment Part: 1

EPA Comment Code: 2070

Comment: Comments of the Styrene Information & Research Center on the US EPA's Proposed List 2 

of Chemicals for EDSP Tier I Testing. EPA-HQ-OPPT-2009-0477-0001. 17 January 2011

January 17, 2011

Document Control Office (7407M)

Office of Pollution Prevention & Toxics

Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460

RE: Comments Supporting the Removal of Styrene from List 2 of EDSP

To Whom It May Concern:

The Styrene Information and Research Center (SIRC) [FN1: The Styrene Information and Research 

Center’s (SIRC’s) mission is to evaluate existing data on potential health effects of styrene, and develop 

additional data where it is needed. SIRC has gained recognition as a reliable source of information on 

styrene and helping ensure that regulatory decisions are based on sound science. For more information, 

visit http://www.styrene.org.] appreciates the opportunity to provide comment on the U.S. 

Environmental Protection Agency’s (EPA’s) announcement of a second list of chemicals and substances 

for which EPA intends to issue test orders under the Endocrine Disruptor Screening Program (EDSP) 75 

Federal

Register, Number 221, November 17, 2010 70248-70254.

SIRC believes that the substantial body of existing data which already exceeds the intent of the 

screening tests for Tier I clearly demonstrates that requiring styrene to undergo the less-stringent battery 

of tests under Tier I would be scientifically inappropriate, and contrary to EPA’s own study redundancy 

principles. Further, requiring this test battery would result in the wholly unnecessary sacrifice of many 

test animals, and would represent a significant and unwarranted economic burden on the styrene 
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industry, which already has funded far more rigorous research to elucidate the potential for styrene to act 

as an endocrine disruptor. This extensive database already has been thoroughly reviewed by the National 

Institute for Environmental Health Sciences (NIEHS), which determined styrene is not a reproductive or 

developmental concern.

1. Styrene should be removed from List 2 for Tier 1 testing based on the weight of the existing scientific 

data.

An extensive database of toxicity studies already exists for styrene that contains data relevant to 

evaluation of the endocrine system.

Existing studies include sub-chronic toxicity in three species, teratology studies in two species, twogeneration reproduction with developmental neurotoxicity in rats, chronic carcinogenicity studies in two 

species, as well as limited evaluations of reproduction and development in workers exposed to styrene.

This database of studies has been reviewed by the NIEHS National Toxicology Program (NTP) Center 

for Evaluation of Risks to Human Reproduction (CERHR). The CERHR Styrene report is accessible at: 

http://cerhr.niehs.nih.gov/evals/styrene/styrene.html. A copy of the CERHR styrene monograph is being 

submitted with this letter as well.

The CERHR reached its conclusion of “negligible concern for adverse developmental and reproductive 

effects resulting from styrene exposure in humans” citing “Studies in humans show no evidence that 

occupational exposures or exposures of the general population to styrene adversely affect reproduction 

or development. Further, data from experimental animal studies show no adverse effects at styrene doses 

far above human exposure levels.”

A list of recommended studies for EPA’s reference is attached. EPA further may wish to review the 

references cited in the CERHR document.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jack Snyder

Commenter Organization: Styrene Information and Research Center (SIRC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0067

Comment Part: 3

EPA Comment Code: 2070

Comment: Furthermore, since any styrene in any water source would be only at very low levels due to 

the chemical’s high volatility, limited solubility and high biodegradation, and styrene shows no evidence 

of endocrine activity in either estrogen, androgen or thyroid receptor binding assays or in mammalian in 

vivo screening and apical reproduction tests, it is unlikely that styrene would impact environmental 

species by an endocrine mechanism.

3. Styrene should be removed from List 2 of chemicals for Tier 1 testing based on study redundancy 

principles supported by EPA. 
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The EPA has announced a plan to address potential adverse effects of chemicals on the endocrine 

system, focused on estrogen, androgen and thyroid. “To address this issue, EPA is developing a twotiered screening and testing process. In Tier 1, EPA hopes to identify chemicals that have the potential to 

interact with the endocrine system.

In Tier 2, EPA will determine the specific effect caused by each endocrine disruptor and establish the 

dose at which the effect occurs. This approach will enable EPA to gather the information needed to 

identify endocrine disruptors and take appropriate regulatory action, as mandated by Congress.”

The endpoints to be examined in the Tier 1 in vivo tests are not only comprehensively examined in the 

published styrene two-generation reproduction studies, but styrene also is inactive in both uterotrophic 

and Hershberger endocrine screening assays; thus there is no need to repeat these endpoints. Further, 

there are no effects on estrogen, androgen, thyroid binding, or in vivo prolactin levels that affect 

reproduction. A mammalian two-generation reproductive toxicity test of styrene using current guidelines 

and including a developmental neurotoxicity assessment was published in 2005 (Cruzan et al. 2005). 

The study demonstrated no adverse effects on reproduction, as well as endpoints responsive to 

alterations in endocrine activity. Thus, there is no reason to conduct additional Tier 2 testing. If there is 

no reason to conduct Tier 2 testing, there is no reason to conduct Tier 1 testing.

Thus, the purpose of Tier 1 is to determine if Tier 2 tests are needed. The guidance provides for the 

submission of Other Scientifically Relevant Information (OSRI) to replace Tier I tests. The existing 

styrene database demonstrates that the endpoints for Tier 2 have already been tested. Therefore, there 

are only two possible conclusions from Tier 1 testing: 1. No positives were identified and therefore Tier 

2 testing is not needed; or 2. Positives were identified in Tier 1 testing, but the definitive assay for Tier 2 

has already been conducted so no further testing is needed.

The Styrene industry has funded over $20 million worth of research as part of its stewardship effort to 

understand any potential adverse effects of styrene. This level of research effort on behalf of a chemical 

is rare, but it is this type of commitment to product stewardship by the chemical industry that EPA 

should be encouraging. If in requiring testing by industry EPA were not to put appropriate weight on 

tests already conducted on the chemical, EPA would be encouraging the chemical industry in the future 

to wait until it receives a governmental directive before it conducts any tests. This is exactly the wrong 

economic incentive and message to send to the chemical industry. Rather than defend its actions by 

arguing that there is not 100% concordance between the studies already conducted and those being 

required, EPA should apply its scientific judgment on a case-by-case basis and exempt those chemicals 

from specific further testing where – as is plainly the case for styrene – the required testing would be 

redundant and unnecessary.

Response: Please see general responses to comment under EPA Comment Codes: 2070 Contaminants 

Not Expected to Produce Estrogen-like Effect and 2030 Contaminants Unlikely to Persist in Drinking 

Water.

Commenter Name: Jack Snyder

Commenter Organization: Styrene Information and Research Center (SIRC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0067

Comment Part: 5

EPA Comment Code: 2070
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Comment: 5. Conclusion.

The above facts clearly support the determination that the available published data on the endocrine 

disrupting potential of styrene already exceed the intent of the Tier 1 screening battery, and further have 

been reviewed by a federal agency which determined that styrene is not a concern as an endocrine 

disruptor.

Accordingly, EPA should remove styrene from List 2 for Tier 1 testing in compliance with its own 

commitment to prevent study redundancy and in the interest of preventing the unnecessary and 

undesirable use of numerous research animals, with no resulting benefit whatever. Further, requiring the 

funding of redundant screening tests places a significant and unjustified economic burden on an industry 

that has aggressively and proactively invested in state-of-the-art health effects research that already has 

addressed the intentions of the Tier 1 screening. Accordingly, SIRC believes that EPA is compelled to 

remove styrene from List 2 based on this information. We would be pleased to discuss these data with 

EPA representatives, or provide more references or background information.

Very truly yours,

Jack Snyder

Executive Director

Styrene Information and Research Center

801 N. Quincy Street – Suite 700

Arlington, VA 22203

Jack_Snyder@styrene.org

(703) 875-0729

RELEVANT REFERENCES

Alexander, M. 1997. “Environmental fate and effects of styrene.” Crit. Rev. Environ. Sci. 5 Technol., 

27, 383-410.

BASF AG; Pruefbericht ueber eine Untersuchung auf biologische Abbaubarkeit im Respirometrischen 

Test (EG-Methode). Testing laboratory: Department of emission control and ecology, Laboratory 

environmental analytics and ecology. Owner company: BASF SE, Styrene REACh consortium. Study 

number: 388576. Report date: 1988-06- 06.

BASF SE; Mackay Level 1 calculation. unpublished data. Testing laboratory: Department of Product 

Safety. Owner company: BASF SE, Styrene REACh consortium. Report date: 2009-10-22.

Beliles RP, Butala J H, Stock CR, Makris S. 1985. Chronic toxicity and three-generation reproduction 

study of styrene monomer in the drinking water of rats. Fund. Appl. Toxicol. 5: 855-868.

Brown NA, Lamb JC, Brown SM, Neal BH. 2000. A review of the developmental and reproductive 

toxicity of styrene. Regul. Toxicol. Pharmacol. 32: 228-247.

Cho S-I, Damokosh AI, Ryan LM, Chen D, Hu YA, Smith TJ, Christiani DC, Xu X. 2001. Effects of 

exposure to organic solvents on menstrual cycle length. J. Occup. Environ, Med. 43: 567-575.

Cohen JT, Carlson G, Charnley G, Coggon D, Delzell E, Graham JD, Greim H, Krewski D, Medinsky 

M, Monson R, Paustenbach D, Petersen B, Rappaport S, Rhomberg L, Ryan PB, Thompson K. 2002. A 
EPA-OGWDW Final EDSP List 2 February 2013

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comprehensive evaluation of the potential health risks associated with occupational and environmental 

exposure to styrene. J. Toxicol. Environ, Health, Part B 5:1-263.

Cruzan, G., Cushman, J.R., Andrews, L.S., Granville, G.C., Miller, R.R., Hardy, C.J., Coombes, D.W., 

and Mullins, P.A. (1997) Subchronic inhalation studies of styrene in

CD rats and CD-1 mice. Fundam. Appl. Toxicol. 35, 152-165.

Cruzan, G., Cushman, J.R., Andrews, L.S., Granville, G.C., Johnson, K.A., Hardy, C.J., Coombes, 

D.W., Mullins, P.A., and Brown, W.R. (1998). Chronic toxicity/oncogenicity study of styrene in CD rats 

by inhalation exposure for 104 weeks. Toxicol. Sci. 46, 266- 281.

Cruzan, G., Cushman, J.R., Andrews, L.S., Granville, G.C., Johnson, K.A., Bevan, C., Hardy, C.J., 

Coombes, D.W., Mullins, P.A., and Brown. W.R. (2001). Chronic toxicity/oncogenicity study of styrene 

in CD- I mice by inhalation exposure for 104 weeks. J. Appl. Toxicol. 21, 186-198.

Cruzan G, Faber WD, Johnson KA, Roberts LS, Hellwig J, Maurissen J, Beck MJ, Radovsky A, Stump 

DG.; Developmental neurotoxicity study of styrene by inhalation in Crl-CD rats; Birth Defects Res B 

Dev Reprod Toxicol. 2005 Jun;74(3):221-32.

Cruzan G, Faber WD, Johnson KA, Roberts LS, Hellwig J, Carney E, Yarrington JT, Stump DG.; Two 

generation reproduction study of styrene by inhalation in Crl-CD rats Birth Defects Res B Dev Reprod 

Toxicol., 2005 Jun;74(3):211-20.

Date K.; Ohno K.; Azuma Y.; Hirano S.; Kobayashi K.; Sakurai T.; Nobuhara Y.; Yamada T. (2002), 

Endocrine-disrupting effects of styrene oligomers that migrated from polystyrene containers into food, 

Food and Chem Tox, Vol 40, No. 1, Jan 2002,

pp. 65-75.

Fu, M. H. and Alexander, M. (1992). Biodegradation of Styrene in Samples of Natural Environments. 

Environmental Science & Technology 26: 1540-1544. ECB (2002). European Union Risk Assessment 

Report. STYRENE. Part I - Environment. CAS No: 100-42-5. EINECS No: 202-851-5. RISK 

ASSESSMENT. Institute for Health and Consumer Protection, European Chemicals Bureau, Existing 

Substances, 1st Priority List Volume 27: i-viii, 1-88.

IARC (International Agency for Research on Cancer). 2002. IARC Monographs on the Evaluation of 

Carcinogenic Risks to Humans. Vol. 82. Some Traditional Herbal Medicines, Some Mycotoxins, 

Naphthalene, and Styrene, IARC Press, Lyon, France, pp. 437-550.

Jelnes JE. 1988. Semen quality in workers producing reinforced plastic. Reproductive Toxicology. 2: 

209-212.

Katakura Y, Kishi R, Ikeda T, Miyake H. 1999. Effects of prenatal exposure to styrene on 

neurochemical levels in the rat brain. Toxicol. Lett. 105: 239-249.

Katakura Y, Kishi R, Ikeda T, Miyake H. 2001. Effects of prenatal exposure to styrene on postnatal 

development and brain serotonin and catecholamine levels in the rat brain. Environ. Res. Sec. A 85: 41-

47.
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Kishi R, Katakura Y, Ikeda T, Chen BQ, Miyake H. 1992. Neurochemical effects in rats following 

gestational exposure to styrene. Toxicol Lett 63, 141-146.

Kishi R, Chen BQ, Katakura Y, Ikeda T, Miyake H 1995. Effect of prenatal exposure to styrene on the 

neurobehavioral development, activity, motor coordination, and learning behavior of rats. Neurotoxicol 

Teratol 17, 121-130.

Kolstad HA, Bonde JP, Spano M, Giwercman A, Zschiesche W, Kaae D, Larsen SB, Roeleveld N, 

1999. Change in semen quality and sperm chromatin structure following occupational styrene exposure. 

Int, Arch. Occup. Environ, Health 72:135-141.

Kolstad HA, Bisanti L, Roeleveld N, Baldi R, Bonde JP, Joffe M. 2000. time to pregnancy among male 

workers of the reinforced plastics industry in Denmark, Italy and the Netherlands. Scand. J. Work 

Environ. Health 26: 353-358.

Lemasters GK, Hagen A, Samuels SJ., 1985. Reproductive outcomes in women exposed to solvents in 

36 reinforced plastics companies. I. Menstrual dysfunction. J. Occup. Med. 27: 490-494.

Lemasters GK. 1989. Reproductive outcomes of pregnant workers employed at 36 reinforced plastics 

companies. II. Lowered birth weight. J. Occup. Med. 31: 115-120.

National Cancer Institute, 1979. Bioassay of styrene for possible carcinogenicity. NCI Technical Report 

#185.

Roycroft JH, Mast TJ, Ragan HA, Grumbein SL, Miller RA, Chou BJ. 1992. Toxicological effects of 

inhalation exposure to styrene in rats and mice. The Toxicologist 12: 397.

Srivastava S, Seth PK, Srivastava SP. 1989. Effect of styrene administration on rat testis. Arch. Toxicol. 

63: 43-46.

Takao T, Nanamiya W, Nazarloo HP, Asaba K, Hashimoto K. 2000. Possible reproductive toxicity of 

tyrene in peripubertal male mice. Endocr. J. 47: 343-347.

Vergieva T, Zaidkov Kh, Palatov S. 1979. Study of the embryotoxic action of styrene. Khig. Zdraveopaz 

22: 39-43. et al. (1979

Zaidi NF, Agrawal AK, Srivastava SP, Seth PK. 1985. Effect of gestational and neonatal styrene 

exposure on dopamine receptors. Neurobehav. Toxicol. Teratol 7: 23-28.

[Attachment: See PDF Docket ID: EP

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.

Commenter Name: Jean Kasakevich

Commenter Organization: The Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0069
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Comment Part: 2

EPA Comment Code: 2070

Comment: 2) There is a significant database already available on mammalian toxicity endpoints related 

to reproductive and developmental toxicity potential of ECH, supplemented with chronic data, that 

basically replaces any Tier 1-type data that would be collected under EDSP and does not support 

endocrine-related effects.

Response: Please see general response to comment under EPA Comment Code: 2070 Contaminants Not 

Expected to Produce Estrogen-like Effect.
EPA-OGWDW Final EDSP List 2 February 2013

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EPA Comment Code: 2080 Contaminants with Low or No Comprehensive Occurrence 

Data and Therefore Do Not Meet SDWA 1457 Requirements

General Response: EPA disagrees that chemicals detected in water at “low concentrations” or at a “low 

rate” of frequency do not meet the SDWA 1457 and therefore should not be listed on the second EDSP 

list. In evaluating all of the occurrence data to finalize the second EDSP list, EPA believes that detection 

in water, whether finished or ambient, is sufficient to determine that a chemical may be found in sources 

of drinking water and that a substantial population may be exposed to that chemical, for example RDX.

Also, please see general response to comment under EPA Comment Codes: 1060 SDWA 1457, 1050 

Evaluation Criteria Review, 1035 Animal Testing, and 2100 Pesticide Registration Review Issues for 

additional information.

Individual Comments

Commenter Name: John Jachetta

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0014

Comment Part: 3

EPA Comment Code: 2080

Comment: Little or no US population exposure to picloram through drinking water

Picloram was placed upon the EDSP 2nd list because it is already regulated with a National Primary 

Drinking Water Regulation (NPDWR) under the SDWA. Picloram's MCLG and MLC have both been 

set at a concentration of 0.5 mg/L (500 ug/L), with the identified source of potential contamination being 

listed as "herbicide runoff”, and the long-term exposure health effect as "liver problems". As the 

drinking water enforcement levels have been set by EPA, local routine monitoring of finished drinking 

water is required under the Act.

Routine reporting of detailed finished drinking water monitoring results for all contaminants is not 

readily accessible to the public at the national level, although individual water system data can be 

queried via the Safe Drinking Water InformationSystem (SDWIS) (l). Based upon summary information 

for fiscal year 2009 (2), there were over 150,000 public water systems in the US, serving a population of 

nearly 313 million people. For fiscal years 2001-2009, NO violations of the MCL for picloram were 

noted; 65% of the violations were for the industrial chemicals Di(2-ethylhexyl) phthalate (used in the 

rubber industry) and Ethylene dibromide (a byproduct of petroleum refining and agricultural fumigant). 

If at least annual sampling was performed, these results reflect the analysis of over 1.3 million finished 

water samples.

Source water monitoring information is maintained in the STORET database, although its reporting is 

voluntary for the States. Extracting information from STORET yielded at total of 1271 surface water 

sites in 20 states that were monitored for picloram from 2000 to 2010. Of these sites, 87% were in 

Kansas and Iowa. In the decade, 9785 samples were analyzed for picloram, and quantifiable residues 

were found in only 56 samples, while 317 samples were reported as "present at less than quantification 

levels"[FN1: Analytical method quantitation limits vary, but the value for picloram is likely on the order 

of 0.005-0.01 ug/L, based upon methods used by the USGS in their monitoring programs]. The 
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maximum concentration found was 24 ug/L; the next highest value found was considerably lower, at 1.8 

ug/L. The 90th percentile detected level was 1.56 ug/L. This low rate of detection is in contrast to values 

reported by EPA in the picloram Registration Eligibility Decision (RED) document (3) where detections 

were reported in 420 of 744 samples taken from 135 locations; the maximum reported value was 4.6 

ug/L. The RED documented samples taken prior to 1988, however, as an outcome of that RED, 

commonly-used picloram application rates have been reduced from a maximum of 2.0 lb ae/A to 0.5 lb 

ae/a (a 75% rate reduction), in specialized and limited applications for invasive weed management, 

picloram rates have been lowered from 2.0 lb ae/A to 1.0 lb ae/A (a 50% rate reduction). This has 

greatly mitigated any off-site movement of this active ingredient.

Additional directed surface water monitoring has also been performed by the US Geological Survey 

(USGS) in its National Water Quality Assessment (NAWQA) program (4). This statistically-designed 

sampling program analyzed for picloram in 204 surface water sites, with detections found at 16 sites 

over the 2000-2010 period. The maximum detected concentration was 1.3 ug/L.

Monitoring for picloram has also been carried out in groundwater, most recently as part of NAWQA 

protocols. In these assessments, 2118 sites were monitored for picloram and residue were detected at 

only 6 sites, with a maximum concentration found of 0.73 ug/L. This compares well with a retrospective 

monitoring study carried out by DAS in the late 1990's (5), which found quantifiable groundwater 

residues at 1 of 95 sites which had been historically treated with picloram; the maximum concentration 

found was 2.3 ug/L. By contrast, the RED cited the EPA Pesticides in Groundwater Database, where a 

maximum concentration of 30 ug/L was reported (this high value was found to be the result of wellhead 

contamination).

The monitoring data currently available indicates a very low prevalence of picloram in either source or 

finished water. The data is a clear indication that the probability of exposure to the US population via 

drinking is extremely low, and thus picloram should be of low priority for EDSP testing.

Response: The use rates and the lack of/low concentration of picloram in water is not a basis for 

removing the chemical from the second list. EPA was directed “to publish within 1 year of enactment a 

second list of no less than 100 chemicals for screening that includes drinking water contaminants...” but 

the list is not exclusively drinking water contaminants. The basic criteria for list 2 chemical selections 

were 1) chemicals that met the finding in accordance with SDWA, and/or 2) pesticides scheduled for 

Registration Review for fiscal years (FY) 2007 and 2008. The agency has elected to keep the FY2007 

and 2008 Registration Review chemicals (which include picloram) on the second list consistent with our 

commitment to integrate the endocrine disruptor screening program into the Registration Review 

process. In the future, the agency intends to look for opportunities to align the issuance of EDSP test 

orders for pesticide active ingredients consistent with the Registration Review schedule. 

Please see general response to comment under this EPA Comment Code: 2080 Contaminants with Low 

or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 Requirements. Please 

also see Response-to-Comments for the Endocrine Disruptor Screening Program’s Draft Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that is being published 

simultaneously with this comment response document.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 4

EPA Comment Code: 2080

Comment: Alachlor

Alachlor is a chloroacetanilide herbicide used primarily for pre-emergent control of annual grasses and 

broadleaf weeds in corn, sorghum, soybeans and other crops. The annual use of alachlor on corn has 

been reduced substantially with the registration of acetochlor in 1994 (National Agricultural Statistics 

Service (NASS) 2010). As there are no residential uses for alachlor, public exposure would be mainly 

through food and drink (EPA 2006a). Tolerances for residues on a variety of foods have been set by 

EPA (40 CFR §180.249) and residues of alachlor in food are usually below the detection limit (WHO 

2003a). EPA has assessed the chronic (non-carcinogenic) dietary risk posed by alachlor, and determined 

that the Anticipated Residue Concentration (ARC) for the overall U.S. population represents less than 

1% of the chronic Reference Dose (RfD), the amount believed not to cause adverse effects if consumed 

daily over a 70-year lifetime (EPA 1998). Levels of parent alachlor were measured in a long-term 

groundwater monitoring study of vulnerable areas, which found detectable levels in less than 1% of the 

10,054 samples collected (De Guzman, Hendley et al. 2005). In a seven-year surface water drinking 

supply monitoring study conducted in a 12-state area in mostly vulnerable watersheds, parent alachlor 

was detected in 7% of the samples and annualized mean concentrations steadily declined from about 

0.015 ppb in 1995 to <0.005 ppb in 2001 (Hackett, Gustafson et al. 2005), and rarely, if ever, exceeded 

the maximum contaminant level (MCL) of 2 ppb alachlor in drinking water as set by EPA (EPA 1998).

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0019

Comment Part: 6

EPA Comment Code: 2080

Comment: Summary and Conclusions regarding alachlor: Alachlor usage has been steadily declining 

since the introduction of acetochlor in 1994. Alachlor was detected infrequently in surface and ground 

waters in vulnerable watersheds where it is used as an agricultural pesticide, and generally at 

concentrations well below the MCL set by EPA. Tolerances for food residue have been established by 

EPA and amounts on food are typically below detection limits. This raises the question as to whether a 

substantial population is, in fact, exposed to alachlor in water and food.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Gregory Dolan

Commenter Organization: Methanol Institute
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EPA Document ID: EPA-HQ-OPPT-2009-0477-0024

Comment Part: 1

EPA Comment Code: 2080

Comment: January 18, 2011 

Document Control Office [7407M] 

Office of Pollution Prevention and Toxics (OPPT) 

U.S. Environmental Protection Agency 

EPA East Building, Room 6428 1201 Constitution Avenue, NW 

Washington, DC 20004-3302 

Re: Comments on EPA’s Endocrine Disruptor Screening Program; Second List of Chemicals for Tier I 

Screening; Docket No. EPA-HQ-OPPT-2009-0477 

Dear Sir or Madam: 

The Methanol Institute submits these comments in response to the Environmental Protection Agency’s 

(EPA’s) publication in the Federal Register of a proposed list of substances subject to testing under the 

Agency’s Endocrine Disruptor Screening Program (EDSP), 75 Fed. Reg. 70,248 (Nov. 17, 2010). For 

the purposes of these comments, we refer to this list of substances as the “EDSP List.” [FN1: This is the 

second list of substances for which testing would be required under the EDSP. The first list was 

published in the Federal Register on April 15, 2009. 74 Fed. Reg. 17579 (April 15, 2009).] 

The Methanol Institute is a not-for-profit organization that serves as the trade association for the global 

methanol industry. The Methanol Institute and its members have a direct and substantial interest in 

EPA’s inclusion of methanol in the EDSP List, since by virtue of methanol’s inclusion on the list, the 

Methanol Institute and/or its members may be required to conduct hundreds of thousands, if not 

millions, of dollars worth of testing. 

EPA included methanol on the EDSP List pursuant to Section 1457 of the Safe Drinking Water Act 

(SDWA). In order to require testing of a substance under SDWA Section 1457, EPA must determine 

that: (i) the substance may be a contaminant of drinking water, and (ii) a substantial population may be 

exposed to the substance. EPA’s decision to include methanol on the EDSP List is flawed for the 

following reasons: 

1. The available data do not support the conclusion that methanol “may be a contaminant in drinking 

water” or that “a substantial population may be exposed” to methanol. Consequently, EPA has no basis 

for including methanol on the EDSP list under SDWA Section 1457; 

2. EPA ignored concerns expressed by the Office of Management and Budget (OMB), and failed to 

follow OMB’s directive that EPA consider and report on experience gained with respect to the first list 

of substances subject to EDSP testing before the Agency publishes the second EDSP List. 

3. EPA’s stated intention of not responding to comments pertaining to the findings required by SDWA 

Section 1457 constitutes a blatant violation of the Administrative Procedure Act. 

We address each of these points in more detail below. 
EPA-OGWDW Final EDSP List 2 February 2013

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Page 375

1. The Available Data Do Not Support The Conclusion That Methanol “May Be A Contaminant In 

Drinking Water” Or That “A Substantial Population May Be Exposed” To Methanol, As Required 

Under SDWA Section 1457 

In developing the EDSP List, methanol appears to have been chosen because it was identified as an 

unregulated contaminant listed in the third Contaminant Candidate List (CCL 3). The Methanol Institute 

submitted detailed comments on May 15, 2008 opposing the inclusion of methanol in CCL 3. See 

Attachment 1. As reflected in those comments, methanol was included in CCL 3 only because it is a 

high production volume chemical, which is not a sufficient basis for inclusion on the EDSP List under 

the authority of Section 1457 of the SDWA. More specifically, in assessing occurrence under the CCL 3 

listing, there were no findings of methanol in finished water systems or in ambient water by EPA; an 

important factor for consideration pursuant to the requirement of Section 1457, that “a substantial 

population may be exposed to the substance.” Similarly, the most recent (2009) Toxic Release Inventory 

data show “Total On-and Off-Site Disposal or Other Releases” of 116,832,130 lbs. for methanol, of 

which fully 101,245,259 is represented by “Total On-Site Air Emissions.” With the vast majority of 

methanol releases being to air, there is little threat that a substantial population would be exposed to the 

chemical through drinking water. Furthermore, the Methanol Institute understands that over 200 

wastewater treatment plants inject methanol into the treatment process for denitrification with no 

significant residual methanol in the effluent. These data, which EPA has apparently not considered, 

provide further empirical support for the conclusion that there is little possibility that methanol will 

become a drinking water contaminant to which a substantial population may be exposed.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements. Please also see Response-to-Comments for the Endocrine Disruptor Screening Program’s 

Draft Policies and Procedures for Screening Safe Drinking Water Act Chemicals (USEPA, 2012c) that 

is being published simultaneously with this comment response document.

Commenter Name: Howard Feldman

Commenter Organization: American Petroleum Institute

EPA Document ID: EPA-HQ-OPPT-2009-0477-0025

Comment Part: 3

EPA Comment Code: 2080

Comment: * EPA’s Office of Ground Water and Drinking Water (OGWDW) had routinely required 

water utilities to monitor for MTBE in both ground water and drinking water sources as part of the 

Unregulated Contaminant Monitoring Rule (UCMR), and the related Contaminant Candidate List 

(CCL). The results of that extensive national monitoring of the UCMR (2001-2005) showed that there 

was minimal MTBE exposure (i.e. detections above 5 ppb occurred in less than 0.5% of the more than 

3000 facilities tested) (EPA, 2008). Subsequently in the most recent UCMR monitoring (2007-2010), 

EPA’s OGWDW did not include MTBE on the list of compounds to be monitored.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 376

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034

Comment Part: 4

EPA Comment Code: 2080

Comment: C. Occurrence Data Do Not Support Including 1, 1, 2-Trichloroethane and EDC on Second 

List

As directed by the SDWA, EPA recently carried out a comprehensive review of existing national 

primary drinking water regulations to identify those which need to be revised. In making these 

determinations, EPA carefully considered contaminant occurrence data from approximately 132,000 

public water systems in 45 states and two Indian tribes, serving 254 million people. [FN6: 75 Fed. Reg. 

15500, 15514 (March 29, 2010).] These occurrence data, as compiled below for 1, 1, 2-trichloroethane 

and EDC (identified as 1, 2-dichloroethane), support EPA's conclusion that "the occurrence and 

exposure analysis based on possible changes in analytical feasibility indicates that any revision to the 

MCL is unlikely to provide a meaningful opportunity to improve public health protection."[FN7: 75 

Fed. Reg. 15500, 15535, 15564.]

Specifically, for 1, 1, 2-trichloroethane EPA found that "[t]he occurrence and exposure analysis shows 

that average concentrations do not exceed the current MCL for any system in the analysis." [FN8: 75 

Fed. Reg. 15500, 15563.] The data are reproduced in the table below:

TABLE VI-28-NUMBER AND PERCENT OF SYSTEMS WITH MEAN CONCENTRATIONS 

EXCEEDING 1, 1, 2-TRICHLOROETHANE THRESHOLDS AND CORRESPONDING 

ESTIMATES OF POPULATION SERVED [See Docket ID: EPA-HQ-2009-0477-0034.1]

For EDC, "[t]he occurrence and exposure analysis shows that average concentrations exceed the current 

MCL for three of 50,442 systems (0.006 percent) serving 150 people (or 0.00007 percent of227 million 

people)".[FN9: 75 Fed. Reg. 15500, 15534.] The data are reproduced in the table below:

TABLE VI-9-NUMBER AND PERCENT OF SYSTEMS WITH MEAN CONCENTRATIONS 

EXCEEDING 1, 2-DICHLOROETHANE THRESHOLDS AND CORRESPONDING ESTIMATES 

OF POPULATION SERVED [See Docket ID: EPA-HQ-2009-0477-0034.1]

These occurrence data demonstrate that a substantial population is not exposed to either 1, 1, 2-

trichloroethane or EDC for purposes of EDSP screening.

Response: Please see general responses to comment under EPA Comment Codes: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements and 2090 Contaminants with MCLG of Zero.

Commenter Name: Sahar Osman-Sypher

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0035

Comment Part: 1

EPA Comment Code: 2080
EPA-OGWDW Final EDSP List 2 February 2013

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Page 377

Comment: The American Chemistry Council Diisocyanates Panel herein submits comments relating to 

the inclusion of 4,4’-methylenedianiline (“MDA,” or “4,4’-MDA” CASRN 101-77-9) among the 

substances included in EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for 

Tier 1 Screening.These comments are submitted pursuant to EPA’s request for comments on the Draft 

EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010. 

January 18, 2011 

OPPT Document Control Office (DCO) 

EPA East Building, Room 6428 

1201 Constitution Avenue, N.W. 

Washington, DC. 20460 

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477 

Submitted via Federal eRulemaking Portal: http://www.regulations.gov 

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] 

Dear Sir or Madam, 

The American Chemistry Council (ACC) [FN1: The American Chemistry Council (ACC) represents the 

leading companies engaged in the business of chemistry. ACC members apply the science of chemistry 

to make innovative products and services that make people's lives better, healthier and safer. ACC is 

committed to improved environmental, health and safety performance through Responsible Care®, 

common sense advocacy designed to address major public policy issues, and health and environmental 

research and product testing. The business of chemistry is a $674 billion enterprise and a key element of 

the nation's economy. It is one of the nation’s largest exporters, accounting for ten cents out of every 

dollar in U.S. exports. Chemistry companies are among the largest investors in research and 

development. Safety and security have always been primary concerns of ACC members, and they have 

intensified their efforts, working closely with government agencies to improve security and to defend 

against any threat to the nation’s critical infrastructure.], in a separate communication, has provided 

overarching comments related to EPA’s Draft EDSP List 2, Draft Policies and Procedures, and the 

EDSP Information Collection Request. The ACC Diisocyanates Panel (“Panel”) [FN2: The Panel 

includes U.S. manufacturers of TDI and/or MDI: BASF Corporation, Bayer Material Science, The Dow 

Chemical Company, and Huntsman Corporation.] herein submits specific comments relating to the 

inclusion of 4,4’-methylenedianiline (“MDA,” or “4,4’-MDA” CASRN 101-77-9) among the substances 

included in EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 

Screening (the “Draft EDSP List 2”). These comments are submitted pursuant to EPA’s request for 

comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010, (the “Listing Notice”). 

1. The physical/chemical, environmental, and toxicological hazards of MDA, as well as the exposures

and risks associated with its manufacture and use, have been previously evaluated and reported by the 

Agency in 1985. [FN3: U.S. EPA (1985). Risk assessment for 4,4’-methylenedianiline (CAS No. 101-

77-9). United States Environmental Protection Agency, Office of Toxic Substances, Washington, D.C. 2 

February 1985. ] These aspects have been more recently evaluated under the European Union Existing 

Substances risk assessment program. [FN4: European Chemicals Bureau (2001). Risk Assessment 

Report for 4,4’-methylenedianiline (CAS #101-77-9). European Chemicals Bureau, Ispra, Italy. Final 

report, November 2001.] The 1985 assessment concluded that, at that time, there was no evidence that 

any drinking water supply is contaminated with 4,4'-MDA. Both the 1985 assessment and the 2001 EU 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 378

assessment indicate that surface waters used for drinking water supply may receive effluents directly or 

indirectly from 4,4-MDA, MDI and polyurethane manufacturing operations which could contain 4,4'-

MDA. However, the EU risk assessment resulted in predicted concentrations in local receiving waters 

associated with seven MDA manufacture sites which were < 0.4 mg/L. Based on these previous 

assessments, the potential for direct/indirect exposures to MDA via the environment, and potential 

effects related thereto, would not appear to be a high priority for further investigation at this time.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: W. Caffey Norman

Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0037

Comment Part: 3

EPA Comment Code: 2080

Comment: C. Occurrence Data for Trans-1, 2-Dichloroethylene and l,l,l-Trichloroethane

Available occurrence data do not support the conclusion that a substantial population may be exposed to 

either trans-l, 2-dichloroethylene and 1,1,1-trichloroethane. Several data sets presented in EPA's October 

2009 Analysis of Regulated Contaminant Occurrence Data from Public Water Systems in Support of the 

Second Six-Year Review of National Primary Drinking Water Regulations are relevant.[FN6: EPA, The 

Analysis of Regulated Contaminant Occurrence Data from Public Water Systems in Support of the 

Second Six-Year Review of National Primary Drinking Water Regulations, EPA-815-B-09-006 

(October 2009) (hereafter "Systems Review") at 15, n 6.]

The National Water-Quality Assessment Program (NAWQA) provides the most extensive coverage of 

potential source waters. The available data indicate “relatively infrequent contaminant occurrence in 

potential source waters at the levels of interest.”[FN7: EPA, Occurrence Analysis for Potential Source 

Waters for the Second Six-Year Review of National Primary Drinking Water Regulations, EPA-815-B09-004 (October 2009) (hereafter "Sources Review") at ES-2 to ES-3.] From 1991-2001, the NAWQA 

Program established a baseline of water-quality conditions in 51 US river basins and aquifers through 

interdisciplinary assessments, including water chemistry, hydrology, land use, stream habitat, and 

aquatic life.[FN8: Id. at 4-1.] The compliance monitoring data in NAWQA are split between two six 

year periods, the first based on data from 1993-1997 and the second on data from 1998-2005. The data 

from both sets of years are not identical with the second period covering 45 states compared to only 16 

states in the first period.[FN9: Id. at 46.] Due to this discrepancy, it is not clear that the differences 

shown are actual differences rather than differences between the datasets.

A second source of occurrence data on which EPA relies in evaluating the level of contaminants in 

waters is EPA's STORET system.[FN10: Sources Review at 4-1.] STORET is short for STOrage and 

RETrieval data system, which is part of EPA's Office of Ground Water and Drinking Water's National 

Contaminant Occurrence Database (NCOD). STORET contains archived data from the Legacy Data 

Center (LDC) through the end of 1998 and new water quality data beginning in 1999. STORET is a 

repository for data collected by local, state and federal agencies, Indian tribes, universities, and 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 379

volunteers. It contains raw biological, chemical, and physical data on surface and ground water for all 50 

states and US territories and jurisdictions.

Table 1[See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0037.1]

Table 2 Summary of 1,1,1-Trichloroethane Occurrence Based on Maximum Sample Values for 

Locations in NAWQA Occurrence Result [See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0037.1]

Table 3 Summary of 1,1,1-Trichloroethane Occurrence Based on Maximum Sample Values for 

Locations STORET Occurrence Result [See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0037.1]

D. Occurrence Data Do Not Support Inclusion of Trans 1,2-Dichloroethylene and 1,1,1-Trichloroethane 

in Tier I Screening

Table 1 above is Exhibit 6-3 in EPA's October 2009 Analysis drawn from the NAWQA data. [FN11: Id. 

at 48. The table included has been excerpted from Exhibit 6-3.] The MRL (Minimum Reporting Level) 

is the lowest contaminant concentration level that can be dependably quantified in the laboratory and 

reported in the contaminant occurrence data. The MCL, as noted above, is the enforceable drinking 

water standard promulgated by EPA. Where there are no occurrences of a substance above the MCL, it 

seems safe to conclude that a substantial population will not be exposed to it.

Trans-1,2-dichloroethylene was not detected above the MCL in either set of six-year studies. 1,1,1-

Trichloroethane was not detected above the MCL in the second six-year period, and the number of 

detects above the MCL (0.01 %) in the first six-year period was inconsequential. Further supporting the 

lack of occurrence data needed for EPA's inclusion of these substances in EDSP is the small dataset 

from which the numbers are drawn. The small dataset is a result of the almost non-existence of the 

substances at a measurable level as demonstrated by the low number of systems above the MRL.

Table 2 above is a reproduction of NAWQA data collected by the EPA relating to 1,1,1- trichloroethane. 

Table 2 shows that 1,1,1-trichloroethane was not detected over the current MCL/MCLG for any of the 

NA WQA sampling locations. [FN12: Id. at 4-16.] Occurrence data from this analysis conducted by the 

EPA demonstrate that 1,1,1-trichloroethane was not present in levels such that a substantial population 

would be exposed to it. 

Table 3 above is a reproduction of the STORET results for 1,1,1-trichloroethane. Less than 0.1 % of the 

STORET locations had concentrations above the current MCL/MCLG.[FN13: Id. At 4-16.]

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 4

EPA Comment Code: 2080
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Page 380

Comment: C. Occurrence Data Do Not Support Including VDC, Methylene Chloride, and Carbon

Tetrachloride on the Second List

As directed by the SDW A, EPA recently carried out a comprehensive review of existing National 

Primary Drinking Water Regulations to identify those which need to be revised. In making these 

determinations, EPA carefully considered contaminant occurrence data from approximately 132,000 

public water systems in 45 states and two Indian tribes, serving 254 million people. [FN6: 75 Fed. Reg. 

15500, 15514 (March 29, 2010).] These occurrence data are compiled below for VDC: 

[Table VI-10 See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0038.1]

"Table VI-10 provides summary data for contaminant occurrence based on maximum sample values for 

the locations included in the STORET and NAWQA data. Although the degree to which these 

occurrence rates represent national drinking water source occurrence is uncertain, the information shows 

no to low occurrence at threshold levels of interest. This information indicates that any resulting 

NPDWR change would affect systems that rely on source water at less than 0.02 percent of the 

NAWQA locations. The STORET results are driven by the 157 sampling locations in Phoenix, Arizona, 

that have a maximum sample above the MCL of 0.007 mg/L. Five of these locations also account for 

those having a maximum sample that exceeds 0.35 mg/L." [FN7: 75 Fed. Reg. 15500, 15535.]

It appears that VDC contamination of drinking water sources is de minimis, with virtually all 

measurements above the MCL attributable to one geographic location.

Occurrence data are compiled below for methylene chloride (identified as dichloromethane):

[Table VI-11 See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0038.1]

This table shows that methylene chloride is present above the MCL for a population of 12,000 (0.005%), 

a level that we submit falls below the "substantial population" criterion. Moreover, the EPA analysis 

indicates significant uncertainty:

"A USGS study of ground water, source water, and drinking water quality indicated consistently lower 

dichloromethane (methylene chloride) occurrence frequencies compared to either PCE or TCE, which 

are among the most frequently occurring VOCs included in the study (Moran, 2006). Table VI-12 

provides a summary of the occurrence results reported in the USGS study. This study also determined 

that population density was the strongest predictor of dichloromethane occurrence. 

[Table VI-12 See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0038.1]

"EPA compared Six-Year Review ICR occurrence patterns for dichloromethane with contaminant 

release information to determine if drinking water occurrence corresponds with potential contaminant 

sources reported in the Taxies Release Inventory (TRI) and found that the states with the majority of 

systems with mean concentrations that exceed 0.0005 mg/L did not tend to be the States with the highest 

dichloromethane releases (Moran, 2006). Table VI-13 provides summary information from that 

comparison. In particular, the numbers of system means exceeding 0.0005 mg/L in Montana and Alaska 

seem inconsistent with TRI release information and the USGS study finding that population density is 

the strongest predictor of dichloromethane occurrence. 
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Page 381

"Because of data gaps regarding the feasibility of PQL reduction and potential occurrence data accuracy 

at the lowest EQL, EPA concluded that revising the MCL may not constitute a meaningful opportunity 

to improve the level of public health protection." [FN8: 75 Fed. Reg. 15500, 15538.]

Thus, EPA concluded:

"In view of the fact that dichloromethane is a common laboratory contaminant, there is uncertainty 

regarding the extent to which a PQL revision is feasible or whether the Six-Year Review ICR data are 

reliable at concentrations well below the current PQL. Furthermore, the occurrence and exposure 

analysis based on possible changes in analytical feasibility indicates that any revision to the MCL is 

unlikely to provide a meaningful opportunity to improve public health protection. " [FN#9: 75 Fed. Reg. 

15500, 15539.] 

Occurrence data are compiled below for carbon tetrachloride:

[Table VI-5 See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0038.1]

This table shows that carbon tetrachloride is present above the MCL for a population of 1700 (0.001 %), 

a level that falls below any reasonable "substantial population" criterion. Accordingly, EPA concluded 

that "the occurrence and exposure analysis based on possible changes in analytical feasibility indicates 

that any revision to the MCL is unlikely to provide a meaningful opportunity to improve public health 

protection." [FN10: 75 Fed. Reg. 15500, 15528.]

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements. Also, see general response to comment under EPA Comment Code: 2090 Contaminants 

with MCLG of Zero for statement related to occurrence of endocrine effects at a level lower than the 

current MCL.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemical Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0041

Comment Part: 5

EPA Comment Code: 2080

Comment: The VCCEP assessment also includes a comprehensive exposure analysis component. The 

VCCEP assessment provides an extensive analysis of ethylbenzene exposure to adults and children, and, 

in all cases, concludes that the major route of exposure to ethylbenzene is inhalation. The available data 

do not support the Agency’s finding that “a substantial population” may be exposed to ethylbenzene in 

sources of drinking water, as required by Section 1457 of the SDWA for inclusion in the EDSP.

As cited on pages 6-10 – 6-11 of the VCCEP report, groundwater data for ethylbenzene were obtained 

from the U.S. Geological Survey’s (USGS’s) National Water Quality Assessment Program (NAWQA). 

These data include 6,324 records collected between September 1996 and September 2003 from sites in 

almost all 50 States. Ethylbenzene was detected in approximately 2% of the samples.
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Page 382

Moreover, as a part of the exposure analysis, data from the National Contaminant Occurrence Database 

(NCOD) were also reviewed (EPA, 2005). The NCOD was developed to satisfy the statutory 

requirements set by Congress in the 1996 SDWA amendments to maintain a national drinking water 

contaminant occurrence database using occurrence data for both regulated and unregulated contaminants 

in public water systems. Groundwater data within the database are segregated into Round 1 and 2 data 

and 6-Year Review Data. Round 1 and 2 data were collected between 1988 and 1997 in 35 to 40 states, 

while the 6-Year Review data were collected between 1993 and 1997 in 16 states. Ethylbenzene was 

detected in less than 1% of the samples in both data sets.

The NAWQA and NCOD information show that exposure to ethylbenzene in drinking water is NOT 

widespread or substantial. Therefore, ethylbenzene does not meet the SDWA’s Section 1457 statutory 

criteria for endocrine screening.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements. 

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 7

EPA Comment Code: 2080

Comment: B. Exposure to Acrylamide from Drinking Water is Negligible 

Given the use of polyacrylamides in the treatment of water, there has been considerable evaluation of 

the potential for acrylamide exposure via drinking water. NSF International prepared an assessment of 

drinking water for Health Canada that evaluated the results of over 1,200 drinking water samples from 

1991 through 1999 (NSF 2000). These samples were performed on “those products which represent the 

worst-case potential for contributing contaminants of concern.” The results indicate that only one initial 

sample detected acrylamide and this sample was still below the 0.5 μg/L (0.5 ppb) treatment technology 

limit (NSF 2000).

These results are consistent with other reviews that have generally found little, if any, acrylamide in 

drinking or surface water. The table below summarizes the data on concentrations in surface and 

drinking water in the US as reported in the EU Risk Assessment (EU RAR 2002). There were no cases 

where acrylamide was detected in drinking water.

U.S. Drinking and Surface Water Monitoring Data for Acrylamide (As Reported in EU Risk 

Assessment, 2002)

[See PDF Docket ID: EPA-HQ-OPPT-2009-0477-0042.2]

As EPA notes in its most recent review of existing drinking water standards, the NPDWR for 

acrylamide: 

...established an MCLG of zero based on a cancer classification of B2, probable human carcinogen. The 

NPDWR imposes a TT requirement that limits the allowable monomer levels in products used during 
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Page 383

drinking water treatment, storage, and distribution to 0.05 percent acrylamide in polyacrylamide 

coagulant aids dosed at 1 part per million (ppm). Each water system is required to certify, in writing, to 

the State (using third-party or manufacturer's certification) that the product used meets these residual 

monomers and use-level specifications. [emphasis added] 

Thus the use of polyacrylamides in drinking water treatment, which provides benefits in terms of water 

treatment, could at the most result in a maximum potential concentration of 0.5 ppb (0.5 μg/L) and is 

likely to be much less. The EU Risk Assessment estimated a maximum concentration of acrylamide in 

drinking water of 0.125 μg/L based upon the maximum allowed dose of active polymer, and an average 

concentration in drinking water of 0.0625 μg/L (2002). However, the EU noted that both of these values 

are “worst-case” and the “actual level is likely to be significantly lower.” These conclusions are 

certainly consistent with the fact that repeat monitoring of drinking water has generally not detected 

acrylamide. 

Based on the upper-bound estimates of 0.125 μg/L acrylamide in drinking water, a 70 kg person 

consuming 2 L of water would have an estimated exposure of 0.0036 μg/kg bw/day. Children may have 

slightly higher estimated doses due to higher consumption of water per body weight; FAO/WHO 

estimates children’s consumption can be a high as 3- 4 times that of adults on a body weight basis. 

Regardless, this indicates that exposure to acrylamide from drinking water is very low (<0.01 μg/kg 

bw/day) and well below that of food and smoking. 

Based on this information, NAPPA does not believe that EPA has met Congress’ intent in selecting 

acrylamide for the EDSP program as there is not any evidence that a significant population is exposed to 

acrylamide via drinking water. Further, the existing technology technique (TT) standard for acrylamide 

in drinking water ensures that acrylamide exposure from the use of polyacrylamides in water treatment 

will remain very low.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 8

EPA Comment Code: 2080

Comment: In fact, the extensive monitoring data already available for Acetochlor, Acetochlor ESA, and 

Acetochlor OA under the SDWA show that human exposure to these materials via drinking water is 

negligible, indicating that inclusion on List 2 is inappropriate. Lastly, reliance on chemical production 

data to trigger EDSP screening under the SDWA is not a scientifically rigorous approach and does not 

necessarily correlate to human exposure.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 384

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 15

EPA Comment Code: 2080

Comment: Extensive water monitoring data show that human exposure to Acetochlor and its degradates 

is negligible:

In addition, the ARP notes that a very extensive water monitoring database exists for Acetochlor and its 

degradates, which demonstrates that human exposure to these materials is negligible. The EPA Office of 

Water has now collected voluminous drinking water monitoring data for Acetochlor, Acetochlor ESA 

and Acetochlor OA) as Unregulated Contaminants (Acetochlor since 2000 and the two degradates since 

2007). Acetochlor parent was not detected in any of the 34,274 samples analyzed during Unregulated 

Contaminant Monitoring Report (UCMR) 1 (2000-2005). During the UCMR 2 monitoring period (2007 

to present), an additional 10,575 samples have been analyzed thus far. Neither Acetochlor parent nor 

Acetochlor OA has been detected in any of these samples. Acetochlor ESA was detected in only three of

the 10,575 samples, at 0.0012 milligrams per liter and less (detection limit 0.001 milligrams per liter). 

This huge body of EPA monitoring data is highly complementary to the ARP monitoring studies, which 

covered the period 1995-2001 and tell a similar story.[FN3: AG Hackett, DI Gustafson, SJ Moran, P 

Hendley, II van Wesenbeeck, ND Simmons, AJ Klein, JM Kronenberg, JD Fuhrman, JL Honegger, J 

Hanzas, D Healy, and C Stone. 2005. The Acetochlor Registration Partnership Surface Water 

Monitoring Program for Four Com Herbicides, J. Environ. Qual, 34:877-889.] [FN4: N de Guzman, DI 

Gustafson, P Hendley, II. van Wesenbeeck AJ Klein, JD Fuhrman, KZ Travis, ND Simmons, WE 

Teskey RB Durham. 2005. The Acetochlor Registration Partnership State Ground Water Monitoring 

Program," J. Environ. Qual. 34:793-803.] The same pattern of occurrence is confirmed by other water 

monitoring data reported by USGS and the States, all showing that concentrations of Acetochlor 

residues are only very rarely present, and at extremely low concentrations (typically less than 0.0001 

milligrams per liter). The water monitoring database for Acetochlor is much larger than for most 

pesticides due to the unique registration agreement formed between the ARP and the EPA in March 

1994. The ARP fully satisfied all of the conditions set forth in that agreement, and the EPA recently 

affirmed its findings regarding residues of Acetochlor and its degradates in water when it approved new 

uses of Acetochlor on cotton and soybeans in September 2009.[FN5: http://www.epa.gov/fedrgstr/EP APEST/2009/SeptemberlDay-16/p21845.pdf.]

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Anthony Wagner

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0046

Comment Part: 6

EPA Comment Code: 2080

Comment: There is no strong evidence that ethylene glycol is a widespread contaminant of surface or 

drinking water.
EPA-OGWDW Final EDSP List 2 February 2013

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The Panel believes that ethylene glycol should not require screening for endocrine disrupting effects as 

prolonged significant exposures to either humans or the environment is unlikely, based on the nature in 

which it is chiefly used and its environmental fate properties. The available data do not support the 

Agency’s finding that “a substantial population” may be exposed to ethylene glycol in sources of 

drinking water, as required by Section 1457 of the SDWA for inclusion in the EDSP. There is no strong 

evidence that ethylene glycol is a widespread contaminant of surface or drinking water and where 

contamination has been found mitigation measures are being implemented.

SDWA Section 1412(b)(1)(B) requires EPA to periodically publish a list of unregulated contaminants 

“which are known or anticipated to occur in public water systems” and may require regulation under the 

SDWA. A finding that a contaminant is anticipated to occur in public water systems does not satisfy the 

statutory criteria of SDWA Section 1457, which requires a finding that a “substantial population may be 

exposed to such substance.” Therefore, listing on CCL 3 is not a sufficient basis for including a 

substance in the EDSP program.

Occurrence

The primary source of environmental contamination of ethylene glycol is a result of its use as a de-icer 

in airports (WHO, 2000; EC, 2000). This may contribute to high amounts being released into the 

environment. However these point-source releases are intermittent, localized and few in number. 

Consequently, it may be assumed that these levels of exposure will only apply to a small population, and 

for a short duration. Although there is environmental monitoring data available at sampling sites within 

the vicinity of airports, there appear to be no data available pertaining to concentrations in ambient 

surface-, ground- and drinking water.

Varying environmental concentrations of ethylene glycol have been reported at monitoring sites around 

Canadian airports. In recent years it has been recognized that the environmental releases should be 

reduced, and, as of 1995, glycol operational management plans (GOMPs) had been put into place in the 

15 largest Canadian airports, which accounts for 90% of ethylene glycol use in aircraft de-icing 

applications. Over the 1997/98 and 1998/99 de-icing seasons, mean concentrations in monitoring sites 

across Canadian airports ranged from below the detection limit (1-10 mg/L) to 411 mg/L and medians 

from below detection limit to 50 mg/L. Out of 3282 individual measurements of storm water near 

Canadian airports over de-icing seasons 1997/98 and 1998/99, the mean and medial ethylene glycol 

concentrations were 23 and 5 mg/L, respectively. This represents a large reduction in the mean average 

concentration of the previous 1996/97 season (108 mg/L), which is accounted for by the implementation 

of a large glycol management infrastructure at Dorval International Airport.

Information regarding concentrations of ethylene glycol in groundwater is limited. Very elevated levels 

(> 10000 mg/L) have been found at Calgary International Airport, however this was attributed to the 

sampling site being shallow (< 1 m) and beneath an apron where almost all aircraft activity takes place. 

The soil type, which was clay till soil, was also considered a reason for the accumulation as it allowed 

for only very slow migration of residual ethylene glycol, supported by the much lower measurements 

taken at nearby sampling sites. At another site (Ottawa International Airport), with permeable soils, 

samples detected from wells adjacent to runways were below detection levels, with only one notably 

elevated concentration ever reported (415 mg/L in June 1986, 600 m from terminal).
EPA-OGWDW Final EDSP List 2 February 2013

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Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Robert Fensterheim

Commenter Organization: Acetaldehyde Working Group

EPA Document ID: EPA-HQ-OPPT-2009-0477-0051

Comment Part: 9

EPA Comment Code: 2080

Comment: A. EPA Has Not Justified Substantial Population Exposure to Acetaldehyde from Drinking 

Water to Support EDSP Testing Pursuant to § 1457 SDWA 

As briefly described in the Federal Register, the Agency identified chemicals for EDSP List 2 that are 

either regulated drinking water contaminants with a national primary drinking water regulation 

(NPDWR), or contaminants listed on the third Contaminant Candidate List (CCL 3). Rather than discuss 

EPA’s interpretation of the statutory language, EPA simply asserts that the inclusion of a chemical on 

the CCL 3 is adequate justification to meet the statutory mandate of §1457 SDWA: 

Because Congress designated these contaminants for regulation due to concerns about occurrence in 

drinking water and adverse impacts on human health, EPA believes that each such substance meets the 

statutory testing criteria from SDWA section 1457. (75 FR (70250); November 17, 2010)

The CCL 3 docket contains two reports summarizing data on chemicals that were considered for the 

Containment Candidate List. One report, titled Contaminant Information Sheets for the Draft CCL 3 

Chemicals (2008), contains informational sheets on 95 chemical contaminants that were considered 

during the development of CCL 3. In this report, EPA compiles available information such as data on 

overall health effects and occurrence of the chemicals. Under the section “Supplemental Water Data,” 

information is presented on measured levels of various contaminates from monitoring programs, 

although in some instances it is difficult to determine the nature and source of the monitoring data.

Data on acetaldehyde, in accordance with the Disinfection by Product Information Collection Rule 

(DBP ICR), was included in EPA’s Contaminant Information Sheets for the Draft CCL 3 Chemicals and 

is summarized in the table below. While it is not possible to determine the type of water tested, the 

report stated that only 27 of the 236 water samples analyzed contained acetaldehyde. In those samples 

where acetaldehyde was measured, the maximum value detected was 18.3 μg/L and the median was 7.4 

μg/L, with the mean value of acetaldehyde detected being 8.04 μg/L.

Acetaldehyde data are also presented from drinking water programs in California. According to the 

California Department of Health Services data, eight public water systems (PWS) were sampled for 

detection of acetaldehyde. Of the eight PWS tested, acetaldehyde was detected in three PWS. Of these 

three PWS, the maximum value detected was 24 μg/L, as summarized in the graph below.

[Table: Summary of Drinking Water Data from the Report Contaminant Information Sheets for the Draft 

CCL 3 Chemicals; SEE DOCKET ID EPA-HQ-OPPT-2009-0477-0051.2]
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A comparison of drinking water, as well as other sources of exposure to acetaldehyde, is presented in the 

WHO Criteria document on acetaldehyde[FN3: Environmental Health Criteria 167: Acetaldehyde, 

prepared by United Nations Environment Programme, International Labor Organization, and World 

Health Organization, 1995]. WHO recognizes that the main source of exposure to acetaldehyde for the 

majority of the general population is through the metabolism of alcohol. Additionally, according to 

WHO, the general population is exposed to acetaldehyde principally from food and beverages, and, to a 

lesser extent, from air. WHO further notes that the contribution from “drinking-water is negligible,” 

noting that “up to 0.1 μg/L” of acetaldehyde was found in drinking waters sampled from Seattle, WA 

and Philadelphia, PA.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 8

EPA Comment Code: 2080

Comment: In fact, the extensive monitoring data already available for Alachlor, Alachlor ESA, and 

Alachlor OA under the SDWA show that human exposure to these materials via drinking water is 

negligible, indicating that inclusion on List 2 is inappropriate. Lastly, reliance on chemical production 

data to trigger EDSP screening under the SDWA is not a scientifically rigorous approach and does not 

necessarily correlate to human exposure.

Response: Please see general responses to comment under EPA Comment Codes: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements and 1060 SDWA 1457.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 15

EPA Comment Code: 2080

Comment: Extensive water monitoring data show that human exposure to Alachlor and its degradates is 

negligible: 

In addition, Monsanto notes that a very extensive water monitoring database exists for Alachlor and its 

degradates, which demonstrates that human exposure to these materials is negligible. The EPA Office of 

Water has now collected voluminous drinking water monitoring data for Alachlor as a Regulated 

Contaminant (since 1992), and for Alachlor ESA and Alachlor OA as Unregulated Contaminants (since 

2007). During the UCMR 2 monitoring period (2007 to present), 10,575 samples have been analyzed 

thus far. Neither Alachlor parent nor Alachlor OA has been detected in any of these samples. Alachlor 

ESA was detected in only six samples, at 0.0013 milligrams per liter and less (detection limit 0.001 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 388

milligrams per liter). This huge body of EPA monitoring data is highly complementary to the Acetochlor 

Registration Partnership (ARP) monitoring studies, which covered the period 1995-2001 and tell a 

similar story..[FN3: AG Hackett, DI Gustafson, SJ Moran, P Hendley, IJ van Wesenbeeck, ND 

Simmons, AJ Klein, JM Kronenberg, JD Fuhrman, JL Honegger, J Hanzas, D Healy, and C Stone. 2005. 

The Alachlor Registration Partnership Surface Water Monitoring Program for Four Corn Herbicides, J. 

Environ. Qual, 34:877-889.], [FN4: N de Guzman, DI Gustafson, P Hendley, IJ. van Wesenbeeck AJ 

Klein, JD Fuhrman, KZ Travis, ND Simmons, WE Teskey RB Durham. 2005. The Alachlor 

Registration Partnership State Ground Water Monitoring Program,” J. Environ. Qual. 34:793-803.] The 

same pattern of occurrence is confirmed by other water monitoring data reported by USGS and the 

States, all showing that Alachlor residues are only very rarely present, and at extremely low 

concentrations (typically less than 0.0001 milligrams per liter).

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Stephen Risotto

Commenter Organization: American Chemistry Council (ACC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0056

Comment Part: 2

EPA Comment Code: 2080

Comment: Exposure to DEHA in Drinking Water Does Not Occur in a Substantial Population

Since the maximum contaminant level (MCL) of 400 micrograms per liter (μg/L) was established for 

DEHA in 1992, EPA has conducted two reviews to determine whether the MCL is sufficiently 

protective of public health. [FN2: The Safe Drinking Water Act (SDWA) requires EPA to review 

National Primary Drinking Water Regulations (NPDWR) at least once every six years and revise them, 

if appropriate. The purpose of the Six-Year Review is to identify those NPDWRs for which current 

health assessments, changes in technology, and/or other factors provide a health or technical basis to 

support a regulator revision that will maintain or strengthen public health protection.] As part of each 

review, the Agency analyzed compliance monitoring sample results provided by 47 states/primacy 

agencies collected between January 1998 and December 2005.

According to the most recent occurrence data, DEHA was detected in only 0.6 percent (759 out of 

almost 122,000) of the samples collected between 1998 and 2005. [FN3: Six- year review 2 contaminant 

occurrence data; available at 

http://water.epa.gov/lawsregs/rulesregs/regulatingcontaminants/sixyearreview/sixyearoccurenecdata/ind

ex.cfm.] More than half of the detections (440 out of 759) occurred in drinking water supplies for 

populations of less than 1,000 people. A majority of the samples (about 400) were below 1 μg/L.

These monitoring data do not support the Agency’s finding that “a substantial population” may be 

exposed to DEHA in sources of drinking water, as required by Section 1457 of the SDWA for inclusion 

in the EDSP. The data collected from around the country over a 7- year period suggest, on the contrary, 

that drinking water exposure to DEHA is quite rare. Therefore, DEHA does not meet the statutory 

criteria for inclusion in the EDSP.
EPA-OGWDW Final EDSP List 2 February 2013

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Page 389

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements. Also, please see general response to comment under EPA Comment Code: 1060 SDWA 

1457.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 1

EPA Comment Code: 2080

Comment: January 13, 2011

EPA Document Control Office (7407M)

Office of Pollution Prevention & Toxics

Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, D.C. 20460

RE: Comments of The Dow Chemical Company on "Endocrine Disruption Screening Program: Second 

List of Chemicals for Tier I Screening" [75 FR 70248; 11/17/2010; EPA-HQ- OPPT-2009-0477; FRL8848-7], specifically concerning 1,2-dichloropropane .

Dear Sir, Madame,

The Dow Chemical Company (Dow) is a processor of 1,2-dichloropropane, (PDC, CASRN 78-87-5) in 

the US . Dow has a strong product stewardship program in place, which includes evaluation of potential 

risk from production, handling, and use of its products, processes, and by-products over their lifecycle. 

As a major processor of PDC, Dow has participated in several efforts to gather, summarize, evaluate, 

and supplement available data to support development of risk assessments for chemicals such as PDC. 

Thus, Dow has a long history of providing and reviewing data to determine the potential hazards and 

risks of PDC.

EPA should drop PDC from this rulemaking. Based on the weight-of-evidence, and particularly in 

keeping with both Dow's and EPA's principle of reducing unnecessary animal testing, Dow strongly 

recommends that propylene dichloride (PDC) be removed from the list of proposed substances to be 

tested for Tier 1 screening under the Endocrine Disruption Screening Program (EDSP). This 

recommendation is based on a variety of facts, including the following:

1) EPA nominated PDC for regulation due to its listing under a drinking water statute. However, 

exposure to this substance via drinking water is not likely to occur for a significant human population in 

the U.S . Emissions to surface waters, according to reporting year 2009 TRI data, totaled 1,057 lbs. 

These emissions occur primarily to surface waters which are known to have water quality attributes (e.g, 

saline or estuarine) that are unsuitable for use as a source for drinking water. And although PDC has 

been identified as a groundwater contaminant, these occurrences are typically associated with regulated 

industrial sites upon which drinking water wells cannot be located. Moreover, recent analyses of 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 390

groundwater by the US Geological Survey report the large majority (1911 out of 1926 total samples) 

contain no detectable PDC (Moran et al., 2002).

Response: This action is not rulemaking. Please see general response to comment under EPA Comment 

Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not 

Meet SDWA 1457 Requirements.

Commenter Name: Jean Kasakevich

Commenter Organization: Dow Chemical Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0058

Comment Part: 3

EPA Comment Code: 2080

Comment: For all these reasons, PDC is very far from being a good candidate for this rulemaking.

Details supporting each of these lines of evidence are provided below:

1) The second list of substances proposed for endocrine screening is presumed to be based on potential 

for exposure to these substances as a result of their occurrence as drinking water contaminants. The 

potential for PDC to occur as a drinking water contaminant can be indicated from the magnitude and 

spatial distribution of surface water emissions, as reported within the Toxics Release Inventory (TRI) 

program. Data for reporting year 2009 indicate a total of 1,057 lbs. was emitted to surface waters, with 

the following geographic distribution:

* 3601bs. The Dow Chemical Company, Plaquemine, LA (lower end of the Mississippi River)

* 515 lbs. The Dow Chemical Company, Freeport, TX (Brazos River)

* 191bs. Shipyard, Channelview, TX (Houston Ship Channel)

* 1601bs. Hercules, Courtland, VA (Chesapeake Bay)

* 3 lbs ICL-IP AMERICA INC., Gallipolis Ferry, WV (Ohio River)

With the exception of the last reported emissions (3 lb), each of these is not expected to be associated 

with a surface water body which is used as drinking water source. For example, the lower Mississippi 

River, e.g., at Plaquemine, LA, is impacted by heavy industry, and water quality parameters are unsuited 

for use as a drinking water source. The Brazos River, Houston Ship Channel, and Chesapeake Bay are 

impacted by salinity, which makes them unsuitable sources of drinking water. Based on these reported 

emissions to surface waters from TRI, it can be concluded that a significant human population is not 

exposed to PDC as a contaminant in drinking water.

While there were old data that indicated PDC was present in drinking water sources, these data were 

generated over two decades ago and the exposure potential has changed markedly during this time. As 

described in the OECD SIDS SIAR document, "Monitoring data from wells and surface water in the US 

and in the EU have demonstrated the presence of PDC in from 1-50% of samples tested (IPCS, 1993). 

Where detectable, the concentrations have ranged from 0 .1 [μg/1 up to 440 [μg/1, with most studies 

reporting maximum levels of <50 [μg/1. These data were published mostly from the late 1980's, just 

after the soil fumigant use of PDC was discontinued. Recent analyses of groundwater by the US 

Geological Survey for the period 1986-1999 point to concentrations in the range <0.2-19.4 [μg/1, with 

the large majority (1911 out of 1926 total samples) containing no detectable PDC (limit of detection 0 .2 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 391

[μg/1) (Moran et al., 2002) . Analyzed concentrations in 13 of the 15 `positive' samples were in a range 

0.2-5.0 [μg/1, and >5 [μg/1 for the remaining two samples." (OECD, 2006).

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Fred Marashi

Commenter Organization: Chevron Phillips Chemical Company LP (CPChem)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0062

Comment Part: 1

EPA Comment Code: 2080

Comment: January 13, 2011 

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, N.W.

Washington, DC. 20460

Attention: Docket ID Number EPA-HQ-OPPT-2009-0477

Re: Comments on "Endocrine Disruptor Screening Program

(EDSP); Second List of Chemicals for Tier 1 Screening"

Dear Sir/Madam,

Chevron Phillips Chemical Company LP (CPChem) has been a major contributor in the success of the 

High Production Volume (HPV) testing program. Product stewardship is a corner stone to our 

company's commercial success and we strongly support sound scientific research to assess the effects of 

our products on human health and the environment.

CPChem is submitting the following two comments in reference to the proposed testing of pDichlorobenzene (CAS# 106-46-7) for endocrine disruptor activities as published in FR Vol. 75, No 

221, pp 70248-54, November 17, 2010.

We would like to submit to EPA that 1,4-dichlorobenzene (p-DCB) is transported under highly 

controlled conditions to our manufacturing sites where the material is used as intermediate in the 

manufacture of our Ryton® brand polyphenylene sulfide polymer. The polymer is further compounded 

for molding or extrusion by our customers in the manufacture of articles used as parts in automobiles, 

electronics, small appliances, etc. The maximum quantity of p-DCB that is extractable from the polymer 

under extreme conditions of reflux extraction with absolute ethanol for 8 hours have been determined to 

be below the detection limit of 0.1+/- 0 .052 ppm . Additionally, it is not expected for p-DCB to be 

release from the manufactured articles during normal use or during recycling or disposal of the articles. 

Therefore, it is highly unlikely that commercial activities associated with polymer manufacturing would 

be source for groundwater or drinking water contamination by p-DCB. On this ground we encourage 

that EPA limits its applicability of the test rule to uses of p-DCB in commercial activities that are more 

likely sources for drinking water contamination than polymer manufacturing.
EPA-OGWDW Final EDSP List 2 February 2013

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Page 392

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements. Please also see Endocrine Disruptor Screening Program; Final Policies and Procedures 

for Screening Safe Drinking Water Act Chemicals (USEPA, 2012a) that is being published 

simultaneously with this comment response document.

Commenter Name: Dru Ann Toman

Commenter Organization: Union Carbide Corporation (UCC), a subsidiary of The Dow Chemical 

Company (DOW)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0065

Comment Part: 1

EPA Comment Code: 2080

Comment: Union Carbide Corporation (UCC) appreciates the opportunity to submit comments on 

EPA’s Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the 

“Draft EDSP List 2”). Pursuant to EPA’s request for comments on the Draft EDSP List 2, 75 Fed. Reg. 

70248; 11/17/2010, (the “Listing Notice”), these comments are specific to the listing of Acrolein (CAS 

No: 107-02-8) and to the intention to issue the test rule to Acrolein manufacturers. 

January 17, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency

1200 Pennsylvania Ave., N.W.

Washington, D.C. 20460-0001

Re: Comments on "Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1

Screening" [75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] and the listing of

Acrolein (CAS No: 107-02-8)

Dear Sir/ Madam:

Union Carbide Corporation (UCC), a subsidiary of The Dow Chemical Company, appreciates the 

opportunity to submit comments on EPA's Endocrine Disruptor Screening Program: Second List of 

Chemicals for Tier 1 Screening (the "Draft EDSP List 2"). Pursuant to EPA's request for comments on 

the Draft EDSP List 2, 75 Fed. Reg. 70248; 11117/2010, (the "Listing Notice"), these comments are 

specific to the listing of Acrolein (CAS No: 107-02-8) and to the intention to issue the test rule to 

Acrolein manufacturers. Please do not hesitate to contact me should you require additional 

information/clarification on any of the provided comments. I can be reached by phone at 732-563-5678 

or by e-mail at tomanda@dow.com.

Sincerely,

Dru Ann Toman

EHS Global Product Leader

Performance Materials
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 393

The Dow Chemical Company

Attachment: Comments of Union Carbide Corporation on "Endocrine Disruptor Screening Program:

Second List of Chemicals for Tier 1 Screening" [75 FR 70248; 11117/2010; EPA-HQ-OPPT-2009-

0477;

FRL-8848-7] and the listing of Acrolein (CAS No: 107-02-8).

Comments of Union Carbide Corporation

"Endocrine Disruptor Screening Program: Second List of Chemicals for Tier l Screening"

[75 FR 70248; 11/17/2010; EPA-HQ-OPPT-2009-0477; FRL-8848-7] and the listing of Acrolein (CAS 

No: l 07-02-8)

Union Carbide Corporation (UCC) appreciates the opportunity to submit comments on EPA's Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the "Draft EDSP List 2"). 

Pursuant to EPA's request for comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 11117/2010, 

(the "Listing Notice"), these comments are specific to the listing of Acrolein (CAS No: 107-02-8) and to 

the intention to issue the test rule to Acrolein manufacturers.

I. Acrolein's presence on the Contaminant Candidate List 3 (CCL3) list does not meet the criteria of the 

endocrine amendments to the Safe Drinking Water Act (SDWA) that a substance "may be found in 

sources of drinking water" and a "substantial population" has been exposed. EPA should therefore 

exclude Acrolein from this rulemaking.

I. Acrolein's presence on the Contaminant Candidate List 3 (CCL3) list does not meet the criteria of the 

endocrine amendments to the Safe Drinking Water Act (SDWA) that a substance "may be found in 

sources of drinking water" and a "substantial population" has been exposed. EPA should therefore 

exclude Acrolein from this rulemaking.

Acrolein (CAS No: 107-02-8) has been included in the second list of chemicals to undergo screening for 

endocrine-mediated toxicity under the EPA EDSP. Acrolein has been included in this list due to its 

presence on the SDWA CCL3 list and the existence of a current pesticide registration 

(http://www.epa.gov/endo/pubs/prioritysetting/draftlist2.htm).

EPA has described its process for prioritizing chemicals for EDSP List 2 and assumes that a chemical on 

CCL3 list per se meets the 1996 endocrine amendments to the SDWA that a substance "may be found in 

sources of drinking water" and a "substantial population" has been exposed. UCC respectfully disagrees.

The CCL3 Contaminant Information Sheet for Acrolein reports that acrolein was detected at 2 of 1,108 

Public Water Systems and sampled at 1.3-3.4 ug/L. This would not be considered exposure to a 

"substantial population."

The 2009 TRI reports 134lbs on site water release for the entire U.S. Previous TRI reported releases to 

surface water:

2008 - 134 lbs

2007- l lb.
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2006- 1 lb

2005 - 234 lbs

2004 –l lb

This is not exposure to a substantial population.

The World Health Organization Concise International Chemical Assessment Document (CICAD) 43 for 

Acrolein (www.who.int/ipcs/publications/en/cicad/43) notes that Acrolein was not detected in 2 surveys 

of drinking water supplies in Canada with detection limits of <0.1 and 1.0-2.5 ug/L respectively.

Per the ATSDR Toxicological profile for Acrolein, (http://www.atsdr.cdc.gov/toxprofiles/TP), there are 

no data to indicate that acrolein is a contaminant of drinking water supplies. The general population is 

reported to be exposed to acrolein through inhalation of contaminated air such as in parking garages and 

heavy traffic, inhalation of cigarette smoke and through ingestion of certain foods.

Even if there were some small level of exposure to a broader population (which there apparently is not), 

the levels that have been reported would be far below anticipated safe exposure levels. 

For example:

Long-term toxicity testing of acrolein indicates no carcinogenic potential in studies up to 2.5 mg/kg/day 

in rats (Parent et al., 1992) and 4.5 mg/kg/day in mice (Parent et al., 1991); IARC has classified it as 

Category 3 (IARC, 1995). No significant findings were noted in a one-year oral toxicity study in dogs; 

the highest dose level tested in this study was 2.0 mg/kg/day (Parent et al., 1993). Thus, the oral 

NOAEL for acrolein is at least 2.0 mg/kg/day.

Based on the aforementioned NOAEL of 2.0 mg/kg x day the resulting drinking water level of concern 

would be 60 mg/L water. This value is based on the following assumptions:

1) 60 kg body weight for an individual

2) 2 L of water consumed per day

60 mg/L water is substantially more than concentrations reported above in water (range of <0.1 to 2.5 

ug/L). Note that the level of concern is expressed in milligrams per liter, while the quantities detected 

are expressed in micrograms per liter. This provides more than a thousand-fold safety factor, indicating 

that the resulting risk from consumption of water is de minimis.

Exposure to acrolein through drinking water sources is trivial in relation to other widespread sources of 

exposure which are not associated with manufacture or processing of acrolein

If the basis for selection of EDSP List 2 chemicals is its presence in drinking water, then there should be 

a correlation between the public's exposure to substance and it's presence in drinking water. Even if 

manufacture of acrolein were discontinued, the primary exposure sources to the general population 

would see little if any reduction.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.
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Commenter Name: Jack Snyder

Commenter Organization: Styrene Information and Research Center (SIRC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0067

Comment Part: 2

EPA Comment Code: 2080

Comment: 2. Styrene should be removed from List 2 of chemicals for Tier 1 testing as it does not meet 

EPA’s stated criteria for List 2.

List 2 of chemicals is claimed to be an examination of chemicals found in drinking water. There are 

extensive analyses of drinking water that include assays for styrene. Styrene is not found in drinking 

water in the U.S. at any appreciably detectable level. Therefore, styrene does not meet the criteria for 

inclusion on List 2.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Sherman Friedman

Commenter Organization: Velsicol Chemical LLC (Velsicol)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0068

Comment Part: 13

EPA Comment Code: 2080

Comment: C. Hex is Not Found in Sources of Drinking Water to Which a Substantial Population is 

Exposed 

EPA's recent review of existing drinking water standards demonstrated Hex is not found in sources of 

drinking water to which a substantial population is exposed. [FN19: EPA, National Primary Drinking 

Water Regulations; Announcement of the Results of EPA's Review of Existing Drinking Water 

Standards and Request for Public Comment and/or Information on Related Issues. 75 Fed. Reg. 15500, 

March, 29, 2010 (the "DWS Review”). The DWS Review reports 2009 EPA Occurrence Data reported 

at: EPA, Office of Water, The Analysis of Regulated Contaminant Occurrence Data from Public Water 

Systems in Support of the Second Six Year Review of National Primary Drinking Water Regulation, 

October 2009, 13PA- 815-B-09-006 ("Occurrence Data Report”).] EPA reported in the DWS Review 

that, none of the reporting water systems (serving 184,738,000 people) reported the presence of Hex in 

drinking water, when setting nondetect results equal to zero. Evaluating this occurrence data, EPA 

determined that because of the low occurrence of Hex in drinking water, it would not revise the 

NPDWR for Hex. DWS Review at 15548-49. 

The Occurrence Data Report, upon which EPA's DWS Review is based, summarizes the results of 

135,290 analyses for Hex reported by drinking water systems. Hex was reported in only 376 of 135,290 

analyses (.278%). Occurrence Data Report, Appendix A42 at 320-325. It is important to note, however, 

that there were no detections of Hex at even one-half of its MCL (the MCL for Hex is 50ppb or 

0.05mg/1) and virtually all the reported "detections" were below the Method Detection Level (MDL) of 

1.0 ppb for Hex. 
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Velsicol believes one problem with the Occurrence Data Report is EPA’s treatment of non-detects. 

Rather than reporting non-detects as submitted by the states, EPA substituted other, non-zero values. 

EPA stated:

The Six-Year Review Stage l non-parametric analyses are not affected by how non-detections are 

recorded. However, to estimate mean contaminant concentration values for each system in the Stage 2 

analyses, a non-zero MRL numeric value must replace all ar1alytical results that were repot1ed either as 

zero, "non-detection," "ND," etc. Similar to replacing missing MRL data above, a convention was 

developed to replace any non-numeric non-detection results from a particular system using the modal 

MRL value for the state in which the system was located. If a state reported no MRL data, the nonnumeric values were replaced with the national modal MRL, derived as the mode of all state modal 

MRL values reported for that contaminant. 

Occurrence Data Report at 15. EPA utilizes a MRL (Minimum Reporting Level) of 0.1 ppb for Hex and 

a MDL (Method Detection Level) of l.0 ppb. 

EPA should consider the description of "limits” by the USGS: 

Recognizing the inadequacies of the MDL as a reporting level, laboratories often set quantification 

limits (operationally minimum reporting levels) at concentrations greater than the determined MDL's 

and in a region that supports quantitative determination. For example, the reporting levels might be set at 

practical quantitation limits (PQL's) that are 5 or 10 times the MDL (U.S. Environmental Protection 

Agency, 1985), or at the limit of quantitation (LOQ), which is a concentration 10 standard deviation 

units above the average blank response (Keith, 1992). More recently, the USEPA has suggested the use 

of a minimum level (ML), which is 3.18 times the MOL (for n = 7) (U.S. Environmental Protection 

Agency, I 993). Gibbons and others (1997a, b) recommend use of an alternative minimum level (AML) 

that is derived from a multiple concentration calibration procedure that eliminates or minimizes many of 

the assumptions and limitations of the USEPA MDL and ML procedures.

USGS website: http://water.usgs.gov/owg/OFR 99-193/level.html.

Consistent with the USGS reasoning, the PQL for Hex should be 5 to 10 times its MDL, or 5 to 10 ppb. 

The Occurrence Data Report demonstrated that Hex values exceeded this PQL in only three instances -

one reported value barely exceed the MDL and the two others were 10pbb and 15ppb. In all other 

instances, reported Hex concentrations in drinking water were below the MDL. Despite these three 

levels reported to exceed the MDL, Velsicol believes it is likely there were no detections of Hex in any 

of the analyzed samples and that reported "detects" are the results of artifacts related to reporting 

detection limits. For example, South Carolina reported 10ppb for Hex. But it also reported minimum, 

maximum and mean detection levels of 10 ppb. It is unclear what any of this means. Unfortunately, EPA 

did not critically review the reported data and it has not provided the underlying data for outside review. 

Therefore, we are unable to assess the quality of the data to determine whether the few values reported 

to exceed the MDL are reporting artifacts. Generally, as we discuss in Comment 1 above, EPA should 

be mindful of all the limitations of the Occurrence database and other sources of data. Those factors 

should be taken into account when assess Occurrence and other data concerning Hex in drinking water. 

It is also important to consider that a typical problem in the analysis for Hex is the choice of analytical 

equipment. Many water suppliers use electron capture gas chromatography (ECGC) to analyze water 

samples. While ECGC is very sensitive and can generate data in the sub-ppb range, it is not specific and 
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Page 397

typically fails to identify the actual concentrations of individual substances. Therefore, ECGC often 

results in false positive results for a particular substance. Other water suppliers may utilize mass 

spectrometer gas chromatography (MSGC), which is very specific but not very sensitive. Because of the 

cost of MSGC, analyses are likely more often conducted with ECGS, resulting in a high rate of false 

positives. For this reason, Velsicol believes it is likely the few positive results for Hex are false 

positives. Again, because EPA did not critically review the reported data and consider the likelihood of 

false positive results, and because it has not provided the underlying data for outside review, it is not 

possible to fully assess the quality of the data to determine whether the few values reported to exceed the 

MDL are analytical artifacts. In any event, even if the few repotted value exceeding the MDL are not 

artifacts, which they likely are, they would not demonstrate Hex may be found in sources of drinking 

water to which a substantial population are exposed.

Finally, EPA should consider the 1997 European Union risk assessment report for Hex. [FN20: 

European Union Risk Assessment Report: hexachlorocyclopentadiene, Risk Assessment, July 2007 (" 

EU Hex Risk Assessment")] Using the European System for the Evaluation of Substances (EUSES), the 

EU Hex Risk Assessment report estimated the concentration of Hex in drinking water as 1.37 x10-8 

mg/l. EU Hex Risk Assessment at 64. The report concluded, concerning human exposures to Hex via the 

environment: "There is at present no need for further information and/or testing and no need for risk 

reduction measures beyond those which are being applied already." EU Hex Risk Assessment at VIII. It 

is important to note that the EU Hex Risk Assessment report estimates values of Hex in drinking water 

orders of magnitude below the MDL for Hex (and the MDL for Hex is 50 times lower than EPA's 

drinking water standard for Hex). Velsicol believes the EU Hex Risk Assessment supports the 

conclusion that Hex is not found in sources of drinking water to which a substantial population may be 

exposed.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 8

EPA Comment Code: 2080

Comment: The data demonstrate that ETU is only rarely found in drinking water, therefore ETU does 

not meet the criteria that a “substantial population has been exposed”:

EPA issued Reregistration Eligibility Decisions (REDs) for the EBDCs mancozeb and metiram in 2005. 

In the REDs, EPA concluded that “estimate concentrations of ETU for both surface and ground water, 

are low and not of concern”. (see for example, Mancozeb, introductory page x.)

The RED states that not ETU was found in treated samples from groundwater.

Specificially:

A groundwater EDWC was selected from a targeted monitoring study conducted in 2001 to 2003 in 

seven states chosen to represent high historic use areas in the US. Based on the monitoring results, the 
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Page 398

highest measured value in a public drinking water well was 0.210 ppb of ETU. In this study, ETU was 

not detected in any of the treated community drinking water sampled from the monitored 84 sites even 

when it was detected in the raw water. The absence of ETU in potable water from community water 

supplies may be related to its rapid degradation resulting from aeration and chemical treatment. (ibid. 

page 23, emphasis added)

Similarly, for surface water, “none of the tested surface water samples had concentrations of the limit of 

detection of 0.1 ppb”. (ibid. page 22)

The data demonstrate that there is no drinking water exposure to ETU of any note. Therefore ETU does 

not meet the criteria that a substantial population may be exposed”,

Based on this analysis, ETU does not meet the criteria EPA has forward regarding drinking water 

exposure and that ETU be removed from List 2.

Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants 

with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 

Requirements.
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EPA Comment Code: 2090 Contaminants with MCLG of Zero

General Response: EPA acknowledges that some of the regulated drinking water contaminants on the 

second EDSP list currently have an established maximum contaminant level goal (MCLG) of zero and a 

maximum contaminant level (MCL) set as close to the MCLG as feasible. EPA recognizes that it may 

not be possible to set more stringent levels for some of these chemicals at this time. However, it is 

important to note that most of the chemicals with MCLGs of zero are based on chronic health endpoints 

and compounds with endocrine disrupting effects can be subchronic. It is important to understand 

whether a chemical might be an endocrine disruptor with subchronic impacts since this may inform the 

agency’s risk assessment and how best to address this contaminant from a regulatory standpoint. In 

addition, if endocrine effects occur at a level lower than the current MCL, the agency might consider 

whether improvements in analytical feasibility can measure at the level of endocrine effects. See general 

response to comment under EPA Comment Code: 1070 Increased Transparency for more information.

Please also see general response to comment under EPA Comment Code: 2020 Contaminants No 

Longer Manufactured or Imported, or Used in the US, also Includes Pesticides with Cancelled 

Registrations. 

Individual Comments

Commenter Name: Thomas Curtis

Commenter Organization: American Water Works Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0028

Comment Part: 2

EPA Comment Code: 2090

Comment: We agree that the SDWA is a good place to start; however, one might question the necessity 

of expending resources on screening a chemical (at least under SDWA) if that chemical has been 

classified as a human carcinogen with a Maximum Contaminant Level Goal (MCLG) of zero. In these 

cases, the Maximum Contaminant Level (MCL) is already set as close to the MCLG as is practical, and 

screening is not likely to add any health effects information that would result in a lower MCL. If the 

MCL is based on a threshold concentration and the original health risk assessment included endocrine 

effects, then endocrine screening may not add any useful information to the compound’s health effects 

database. Again, the compound should not be on the screening list. The only time a compound with a 

threshold MCL should be on the list is when endocrine health effects were not adequately considered in 

the establishment of the MCL (e.g., data did not exist at the time or the data were deemed 

unsatisfactory).

Response: Please see general response under EPA Comment Code: 2090 Contaminants with MCLG of 

Zero.

Commenter Name: Peter Voytek

Commenter Organization: HAP Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0034
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Page 400

Comment Part: 5

EPA Comment Code: 2090

Comment: D. Available Health Effects Information Does Not Support Including 1,1,2-Trichloroethane 

and EDC on Second List

Both 1,1,2-trichloroethane and EDC are already regulated as drinking water contaminants with MCLs of 

5 parts per billion (ppb). The MCLG for 1, 1, 2-trichloroethane is 3 ppb, while the MCLG for EDC is 

zero. The SDWA requires the MCL of a contaminant in water delivered to a user of a public water 

system to be "as close to the maximum contaminant level goal as is feasible." SDWA § 1412(b)(4)(B). 

The MCLG, in turn, must be "set at the level at which no known or anticipated effects on the health of 

persons occur and which allows an adequate margin of safety."[FN10: SDWA § 1412(b)(4); 42 U.S.C. § 

300g-1(b)(4).] Where available treatment technology can reliably remove a contaminant to levels below 

the MCLG, it is feasible to set the MCL equal to the MCLG. As EPA has recognized, however, "[f]or 

contaminants with MCLGs at zero (substances in Group A or B), the analysis is somewhat different 

because detection and achievement of zero concentration in principle cannot be achieved. In the MCLsetting process, therefore, EPA evaluates the feasibility of achieving levels as close to zero as feasible." 

52 Fed. Reg. 25690, 25699 (July 8, 1987). "Feasible" is defined as "feasible with the use of the best 

technology, treatment techniques, and other means, which the Administrator finds, after examination for 

efficacy under field conditions and not solely under laboratory conditions, are available (taking costs 

into consideration)." [FN11: SDWA § 1412(b)(5); 42 U.S.C. § 300g-1(b)(5). For present purposes, the 3 

ppb MCLG for 1,1,2-trichloroethane may be viewed as equivalent, in practical effect, to the zero MCLG 

for EDC, as feasibility is the sole constraint on a lower MCL in each case.] 

In simplest terms, EPA already has a mandate to establish an enforceable MCL for 1,1,2-trichloroethane 

and EDC as close as possible to 3 ppb and zero, respectively. It is inconceivable that the results of EDSP 

screening would drive the MCL lower. Both 1,1,2-trichloroethane and EDC have much simpler 

structures than the natural more complex steroid, amine, and peptide hormones, and have very different 

chemical/physical properties. Since the receptor site-hormone binding potency depends on very specific 

structures and chemical/physical properties, and the properties of 1,1,2-trichloroethane and EDC are so 

different from the natural hormones, it is highly unlikely that either compound would have any 

significant effects on binding to any hormone receptors or interfere with the binding of natural 

hormones.

Moreover, the results of the testing required by EPA for 1,1,2-trichloroethane, and comparable available 

test data for EDC, establish that neither is likely to evidence endocrine effects.

Response: Please see general response under EPA Comment Code: 2090 Contaminants with MCLG of 

Zero.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 6

EPA Comment Code: 2090

Comment: D. Available Health Effects Information Does Not Support Including VDC and
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Page 401

Methylene Chloride on the Second List

Both VDC and methylene chloride are already regulated as drinking water contaminants with MCLs of 

7 parts per billion (ppb) and 5 ppb respectively. The MCLG for VDC is also 7 ppb, while the MCLG for 

methylene chloride is zero. The SDWA requires the MCL of a contaminant in water delivered to a user 

of a public water system to be "as close to the maximum contaminant level goal as is feasible." SDWA § 

1412(b)(4)(B). The MCLG, in turn, must be “set at the level at which no known or anticipated effects on 

the health of persons occur and which allows an adequate margin of safety."12 [FN12: SDWA § 

1412(b)(4); 42 U.S.C. § 300g-l(b)(4).] Where available treatment technology can reliably remove a 

contaminant to levels below the MCLG, it is feasible to set the MCL equal to the MCLG. As EPA has 

recognized, however, "[f]or contaminants with MCLGs at zero (substances in Group A or B), the 

analysis is somewhat different because detection and achievement of zero concentration in principle 

cannot be achieved. In the MCL-setting process, therefore, EPA evaluates the feasibility of achieving 

levels as close to zero as feasible." 52 Fed. Reg. 25690, 25699 (July 8, 1987). "Feasible" is defined as 

"feasible with the use of the best technology, treatment techniques, and other means, which the 

Administrator finds, after examination for efficacy under field conditions and not solely under 

laboratory conditions, are available (taking costs into consideration)."[FN#13: SDWA § 1412(b)(5); 42 

U.S.C. § 300g-l(b)(5). For present purposes, the 7 ppb MCLG for VDC may be viewed as equivalent, in 

practical effect, to the zero MCLG for methylene chloride, as feasibility is the sole constraint on a lower 

MCLin each case. Each of the other compounds addressed in these comments also has an MCLG of 

zero, so that the MCLs are already constrained only by feasibility. 

EPA already has a mandate to establish an enforceable MCL for VDC and methylene chloride as close 

as possible to 7 ppb and zero, respectively. It is inconceivable that the results of EDSP screening would 

drive the MCLs lower.

Moreover, available test data for VDC and methylene chloride establish that neither is likely to evidence 

endocrine effects.

Response: Please see general response to comment under EPA Comment Code: 2090 Contaminants 

with MCLG of Zero.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 9

EPA Comment Code: 2090

Comment: E. Trichloroethylene and Tetrachloroethylene Also Should be Removed from the Second 

List

Trichloroethylene and tetrachloroethylene are important solvents used in a variety of industrial and 

commercial applications. HSIA has not had an opportunity, in the limited time available, to review the 

exhaustive body of health effects information relevant to these compounds (and carbon tetrachloride, 

discussed above) and endocrine effects. Nevertheless, there is a compelling reason that they should be 

removed from the second list. 
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Page 402

EPA recently determined, after a review of the existing National Primary Drinking Water Regulations, 

that the MCLs for trichloroethylene and tetrachloroethylene are candidates for revision. [FN22: 75 Fed. 

Reg. 15499, 15558, 15565.] EPA established a practical quantification level (PQL), the lowest level that 

can be reliably measured, of 1 ppb for these compounds, and an estimated quantitation level (EQL) of 

0.5 ppb. HSIA has questioned the basis for these levels, but nevertheless they are the basis for EPA's 

consideration of revised MCLs in a range between 0.5 and 5 ppb. Specifically, EPA concluded: "The 

Agency's review indicates that analytical feasibility could be as much as 10 times lower (~ 0.0005 mg/L) 

and occurrence at this level appears to be relatively widespread. Hence, revisions to the 

tetrachloroethylene [and trichloroethylene] NPDWR may provide a meaningful opportunity for health 

risk reduction."[FN23: Id.]

EPA must consider the implications of this statement for any further testing of trichloroethylene and 

tetrachloroethylene. Both already have MCLGs of zero, and thus under EPA policy as described above, 

must have MCLs as close to zero as feasible. Unlike the other contaminants on the second list, EPA has 

concluded for these two that a lower MCL is feasible. It appears that an MCL of lower than 5 ppb will 

be proposed. If a lower MCL is adopted, trichloroethylene and tetrachloroethylene will be more 

stringently regulated in drinking water than virtually any other compounds, indeed, to the limit of 

feasibility. Thus, even more than for the other compounds on the second list, there is no benefit (indeed, 

no practical purpose) to require expensive, animal-intensive testing of potential effects on the endocrine 

system of these compounds.

Response: Please see general response under EPA Comment Code: 2090 Contaminants with MCLG of 

Zero.

Commenter Name: Faye Graul

Commenter Organization: Halogenated Solvents Industry Alliance, Inc.

EPA Document ID: EPA-HQ-OPPT-2009-0477-0038

Comment Part: 12

EPA Comment Code: 2090

Comment: • Requiring screening/testing for endocrine effects for methylene chloride, trichloroethylene, 

tetrachloroethylene, carbon tetrachloride, and VDC serves no purpose, as the MCLs already must be as 

close to zero (7 ppb for VDC) as feasible based on other effects and the precautionary principle. This is 

particularly the case for trichloroethylene and tetrachloroethylene, where EPA has indicated an intent to 

lower the MCLs by as much as 10-fold.

• Put another way, EPA has advanced no rationale for requiring information on the possible endocrine 

activity of chemicals whose principal toxicities have been well characterized and which are already 

restricted in drinking water to the maximum extent. 

Respectfully submitted,

Faye Graul

Executive Director

Enclosure [See PDF Docket ID: EPA-HQ-OPPT- 2009-0477-0038.1]
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Page 403

Response: Please see general response to comment under EPA Comment Code: 2090 Contaminants 

with MCLG of Zero.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 1

EPA Comment Code: 2090

Comment: Please find comments from the North American Polyelectrolyte Producers Association 

(NAPPA) regarding the inclusion of Acrylamide (CAS No. 79-06-1) in the “Endocrine Disruptor 

Screening Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPAHQ-OPPT-2009-0477] attached. 

January 18, 2011 

Document Control Office (7407M) 

Office of Pollution Prevention & Toxics 

Environmental Protection Agency 

1200 Pennsylvania Avenue, NW 

Washington, DC 20460 

RE: Comments on Inclusion of Acrylamide (CAS No. 79-06-1) in “Endocrine Disruptor Screening 

Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA-HQ-OPPT2009-0477] 

Dear Sir or Madam: 

The North American Polyelectrolyte Producers Association (NAPPA)[FN1: Current members of 

NAPPA include Ashland Inc., BASF, Kemira Water Solutions, Inc., and Nalco Company.] provides the 

attached comments on the US Environmental Protection Agency’s (EPA) announcement of a second list 

of chemicals and substances for which EPA intends to issue test orders under the Endocrine Disruptor 

Screening Program (EDSP). The members of NAPPA are major North American manufacturers and 

importers of synthetically produced coagulants and flocculants, which are generically referred to as 

polyelectrolytes. Polyacrylamides are a significant class of these polyelectrolytes. NAPPA members 

produce polyacrylamides and also the acrylamide monomer and have been very active in the assessment 

of the toxicology of acrylamide

Acrylamide has been extensively tested and evaluated by EPA, the US Food and Drug Administration 

(FDA) and other agencies worldwide. Further, acrylamide use is highly controlled and regulated, 

including a National Primary Drinking Water Regulation (NPDWR) with a Public Health Goal (PHG) of 

zero (0). NAPPA sees little benefit to public health or the environment from the inclusion of acrylamide 

in the EDSP. Tier 1 EDSP testing of acrylamide will provide little useful additional information to the 

already extensive toxicology database available on acrylamide (which includes higher tier EDSP studies 

such as 2-generation reproductive effective studies) nor will it impact the regulation of acrylamide in 

drinking water as the current regulation already has a goal of zero acrylamide in water. In its recent IRIS 

assessment, EPA concluded that the available toxicology data on acrylamide is “robust” and includes “a 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 404

large database for reproductive effects from oral exposure to acrylamide.” This available higher-tier in 

vivo data on acrylamide should eliminate any need to conduct EDSP Tier 1 testing.

Response: Please see general responses to comment under EPA Comment Codes: 2090 Contaminants 

with MCLG of Zero and 2060 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other 

Reproductive Developmental Endpoints.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 4

EPA Comment Code: 2090

Comment: Acrylamide has been extensively tested and evaluated by EPA, the US Food and Drug 

Administration (FDA), Canada, the European Union (EU), the World Health Organization and others. 

Further, acrylamide use is highly controlled and regulated, including by a National Primary Drinking 

Water Regulation (NPDWR) with a Public Health Goal (PHG) of zero (0). As these comments will 

detail, NAPPA sees little benefit to public health or the environment from the inclusion of acrylamide in 

the EDSP. Tier 1 EDSP testing of acrylamide will provide little useful additional information to the 

already extensive toxicology database available on acrylamide (which includes higher tier EDSP studies 

such as 2-generation reproductive effective studies) nor will it impact the regulation of acrylamide in 

drinking water as the current regulation already has a goal of zero acrylamide in water. 

EPA’s sole basis for the inclusion of acrylamide in this proposed rule is the fact that it has a NPDWR. 

EPA has not, however, established that a “substantial population” is actually exposed to acrylamide in 

drinking water, which was the clear intent of Congress in directing EPA to consider chemicals in 

drinking water. In fact, NAPPA’s assessment has found that the potential for acrylamide exposure from 

drinking water is likely to be very low given existing monitoring data and the fact that EPA’s own 

technology-based (treatment technique) standard for polyacrylamides used in water treatment limits the 

potential for acrylamide contamination to extremely low levels (<0.5 ppb).

Response: Please see general responses to comment under EPA Comment Codes: 2090 Contaminants 

with MCLG of Zero and 2080 Contaminants with Low or No Comprehensive Occurrence Data and 

Therefore Do Not Meet SDWA 1457 Requirements.

Commenter Name: Andrew Jaques

Commenter Organization: North American Polyelectrolyte Producers Association

EPA Document ID: EPA-HQ-OPPT-2009-0477-0042

Comment Part: 8

EPA Comment Code: 2090

Comment: III. EDSP Testing of Acrylamide will not Assist the Agency in Developing a Revised 

NPDWR 

EPA’s position is that the testing of the substances on the EDSP second list will have the benefit of 

assisting the Agency in developing new NPDWRs, PHGs, MCLs, etc. EPA states: 
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SDWA section 1412(b)(9) requires the Agency to periodically review the existing NPDWRs and revise 

them, if appropriate. Information about the potential for endocrine disruption will assist the Agency in 

updating human health assessments, which the Agency considers in its periodic review of NPDWRs to 

ensure that they are protective of human health. 

While this position may be true for some substances on the list [FN2: NAPPA has not evaluated the 

basis for any of the other substances included in this proposal.], NAPPA does not believe that this is the 

case with acrylamide. Acrylamide has PHG of zero in drinking water, which is unlikely to change based 

on new screening level toxicology data developed under EDSP. As such, NAPPA sees little benefit to 

EPA’s regulation of acrylamide in drinking water from the data that would be generated under this 

testing program. Mandating testing that provides no real value towards the regulation of a substance was 

clearly not the intent of Congress when directing EPA to evaluate drinking water contaminants for 

possible endocrine disrupting effects. 

As discussed in the previous section, EPA’s treatment technique standard would result in a maximum 

theoretical contamination of 0.5 ppb (0.5 μg/L) from the use of polyacrylamide in treated water. In most 

cases it will likely be much less. Given that the resulting exposure from even this contamination is 

exceedingly small (<0.01 μg/kg bw/day), there again appears to be no benefit to EPA’s regulation of 

acrylamide in drinking water from this test program.

Response: Please see general responses to comment under EPA Comment Codes: 2090 Contaminants 

with MCLG of Zero.

Commenter Name: Terry F. Quill

Commenter Organization: Quill Law Group, LLC on behalf of Velsicol Chemical, LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0073

Comment Part: 3

EPA Comment Code: 2090

Comment: EPA suggested that it could use the results of EDSP testing to lower the allowable level of 

those contaminants in drinking water. Velsicol would like to clarify that chlordane and heptachlor are 

already regulated as carcinogens, and endrin is also strictly regulated due to its high toxicity. More 

specifically, chlordane and heptachlor have MCLGs of zero. Therefore, EPA should already be 

regulating these substances in drinking water to the lowest level feasible (the MCLs for those substances 

are.002 and .0004mg/l, respectively). While additional endocrine data may be interesting, it is not clear 

how they will result in greater regulation of these substances. Further, the MCLG and MCL for endrin is 

.002 mg/l. Velsicol believes that EDSP testing is unlikely to provide data that would result in more 

stringent regulation of endrin in drinking water. We ask that EPA consider this factor as well as the 

other science and regulatory issues we provided in our comments when it creates a final EDSP list 2.

Response: Please see general response under EPA Comment Code: 2090 Contaminants with MCLG of 

Zero.
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EPA Comment Code: 2100 Pesticide Registration Review Issues

General Response: The agency is working toward integrating the EDSP and the Registration Review 

program by aligning the business processes involved with the programs so that the agency no longer 

uses a fixed list approach for active ingredients. The timing of the Registration Review process would 

trigger the issuance of EDSP test orders. 

Once clearance to issue EDSP orders for future registration review chemicals is obtained, the process 

alignment will be in place to achieve simultaneous EDSP and Registration Review decisions, greatly 

enhancing efficiency for both the agency and pesticide registrants. 

While that process is in its early stages, the List 2 effort provides an opportunity to include the fiscal 

year (FY) 2007 and 2008 registration chemicals in an attempt to begin addressing the early Registration 

Review chemicals. Chemicals that are new registrations would also be addressed when those chemicals 

become due for re-evaluation under Registration Review. 

This being said, the agency undertakes a comprehensive review of each new registration and, in 

reaching its decisions regarding registration eligibility, considers a wide range of toxicity studies that 

provide information on endocrine-related effects, including: the rat 2-generation reproduction study (or 

the extended 1-generation reproduction study), mammalian subchronic bioassays (in rats and dogs), 

mammalian chronic bioassays (in rats and dogs), cancer bioassays (in rats and mice), mammalian 

prenatal developmental studies (usually in rats and rabbits), the developmental neurotoxicity study (in 

rats), fish development and reproduction studies (usually in fathead minnow and rainbow trout), avian 

reproduction studies (usually in bobwhite quail and mallard duck), and an estuarine/marine invertebrate 

life cycle study (usually in daphnid or mysid shrimp). The agency will continue to use the best available 

science, as it evolves (such as through the work on EDSP21), to assess the potential risks posed by 

pesticides and will modify its assessment methodologies, as appropriate. 

The Federal Food, Drug, and Cosmetic Act (FFDCA) provides for the testing of all pesticide active 

ingredients and pesticide inert ingredients, as well as discretionary authority to “provide for the testing 

of any other substance that may have an effect that is cumulative to an effect of a pesticide chemical if 

the Administrator determines that a substantial population may be exposed to such a substance.” 

SDWA authorizes EPA to require testing, under the FFDCA section 408(p) screening program, of any 

other substances that may be found in sources of drinking water, based on a determination that a 

substantial population may be exposed to such a substance.

Numerous reasons were provided by commenters to remove chemicals from the second list of chemicals 

for EDSP screening, e.g. low toxicity, water monitoring data available, low use rates, low/no 

concentrations in water, on an upcoming registration review schedule, low/no dietary risks and 

laboratory capacity, to name a few. These reasons are not a basis for removal of a pesticide from the 

second list of chemicals. The basic criteria for list 2 chemical selections were 1) chemicals that met the 

finding in accordance with SDWA, and/or 2) pesticides scheduled for Registration Review for FY 2007 

and 2008. The agency has elected to keep the FY 2007 and 2008 Registration Review chemicals on the 

second list consistent with our commitment to integrate the endocrine disruptor screening program into 

the Registration Review process.

While the Toxic Substances Control Act (TSCA) does not contain equivalent FFDCA or SDWA 
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language, it does contain statutory authority for the issuance of regulations requiring manufacturers 

and processors to generate data for a chemical regulated under TSCA section 4. EPA will use such 

authority to require the screening and testing of chemicals for their potential effects on the endocrine 

system if EPA is able to make the necessary findings to support such action. 

EPA was directed “to publish within 1 year of enactment a second list of no less than 100 chemicals for 

screening that includes drinking water contaminants...” but the list is not exclusively drinking water 

contaminants and the agency felt it was important to include pesticides to continue advancing the 

program.

Please also see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Individual Comments

Commenter Name: Sushma Bhatia et al.

Commenter Organization: San Francisco REACH Team

EPA Document ID: EPA-HQ-OPPT-2009-0477-0012

Comment Part: 4

EPA Comment Code: 2100

Comment: 4.0 Proposed alternate methodology to identify Tier 1 chemicals 

The chemicals mentioned in Section 2.0 serve as examples of excluded chemicals that need to be added 

to list and highlight the inadequacy of EPA’s methodology in identifying chemicals for screening. We 

propose that EPA adopt an alternate methodology to identify chemicals to screen for endocrine 

disruption concerns, as the EPA’s current approach has led to the exclusion of key chemicals. 

Specifically, we ask that EPA: 

* 4a. Add all pesticides up for registration review from 2007 to present to the second list of chemicals. 

EPA has chosen to include only pesticides that applied for registration in 2007 and 2008. The federal 

register notice does not explain why only these two years are chosen and why pesticide registration 

candidates of 2009 -2010 have been excluded. We strongly recommend adding all new pesticide 

candidates that apply for registration up until the time the revised second list is developed and published. 

* 4b. Add all pesticides up for re-registration review between now until 2013 to the second list of 

chemicals. This will allow EPA to collect Tier 1 screening data from manufacturers in advance of 

making the re-registration decision. As indicated in Section 2.0 above, Triclosan is up for re-registration 

in 2013 and some strong evidence of endocrine disruption effects has already become available for 

triclosan, however, this pesticide has been excluded. By adopting this recommendation, EPA will be 

able to act proactively to protect public health by preparing for upcoming re-registrations. In addition, 

this approach (combined with 4d) will give EPA 3 years to integrate Tier 1 screening into existing EPA 

protocols (registrations, re-registrations) for pesticide chemicals, as proposed in 4d. 

* 4c. Create a mechanism to capture non-pesticide chemicals regulated under Toxic Substances Control 

Act (TSCA) with strong evidence of (or potential for) endocrine disruption. Although Section 2.0 only 

discusses the exclusion of phthalates and BPA from the second list, there are several other examples of 

TSCA chemicals that have the potential for endocrine disruption, but, have been excluded from this list. 
EPA-OGWDW Final EDSP List 2 February 2013

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Unlike pesticide chemicals that undergo a review and approval process, many TSCA chemicals that lack 

sufficient health impact data are being used in everyday consumer products and showing up in our 

environment and our bodies. Currently, the EDSP process does not provide a way for the public to 

provide input in the development stage and request addition of TSCA chemicals of high public concern. 

By creating a mechanism for the public to propose addition of non-pesticide chemicals (based on 

production volume, high exposure among certain populations etc.) EPA will significantly restore public 

faith in the EDSP process, while signaling to the manufacturers that EPA is serious about responding to 

endocrine disruption concerns. 

* 4d. Integrate Tier 1 screening into the pesticide registration process by 2013. At this time, EPA does 

not request Tier 1 screening data from new pesticide registration candidates or perform any screening 

for endocrine disruption effects. Since existing regulatory screening and testing schemes do not address 

endocrine disrupting mechanisms, integration of Tier 1 screening into the pesticide registration process 

will ensure that no new pesticide chemicals with these types of effects are allowed to enter the market 

OR at the very least ensure that data is available to assess potential risks due to proliferation of the new 

pesticide. Although EPA states that “testing will eventually be expanded to cover all pesticide 

chemicals,” no timeline for expansion or methodology is clear. In order to proactively prevent new 

EDCs from entering commerce, we recommend that EPA require Tier 1 screening data in all new

pesticide registration applications. 

If EPA chooses to adopt recommendations 4a-4d above, starting 2013, all new pesticide registration 

candidates will include Tier 1 screening results in their application, so new Tier 1 screening chemicals 

need only include pesticide re-registration candidates and TSCA chemicals of high concern only. 

The changes proposed here will allow EPA to take full advantage of the opportunity presented by the 

EDSP to exercise leadership and prevent introduction of new chemicals with endocrine disrupting 

properties into our environment and, subsequently, our bodies. By taking action to strengthen the EDSP, 

EPA will help protect the public health of our communities in the present and safeguard future 

generations.

If you have any questions about our comments, please contact Sushma D. Bhatia at (415) 355.3758. 

Sincerely, 

San Francisco REACH Team[FN56: Reach the Decision Makers (Reach), a project of the UCSF 

Program on Reproductive Health and the Environment, is an innovative science and policy training 

program that works to increase the number of scientists, community-based leaders, public health 

professionals and health care providers who are actively involved in informing the US Environmental 

Protection Agency (USEPA) of current and relevant scientific findings impacting their decisions in 

setting policy.]

Connie Engel, Francisco Meza, Kimberly Irish, Shira Rutman, Sushma Dhulipala Bhatia

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: John Jachetta

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0014
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Comment Part: 1

EPA Comment Code: 2100

Comment: Dow AgroSciences LLC is providing specific comments regarding inclusion of picloram on 

"Draft Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening, 75 Fed. 

Reg. 70248; 11/17/2010.

January 7, 2011

Document Control Office (7407M)

Office of Pollution Prevention and Toxics (OPPT)

U.S. Environmental Protection Agency

One Potomac Yard

2777 S. Crystal Drive

Arlington, VA 22202

Docket ID number EPA-HQ-OPPT-2009-0477

Endocrine Disruptor Screening Program (EDSP)

Dow AgroSciences LLC (DAS) appreciates the opportunity to submit comments on EPA's Endocrine 

Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening (the "Draft EDSP List 2"). 

Pursuant to EPA's request for comments on the Draft EDSP List 2, 75 Fed. Reg. 70248; 11/17/2010, 

DAS is providing specific comments regarding the inclusion of picloram on List 2 at this early date.

Picloram is schedule to enter Registration Review in 2014 and we believe that for the reasons discussed 

below, that the Agency's resources would be conserved by using Registration Review as the vehicle for 

assessment for Tier 1 EDSP screening. EPA has previously addressed the timing of chemicals for the 

program in their document entitled "Response to Comments on the draft List of Initial Pesticide Active 

Ingredients and Pesticide Inert Ingredients to be Screened under the Federal Food, Drug, and Cosmetic 

Act”. In that text, EPA stated: “ While the initial group of pesticide active ingredients were selected for 

EDSP Tier 1 screening based on an analysis of exposure potential, EPA generally intends that the 

remaining active ingredients will be screened based on their schedule for docket opening in the 

registration review program.” [72 FR 33486, June 18, 2007 (FRL-8129-3)]. DAS agrees with the stated 

EPA position that there is value in aligning the issuance of test orders under EDSP with the opening of 

the active ingredient's registration review dockets; we believe this will contribute to efficiencies and 

coordinated resolution of technical and regulatory issues associated with the EDSP.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Cindy Loy

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0015

Comment Part: 2

EPA Comment Code: 2100

Comment: As a general comment, DAS respectfully requests that pesticides on the Draft EDSP List 2, 

due to their registration review schedule of FY 2007/2008, be removed and rescheduled at a later date to 
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reduce the burden on the pesticide industry at this time. Listing these pesticides now comes very late in 

the registration review process and, therefore, has the potential to disrupt that process for these 

pesticides. If the 28 pesticides scheduled for registration review in FY 2007 or FY 2008, including 

flumetsulam, were removed from List 2 and deferred to a later date, the congressional request in the 

House appropriations language would still be honored, with over 100 chemicals remaining on the draft 

list. For all pesticides, the EPA should evaluate the appropriate timing and procedure for EDSP 

screening within the existing pesticide evaluation and registration review processes.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Nneka T. Breaux

Commenter Organization: Dow AgroSciences LLC

EPA Document ID: EPA-HQ-OPPT-2009-0477-0020

Comment Part: 4

EPA Comment Code: 2100

Comment: Issuance of test orders should coordinate with Registration Review schedule.

When oxyfluorfen is scheduled to enter Registration Review[FN9: 

http://www.epa.gov/oppsrrd1/registration review/2010-13-conventional.pdf], we believe that for the 

reasons discussed below that the Agency's resources would be conserved by using Registration Review 

as the vehicle for assessment for Tier 1 EDSP screening. EPA has previously addressed the timing of 

chemicals for the program in their August 2008 document entitled “Status on EPA's Endocrine 

Disruptor Screening Program.”[FN10: http://www.epa.gov/endo/pubs/082808 qas.pdf] In that text, EPA 

stated it “... anticipates making endocrine disruptor screening a routine part of the registration review 

process.” DAS agrees with the stated EPA position that aligning the issuance of test orders under EDSP 

with the opening of the active ingredient's registration review docket has value. We believe this 

alignment will contribute to efficiencies and coordinated resolution of technical and regulatory issues 

associated with the EDSP.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Stephen Longacre

Commenter Organization: FMC Corporation

EPA Document ID: EPA-HQ-OPPT-2009-0477-0040

Comment Part: 1

EPA Comment Code: 2100

Comment: January 18, 2011

Document Control Office (7 407M)

Office of Pollution Prevention and Toxics (OPPT)

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, DC 20460-0001
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Electronic Submission to

Docket ID EPA-HQ-OPPT -2009-0477

Subject: FMC Corporation's Comments on EPA's Proposed Inclusion of Clomazone on the Second List 

for Endocrine Disruptor Screening [Docket ID EPA-HQ-OPPT-2009-0477]

FMC Corporation is pleased to submit the following comments on EPA's proposed inclusion of 

clomazone on the second list for endocrine disrupter screening as indicated in 75 Fed. Reg. 70248, Nov. 

17, 2010.

Specific Comments on Proposed Inclusion of Clomazone on the Second List for Endocrine Disruptor 

Screening:

1) Inclusion of Clomazone on the Second List for Endocrine Disrupter Screening Will Significantly 

Delay Completion of the Clomazone Registration Review:

EPA's Registration Review program is designed to evaluate each registered active ingredient every 15 

years to ensure its database is up to current scientific standards. Clomazone was one of the first active 

ingredients put into Registration Review; the clomazone Registration Review docket was opened in FY 

2007 [Docket EPA-HQ-OPP-2006-0113].

The clomazone Registration Review was to have been completed by the end of 2009 according to EPA's 

schedule published on page 3 in the Agency's Clomazone Summary Document Registration Review: 

Initial Docket in January 2007/revised July 2007 [EPA-HQ-OPP-2006- 0113-0022[1 [], reprinted below:

"Timeline:

EPA has created the following estimated timeline for the completion of the clomazone Registration 

Review. Table [See PDF Docket ID EPA-HQ-OPPT-2009-0477-0040.1]”

The clomazone Registration Review completed the public comment period for preliminary risk 

assessments August, 2009, but has not yet begun Phase 3 (Registration Review Decision), indicating 

that the clomazone Registration Review is already at least two years behind schedule.

Current estimates for conducting endocrine disruption Tier 1 screening, EPA evaluation of Tier 1 

results, and then possible conduct and evaluation of Tier 2 endocrine testing is now estimated to be at 

least four to five years. Including clomazone endocrine disruption Tier 1 screening now as part of the 

clomazone Registration Review will significantly further delay completing the clomazone Registration 

Review by at least four to five more years beyond the current two year delay, resulting in an overall 

delay of clomazone Registration Review by at least six to seven years.

Consequently, it would be more prudent and efficient for EPA to remove clomazone from the proposed 

second list of endocrine disruption screening and not include clomazone endocrine disruption Tier 1 

screening as part of the current clomazone Registration Review, in order to avoid the inevitable huge 

delay in completion of the clomazone Registration Review, which would negatively impact the 

credibility of the clomazone Registration Review, and the overall Registration Review program itself.
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2) Inclusion of Clomazone on the Second List for Endocrine Disrupter Screening Would Inappropriately 

and Unfairly Taint Clomazone as a Potential Drinking Water Contaminant with Substantial Human 

Exposure:

Federal Register Notice 75 Fed. Reg. 70248, Nov. 17, 2010 described the criteria for selection of 

chemicals for the proposed second list of endocrine disrupter Tier 1 screening. The main driver for 

selection of this second list of chemicals for endocrine disrupter screening was Congress' requirement 

for EPA to screen potential drinking water contaminants for endocrine disruption:

"In addition, in Congress's House Appropriations Committee report for EPA's FY 2010 appropriations 

(H.R. 2996, H. Rept. 111-180) (Ref. 1), it directed EPA "to publish within 1 year of enactment a second 

list of no less than 100 chemicals for screening that includes drinking water contaminants, such as 

halogenated organic chemicals, dioxins, flame retardants (PBDEs, PCBs, PFCs), plastics (BPA), 

pharmaceuticals and personal care products, and issue 25 orders per year for the testing of these 

chemicals."

The notice indicated that most (84 of 134) chemicals proposed for the second list of endocrine disruption 

screening are potential drinking water contaminants with potential substantial human exposure. These 

84 chemicals were selected from various drinking water contamination lists. Pesticides placed into 

Registration Review during FY2007 and FY2008 were also added to the proposed second list for 

endocrine disruption screening.

Registration Review pesticides comprise only 35 of the proposed 134 second list of chemicals for 

endocrine disruption screening. Although EPA stated in the Federal Register notice that the public 

should not presume that the listing of a chemical or substance on the second list for endocrine disruption 

screening indicates in any way that EPA currently suspects that such chemical or substance is an 

endocrine disrupter, inclusion of clomazone on this second list of chemicals for endocrine disruption 

screening will unfairly taint and implicate clomazone as a drinking water contaminant with wide 

potential human exposure and/or as a possible endocrine disrupter, which may cause confusion and 

possibly de-selection of clomazone in the marketplace. Therefore, it would be prudent and fair not to 

include clomazone in the second list of chemicals for endocrine disruption screening, and focus the 

second list of chemicals only on potential drinking water contaminants.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues. Also, please see general response to comment under EPA Comment Code: 

1050 Evaluation Criteria Review.

Commenter Name: Gregory Watson

Commenter Organization: Acetochlor Registration Partnership

EPA Document ID: EPA-HQ-OPPT-2009-0477-0044

Comment Part: 20

EPA Comment Code: 2100

Comment: Acetochlor should be evaluated under EDSP during its scheduled Registration Review:

The EPA has previously addressed prioritization of further chemicals for the EDSP program in 

document entitled "Response to Comments on the draft List of Initial Pesticide Active Ingredients and 

Pesticide Inert Ingredients to be Screened under the Federal Food, Drug, and Cosmetic Act" which 
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states: "While the initial group of pesticide active ingredients were selected for EDSP Tier 1 screening 

based on an analysis of exposure potential, EPA generally intends that the remaining active ingredients 

will be screened based on their schedule for docket opening in the registration review program." [72 FR 

33486, June 18, 2007 (FRL-8129-3)]. The ARP agrees with the stated EPA position that there is 

economic and scientific value to aligning the issuance of test orders under EDSP with the opening of the 

chemical's Registration Review dockets. We believe this will contribute to efficiencies and coordinated 

resolution of technical and regulatory issues associated with the EDSP. The ARP therefore suggests that 

Acetochlor be evaluated under EDSP during its Registration Review, currently scheduled for 2016, after 

the overall system for evaluation for potential endocrine disruption effects has been fully developed and 

validated using List 1 Chemicals.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Gregory Watson

Commenter Organization: Monsanto Company

EPA Document ID: EPA-HQ-OPPT-2009-0477-0052

Comment Part: 19

EPA Comment Code: 2100

Comment: Alachlor should be evaluated under EDSP during its scheduled Registration Review: 

The EPA has previously addressed prioritization of further chemicals for the EDSP program in 

document entitled “Response to Comments on the draft List of Initial Pesticide Active Ingredients and 

Pesticide Inert Ingredients to be Screened under the Federal Food, Drug, and Cosmetic Act” which 

states: “While the initial group of pesticide active ingredients were selected for EDSP Tier 1 screening 

based on an analysis of exposure potential, EPA generally intends that the remaining active ingredients 

will be screened based on their schedule for docket opening in the registration review program.” [72 FR 

33486, June 18, 2007 (FRL-8129-3)]. Monsanto agrees with the stated EPA position that there is 

economic and scientific value to aligning the issuance of test orders under EDSP with the opening of the 

chemical’s Registration Review dockets. We believe this will contribute to efficiencies and coordinated 

resolution of technical and regulatory issues associated with the EDSP. Monsanto therefore suggests that 

Alachlor be evaluated under EDSP during its Registration Review, currently scheduled for 2016, after 

the overall system for evaluation for potential endocrine disruption effects has been fully developed and 

validated using List 1 Chemicals.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 5

EPA Comment Code: 2100

Comment: 2. Pesticides that are scheduled for re-registration in the next 5-7 years should not be 

excluded from Tier 1 screening. 
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EPA has streamlined the potential second list of chemicals for Tier 1 screening by excluding any 

pesticides which is scheduled for registration review after FY 2008. However, as we are now in FY 

2011, the rationale for excluding these pesticides is not clear, especially since the re-registration of a 

pesticide may be influenced by the outcome of screening and testing in the EDSP. 

In fact, as we have noted in previous comments that a ‘Catch-22’ at EPA exists regarding the 

registration of pesticides with endocrine disrupting effects. Pesticides known to be endocrine disruptors, 

such as endosulfan, atrazine, have not being regulated on the basis of their endocrine disrupting modes 

of action. Instead, EPA has insisted in the REDs and tolerance reassessments that they are awaiting the 

implementation of the EDSP before regulating on this endpoint.[FN6: “When the appropriate screening 

and/or testing protocols being considered under the Agency’s EDSP have been developed, endosulfan 

may be subjected to additional screening and/or testing to better characterize effects related to endocrine 

disruption.” (Endosulfan RED p. 48-49 EPA 738-R-02-013, November 2002] Therefore, it doesn’t make 

sense to exclude pesticides coming up for re-review if EPA is waiting for information on endocrine 

disrupting potential before acting on that endpoint. If EPA is unable to regulate a pesticide based on 

endocrine disrupting effects until the chemical has undergone the EDSP, then all pesticides which are 

going to undergone re-registration in the next 5-7 years should be required to go through the EDSP. 

Conversely, if EPA is able to regulate a pesticide based on other scientifically relevant information 

which indicates that a pesticide has endocrine disrupting effects, then the Agency should incorporate 

endocrine disrupting endpoints in all re-registration decisions. Regardless, the Agency must be 

consistent on how this endpoint is evaluated from one pesticide re-registration to another and should 

place a priority on obtaining all the necessary information for upcoming re-registrations.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.

Commenter Name: Janet Ollinger

Commenter Organization: EBDC/ETU Task Force

EPA Document ID: EPA-HQ-OPPT-2009-0477-0072

Comment Part: 5

EPA Comment Code: 2100

Comment: The extensive toxicity profile available on a pesticide across its FIFRA dataset provides an 

appreciable amount of information about patterns of effects and downstream outcomes all of which are 

relevant in the assessment of a compound. In addition, the Office of Pesticide Programs has indicated 

that the EDSP will be implemented in the Registration Review process. Given this decision, it is 

unnecessary to continue to list pesticides or their metabolites like ETU for screening. We would suggest 

pesticides that at a later date would be in Registration Review not be included on List 2, and instead, 

EPA should evaluate the appropriate timing and procedure for EDSP screening of pesticides within the 

existing pesticide evaluation and registration review processes.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide 

Registration Review Issues.
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EPA Comment Code: 4000 Chemicals Currently Not Included on the EDSP List

General Response: A few commenters submitted information on chemicals that they thought should 

have been included on the second EDSP list. When compiling the second EDSP list, EPA focused on 

priority drinking water contaminants and pesticides previously identified by EPA. These priority 

chemicals included the Contaminant Candidate List 3 (CCL 3) chemicals, chemicals with National 

Primary Drinking Water Standards, and Registration Review pesticides. While the chemicals mentioned 

in the comments were not included on the current EDSP list, they may be included on future EDSP lists. 

The chemicals suggested by commenters were evaluated as part of the CCL 3 process but did not make 

the final CCL 3. 

As for the current approach for selecting chemicals for the second EDSP list, EPA did not use 

information on the potential for a chemical to cause endocrine effects as criteria for listing. For more 

information please see general response to comment under EPA Comment Code: 1050 Evaluating 

Criteria Review. 

Individual Comments

Commenter Name: Sushma Bhatia et al.

Commenter Organization: San Francisco REACH Team

EPA Document ID: EPA-HQ-OPPT-2009-0477-0012

Comment Part: 2

EPA Comment Code: 4000

Comment: 2.0 Exclusion of chemicals with evidence of endocrine disruption 

While we applaud the EPA’s efforts to take on this complex and vitally important area of research, 

EPA's methodology has led to the exclusion of several chemicals of high public concern with 

demonstrated endocrine disrupting properties, such as BPA, phthalates and triclosan. It is essential that 

these chemicals be added to the list of chemicals for two reasons: 

* Rationale 2a. There is strong evidence that these chemicals disrupt endocrine function. Furthermore, 

the potential harms to human health linked to these chemicals have garnered considerable public 

attention as well as EPA action and their exclusion will undermine public confidence in the EDSP 

review process. 

* Rationale 2b. The use of these chemicals and, subsequently, public health exposure to these chemicals 

is widespread. In cases of bisphenol A and phthalates, the data suggests that select vulnerable groups are 

impacted inequitably. 

Considerable data have amassed regarding the endocrine disrupting properties of bisphenol A, the 

family of phthalate chemicals, and triclosan. These data emerge from studies of cell cultures, animal 

models, human exposure/biomonitoring studies, and correlational studies relating increased levels with 

physiological markers closely associated with health outcomes in humans. A number of scientific 

experts have highlighted concerns about these particular chemicals in the past two years.
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In 2009, the Endocrine Society, a highly regarded scientific organization devoted to endocrine research, 

released a report called Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement 

[FN2: The Endocrine Society (2009). Endocrine-Disrupting Chemicals: An Endocrine Society Scientific 

Statement. http://www.epa.gov/endo/pubs/edspoverview/finalrpt.htm] that highlighted the diverse and 

complex mechanisms of endocrine disruption and the array of chemicals and classes of chemicals with 

endocrine disrupting properties. In addition, they discussed health outcomes related to female and male 

reproductive systems, mammary development and breast cancer, neuroendocrine systems, and 

metabolic, growth and thyroid function. 

Chemicals discussed in this key document included a number of pesticide chemicals, dioxins, the 

banned PCB’s and notably the chemical bisphenol A, and a number of phthalates and phthalate 

metabolites (DnBP, BBP, DnOP, DEHP). Bisphenol A was linked to mammary development and breast 

cancer, prostate cancer and thyroid receptors. Phthalates were linked to semen quality and male genital 

development. 

In April 2010, the President’s Cancer Panel (PCP), a panel of physicians which is mandated by the 

National Cancer Act of 1971 to review annually the research on cancer, released the findings of its 

2008-2009 review. During this year, the panel explored the contribution of environmental exposures to 

the cancer burden in the United States. Their overall findings indicted that the impact of environmental 

exposures to cancer has been grossly underestimated.[FN3: President’s Cancer Panel (2010). 2008-2009 

Annual Report. Reducing Environmental Cancer Risk: What We Can Do Now. 

http://deainfo.nci.nih.gov/advisory/pcp/annualReports/pcp08-09rpt/PCP_Report_08-09_508.pdf] They 

highlighted concerns about bisphenol A in the preface of the document, and noted it as an endocrine 

disruptor linked to breast cancer and prostate cancer. The PCP also identified phthalates as chemicals of 

concern because of their hormone-disrupting properties, including inhibition of normal binding to 

estrogen receptors and suppression of male androgens. 

Finally, concerns about all bisphenol A, phthalates and triclosan have all led to action by the EPA. The 

EPA currently has an action plan on phthalates to address cumulative exposures 

(http://www.epa.gov/oppt/existingchemicals/pubs/phthalates_ap_2009_1230_final.pdf), an action plan 

on bisphenol A (http://www.epa.gov/opptintr/existingchemicals/pubs/actionplans/bpa_action_plan.pdf), 

and a federal register seeking public comment on a ban of triclosan due to public health concerns. 

In spite of EPA's identification of these chemicals for special action, these chemicals have not yet been 

designated by EPA as endocrine disrupting chemicals and have not been included in the Tier 1 screening 

list, which would eventually grant them EDC status. 

Rationale 2b. The use of these chemicals and, subsequently, public health exposure to these chemicals is 

widespread. In cases of bisphenol A and phthalates, the data suggests that select vulnerable groups are 

impacted inequitably.

The three examples below illustrate the potential social burdens and costs associated with excluding 

chemicals already suspected as endocrine disruptors from the EPA’s analysis. 

Bisphenol A (BPA): 

The CDC’s National Health and Nutrition Examination Survey (NHANES) found BPA in 92.6% of a 

2003-2004 representative sample of Americans[FN4: Calafat AM, Ye X, Wong L-Y, Reidy JA, 
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Needham LL. (2008). Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-

2004. Environ Health Perspect, 116:39-44.] and similar widespread exposure again in 2005-2006[FN5: 

CDC: Center for Disease Control and Prevention. (2009). Fourth national report on human exposure to 

environmental chemicals. Data Table: Urinary Bisphenol A. Atlanta: Centers for Disease Control and 

Prevention. http://www.cdc.gov/exposurereport/data_tables/URXBPH_DataTables.html]. Children, 

people in lower income strata, and non-Hispanic blacks had higher geometric means of BPA in their

urine than did adults, people in higher income strata, and non-Hispanic whites and Mexican-Americans, 

respectively. This indicates disproportionate exposures across the population. Since the EPA is required 

to “take into consideration, among other factors of public health concern, the effect of such 

contaminants upon subgroups that comprise a meaningful portion of the general population (such as 

infants, children, pregnant women, the elderly, individuals with a history of serious illness, or other 

subpopulations) that are identifiable as being at greater risk of adverse health effects due to exposure to 

contaminants in drinking water than the general population.” when selecting contaminants for the CCL, 

SDWA section 1412(b)(1)(C), these inequities are particularly relevant for the EDSP. 

The production profile of BPA is extremely high—the U.S. alone manufactured 1 billion kilograms of 

BPA in 2007. It has been found in wastewater [FN6: Benotti (2009). Pharmaceuticals and endocrine 

disrupting compounds in U.S. drinking water. Environ Sci Tech, 43:597-603.] [FN7: Nakada (2007). 

Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting 

chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant. Water 

Research, 41: 4373-4382.] [FN8: Duran-Alvarez, J.C., E. Becerril-Bravo, V. Silva Castro, B. Jimenez, 

and R. Gibson. (2009). “The analysis of a group of acidic pharmaceuticals, carbamazepine, and potential 

endocrine disrupting compounds in wastewater irrigated soils by gas chromatography–mass 

spectrometry”. Talanta, 78(3):1159-66.] and wastewater irrigated soils.[FN9: Gibson R, Durán-Álvarez, 

JD, Estrada, KL (2010). Accumulation and leaching potential of some pharmaceuticals and potential 

endocrine disruptors in soils irrigated with wastewater in the Tula Valley, Mexico. Chemosphere, 81: 

1437-1445.] BPA and other hormonally active and endocrine disrupting compounds are not removed in 

wastewater treatment, meaning they re-circulate back into people’s drinking water. The impacts of these 

exposures are evident from scientific studies associating BPA exposures to increased risk of cancer, and 

problems in neurological development, female fertility, and metabolic functioning. 

Considerable animal research has demonstrated BPA’s hormone-disrupting properties and the health 

sequelae resulting from exposures to levels that are comparable to human exposures. These include 

effects on the brain that mirror estrogen effects[FN10: Nishizawa H, Manabe N, Morita M, et al (2003) 

Effects of in utero exposure to bisphenol A on mRNA expression of nuclear receptors in murine 

placentae assessed by DNA microarray. Journal of Reproduction and Development, 49:539-45.], 

reduced sperm motility[FN11: Chitra KC, Latchoumycandane C, Mathur PP (2003). Induction of 

oxidative stress by bisphenol a in the epididymal sperm of rats. Toxicology, 185:119-127.] [FN12: 

Chitra KC, Rao KR, Mathur PP (2003). Effect of bisphenol A and co-administration of bisphenol A and 

vitamin C on epididymis of adult rats: a histological and biochemical study. Asian Journal of 

Andrology, 5:203-8.], decreased antioxidant enzymes[FN13: Chitra KC, Latchoumycandane C, Mathur 

PP (2003). Induction of oxidative stress by bisphenol a in the epididymal sperm of rats. Toxicology, 

185:119-127.], changes in mammary gland structure[FN14: Munoz de Toro M, Markey CM, WAdia PR, 

et al 2005. Perinatal exposure to bisphenol A alters peripubertal mammary gland development in mice. 

Endocrinology, 146:4138-47.] [FN15: Vandenberg LN, Maffini MV, Wadia PR, et al (2007). Exposure 

to environmentally relevant doses of the xenoestrogen bisphenol A alters development of the fetal 

mouse mammary gland. Endocrinology, 148:116-127.], development of mammary hyperplasias and 

ductal carcinoma in situ[FN16: Murray TJ, Maffini MV, Ucci AA, et al (2007). Induction of mammary 
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gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reproductive 

Toxicology, 23:383-90.], changes in female reproductive organs[FN17: Markey CM, Wadia PR, Rubin 

BS, et al (2005). Long-term effects of fetal exposure to low doses of the xenoestrogn bisphenol A in the 

female mouse genital tract. Biology of Reproduction, 72:1344-51.], prolonged estrous cycles[FN18: 

Honma S, Suzuki A, Buchanan DL, et al (2002). Low dose effect of in utero exposure to bisphenol A 

and diethylstilbestrol on female mouse reproduction. Reproductive Toxicology, 16:117-22.], prostate 

changes[FN19: Nagel SC, vom Saal FS, Thayer KA, et al (1997). Relative binding affinity-serum 

modified acces (RBA-SMA) assay predict the relative in vivo bioactivity of the xenoestrogens bisphenol 

A and octylphenol. Environmental Health Perspectives, 105: 70-6.], changes in testosterone 

levels[FN20: Akingbemi BT, Sottas CM, Koulova AI (2004). Inhibition of testicular steroidogenesis by 

the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and 

decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology, 145:592-603.], 

increased post-natal growth[FN21: Howdeshell KL, Hotchkiss AK, Thayer KA, et al (1999). Exposure 

to bisphenol A advances puberty. Nature, 401:763-4.], and autoimmune effects[FN22: Sawai C, 

Anderson K, Walser Kuntz D (2003). Effect of bisphenol A on murine immune function: Modification 

of interferon-y, IgG2a, and disease symptoms in NZB x NXW F1 mice. Environmental Health 

Perspectives, 111:1883-7.].

Recent research has examined correlations between BPA levels and physiological predispositions to 

disease in humans. Findings include associations between higher BPA levels in the NHANES sample 

and increased risk of heart disease and diabetes,[FN23: Lang IA, Galloway TS, Scarlett A (2009). 

Association of urinary bisphenol A concentrations with medical disorders and laboratory abnormalities 

in adults. JAMA, 300:1303-1310.] [FN24: Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS 

(2010). Association of urinary bisphenol A concentration with heart disease: Evidence from NHANES 

2003/6. PLoS ONE, 5: e8673.] and associations between higher levels of BPA in a Korean sample and 

oxidative stress and inflammation[FN25: Yang YJ, Hong YC, Oh SY, Pak MS, Kim H, Leem JH, Ha 

EU (2009). Bisphenol A exposure is associated with oxidative stress and inflammation in 

postmenopausal women. Environmental Research, 109:797-801.]. In addition, women with polycystic 

ovarian syndrome had higher levels of BPA than did healthy women[FN26: Takeuchi T, Tsutsumi O, 

Ikezuki Y, Takai Y, Taketani Y (2004). Positive relationship between androgen and the endocrine 

disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocrine Journal, 

51(2):165-9.], and environmentally relevant doses of BPA reduced the efficacy of chemotherapeutic 

agents targeting breast cancer cells in cell culture[FN27: LaPensee EW, Tuttle TR, Fox SR, BenJonathan N (2009). Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptorα-positive and –negative breast cancer cells. Environmental Health Perspectives, 117:175-180.]. Similar 

low doses also affected hormones related to metabolic disorders, such as type-2 diabetes, obesity and 

insulin-resistance[FN28: Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N 

(2008). Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose 

tissue explants and adipocytes. Environmental Health Perspectives, 116:1642-1647.].

Phthalates:

Like BPA, phthalates are also extremely high-production chemicals, with one billion tons produced 

worldwide each year. Phthalates are used in a variety of common consumer products, including vinyl 

plastics, building materials, pharmaceuticals, modeling clay, automobiles, pesticides, IV tubing, and 

fragrances used in air fresheners, detergents, cleaning products and more. They are a binding agent, and 

as such are used in cosmetics to hold color and scent. 
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Exposure to phthalates is widespread, and NHANES bio-monitoring data suggests that levels are highest 

among children aged 6 to 11, and in women. In addition, non-Hispanic blacks have the highest levels of 

MEP (a metabolite of DEP, which is widely used in fragrance); Mexican Americans have intermediate 

levels of MEP; and non-Hispanic Americans have the lowest levels, which are less than half the levels 

of non-Hispanic blacks[FN29: CDC: Center for Disease Control and Prevention. (2009). Fourth national 

report on human exposure to environmental chemicals. Data Table: Urinary Mono-ethyl Phthalate. 

Atlanta: Centers for Disease Control and Prevention. 

http://www.cdc.gov/exposurereport/data_tables/URXMEP_DataTables.html]. People are exposed 

through ingestion, inhalation, and, to a lesser extent, dermal contact with products that contain 

phthalates. For the general population, dietary sources have been considered as the major exposure 

route, followed by inhalation of indoor air. Infants may have relatively greater exposures from ingesting 

indoor dust containing some phtalates.[FN30: Clark K, Cousins IT, Mackay D (2003).Assessment of 

critical exposure pathways. In Staples CA (ed), The Handbook of Environmental Chemistry, Vol.3, Part 

Q: Phthalate Esters, pp. 227-262. New York, Springer.]. Phthalates have also been found in human 

breast milk, which exposes nursing infants.[FN31: Calafat AM, Slakman AR, Silva MJ, Herbert AR, 

Needham LL (2004). Automated solid phase extraction and quantitative analysis of human milk for 13 

phthalate metabolites. J Chromatogr B, 805:49-56.] [FN32: Mortensen GK, Main KM, Andersson A-M, 

Leffers H, Skakkebaek NE (2005). Determination of phthalate monoesters in human milk, consumer 

milk, and infant formula by tandem mass spectrometry (LC-MS-MS). Anal Bioanal Chem, 382:1084-

1092.] Phthalates have also been found in wastewater[FN33: Benotti MJ, Trenholm RA, Vanderford BJ, 

et al. (2009). Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water. Environ Sci 

Tech, 43:597-603.] and wastewater sewage sludge.[FN34: Beauchesne, I., S. Barnabé, D.G. Cooper and 

J.A. Nicell. 2008. “Plasticizers and related toxic degradation products in wastewater sludges”. Water 

Sci. Technol., 57(3):367-74.]

Research suggests that phthalates exert complex effects on several hormonal systems, including estrogen 

and androgen systems. Phthalates’ effects may be most pronounced at critical periods of development, 

such as during prenatal development. Phthalates can cross the placenta, and exposure in pregnant 

women, as measured by urine samples, has been associated with a shortened distance between the anus 

and genitals in male babies, indicating a feminization had occurred during genital development.[FN35: 

Swan SH, Main KM, Liu F, et al.(2005). Decrease in Anogenital Distance among Male Infants with 

Prenatal Phthalate Exposure. Environmental Health Perspectives, 113: 1056-1061. Available online: 

http://www.ehponline.org/members/2005/8100/8100.pdf. Accessed July 24, 2008.] Shorter anogenital 

distance is characteristic of female sex in both humans and animals. Other research in humans has 

shown that baby boys exposed to phthalates in breast milk had alterations in their hormone 

levels.[FN36: Main KM, Mortensen GK, Kaleva MM, et al. (2006). Human breast milk contamination 

with phthalates and alterations of endogenous reproductive hormones in infants three months of age. 

Environmental Health Perspectives, 114:270-276.]

Research in adult human males has found exposure to some phthalates is associated with poor sperm 

quality and infertility.[FN7: Hauser R, Meeker JD, Singh NP, et al. (2007). DNA damage in human 

sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human 

Reproduction. 22:688-695.] Female laboratory animals exposed to phthalates also have been found to 

have alterations in sex hormones and experience fetal loss.[FN38: Gray LE, et al. (2006). Chronic di-nbutyl phthalate exposure in reats reduces fertility and alters ovarian function during pregnancy in female 

Long Evans hooded rats. Toxicological Science, 93(1):189-95.]
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One of the ways that phthalates interfere with reproductive functioning is by reducing the levels of sex 

hormones, which are critical for development and functioning of the sex organs.[FN39: Borch J, 

Axelstad M, Vinggaard AM, Delgaard M (2006). Mechanisms underlying the anti-androgenic effects of 

diethylhelxyl phthalate in fetal rat testis. Toxicology, 223: 144-155.] Additional research suggests that 

these same mechanisms may link phthalates to breast cancer.[FN40: Jobling S, Reynolds T, White R, 

Parker MG, Sumpter JP (1995). A variety of environmentally persistent chemicals, including some 

phthalate plasticizers, are weakly estrogenic. Environmental Health Perspectives 103(6):582-7.] [FN41: 

Kang SC, Lee BM (2005). DNA methylation of estrogen receptor agene by phthalates. Journal of 

Toxicology and Environmental Health Part A, 68: 1995-2003.] Phthalates have also been shown to 

cause proliferation of breast tumor cells and render anti-estrogen treatments, such as tamoxifen, less 

effective against tumors.[FN42: Kim IY, Han SY, Moon A (2004). Phthalates inhibit tamoxifen-induced 

apoptosis in MCF-7 human breast cancer cells. Journal of Toxicology and Environmental Health 67: 

2025-2035.]

Triclosan: 

Triclosan is used in a wide array of consumer products, including 75% of hand soaps, as well as 

toothpaste, clothing, furniture, and other products. It makes its way from these products into wastewater 

systems and sewage sludge, and a recent study found that soybean crops treated with sewage sludge and 

irrigated with wastewater had triclosan in the roots and the beans. Beans treated with sewage sludge had 

higher levels of triclosan than those irrigated with wastewater.[FN43: Chenxi Wu, Alison L. Spongberg, 

Jason D. Witter, Min Fang, and Kevin P. Czajkowski, Environmental Science and Technology, July 21, 

2010, Accessed August 5, 2010. http://pubs.acs.org/doi/abs/10.1021/es1011115] Triclosan can persist 

through wastewater treatment and be discharged into waterways and biosolids[FN44: Rolf U. Halden 

and Daniel H. Paull. 2005. Co-Occurrence of Triclocarban and Triclosan in U.S. Water Resources. 

Environmental Science and Technology, 39: 1420-1426.] [FN45: Jochen Heidler, Amir Sapkota, and 

Rolf U. Halden. 2006. Partitioning, Persistence, and Accumulation in Digested Sludge of the Topical 

Antiseptic Triclocarban during Wastewater Treatment. Environmental Science and Technology, 40(11): 

3634 – 3639.]. Triclosan has already been detected in U.S. waterways[FN46: Kolpin, Dana W., E. T. 

Furlong, M. T. Meyer, E. M. Thurman, S. D. Zaugg, L. B. Barber and H. T. Buxton. 2002. 

Pharmaceuticals, Hormones, and Other Organic Waste Contaminants in U.S. Streams, 1999-2000: A 

National Reconnaissance. Environmental Science and Technology, 36: 1202-1211.] [FN47: Rolf U. 

Halden and Daniel H. Paull. 2005. Co-Occurrence of Triclocarban and Triclosan in U.S. Water 

Resources. Environmental Science and Technology, 39: 1420-1426.], where it has been found to 

degrade into a compound with dioxin-like characteristics upon exposure to UV light. Scientists have 

also raised concerns about bacterial resistance as a result of exposure to triclosan[FN48: Levy, S. 2000. 

"Antibacterial Household Products: Cause for Concern," Presentation from the 2000 Emerging 

Infectious Diseases Conference in Atlanta, Georgia.].

CDC scientists tested the urine of 2,517 people ages six years and older who took part in NHANES 

during 2003-2004. They found that (1) triclosan was detected in the urine of nearly 75% of those tested; 

(2) triclosan levels were greater among people in the highest income bracket than among those in either 

the middle or lower income brackets; and (3) no differences in triclosan levels were found either by sex 

or race/ethnicity. The latest CDC data show a 40 percent jump in triclosan levels in people over a twoyear period.[FN49: SCCS (Scientific Committee on Consumer Safety), Preliminary opinion on triclosan 

antimicrobial resistance), 23 March, 2010. European Commission, Brussels.] 
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Recent evidence points to triclosan as an endocrine disruptor, impacting, in particular, thyroid function 

and thyroid homeostasis. One recent study on rats and frogs found that triclosan had an effect on thyroid 

hormone concentrations and showed it was an endocrine disruptor.[FN50: Crofton, KM, KB Paul MJ 

Devito and JM Hedge, 2007. Short term in vivo exposure to the water contaminant triclosan: Evidence 

for disruption of thyroxine. Environmental Toxicology and Pharmacology, 24: 194-197.] Another study 

showed that it also effected expression of thyroid related genes.[FN51: Veldhoen, N, RC Skirrow, H 

osachoff et al 2006. The bactericidal agen triclosan modulates thyroid hormone-associated gene 

expression and disrupts postembryone anuran development. Aquatic Toxicology, 80: 217-227.] 

Triclosan has also been shown to have both andrgenic and estrogenic activity in breast cancer 

cells.[FN52: Gee RH, A Charles, N Taylor and PD Darbre. 2008. Oestregenic and androgenic activity of 

triclosan in breast cancer cells. Journal of Applied Toxicology, 38: 78-91.] Further evidence suggests 

that triclosan can hormonal systems of mice.[FN53: Kumar V, Chakraborty A, Kural MR, Partha 

(2009). Alteration of testicular steroidogenesis and histopathology of reproductive system in male rats 

treated with triclosan. Reprod Toxicol, 27: 177-85.] [FN54: Zorilla LM, Gibson EK, Jeffay SC, Crofton 

KM, Setzer WR, Coper RL, Stoker TE. 2009. The effects of triclosan on puberty and thyroid hormones 

in male wistar rats. Toxicological Sciences, 107, 56-64.] [FN55: Ahn KC, Zhao B, Chen J, 

Cherednichenko G, Sanmarti E, Denison MS, Lasley B, Pessah IN, Kultz D, Chang DPY, Gee SJ, 

Hammock BD (2008). In Vitro biologic activities of the antimicrobials triclocarban, its analogs and 

triclosan in bioassay screens: Receptor-based bioassay screens. Environmental Health Perspectives, 

116(9).] 

Since the EDSP process is the keystone to identify and require official labeling of chemicals as 

endocrine disruptors, it is vital to include chemicals that are most strongly suspected of having endocrine 

disrupting properties, such as BPA, phthalates and triclosan, in the Tier 1 testing from the outset of the 

program.

Response: Please see general response to comment under EPA Comment Code: 4000 Chemicals 

Currently Not Included on the EDSP List.

Commenter Name: Gail Charnley

Commenter Organization: HealthRisk Strategies

EPA Document ID: EPA-HQ-OPPT-2009-0477-0013

Comment Part: 1

EPA Comment Code: 4000

Comment: Comments on USEPA’s Endocrine Disruptor Screening Program’s 

Proposed Second List of Chemicals for Tier 1 Screening 

Docket ID# EPA-HQ-OPPT-2009-047 

17 December 2010 

Thank you for the opportunity to comment on the second list of chemicals proposed by USEPA for Tier 

1 screening under the Endocrine Disruptor Screening Program (EDSP). I am concerned about the 

inclusion of perchlorate, classified by USEPA as a non-natural environmental contaminant. If 

perchlorate is included, USEPA should also include nitrate and thiocyanate on the second list of 

chemicals. 
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Perchlorate exposure does not occur in isolation from exposure to other goitrogens, or anti-thyroid 

agents, that have the same iodine uptake inhibition mode of action as perchlorate. Despite being less 

potent, nitrate and thiocyanate represent by far the greatest part of the environmental goitrogen pool, so 

it is surprising that they are not included on the list. All three substances occur naturally in the 

environment and also as anthropogenic contaminants, nitrate through synthetic fertilizers and 

thiocyanate as a result of conversion from cyanide (itself a goitrogen) in the body. Naturally occurring 

nitrates and thiocyanates are ubiquitous in the diet and occur in such quantities and with such potencies 

that determining the additional contribution to public health risk made by perchlorate is potentially 

meaningless when only perchlorate is considered in isolation. 

The potential public health significance of the two other goitrogens and the need to consider them 

together with perchlorate was highlighted recently by a USEPA Office of Inspector General report, 

Scientific Analysis of Perchlorate (Report No. 10-P-0101, April 2010). 

For those reasons I respectfully request that USEPA include nitrate and thiocyanate, in addition to 

perchlorate, on the second list of chemicals proposed for Tier 1 screening under the EDSP. Testing only 

perchlorate will produce results with little public health relevance.

Response: Please see general response to comment under EPA Comment Code: 4000 Chemicals 

Currently Not Included on the EDSP List.

Commenter Name: Sarah Janssen

Commenter Organization: Natural Resources Defense Council (NRDC)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0055

Comment Part: 3

EPA Comment Code: 4000

Comment: Specific comments on the proposed second screening list follow: 

1. NRDC supports EPA’s decision to include chemicals found in drinking water sources in the EDSP. 

Section 136 of the SDWA Amendments states that: 

In addition to the substances referred to in [the FQPA], the Administrator may provide for testing under 

the screening program authorized by [the FQPA] of any other substance that may be found in sources of 

drinking water if the Administrator determines that a substantial population may be exposed to such 

substance.[FN1: 42 U.S.C. § 300j-17. ]

Congress recognized that drinking water was likely to be a significant source of exposure to endocrine 

disrupting chemicals and has granted the authority to EPA for prioritizing drinking water contaminants 

for endocrine disruption testing. Unfortunately, in the 14 years since the amendments were passed, there 

has been ever-mounting evidence documenting the presence of endocrine disrupting chemicals in 

drinking water sources. 

Scientific studies have documented the endocrine disrupting effects of multiple contaminants in our 

nation’s waterways, including in the water that millions of people rely on for drinking. Studies by the 

U.S. Geological Survey (USGS) have revealed a chemical soup of pharmaceuticals, steroid hormones, 
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unregulated pesticides, flame retardants, rocket fuel chemicals, plasticizers, detergents, fragrance 

ingredients and stain repellants in drinking water sources (ground water and surface water) and in 

drinking water itself.[FN2: Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, 

Buxton HT. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 

1999-2000: a national reconnaissance. Environ Sci Technol. 2002 Mar 15;36(6):1202-11.] [FN3: Barnes 

KK, Kolpin DW, Furlong ET, Zaugg SD, Meyer MT, Barber LB. A national reconnaissance of 

pharmaceuticals and other organic wastewater contaminants in the United States--I) groundwater. Sci 

Total Environ. 2008 Sep 1;402(2-3):192-200.] [FN4: Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, 

Meyer MT, Zaugg SD, Barber LB, Thurman ME. A national reconnaissance for pharmaceuticals and 

other organic wastewater contaminants in the United States--II) untreated drinking water sources. Sci 

Total Environ. 2008 Sep 1;402(2-3):201-16.] Among the chemicals most commonly detected in these 

national surveys are known and suspected endocrine disruptors, including the antibacterial chemical 

triclosan, alkylphenols and alkylphenol polyethoxylates, bisphenol A, musk fragrances, and 

pharmaceutical estrogens. Because conventional drinking water treatment does not eliminate many 

contaminants, drinking water is likely to be contributing to our daily exposure to these chemicals. 

Although they are found in low levels in the water, these levels are nonetheless concerning because 

hormones normally circulate and exert their effects in the body at the parts per billion to parts per trillion 

level. Water is certainly not the only source of these chemicals, but trace amounts from one source add 

up with traces from other sources, and the sum total becomes a threat to human health.

The soup of chemicals that has been measured in drinking water sources also exists in the majority of 

American’s tested for chemicals such as triclosan, phthalates, BPA, flame retardants, perchlorate and 

other contaminants.[FN5: Centers for Disease Control and Prevention. National Report on Human 

Exposure to Environmental Chemicals. Fourth Report, 2009. http://www.cdc.gov/exposurereport/.] 

Biomonitoring has also confirmed that we are exposed to multiple chemicals at the same time and the 

impacts of exposure to these chemicals as a mixture are not very well understood but are concerning for 

additive or multiplicative effects. For example, certain phthalates are well-characterized for decreasing 

testosterone production and mixtures of these phthalates at relatively low individual doses is capable of 

lowering of testosterone just as is seen after exposure to one phthalate at a high dose. Therefore, 

exposure to a mixture of phthalates and other anti-androgenic chemicals in drinking water, even at very 

low doses, could be harmful because of this mixture effect. 

In addition to the known and suspected endocrine disrupting chemicals in water, there are potentially 

hundreds of other chemical contaminants for which we have no information about their endocrine 

disrupting effects. The result of the decade of foot-dragging on testing chemicals for hormonal activity 

means that the vast majority of chemicals in our water supply and environment are “unknowns” when it 

comes to their hormonal effects. Due to the well-known flaws in the Toxic Substances Control Act 

(TSCA), almost all chemicals come onto the market with no toxicity information, and older chemicals 

remain untested too.

Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation 

Criteria. Also, please see general response to comment under EPA Comment Code: 4000 Chemicals 

Currently Not Included on the EDSP List.
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EPA Comment Code: 5000 Comments Related to a Deadline Extension

General Response: EPA received several comments requesting an extension of the public comment 

period established for the Second List of Chemicals for Tier 1 Screening (75 FR 70248, November 17, 

2010) (USEPA, 2010b) beyond its original December 17, 2010 deadline. In response to this request, 

EPA extended the comment period until January 18, 2011. The extension was published in 75 FR 

77869, December 14, 2010 (USEPA, 2010c). 

The 30-day extension date corresponded to the close of the comment periods for the Draft Policies and 

Procedures for Screening Safe Drinking Water Act Chemicals (75 FR 70558, November 17, 2010) 

(USEPA, 2010a) and the Agency Information Collection Activities; Proposed Collection; Comment 

Request; Addendum for the Second List of Chemicals; Tier 1 Screening of Certain Chemicals Under the 

Endocrine Disruptor Screening Program (75 FR 70568, November 17, 2010) (USEPA, 2010d).

Individual Comments

Commenter Name: Wendelyn Jones

Commenter Organization: CropLife America

EPA Document ID: EPA-HQ-OPPT-2009-0477-0006

Comment Part: 1

EPA Comment Code: 5000

Comment: November 22, 2010

Mr. Stephen A. Owens

Assistant Administrator

Office of Chemical Safety and Pollution Prevention

U.S. Environmental Protection Agency

1200 Pennsylvania Ave., N.W.

Washington, D.C. 20460-0001

RE: Request for extension of public comment period for “Endocrine Disruptor Screening Program; 

Second List of Chemicals for Tier 1 Screening”, 75 Fed. Reg. 70248, Nov. 17, 2010 (EPA-HQ-OPPT2009-0477).

Dear Mr. Owens:

CropLife America [FN1: CropLife America (CLA) is the not-for-profit trade organization representing 

the nation’s developers, manufacturers, formulators and distributors of plant science solutions for 

agriculture and pest management in the United States. Our member companies produce, sell and 

distribute virtually all the crop protection technology products used by American farmers and other 

consumers. We are committed to the safe and responsible use of the industry's products in order to 

provide safe and abundant food, as well as for the control of insect and plant disease vectors for the 

protection of human health, all providing valuable benefits back to the consumer.] and the Endocrine 

Policy Forum (EPF) [FN2: The Endocrine Policy Forum is a consortium of CLA members and nonmember stakeholders formed to address the aggregate needs of the group with respect to technical 

guidance and regulatory policy in response to the implementation of the EPA Endocrine Disruptor 

Screening Program.] are committed to assisting their members in complying with the Agency’s 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 425

Endocrine Disruptor Screening Program (EDSP) including complying with the EDSP Test Orders. To 

ensure that CLA/EPF members can thoroughly review and comment on the second list of chemicals for 

Tier 1 screening published in the November 17, 2010 Federal Register (75 FR 70248), CLA/EPF 

requests that EPA extend the public comment period until January 18, 2011.

On November 17, 2010, two documents were published in the Federal Register (75 FR 70248 and 75 FR 

70558) on EPA’s Endocrine Disruptor Screening Program (EDSP). The public comment period on 

EPA’s proposed Endocrine Disruptor Screening Program (EDSP) Second List of Chemicals for Tier 1 

Screening (75 FR 70248) is scheduled to end on December 17, 2010. The public comment period on the 

related EDSP draft policy and procedures and ICR notices (75 FR 70558) is scheduled to end on January 

18, 2011. This comment period for the proposed second list of chemicals for Tier 1 screening is 30 days 

shorter than the comment period on the related EDSP draft policy and procedures and ICR notices.

In order for our members (including potentially affected manufacturers/importers of the listed chemicals 

on the proposed second list) to develop meaningful comments on the draft candidate list for endocrine 

screening, they need to fully understand the specific authority and procedures EPA proposes to exercise 

to implement this phase of the EDSP. EPA has proposed some significant changes to the policies and 

procedures compared to those that were developed for Phase 1 of the program. These changes could 

have a significant impact on which entities will actually be responsible for performing and reporting the 

testing. To ensure that potentially affected CLA/EPF members carefully review the second list and 

provide comment on its appropriateness, it is critical that the comment periods of the two notices be 

synchronized. Therefore, CLA/EPF requests that EPA extend the public comment period on 75 FR 

70248 by 30 days until January 18, 2011.

Thank you for your promptly considering of our request. We look forward to receiving a swift response 

from the Agency. Please contact me at wjones@croplifeamerica.org or at 202-872-3885 if you have any 

questions.

Sincerely,

Wendelyn Jones, Ph.D.

Senior Director, Human Health Policy

CropLife America

Response: Please see general response to comment under EPA Comment Code: 5000 Comments 

Related to a Deadline Extension.

Commenter Name: Richard Becker, on behalf of Michael P. Walls

Commenter Organization: American Chemistry Council

EPA Document ID: EPA-HQ-OPPT-2009-0477-0007

Comment Part: 1

EPA Comment Code: 5000

Comment: The American Chemistry Council requests a 30 day extension of the comment period on the 

proposed second list of chemicals for Tier 1 screening for the reasons described in the attached letter.

November 18, 2010

Mr. Stephen A. Owens 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 426

Assistant Administrator 

Office of Chemical Safety and Pollution Prevention 

U.S. Environmental Protection Agency 

1200 Pennsylvania Ave., N.W. 

Washington, D.C. 20460-0001 

Re: Request for extension of public comment period for “Endocrine Disruptor Screening Program; 

Second List of Chemicals for Tier 1 Screening”, 75 Fed. Reg. 70248, Nov. 17, 2010, (EPA-HQ-OPPT2009-0477) 

Dear Mr. Owens: 

As published in the Nov. 17, 2010 Federal Register (75 Fed. Reg. 70248), the public comment period on 

EPA’s proposed Endocrine Disruptor Screening Program (EDSP) Second List of Chemicals for Tier 1 

Screening is scheduled to end on December 17, 2010. This comment period is 30 days shorter than the 

comment period on the related EDSP draft policy and procedures and ICR notices, also published on 

November 17 (75 Fed. Reg.70558). For the reasons discussed below, ACC requests a 30 day extension 

of the comment period on the proposed second list of chemicals for Tier 1 screening. 

In contrast to the Phase 1 EDSP program, EPA’s predicates this action on several different 

Congressional actions, including the Federal Food, Drug and Cosmetic Act, the Safe Drinking Water 

Act and the House Appropriations Committee report for EPA’s FY 2010 appropriations. Beyond 

pesticide chemicals, this second list of chemicals for Tier 1 endocrine screening also includes chemicals 

selected on the grounds that they “may occur in sources of drinking water to which a substantial 

population may be exposed.” The FR notice on the draft policies and procedures requests comments on 

what entities should be required to conduct this EDSP testing, including the possibility of requiring past 

registrants, manufacturers, and importers to test or share the cost of the EDSP testing. Further, EPA is 

considering dropping the “opt out” option of Phase 1 for companies which agree to cease 

manufacture/import of an SDWA listed chemical. 

In order for potentially affected manufacturers/importers of the listed chemicals to develop meaningful 

and complete comments on the draft candidate list for endocrine screening, they need to fully understand 

the specific authority and procedures EPA proposes to exercise to implement this phase of the EDSP. 

EPA has proposed some significant changes to the policies and procedures compared to those that were 

developed for Phase 1 of the program. Our review of these changes has just begun. These could have a 

significant impact on which entities will actually be responsible for performing and reporting the testing. 

To ensure that potentially affected ACC members carefully review the second list and provide comment 

on its appropriateness, it is critical that the comment periods of the two notices be in sync. Therefore, the 

American Chemistry Council requests that EPA extend the public comment period on the Second List 

by 30 days, i.e., until January 18, 2011. Thank you for promptly considering our request. We look 

forward to receiving a swift response from the Agency. Please contact me if you have any questions 

concerning the particulars of our extension request. I can be reached at 202-249-6400. 

Sincerely, 

Michael P. Walls 

Vice President 

Regulatory and Technical Affairs 
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 427

Frank Sanders, OSCP 

Bill Wooge, OSCP 

Wendy Cleland-Hamnett, OPPT 

Susan Sharkey, OPPT 

Peter S. Silva, OW

Response: Please see general response to comment under EPA Comment Code: 5000 Comments 

Related to a Deadline Extension.

Commenter Name: Catherine Willett

Commenter Organization: People for the Ethical Treatment of Animals

EPA Document ID: EPA-HQ-OPPT-2009-0477-0008

Comment Part: 1

EPA Comment Code: 5000

Comment: December 3, 2010

William Wooge

Office of Science Coordination and Policy

Environmental Protection Agency

1200 Pennsylvania Ave. NW

Washington, DC 20460-0001

Via USPS and email to: wooge.william@epa.gov

Dear Mr. Wooge:

On behalf of our two million members and supporters worldwide who are concerned about the use of 

animals in toxicity testing and interested in promoting good science, we respectfully request an 

extension of the public comment period for Docket EPA-HQ-OPPT-2009-0477 in order to afford time to 

thoroughly review and comment on the second list of chemicals for Tier 1 screening published in the 

November 17, 2010 Federal Register (75 FR 70248). Given that there are 134 chemicals on the list, 

many of which have been extensively studied, 30 days to respond is inadequate. PETA requests that 

EPA extend the public comment period until January 31, 2011.

Response: Please see general response to comment under EPA Comment Code: 5000 Comments 

Related to a Deadline Extension.

Commenter Name: Peter Voytek

Commenter Organization: The HAP Task Force (HAP)

EPA Document ID: EPA-HQ-OPPT-2009-0477-0010

Comment Part: 1

EPA Comment Code: 5000

Comment: December 8, 2010

BY HAND
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Page 428

OPPT Document Control Office (DCO)

EPA East Building, Room 6428

1201 Constitution Avenue, NW

Washington, DC 20004

Re: EPA-HQ-OPPT-2009-0477

Dear Sirs:

The HAP Task Force is a testing consortium of US producers of ethylene dichloride (EDC). It was 

formed to conduct testing pursuant to Enforceable Consent Agreements (ECAs) for EDC and 1,1,2-

trichloroethane, two of the 134 chemicals on the second list of chemicals for which EPA intends to issue 

test orders under the Endocrine Disruptor Screening Program (EDSP).[FN1: 75 Fed. Reg. 70248 (Nov. 

17, 2010)]. The HAP Task Force intends to comment on the inclusion of these two compounds, but in

order to do so respectfully requests an extension of the comment deadline (currently December 17, 

2010) by 60 days.

EDSP is the current iteration of an effort begun in 1998 to screen pesticides for endocrine effects, as 

required by the 1996 Amendments (the Food Quality Protection Act) to the Federal Food, Drug, and 

Cosmetic Act (FFDCA). The first list of chemicals for which the Agency intends to issue test orders 

under EDSP was directed at active and inert pesticide ingredients.[FN2: 74 Fed. Reg. 17560 (April 15, 

2009)]. The second list was issued in response to language in the House Appropriations Committee FY 

2010 EPA Appropriations Report, directing EPA to “publish within one year of enactment a second list 

of no less than 1 00 chemicals for screening that includes drinking water contaminants, such as 

halogenated organic chemicals ... and issue 25 orders per year for the testing of those chemicals.”[FN3: 

H.R. 2996, H. Rept. 111-180].

Significantly, the SDWA directs testing only for “a substance that may be found in drinking water if the 

Administrator determines that a substantial population may be exposed to such substance.”[FN4: SDWA 

§ 1457; 42 U.S.C. § 300j-17]. Moreover, EPA is also authorized to exempt a chemical from screening 

upon a determination that “the substance is anticipated not to produce any effect in humans similar to an 

effect produced by a naturally occurring estrogen.”[FN5: FFDCA § 408(p)(4); 21 U.S.C. § 346a(p)(4). 

5136128]. 

Given the numerous interested parties, some of whom have not yet been identified, the current deadline 

of December 17, 2010 is not a realistic period in which to develop information on potential exposure to 

a long list of compounds in drinking water, much less to collect the data needed to show that a chemical 

is not anticipated to produce any effect in humans similar to an effect produced by a naturally occurring 

estrogen. To produce the necessary information, more time is needed to identify different manufacturers, 

contact them, and make arrangements for costs. Obtaining and reviewing the necessary occurrence data 

and producing a substantive response simply will require more than the 30 days provided.

Response: Please see general response to comment under EPA Comment Code: 5000 Comments 

Related to a Deadline Extension.

Commenter Name: Peter Voytek

Commenter Organization: The HAP Task Force (HAP)
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 429

EPA Document ID: EPA-HQ-OPPT-2009-0477-0010

Comment Part: 3

EPA Comment Code: 5000

Comment: Furthermore, the Task Force is scheduled to initiate a mammalian reproductive toxicity 

study for EDC in 2011. We request that EPA extend the comment period for 60 days to provide the Task 

Force with additional time to develop and assess existing information for 1,1,2-trichloroethane and 

EDC. EPA must provide more time if it is serious about avoiding duplicative testing and the 

unnecessary suffering and sacrifice of test animals. 

We request that EPA extend the comment period for 60 days in order to give interested parties adequate 

time to respond. 

Please do not hesitate to contact me if there is any question about this request

Sincerely,

Peter E. Voytek, Ph.D.

Manager

Response: Please see general response to comment under EPA Comment Code: 5000 Comments 

Related to a Deadline Extension.
EPA-OGWDW Final EDSP List 2 February 2013

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Page 430

References

Dasgupta PK, Dyke JV, Kirk AB, Jackson WA. 2006. Perchlorate in the United States. Analysis of 

relative source contributions to the food chain. Environmental Science and Technology 40(21):6608-14.

De Guzman NP, Hendley P, Gustafson DI, van Wesenbeck I, Klein AJ, Fuhrman JD, Travis K, 

Simmons ND, Teskey WE, Durham RB. 2005. The acetochlor registration partnership state ground 

water monitoring program. J Environ Qual 34(3): 793-803. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843642. 

Hackett AG, Gustafson DI, Moran SJ, Hendley P, van Wesenbeeck I, Simmons ND, Klein AJ, 

Kronenberg JM, Fuhrman JD, Honegger JL, Hanzas J, Healy D, Stone CT. 2005. The acetochlor 

registration partnership surface water monitoring program for four corn herbicides. Journal of 

Environmental Quality 34(3): 877-889. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=

15843651.

Kalkhoff SJ, Kolpin DW, Thurman EM, Ferrer I, Barcelo D. 1998. Degradation of Chloroacetanilide 

Herbicides: The Prevalence of Sulfonic and Oxanilic Acid Metabolites in Iowa Groundwaters and 

Surface Waters. Environmental Science and Technology 32: 1738-1740.

National Drinking Water Advisory Council (NDWAC). 2004. National Drinking Water Advisory 

Council Report on the CCL Classification Process to the U. S. Environmental Protection Agency, May 

19, 2004.

Sullivan DJ, Vecchia AV, Lorenz DL, Gilliom RJ, Martin JD. 2009. Trends in pesticide concentrations 

in corn-belt streams, 1996–2006. Scientific Investigations Report. (USGS): 2009–5132. p.75. 

http://pubs.usgs.gov/sir/2009/5132/.

Thurman, E. M., Goolsby, D. A., Aga, D. S., Pomes, M. L., and Meyer, M. T. (1996). Occurrence of 

alachlor and its sulfonated metabolite in rivers and reservoirs of the Midwestern United States: The 

importance of sulfonation in the transport of chloroacetanilide herbicides. Environmental Science and 

Technology 30: 569-574.

United States Environmental Protection Agency (USEPA). 2006. Acetachlor/Alachlor: Cumulative Risk

Assessment for the Chloroacetanilide. Available on-line at 

http://www.epa.gov/oppsrrd1/cumulative/chloro_cumulative_risk.pdf. March 8, 2006.

USEPA. 2007. Draft List of Initial Pesticide Active Ingredients and Pesticide Inerts to be Considered for 

Screening under the Federal Food, Drug, and Cosmetic Act; Notice. Federal Register, Vol. 72, No. 116, 

p. 33486, June 18, 2007.

USEPA. 2008. Drinking Water Contaminant Candidate List 3 Draft; Notice. Federal Register. Vol. 73, 

No. 35, p. 9628. February 21, 2008.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

Page 431

USEPA. 2009a. Response to Comments on the Draft Endocrine Disruptor Screening Program (EDSP): 

Policies & Procedures for Initial Screening and Testing. Available on-line at: 

http://www.regulations.gov under Docket ID #: EPA-HQ-OPPT-2007-1080, March 26, 2009.

USEPA. 2009b. Endocrine Disruptor Screening Program; Policies and Procedures for Initial Screening; 

Notice. Federal Register. Vol. 74, No. 71, p. 17560, April 15, 2009. 

USEPA. 2009c. Drinking Water Contaminant Candidate List 3—Final; Notice. Federal Register. Vol. 

74, No. 194, p. 51850, October 8, 2009.

USEPA. 2010a. Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals; Notice. Federal Register. Vol. 75, No. 221, p. 70558, November 

17, 2010.

USEPA. 2010b. Endocrine Disruptor Screening Program (EDSP); Second List of Chemicals and 

Substances for Tier 1 Screening; Notice. Federal Register. Vol. 75, No. 221, p. 70248, November 

17, 2010.

USEPA. 2010c. Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 

Screening; Extension of Comment Period; Notice. Federal Register. Vol. 75, No. 239, p. 77869, 

December 14, 2010.

USEPA. 2010d. Agency Information Collection Activities; Proposed Collection; Comment Request; 

Addendum for the Second List of Chemicals; Tier 1 Screening of Certain Chemicals Under the 

Endocrine Disruptor Screening Program (EDSP); EPA ICR No. 2249.02, OMB Control No. 2070-0176; 

Notice. Federal Register. Vol. 75, No. 221, p. 70568, November 17, 2010.

USEPA. 2011. Endocrine Disruptor Screening Program. Weight-of-Evidence: Evaluating Results of 

Tier 1 Screening to Identify the Need for Tier 2 Testing. Available on-line at: 

http://www.regulations.gov under Docket ID #: EPA-HQ-OPPT-2010-0877-0021, September 14, 2011. 

USEPA. 2012a. Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening 

Safe Drinking Water Act Chemicals; Notice. Federal Register. 

USEPA. 2012b. Endocrine Disruptor Screening Program (EDSP); Final Second List of Chemicals 

and Substances for Tier 1 Screening; Notice. Federal Register. 

USEPA. 2012c. Response-to-Comments for the Endocrine Disruptor Screening Program’s Draft Policies 

and Procedures for Screening Safe Drinking Water Act Chemicals. Available on-line at: 

http://www.regulations.gov under Docket ID #: EPA-HQ-OPPT-2007-1080.

USEPA. 2012d. Response to Comments on the Public Review Draft of the Information Collection

Request (ICR) entitled: “Addendum for the Second List of Chemicals; Tier 1 Screening of Certain 

Chemicals Under the Endocrine Disruptor Screening Program (EDSP)”. Available on-line at: 

http://www.regulations.gov under Docket ID #: EPA-HQ-OPPT-2007-1081.
EPA-OGWDW Final EDSP List 2 February 2013

Comment Response Document

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USEPA. 2012e. U.S. Environmental Protection Agency Endocrine Disruptor Screening Program 

Comprehensive Management Plan. June 2012. Available on-line at: http://epa.gov/endo/pubs/EDSPcomprehensive-management-plan.pdf.