# 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 201 3 http://water.epa.gov/drink/EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page i 

### Contents

1. I NTRODUCTION AND O VERVIEW

................................ ................................ ................................ 1

2. C OMMENTS AND EPA R ESPONSES BY C OMMENT C ODE

................................ ........................ 12

EPA Comment Code: 1000 General Comments

................................ ................................ ..... 12
EPA Comment Code: 1010 General Comments Agreeing with EPA

................................ .... 22

E PA Comment Code: 1020 Continue U se 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 Complet e List 1

- Eva luate Tier 1 Screening Results b efore 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 a s 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 Chemica ls with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

................................ ....................... 288

EPA Comment Code: 2070 Conta minants 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 Current ly Not Included on the EDSP List

.............. 415

EPA Comment Code: 5000 Comments Related to a Deadline Extension

............................ 424



### List of Exhibits

E XHIBIT 1: EDSP C ONTAMINANTS AND A SSOCIATED EPA C OMMENT C ODES

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

E XHIBIT 2: O RGANIZATIONS AND I NDIVIDUALS C OMMENTING ON THE S ECOND EDSP L IST

.. 10EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 1 

## 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 t he a gency ) “ to develop a s creening 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 hu man health or the
environment due to disru ption 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 necessar y 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 bet ween the d ose 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 W eb 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 reg ulation (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 order s have already been issued for these
chemicals ; (iv) chemicals t hat 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 sche duled 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). T here were approximately 134 chemicals on the second ESDP list. The final list
includes 109 chem icals 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. T his document presents the comments received and responses from EPA

. Approximately 59 public submission s (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 c an be found in their respective docket locations at www.regulations.gov

, under Docket ID EPA

– HQ

– OW

– 200 9

– 0 477

.

EPA’s Categorization of Public Comments and D ocument Organization EPA has divided the public comments received into a list of numerically ordered topics ( referred to as

“ EP A Comment C odes ” )

. To organize and track public submissions, EPA assigned a docu ment identification ( ID ) number

. These “ document IDs ” were assigned to give each public submission a unique identifier

.

EPA has read e ach public submissio n and

, where appropriate, subdivided the comments into “ comment
sections

, ” or distinct issue areas, based on topic al 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 c omments and EPA’s responses . These are organize d first by EPA
Comment Code

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

, comments are organized numerically by EPA Document ID

. Readers can first find the comment code for topic s they are interested in

, and then find responses to specific individual comments . T he commenter s’ 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 attach ment s in the comm enter’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 p rogrammatic 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

Contaminan t 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 Reproductiv e 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 ZeroEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 3 5000 Comments Re lated 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

- Dichloro ethane 1060 SDWA 1457 1065 EPA's Authority to Require Testing 2070 Contaminants Not Expected to Produce Estrogen

- like

Eff ect 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 Ch emicals 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

1 075 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

- Eva luate Tier 1 Screening Results b efore 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 EffectEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 4 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 Requirements 2100 Pesticide Registra tion Review Issues Acetochlor ethane sulfonic acid (ESA) 1040 Complete List 1

- Eva luate Tier 1 Screening Results b efore 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

- Eva luate Tier 1 Screening Results b efore Proceeding with EDSP List 2
1050 Evaluation Criteria Re view 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

- Eva luate Tier 1 Screening Results b efore 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

- Eva luate Tier 1 Screening Results b efore Proceeding with EDSP List 2
1050 Evaluation Criteria Review
2080 Contaminants with Lo w 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 b efore 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

- Eva luate Tier 1 Screening Results b efore 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 ReviewEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 5 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 hydroperox ide (CHP) 1040 Complete List 1

- Eva luate Tier 1 Screening Results b efore 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 Pesticid es 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 Pestici des with Cancelled Registrations 2030 Contaminants Unlikely to Persist in Drinking Water
2090 Contaminants with MCLG of Zero Epichlorohydrin (ECH) 1035 Animal TestingEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 6 2030 Contaminants Unlikely to Persist in Drinking Water 2070 Contaminants Not Expected t o 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
20 80 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

- Eva luate Tier 1 Screening Results b efore 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 N o 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 Pesticid es 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 U sed in the US, also Includes Pesticides with Cancelled Registrations

Flumetsulam 1020 Continue U se 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 L onger 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 1457EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 7 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 Manufac tured 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 Requireme nts Hydrazine 1040 Complete List 1

- Eva luate Tier 1 Screening Results b efore 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

- Eva luate Tier 1 Screening Results b efore 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

2 060 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 E PA's Authority to Require Testing
1075 Request for Formal ResponseEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 8 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 Ef fect Oxyfluorfen 1040 Complete List 1

- Eva luate Tier 1 Screening Results b efore 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 U se 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 Pesticid es with Cancel led 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 wit h 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 Pr oduce 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 RegistrationsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 9 Styrene 2030 Contaminants Unlikely to Persist in Drinking Water 2070 Contaminants Not Expected to Produce Est rogen

- 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

- Dichloroethyle ne 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 Prod uce 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

- Eva luate Tier 1 Screening Results b efore 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. Fo r these comments, EPA has

cross

- referenced responses to avoid redundancy and to ensure consistency. Responses are cross

referenced by providing the pertinent EPA Document ID and part number , along with the EPA
Comment Code where the c omment 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 , wher e applicable . Responses to individual comments may point the reader to the appropriate Response to Comment Code.

Who Submitted Comment s EPA received 59 public submissions with the majority of comment s coming from the industry, or consultants writing on b ehalf 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

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- 0020 Nneka T. Breaux Dow AgroSciences LLC

EPA

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- 0021 Linda G. Ferguson American Pacific Corporation

EPA

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- 0022 Marie R. Martinko Society of the Plastics Industry, Inc.

EPA

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- 0023 Patricia Kablach Casano General Electric Company

EPA

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- 0024 Gregory A. Dolan Methanol Institute

EPA

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- 0025 Howard J. Feldman American Petroleum Institute

EPA

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- 0026 Nneka T. Breaux Dow AgroSciences LLC

EPA

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- 0027 Leslie Berry American Chemistry Council Oxo Process
Panel

EPA

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- 0028 Thomas W. Curtis American Water Works Association

EPA

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- 0029 Richard A. Becker American Chemistry Council

EPA

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- 0030 James C. Lamb Hercules, a wholly owned subsidiary of
Ashland

, Inc.

EPA

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- 0031 Francis X. Sherman AkzoNobel

EPA

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- 0032 Paul H. Dugard Honeywell International, Inc., and Mexichem Fluor, Inc.

EPA

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- 0033 Rebecca J. Bernstein Arkema Inc.

EPA

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- 0034 Peter E. Voytek HAP Task Force

EPA

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- 0035 Sahar Osman

- Sypher American Chemistry Council

EPA

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- 0036 Sahar Osman

- Sypher American Chemistry Council

EPA

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- 0037 W. Caffey Norman Patton Boggs LLP on behalf of PPG Industries, Inc.

EPA

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- 0038 Faye Graul Halogenated Solvents Industry Alliance, Inc.

EPA

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- 0039 Intertox, Inc. Intertox, Inc. on behalf of Perchlorate Study Group

EPA

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- 004 0 Stephen L. Longacre FMC Corporation

EPA

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- 0041 Anthony D. Wagner American Chemical CouncilEPA

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Page 11 Document ID Commenter Name Organization

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- 0042 Andrew M. Jaques North American Polyelectrolyte Producers
Association

EPA

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- 0044 Gregory R. Watson Acetochlor Registration Partnership

EPA

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- 0046 Anthony D. Wagner American Chemistry Council

EPA

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- 0047 D. Douglas Fratz Consumer Specialty Products Association

EPA

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- 0048 Robert J. Simon American Chemistry Council

EPA

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- 0049 Michael C. White Chemical Producers and Distributors
Association

EPA

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- 0050 Wendelyn Jones CropLife America and Endocrine Policy

Forum

EPA

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- 0051 Robert J. Fensterheim Acetaldehyde Working Group

EPA

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- 0052 Gregory Watson Monsanto Company

EPA

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- 0053 Kathleen M. Roberts Methyl Tertiary Butyl Ether (MTBE)
Consortium

EPA

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- 0054 Niamh McMahon Dow AgroSciences LLC (DAS)

EPA

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- 0055 Sarah Janssen Natural Resources Defense Council (NRDC)

EPA

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- 0056 Stephen P. Risotto American Chemistry Council (ACC)

EPA

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- 0058 Jean Kasakevich Dow Chemical Company (DOW)

EPA

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- 0060 Jean Kasakevich Dow Chemical Company (DOW)

EPA

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- 0061 Susan Van Volkenburg LANXESS Corporation

EPA

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- 0062 Fred Marashi Chevron Phillips Chemical Company LP (CPChem)

EPA

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- 0064 Michael Boucher McKenna Long & Aldridge LLP on behalf of Ferro Corporation

EPA

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- 0065 Dru Ann Toman EHS Global Product Leader, Performance Materials, Union Carbide Corporation (UCC), a subsidiary of The Dow Chemical Company (DOW)

EPA

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- 0066 The Bayer CropScience
Endocrine Drive Team Bayer CropScience LP

EPA

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- 0067 Jack Snyder Styrene Information and Research Center (SIRC)

EPA

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- 0068 Sherman Friedman Velsicol Chemical LLC (Velsicol)

EPA

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- 0069 Jean Kasakevich Dow Chemical Company (DOW)

EPA

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- 0072 McDermott Will & Emergy
LLP on behalf Janet Ollinger EBDC/ETU Task Force

EPA

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- 0073 Terry F. Quill Quill Law Group, LLC on behalf of Velsicol Chemical, LLCEPA

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Page 12 

## 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

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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

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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

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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 a nd 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 infrastructu re.] 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 th e 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 th e 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, ACCEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 13 has consistently supported increased funding for the Agency’s research and lab oratory 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 broade r 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.

Res ponse: Thank you for your comment.

Commenter Name: Francis Sherman Commenter Organization: AkzoNobel
EPA Document ID: EPA

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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: Co mments on "Endocrine Disrupter Screening Program; Second List of Chemicals for Tier 1 Screening" [75 FR 70248; 11/17/2010; EPA

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Dear Sir or Madam,

AkzoNobel is proud to be one of the world's leading industrial companies. He adquartered 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 p roducer 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 14 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 pr inciples 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

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Comment Part: 5
EPA Comment Code: 1000

Comment: 4.0 PERCHLORATE IS NOT AN AGONIST OR ANTAGONIST TO ANT ERIOR
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., incr eases 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
biochemi cal 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 o f effect occurs for other receptor mediated hormones, such as thyroid hormones.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 15 Environmental exposure to estrogens has received a significant amount of attention from scientists, regulators, and the media. Estrogenic effects from industrial chemicals, pe sticides, 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 o ccur 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 e xposure 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 U se of Qualifying Language , general response to comment under EPA Code: 1050 Evaluation Criteria a nd the individual response to EPA Doc ument ID: EPA

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- 0039, Comment Part: 3 of that section. Also, p lease 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

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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 a dditive 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 cle arly 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 d istinct manufacturer is not identifiable.

Similar to perchlorate, the remaining criteria do not apply to bromate.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 16 Like nitrate, another chemical that was excluded from the November 17th list was chlorate. Chlorate is a water disinfection byproduct. It to o 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 criterio n 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 gener al 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

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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

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Crop Life America [FN1: CropLife America (CLA) is a not

- for

- profit trade organization represen ting 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 pr oducts 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 o f 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 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 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 implementati on 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 dete rmine 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,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 17 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 an d/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 determi ne 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/PRAVie wICR ?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 (wi thin 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 pe rform 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 Chem icals 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; T ier 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 pro viding 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, D rug, 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 fee d 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 t his product have the potential to interact with certain hormonal systems?" [the ultimate goal of EDSP Tier I screening].EPA

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Page 18 Response: P lease see general response to comment under EPA Comment Co de: 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

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

.

Commenter Name: Robert Fensterheim Commenter Organization: Acetaldehyde Working Group
EPA Document ID: EPA

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Comment Part: 3
EPA Comment Code: 1000

Commen t: 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

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- 0477 Submitted by the Acetaldehyde Working G roup 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 whic h 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: C elanese, 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 fo r 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 emi t acetaldehyde (as reflected in the Toxic Release Inventory) even though the majority of these companies did not manufacture (for commercial purposes) or purchase acetaldehyde.EPA

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Page 19 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

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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 [t he 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 secti on 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 51 850 (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 sufficien t 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

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Comment Part: 1EPA

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Page 20 EPA Comment Code: 1000

Comment: April 11, 2011

OPPT Document Control Office (DCO) EPA East Bldg., Rm. 6428 1201 Constitution Ave., NW Washington, DC

Att ention: Docket ID Number EPA

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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

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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 c omments 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 (hexachlorocyclopentadien e, 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 Sc reening" [75 FR 70248; 11/17/2010; EPA

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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: Hexac hlorocyclopentadiene. 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, i t is more recent.]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 21 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 hexachloro cyclopentadiene 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. F inal 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, 20 11 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 [T his 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 22 

### EPA Comment Code: 101 0 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 wa ter 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 mus t 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 an d 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 p rocess, 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 23 Response: Please see general response s to comment under EPA Comment Code s: 1070 Increase

Tr ansparency 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”. Docke t 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 und er 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 i nterest 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 C omments 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. Man y 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 theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 24 chemicals on this list, very little toxicity data exists at all. The Endocrine Disrupto r 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 a ctions 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 und ertaken 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

Co mment: 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 majo rity 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 comm ent.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 2 5 

### EPA Comment Code: 1020 Continue U se 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 in dicates 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 702 48 ) . EPA plans on maintaining this comm unication 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)” (USEP A, 2012 d ) 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 disrupti ng 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

- 019EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 26 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

Surv eillance 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., Mc Dermott, 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. Unpubli shed 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. Un published 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. Ja nuary 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 Piclora m 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 ES

DR

- 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 Toxi cology 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., Massac husetts, 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
Toxic ology Research Laboratory, Michigan, USA. Dow AgroSciences, unpublished report number ES

690, 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 U se 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) appreci ates 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 curre ntly based upon pesticide registration status or population exposure potential via drinking water. Including pesticides on List 2 erroneously suggestsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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. DA S encourages the Agency to continue to stress the qualifying language that highlights that chemicals and sub stances subject to listing (either under List 1 or List 2) are not endocrine disrupting chemicals.

Response: Please see general response to comment under E PA Comment Code: 1020 Continue U se of Qualifying Language.

Commenter Name: Nneka T. Breaux
Commen ter 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 E PA Comment Code: 1020 Continue U se 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 o r 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

- 3248EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 29 Fax: (317) 337

- 4649

E

- mail: ntbreaux@dow.com

Response: Please see general response to comment under E PA Comment Code: 1020 Continue U se 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 do ne 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 ch emical 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 b elieves 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 substant ial 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 c ommunicate 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 c urrent 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 E PA Comment Code: 1020 Continue U se 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 scree ning. The screening selection process is basedEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 E PA Comment Code: 1020 Continue U se of Qualifying Language.

Commenter Name: Int ertox, 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 Pe rchlorate 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 OREPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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
examine d............................................................................................................................

........................... 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
CO NCLUSIONS.................................................................................................................... ................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 lis t 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 streamli ning 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 U se of Qualifying Language , general respo nse t o 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, p lease see general response to comment under EPA Comment Code : 1070 Increase Transparency.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 32 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 17 th 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 subst ance 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 che mical 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, w e 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 perchl orate and are absent from the November 17th
list.

Response: Please see general response to comment under EPA Comment Code: 1020 Continue U se of Qualifying Language

, general response to comment under EPA C ode: 1050 Evaluation Criteria and the individual response to EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0039, Comment Part: 3 of that
section. Also

, p lease 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

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- 0039
Comment Part: 13
EPA Comment Code: 1020EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 33 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 che mical is an endocrine disruptor.

Response: Please see general response to comment under E PA Comment Code: 1020 Continue U se of Qualifying Language.

Commenter Name: Gregory Watson Commenter Organization: Acetochlor Registration Partnership
EPA Document ID: EPA

- HQ

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- 2009

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- 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 n ot 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 onl y 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 g eneral response to comment under E PA Comment Code: 1020 Continue U se 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 Comm ent 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 base d 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
dri nking 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 (CC L 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 Age ncy made a similar statementEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 34 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 E PA Comment Code: 1020 Continue U se of Qualifying Language.

Commenter Name: D. Douglas Fratz Commenter Organization: Consumer Specialty Products Association
EPA Document ID: EPA

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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

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Dear Mr. Owens:

The Consumer Specialty Products Association[FN1: 1 The Consumer Specialty Products Association (CSPA) is a voluntary, non

- profit national trade ass ociation 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, Produ ct 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,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 35 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 respondin g 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 co mments 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 o pportunity. 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 through out 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) tes ting 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 conv ey 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 gener al response to comment under EPA Comment Code: 1020 Continue U se 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,
2012 d ) that is being published simultaneously with this comment response document

.

Commenter Name: Michael White Commenter Organization: Chemical Producers and Distributors AssociationEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 36 EPA Document ID: EPA

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Comment Part: 3
EPA Comment Co de: 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 scree ning 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 U se of Qualifying Language.

Commenter Name: Wendelyn Jones
Commenter Organization: CropLife America and Endocrine Policy Forum
EPA Document ID: EPA

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- 2009

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- 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 E PA Comment Code: 1020 Continue U se of Qualifying Language.

Commenter Name: Wendelyn Jones Commenter Organization: CropLife America and Endocrine Policy Forum
EPA Document ID: EPA

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Comment Par t: 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 endocrin e 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
ha s 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 ba sed on potential exposure (SDW A chemicals) or registration review status (most pesticide active ingredients) and not based on suspected endocrine activity.

Description of EDSP Tier I and Tier II:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 37 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. 7154 5 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 relatio nship 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 stru cture 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 substan ces, 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 wheth er 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
eff ects 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 EP A 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 mo re 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 specif icity 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 describ ing 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. CLAIEP F 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 des igned 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 pu rpose 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 throughEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 38 an endocrine mechanism. Th is 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 an d 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 th at 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, endoc rine 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 vit ro 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 th e 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 chan ges 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 b iological 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 effec ts 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 E PA Comment Code: 102 0 Continue U se 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 Endocr ine Disruptor Screening Program (EDSP)” (USEPA,
2012 d ) and the Response

- to

- Comments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for Screening Saf e Drinking Water Act Chemicals (USEPA, 2012c). Both of these
documents are be ing published simultaneously with this comment response document.

Commenter Name: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

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- 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 exposu re criteria and registration status.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 39 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 te sting (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 U se of Qualify ing Language.

Commenter Name: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

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- 2009

- 0477

- 0052
Comment Part: 11
EPA Comment Code: 1020

Comment: The Agency should continue to emphasize this is not a list of Endocrine D isruptors: 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 Ca ndidate 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 th e 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 disrupt ors. 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 E PA Comment Code: 1020 Continue U se of Qualifying Language

.

Commenter Name: Niamh McMahon Commenter Organization: Dow AgroSciences LLC (DAS)
EPA Document ID: EPA

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- 2009

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- 0054
Comment Part: 2
EPA Comment Code: 1020EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 40 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 E PA Comment Code: 10 20 Continue U se of Qualifying Language.

Commenter Name: Frank Sanders Commenter Organization: Bayer CropScience LP
EPA Document ID: EPA

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Comment Part: 1
EPA Comment Code: 1020

Comment: January 14, 2011

Steve A. Owens,
Assistant A dministrator 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

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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 lis t 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 secti on 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

awa re, 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 E PA Comment Code: 1020 Continue U se of Qualifying L anguage.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 41 Commenter Name: Janet Ollinger Commenter Organization: EBDC/ETU Task Force
EPA Document ID: EPA

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- 0072
Comment Part: 3
EPA Comment Code: 1020

Comment: List 2 is not a list of endocrine disrupting chemicals: We encourage the Age ncy'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 t he 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 th eir 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: Ple ase see general response to comment under E PA Comment Code: 1020 Continue U se of Qualifying Language.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 42 

### 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

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Comment Part: 2
EPA Comment Code: 1030

Comment: Furthermore, there is very little required toxicity information for non

- pesticide chemicals
such a s 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 chemic als 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 slo w 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 deadl ine 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 t o 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 Saf e Drinking Water Act Chemica ls (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

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Comment Part: 7
EPA Comment Code: 1030EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 43 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 impor tant 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 44 

### EPA Comment Code: 1035 Animal Testing

General Response : The tests for chemicals on the s econd EDSP list for Tier 1 s creening 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 objec tive. 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 Scien tifically Relevant Information (OSRI) as part of their initial r esponse 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 R egister

, 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
Disru ptor 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

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- 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 chemi cals 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 publicati on 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 PreventionEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 45 Response: P lease 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

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- OPPT

- 2009

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- 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 informati on 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 app reciate 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 AgroScience s, 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 Comment Response Document

Page 46 Response: Please see gener al 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 studi es 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 al l 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 Pane l 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 w ell 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 rep lace 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 acc ordance 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 u se 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 andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 47 laboratory resources only for substances which have a high potential to occur as drink ing 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: An thony 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 e ndocrine 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 b een 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 response s to comment under EPA Comment Code s : 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 no t 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: 7EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 48 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) ef

forts 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, Do w 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 weight

of

- evidence of available data, as indicated by the details and references discussed above and provided
below.

Sincerely,
Jean Kasak evich 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. Nati onal 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 developm ental 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. Tox icol. 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 Comment Response Document

Page 49 Meylan W, Papa L, De Rosa CT, Stara JF. 1986. Chemical o f 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, p lease 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, a nd 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 50 

### 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 test ing. 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 Appropri ations 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

o f 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 occu r 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 c ompletions 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 51 Response: Please see general response to comment under EPA Comment Code: 1040 Complete List 1

- Evaluate Tier 1 Screening Results before Proc eeding 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 human s 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 end ocrine 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
commit ted 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, p lease 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 Plastic s 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 t he 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

- 0477EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 52 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 mem ber 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 sh ipments.

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 w ho 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 th e 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 screen ing 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 hig h 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 & HealthEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 53 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 grou ps 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 assay s, 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 re

estimating the burden of this information col lection 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 a ssays 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 pro ceed 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 Polic y 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 significantl y 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 Attach ment 3.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 54 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 Cle arance 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 r ecommended 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 th e 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 implemen tation 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 studi es 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 L etter 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 Comment Response Document

Page 55 EPA (2005). U.S EPA Report Titled: Monitored Natural Attenuation of MTBE as a Risk Management Option at Leaking Underground Storage Tank Sites (EP A/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 Candi date 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/Existing

Chemicals/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

.

Co mmenter 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 chemi cals 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 r eport 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 occurEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 56 before scheduling and issuing the next set of test orders. The value for EPA of usi ng 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 iso xaben 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 i mportant 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 dist ributing 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 un der 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 ED SP 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 believ e 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 Subcommitte e 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

re view 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 additi onal 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 57 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 Age ncy’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 addit ional 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 Chemi stry 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 priori tizing 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 componen t 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 a s 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
b attery, 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 E DSP 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 wi th the SAB/SAP guidance set forth in the July 1999 SAB/SAP Review of the EPA's Proposed Environmental Endocrine Disruptor ScreeningEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 58 Program[FN20: EPA (1999). Review of the Endocrine Disruptor Screening Program by a Joint
Subcommittee of the Science Advisor y 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 d ata 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 conven e 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 chem icals 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 o n 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 I nitial 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 p roceeds 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 t o 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 a s 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 potentia l 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 biolog ically 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 T esting 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]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 59 As a general matter, EPA can ensure effi cient, 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 fill ing 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 r ats 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 stagin g) 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 m ode 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: 10 40

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 prop erties of hydrazine, to determine the impact of non

specific 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 include s 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/i ndex;_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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 60 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 che micals 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 CorporationEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 61 EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0040
Comment Par t: 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 subse quent 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, severa l 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 ev aluation 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

F MC 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: 1040EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 62 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

Se cond 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 (Managin g Agent).]) 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. The ARP is submitting comments with regard to the herbicide active ingredient
Acetochl or (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: 1040EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 63 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 t o 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 o rders 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 Acet ochlor 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

- to

Comments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for Screening Saf

e 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 Li st 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 d ata 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 adequ ately 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, th e 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 regula tory 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/SA P recommendation for List 1 before proceeding with List 2. If theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 64 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 unreal ized. 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 pla ced 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 gene ral 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

- 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: 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 $1,0 00,000 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 ot her 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?EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 65 • Can more refined weight

- of

- evidence criter ia 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 lie u 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 t he 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 response s to comment under EPA Comment Code s : 1040 Complete List

1

- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2 and 10 50 Evaluation Criteria
Review. Also , please see Response

- to

- Comments for the Endocrine Disru ptor 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 her e 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

fu nctional 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 de cisions 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 screenin g 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”), [FN 4: 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 timeEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 66 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
constitutio nally 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 sc ience

- 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 W hite 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, labora tories 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 t esting, 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 Boa rd/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 f or 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 st atutory 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

- 0049EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 67 Comment Part: 10
EPA Comment Code: 1040

Comment: Conclusion

CPDA believes that EPA has unnecessarily rushed forward wi th 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 Tie r 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.

C LA/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 r egarding 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
AttachmentEPA

- OGWDW Final EDSP List 2 February 2013 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 bef ore 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 201 2. 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 recommend ations (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 t his 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 initi ate 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 Agen cy: • 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] b y 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

- 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

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 69 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 Mo nsanto 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 pro vide 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 degrada tes, 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

Endocrin e 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 Proc eeding with EDSP List 2

.

Commenter Name: Gregory Watson Commenter Organization: Monsanto CompanyEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 70 EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 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 comp ounds 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 Screenin g Results before Proceeding with EDSP List 2

. 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: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0052
Comment Part: 10
EPA Comment Code: 1040

Comment: Expanded c omments 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 w ould 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 vastEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 recommendati on 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
“lea rrn 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 ev aluation 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 T est 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 res olving 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 respo nse 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

- to

Comments for the Endocrine Disruptor Screening Program’s Draft Policies and Procedures for

Scree ning 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

- 0001EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 72 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 comme nts 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 t o 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 ste p, 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 Tie r 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, p lease see general response to comment unde r 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. Environmen tal 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

- 0477EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 73 Dow AgroSciences (DAS) appre ciates 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 registra tion under FIFRA. As an active member of the Endocrine Policy Forum [FN1: 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 regula tory 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.

I n 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 ma ny 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 ph ase 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 expedit e 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 cr iteria. [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 wit h 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 Li st 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 amon g 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 towardsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 74 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 sensiti vity 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 settin g 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 issua nce 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

c hemical 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] o ffers 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 c omment 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 Dr inking 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 Disrup tor 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: 3EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 Agen cy 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 expens e of endocrine screening and testing, and the lack of experience with the EDSP screening and testing assaysEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 proceedi ng 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 OS RI. 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

- 047 7 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 Forc e, 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, theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 77 members are registrants of an et hylene 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 commen ts, 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 u nderway 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 firs t 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

c omment 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 pote ntial contamination of drinking water.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 78 Response: Please see general response to c omment 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

ex tended 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 th e 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 th e 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 the se 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 a n 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 79 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 gene ral response to comment under EPA Comment Code: 1040 Complete List 1

- Evaluate Tier 1 Screening Results before Proceeding with EDSP List 2

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 80 

### 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
selection s were chemicals that 1) met the criteria of SDWA 1457 and/or 2) were pesticides scheduled for Registration Revi ew for years FY 2007 and 2008. The chemical selection process used to develop the
second EDSP l ist did not place any we ight on the chemicals potentia l 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 bec ause such substances may occur in sources of drinking water to which a substantial population may be exposed.

The a gency 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 n oting: 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 chemical s could include: public input; the results of testing chemicals on the initial list; management considerations to increase the integration of screening with other re gulatory activities
within the a gency; implementation considerations flowing from a decisio n 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) mod els).

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, d ata from the second group of EDSP chemicals and substances may have some utility in the context of drinking water regulations. Please see general r esponse 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 t heir initial r esponse to receiving an order. For specific information on submitting or citing existing data or other OSRI

, p lease 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 co mputational toxicology methods. An EDSP21 Work Plan has been developed that describes an approach for us ing 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

.

P lease also see general response to comment under E PA Comment Code: 1020 Continue U se of Qualifying Language.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 81 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 Tox ics (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. Whil e 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 pr operties 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 di srupting 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 Ti er 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/pu bs/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 privateEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 82 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 great est 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 chem icals 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 sec ond 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 ref

erences 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 inad equate

* 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 contamina nts, 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 i nclude: 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

o ccurrence, 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 se lection 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 ex plain why only new pesticide registration candidates for 2007

- 2008 are included in
this list.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 83 Response: Please see general response to comment under EPA Comment Code: 1050 Evaluation
Criteria Review.

Commenter Name: Sushma Bhatia et al. Commenter Organ ization: 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 scr eening . . . 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 resp ectfully 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 Fed eral 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 measu res 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, p lease 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

- 2 009

- 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 ma y 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 ED SP 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 testingEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 84 under EDSP a nd 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 com ment 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), an d 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...” (emph ases 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

endocri ne 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.

E xemptions

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, F ungicide, 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 sh ould be listed here as well.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 85 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 registra nt 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 afte r 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 che micals, 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

- trichlor obenzene 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 a gency has an obligation to minimize testing and plans on issuing exemptions in the future; however, as of June 25 , 2012, the a gency has not issued any FFDCA exemption orders. The exclusion of a chemical from a list of chemicals designated to receive FFDCA order s is not an FFDC A 408(p) exemption order. The a gency 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 s ection 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 natu rally occurring es trogen.” In 1998, the a gency 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 (Se e 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 suffic ient data that w ould allow the a gency 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 ofEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 86 toxicity data are available for pesti cide 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 ef fect 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 recip ient believes that this showing can be made for its chemical, the

a gency would consider requests to issue such an exemption order on a case

- by

- case or chemical

by

- chemical basis in response to individual submissions

. In order for the a gency 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., i s not anticipated “ to produce any effect in humans similar to an effect produced by a naturally occurring estrogen ”

.

Please also see general response to c omment 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 Drink ing 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, hexyth iazox, 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 di spersants 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 determ ining 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” (Juds on, 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)EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 87 offer a “huge opportunity” to screen a large number of environmentally relev ant 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 o f 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 reproductiv e 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), especia lly 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 appro ximately 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 Regulat ory 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 MakEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 88 Research Analyst
American Anti

- Vivisection Society

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6740699.

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

Commenter Name: Linda F erguson 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 curren tly 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 perchlo rate'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., hypochlori te) 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 fer tilizer 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 thoughtEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 106 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:

P lease refer to Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening Safe Drinking Water Act Chemica ls (USEP A, 2012a) that is being published simultaneously with this comment response document

. EPA agrees that “ Because of the variety of derivations of perchlorate

cu rrently being manufactured that identification of the manufacturer, importer, or registrant become s 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 pes ticides in the end use product. The similar approach will be used for perchlo rate 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 me thanol 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’sEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 107 d etermination 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 response s to comment under EPA Comment Code s : 1050 Evaluation
Criteria Review and 1060 SDW A 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 s ubstance 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

c annot 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 c omment under EPA Comment Code: 1060 SDWA 1457.

A lso, 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

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- 2009

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- 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 su pply 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., co st 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 tradeoffsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 108 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 pr ovides 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 exa mple, 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 eff ects 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, pleas e 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 disinfectant s i n 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 ; p lease 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

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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 excl usion 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 theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 109 Agency to consider these concerns, and suggestions as it implements the second phase of its EDSP.
These are contained in ACC’s detail ed 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

- HQOPPT

2009

- 0477; FRL

- 8848

- 7]

Comments of the American Chemistry Council “Endocr ine 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 Endocr ine 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 pa nels 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 i ts 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 to xicity, 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 challeng es 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, EP A 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 110 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 Cod e: 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
la rge 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 hav e 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 n ot 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 m ay 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 eff

ects

-- 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, DecemberEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 111 28, 1998) page 71542.] Existing toxicity test results that have evaluated established apical adverse effect endpoints, primarily r eproductive 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 haz ards 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 re peated 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 critic al 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 disru ption 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 haz ard 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., identif y 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 commod ity 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/basicinforma tion.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 subst ances 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 Sys tem (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 susceptibl e 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/uploa d/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

commo dity 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 e ndocrine 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 DrinkingEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 112 Water Standards and Health Advisories,[FN12: Ibid.] IRI S 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 t he 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 hormon e 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., hepatotox icity) 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 res ponse. 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 EP A’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, trans port, 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 t he 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:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 113 The purpose of Tier 1 is to identify substances that have the potential to interact with the endocrine system. The purpo se 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 com pletion 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). E ndocrine 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 foun d 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 Envi ronment (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 specific ally 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 fo r 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 propose d 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 shif ting the Agency’sEPA

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Page 114 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 an y 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 add ed.).[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 f or 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 le ad 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

describi ng 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 polic ies 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 as says 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 e stablish 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 toEPA

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Page 115 determine whether a particular substance may have an effect in humans that is similar to a n 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; Poli cies 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 t heir 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 res ult 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 Ti er 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 c omment 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

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- OPPT

- 2009

- 0477

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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).

Gu idelines 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 state s, “[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 o n 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.EPA

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Page 116 VI. EPA Must Interpret Key SDWA Provisions Before it Lists Phas e 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 criteri a 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: P lease see general response to comment under EPA Comment Code: 10 50 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

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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 sta tutory 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 p ublicly 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 conside r 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 a ssurance/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.EPA

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Page 117 * Frequency of occurrence of measured concentrations within the database (e.g., whether the data represent an isolated incident and whether the data are statisticall y 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
consi derable 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

- OEIIQG

FINAL

- 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 ha s 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 d eveloped 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 as sessing 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 1457EPA

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Page 118 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 accept ed 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 wi th 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 c omment under EPA Comment Code: 1060 SDWA 1457. Also, please see gen eral 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

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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 throug h 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 Pest icide 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 i n 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 m ore of the following categories:EPA

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Page 119 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.,
d isinfection 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

- l ike 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 to xaphene 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 wh erein 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 deter mining 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: Pl ease see general response to comment under EPA Comment Cod e: 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

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Comment Part: 1
EPA Comment Code: 1050

Comment: January 18, 2011EPA

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Page 120 Submitted Electronically to:

EPA Docket: EPA

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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

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- 0477] (the Draft EDSP List 2")

Dear Mr. Owens:

Arkema Inc. ("Arkema") is a world class diversified chemical manufacturer with more than 2,000

em ployees 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 agrichemic als. 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

Pro ducers 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 s atisfy 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 crit eria 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

- 0 9

- 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; andEPA

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Page 121 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 ba sic, 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 F

ederal Register notice

, the agency considered priority chemicals contained on Office of Water (OW) and Offic e of Pesticide Programs (OPP) priority lists for inclusion on the second EDSP
list.

Also, see general response s to comment under EPA Comment Code s : 1050 Evaluation Criteria Review
and 1060 SDWA 1457.

Commenter Name: Peter Voytek
Commenter Organization: HAP Task Force
EPA Document ID: EPA

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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 t hat 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
demonstra ted 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 unregul ated 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

MCLG s 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 trac ed 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
drin king water contaminants is ordinarily undertaken at or near the levels of detection, which for mostEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 122 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 alternative means of identifying human popu lations 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 usi ng 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 s to comment under EPA Comment Code: 1060 SDWA 1457. Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criter ia
Review.

Commenter Name: Sahar Osman

- Sypher Commenter Organization: American Chemistry Council
EPA Document ID: EPA

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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 invest igating 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_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: 10 50 Evaluation
Criteria Review. Also, please see general response to c omment under EPA Comment Code: 1070 Increase Transparency to see how EPA may use EDSP information.

Commenter Name: W. Caffey NormanEPA

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Page 123 Commenter Organization: Patton Boggs LLP on behalf of PPG Industries, Inc.
EPA Document I D: EPA

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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 hypothe tically, 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 reco rded 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 promulgati on 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 allow s 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, accura cy 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 i s 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 Age ncy 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, b ut 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 unregulat ed 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 c omment under EPA Comment Code: 1060 SDWA 1457. Also, please see general response to comment under EPA Comment Code: 1050 Evaluation Criteria
Review.EPA

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Page 124 Commenter Name: Faye Graul Commenter Organization: Halogenated Solvents Industry Alliance, Inc.
EPA Do cument ID: EPA

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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 t o 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 managem ent 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 issue s 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 t hat 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 conducte d 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

bil lion 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. EP A 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 d ata 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.EPA

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Page 125 Commenter Name: Intertox, Inc. Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group
EPA Document ID: EPA

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- 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 endo crine 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 Agenc y 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 INTRODUCT ION 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 ef fect 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 it s tentative second list of 134 chemicals for Tier 1 testing under EDSP [the Notice; EPA

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– 7]. This list was generated from an initial compilation of US EPA Office of Water candidate chemicals, in contrast to the first list which

f ocused 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. Perchlor ate is listed in CCL 3; therefore, it was automatically included on the second list for Tier 1 Testing.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 126 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 che micals 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 clea rly 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, str ongly 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 natural ly occurring

sources. Ho wever, 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 perchlorat e 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: 1 050 Evaluation Criteria Review.

Commenter Name: Intertox, Inc. Commenter Organization: Intertox, Inc. on behalf of Perchlorate Study Group
EPA Document ID: EPA

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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

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Page 127 Dasgupta PK, Martinelango PK, Jackson WA, Anderson TA, Kang T, TDCK RW, Rajagopalan S. 2005. The Orig in 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

- Occurri ng 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. 4 4(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.

Orr is 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. Perchlo rate 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.

Urba nsky 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.EPA

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Page 128 US EPA. 2005. Endocrine Disruptor Screening Program; Chemical Selection Approach for I nitial 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

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– OPPT

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– 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

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- 0039, part 3 under this same comment c ode 1050.

Commenter Name: Anthony Wagner Commenter Organization: American Chemical Council
EPA Document ID: EPA

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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

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- 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

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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 D isruptor 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 commen ts 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 ma y 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 t he substance, and a determination thatEPA

- 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

che mical 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 wate r 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”: 17alpha

estradiol, equilenin, equilin, e stradiol, estrone, e thinyl 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 hormona l
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

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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 o f 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) d ataset. EPA ana lysis of the NAWQA data showed that ethylbenzene was detected in 5.7% of 6,055 sampl es 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 19 98 to 2005 h ad detections of ethylbenzene. The percentage of the population served by these PWS s with detections was 11. 9% of over 200 million people. This percentage covered PWS s with both ground wa ter and surface water sources. Based on this evidence that ethylbenzene has been detected in both ambient sources and PWS s , 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 expose d.” 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

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Comment Part: 6
EPA Comment Code: 1050EPA

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Page 130 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 d istinguish “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: Ty pically, 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, e xperience 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 typica lly 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 sho uld 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 t he 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, in cluding 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 co ntact 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 response s to comment under EPA Comment Code s : 1060 SDWA
1457 and 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 Documen t ID: EPA

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Comment Part: 6
EPA Comment Code: 1050EPA

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Page 131 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 pr opagate 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 th e general response to

c omment 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 Chloroacetan ilide
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 Partne rship
EPA Document ID: EPA

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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 counterp roductive 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

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Page 132 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

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- 0193 [EPA 815

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- 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 occ urrence 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 d egradates 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 sci entific 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 gener al response to comment EPA Document ID: EPA

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- 0044, part 6 under this same comment c ode 1050.

Commenter Name: Gregory Watson Commenter Organization: Acetochlor Registration Partnership
EPA Document ID: EPA

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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 tha t 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 li sted 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

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- 0014, part 2 under this same comment code 1050.

Commenter Name: Anthony Wagner Commenter Organization: American Chemistry Council
EPA Document ID: EPA

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Comment Part: 1
EPA Comment Code: 1050EPA

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Page 133 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

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- 0477 Submitted via Federal eRulemaking Portal: http://www.regulatio ns.gov

Re: Comments on “Endocrine Disruptor Screening Program: Second List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA

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- 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: Se cond 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 Cou ncil 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 in cluded 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 response s to comment under EPA Comme nt Code s : 1050 Evaluation
Criteria Review and 1060 SDWA 1457

.

Commenter Name: Anthony Wagner Commenter Organization: American Chemistry Council
EPA Document ID: EPA

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Comment Part: 3
EPA Comment Code: 1050EPA

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Page 134 Comment: Additionally, th e 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 f ate 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 Evalu ation Criteria Review, 1060 SDWA, and 2030 Contaminants Unlikely to Persist in Drinking Wat er.

Commenter Name: D. Douglas Fratz Commenter Organization: Consumer Specialty Products Association
EPA Document ID: EPA

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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 crite ria 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 a ppears 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 propo sed list are naturally

- o ccurring 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 bi omass 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 drink ing 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 manufa ctured 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 propertie s, 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 thereEPA

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Page 13 5 is room for further study regarding whether many of the se 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 final izing 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 gene ral 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

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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

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- 2007

- 1080; and “Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening,” Docket EPA

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To Whom It May Concern:

The American Chemistry Council (ACC) respectfully submits to the Environmental Protect ion 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 glob al 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

- performanc e 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. Howe ver, 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 orEPA

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Page 136 urine does not mean that it will cause e s ffects or disease. The toxicity of a che mical 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 Env ironmental 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 thi s 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 comm ent under EPA Comment Code s : 1050 Evaluation
Criteria Review and 1060 SDWA 1457

.

Commenter Name: Robert Fensterheim Commenter Organization: Acetaldehyde Working Group
EPA Document ID: EPA

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Comment Part: 1
EPA Comment Code: 1050

C omment: 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

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2009

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Dear Sir or Madam:

The Acetald ehyde 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 aceta te monomer, an important commercial product manufactured and/or processed by members of the Vinyl Acetate Council.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 137 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 t esting 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 occurren ce 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 Coll ection 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 18.3 μ /L and the maximum detection value in CAL

DHS dataset was 24 μ /L. EPA also reviewed Toxic Rele ase Inventory (TRI) data with 15,146,4 48 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

response s to comment u nder EPA Comment Code s : 1050 Evaluation Criteria Review and 1060 SDWA
1457

.

Commenter Name: Robert Fensterheim Commenter Organization: Acetaldehyde Working Group
EPA Document ID: EPA

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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 man dates 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) re lating 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
defin ed 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 Evaluatio n Criteria Review.

Commenter Name: Robert Fensterheim Commenter Organization: Acetaldehyde Working Group
EPA Document ID: EPA

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Comment Part: 11
EPA Comment Code: 1050EPA

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Page 138 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

conce ntration 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

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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 drink ing 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 drinki ng 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

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It i s 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 th at 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 d id 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 seco nd 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 manufacture r, 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

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Page 139 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 ha ve 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 inc lusion 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 response s to comment under EPA Comment Code s : 1050 Evaluation Criteria
Review and 2040 Na turally Occurring Contaminants

.

Commenter Name: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

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Comment Part: 6
EPA Comment Code: 1050

Comment: Upon review of the CCL3 Contaminant information sheets f or 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 l isting 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 f or including them on
EDSP List 2.

Response: EPA’s listing of contaminants on the CCL 3 list is discussed in the general response to

c omment under EPA Comment Code s : 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 progr am. 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 herbici des. Journal ofEPA

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Page 140 Environmental Quality 34(3): 877

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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 Techn ology 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 a ttribute 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 att ribute 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 justifica tion 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,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 141 acetochlor. In addition to staff from “Toxicology Excellence for Risk Assessment” (TERA), the panel included the following experts:

*John P. Christopher, Department of Toxic Su bstances 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 Alach lor 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 abse nce 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 c ode 1050. Also, please see gen eral response s to comment under EPA
Comment Code s : 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 appropriat e selection for prioritization of a List 2 for the EDSP program, which clearly specifies that the administr ator 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: P lease see general response to comment under EPA Comment Code s : 1050 Evaluation
Criteria Review and 1060 SDWA 1457

.

Commenter Name: Sarah JanssenEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 142 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

n ot 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 un til 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 persi stent 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
C ommenter 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

- HQ

OPPT

- 2009

- 0477, 75 Federal Register 70248 (November 17, 2010)EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 143 To Whom It May Concer n:

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 P anel 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 Counci l 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 substant ial 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 curr ently 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

becau se “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 expo sure 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 candida te list of potential endocrine disruptors.

Response: Di(2

- ethylhexyl)adipate is regulated with a National P rimary 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 regulationEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 144 due to concerns about occurrence in drinking water and adverse impacts on human health, EPA believes that each such substance meets the statutory testing cr iteria from SDWA sect ion 1457. As required b y SDWA section 1412(b)(9), the a gency 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) adipat e 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 o f systems reported detections. For di(2

- ethylhexyl)adipate, 1.754 percent of 28,90 2 systems reported
detections. The percentage of the population s erved by the systems with detections is 6.767% of over 18.4 million people.

Also, please see general response s to comment under EPA Comment Code s : 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

amou nt 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 s cientific 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
Commente r 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 identi fied 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 dataEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 145 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

IR IS 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 o

dichlorobenzene. These validated end point tests are designed t o 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 manuf acture, 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, procedu ral 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 wash ing 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), o

dichlorobenzene 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 thi s 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 Code s : 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: Sh erman FriedmanEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 146 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 include d 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 solel y 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 NPDW R 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 (af

ter 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 not ed 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 d ata 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 wh ether 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 pursu ant 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 ba sed 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 list s 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 orEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 147 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 environ ment. 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 implementatio n 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 chemical s 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 t hat 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 on ly 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 t echniques; 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 a nd whether the data are statistically significant).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 148 • 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 a ttention 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, pr ocedures 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/qs

docs/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 EP A 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 Chem ical 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 sou rces 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 concentration s 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 149 Commenter Name: Sherman Friedman Commenter Organization: Velsi col 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 Ag ency 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 manuf

actured 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 De termine 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 informatio n 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 wa ter 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) assu med (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 E PA's EDSPEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 150 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 response s to comment under EPA Comment Code s : 2020 Contaminants No Longer Ma nufactured or Imported, or Used in t he US, al s o Includes Pesticides with Cancelled Registrations

, 1050 Evaluation Criteria Review , and 1060 SDWA 1457

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 151 

### 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 ex posed to such
substance.” As stated in 75 FR 70248, November 17, 2010 (U SEPA, 2010b) , i n 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 drin king 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 Chemic al 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: relevanc e, 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

mov e 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 weigh ted 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 publ ished 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 devel op 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 he alth, 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 sc reening program it
authorizes. Section 1457 does not require the a gency 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 Comment Response Document

Page 152 Please note t he E ndocrine D isruptor S creening P rogram SDWA orders will not be issued under the authority of T SCA

. 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

- 8 848

- 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 support s 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

Sec tion 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”. Ac cordingly, 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

Page 153 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

- buta nol’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 autho rity 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 r equiring 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 m onitoring 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 reg ulation 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 wa ter 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 therefor e, 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 occurrenc e 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 Conta minant 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 suppl iers 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, topogr aphic, 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

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- 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 requir ements 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 thes e 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 H A, 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). Chemi cals 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 s ee 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.comEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 155 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 Che micals 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., a nd 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 40 8(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 subst ance 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 sectio n 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

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- 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 (EDS P), 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 t his 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 th e 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 expose d 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 construi ng "substantial population" in

SDW A § 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 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 b eing 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: S ahar Osman

- Sypher Commenter Organization: American Chemistry Council
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 0035
Comment Part: 3
EPA Comment Code: 1060EPA

- 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 populati on” 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 expose d. 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 ha s 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 Compan y 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 f rom 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 Pan el 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 shou ld 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 CC L3 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 f ound 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 resp onse 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

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- 0036
Comment Part: 4
EPA Comment Code: 1060EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 158 Comment: 3. The Panel does n ot 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 p resence 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 th e 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 rel eases. 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

- TD I, 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 drin king 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 rev isit 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 dutie s 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 A ct, 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 NormanEPA

- 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

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- OPPT

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- 0037
Comment Part: 1
EPA Comment Code: 1060

Comment: January 18, 2011

BY HAND

OPPT Document Control Office (DCO) Environmental Protection Agency, Eas t 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 Endocri ne 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 D rinking 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 su ch 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) i s 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 "su bstantial 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 e xposure 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, 89 9 F.2d 344 (5thEPA

- 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 § 14 57.] 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 a rbitrary 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

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- OPPT

- 2009

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- 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 Di sruptor 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 o f 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, SD WA § 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 pu rpose of the Act. The language providing for testing of "any other substance that may be foundEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 161 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 e xposed 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 u nder 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 N ame: Faye Graul Commenter Organization: Halogenated Solvents Industry Alliance, Inc.
EPA Document ID: EPA

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- OPPT

- 2009

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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

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Comment Part: 2
EPA Comment Code: 1060

Comment: NAPPA also notes that E PA has not met the Congressional intent for EDSP that EPA consider substances where a “substantial population” is exposed. Numerous studies have shown noEPA

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Page 162 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

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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 14 57 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, s cale 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 dewater ing 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 po lyacrylamides 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 Orga nization: Acetochlor Registration Partnership
EPA Document ID: EPA

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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 t hat a substantial population has been exposed to the chemical.

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.EPA

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Page 163 Commenter Name: Gregory Watson Commenter Organization: Acetochlor Registration Partnership
EPA Document ID: EPA

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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 amendme nts 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 Inv entory 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 necessaril y 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

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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 thi rd 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 t o determine that a 'substantial population may be exposed to suchEPA

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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 exposur e 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 manu facturers 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 se lect 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."

Res ponse: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Gregory Watson Commenter Org anization: Monsanto Company
EPA Document ID: EPA

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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 Relea se 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 WatsonEPA

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Page 165 Commenter Organization: Monsanto Company
EPA Document ID: EPA

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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 scree n 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 R elease 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 negli gible.

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 bee n 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

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Comment Part: 3
EPA Comment Code: 1060

Comment: While reliance on lists of drinking water contami nants 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 sho uld 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 genera l 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

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Comment Part: 2EPA

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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 bo th 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 antic ipate 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 expose d 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

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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 “subs tantial population has been exposed.”

Response: Please see general response to comment under EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman FriedmanEPA

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Page 167 Commenter Organization: Velsicol Chemical LLC (Velsicol)
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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

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Dear Mr. Owens:

Velsicol Chemical LLC (Velsicol) [FN1: Velsicol i s 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 subst ance 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 Prog ram: 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. 7024 8, 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
Screenin g 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 t he 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 wate r" 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

Sect ion 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 un der EPA Comment Code: 1060 SDWA 1457.

Commenter Name: Sherman Friedman Commenter Organization: Velsicol Chemical LLC (Velsicol)
EPA Document ID: EPA

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Comment Part: 4
EPA Comment Code: 1060EPA

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Page 168 Comment: Comments of Velsicol Chemical LL C On EPA's Endocrine Disruptor Screening Program Second List of Chemicals for Tier 1 Screening [EPA

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January 17,2011

Velsicol Chemical LLC [FN1: Velsicol is a US based, medium sized chemical company, which supplies
intermedi ates 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 manufa cturer 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) de veloped 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, Endocrin e 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 L ist 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 withi n 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 whic h 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

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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 §1457EPA

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Page 169 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 r equirements 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 l imited 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 co nstrue 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 Administr ative 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 authori ty 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

po pulation 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 sc enarios 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 benefit s. 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 wat er 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 w ay 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 EDS P 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.EPA

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Page 170 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 b e 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 co nclusion 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 s ources 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 am bient 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 scient ific 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 believ es 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
C ommenter Organization: Velsicol Chemical LLC (Velsicol)
EPA Document ID: EPA

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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 th at 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 listi ng. 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.EPA

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Page 171 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 an d 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 f ound 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 term s "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
tho se 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 remo ved 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

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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 ch emical 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 mate rials, 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 expos ed” 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 Comm ent Code: 1060 SDWA 1457.EPA

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Page 172 

### 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 scientifica lly 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 stat ute generally requires EPA to “ provide for the testing of all pesticide chemicals ” and gives EPA discretionary a uthority 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 chemi cal upon a determination that “ the substance is anticipated not to produce any
effect in hu mans similar to an effect produced by a naturally occurring estrogen. ” (21 U.S.C. 346a(p)(4)). The EDSP is not a rulemaking process.

Secti on 1457 of SDWA provides that “ in addition to the substances ” referred to i n 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 Admini strator 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 Comm ittee report for EPA's FY 2010 appropriations (H.R. 2996, H. Rept. 111

- 1 80), 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

org anic 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 (FQ PA) and SDWA , along with the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Toxic Substan ces 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
th e 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 tes ting (USEPA, 2011).

Individual CommentsEPA

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Page 173 Commenter Name: Cindy Loy Commenter Organization: Dow AgroSciences LLC
EPA Document ID: EPA

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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

ap pear 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 ena ctment 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 gene ral 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

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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 w ould 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

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Comment Part: 1
EPA Comment Code: 1065EPA

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Page 174 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

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- 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 o f 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) t hat 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 chemical s 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 m ay 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 e nactment 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 an d 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.EPA

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Page 175 Commenter Name: James Lamb Commenter Organization: Hercules, a wholly owned subsidiary of Ashland Inc.
EPA Document ID: EPA

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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 p lasticizers, 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 Wate r 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 drinkin g 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 scre ening 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 §30 0j

- 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

relie s 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 ke y 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
d efine 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.EPA

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Page 176 Commenter Name: Peter Voytek Commenter Organization: HAP Task Force
EPA Document ID: EPA

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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 appro priate 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 [EP A] 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 estab lishing 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, EDSTA C 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 defin itive 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 t o 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
endo crine 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 prod uced by a naturally occurring estrogen, thus they are exempt from testing.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 177 • 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

- tr ichloroethane 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 endo crine 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 response s to comment under EPA Comment Code s : 2070 Contaminants Not Expected to Produce Estrogen

- like Effect , 2060 Chemicals with Toxicity Data Indicating End ocrine 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

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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 produ ced 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 re commendations 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 Fede ral 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 recommend ations 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 req uire EDSPEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 amphibia n 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 E PA’s Authority to Require Testing.

Commenter Name: Andrew Jaques Commenter Organization: North American Polyelectrolyte Producers Association
EPA Document ID: EPA

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Comment Part: 9
EPA Comment Code: 1065

Comment: IV. No Basis for E cological 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 reg ulate 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 re commendations 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 endocr ine 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 pr ovide 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 (wildl ife) 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 HouseEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 179 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

c hemicals, 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 pro gram 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.]. S ection 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 accor dance 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 Congr ess 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. Nowhe re 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 healt h.

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, whi ch 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 Congres s 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 in tended 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 180 Commenter Name: Michael White Commenter Organizati on: Chemical Producers and Distributors Association
EPA Document ID: EPA

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Comment Part: 1
EPA Comment Code: 1065

Comment: Attached please find the public comments submitted by the Chemical Producers and
Distributors Association for i nclusion in docket ID Number EPA

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- 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 & Distributor s 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 advoca te 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 m andate 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 e xperience 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

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- 0477

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Comment Part: 5
EPA Comment Code: 1065EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 181 Comment: CPDA is particularly concerned about EPA’s unsupported reliance on a non

- legislative Congressional di rective 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 che micals 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 e nd 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, legislativ e 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 individu al 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 m embers

- or, worse yet, unelected staffers and lobbyists

both 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. Allapatt ah 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 §145 7; 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

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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 directedEPA

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Page 182 EPA to address “human health” effects. Even though EDSTAC incorp orated 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: Pl ease 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

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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 Drinkin g 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 (EDST AC), 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 n ot 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]oge ther 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

e cological (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

- HQ

OPPT

- 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 fo r 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 183 In the pr esent 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 r etardants (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 dr inking 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 provisi ons 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 s tates:

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 Ac t, 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 wa ter 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 wate r 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

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Comment Part: 4
EPA Comment Code: 1065EPA

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Page 184 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

- industri al 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 t he 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 res ponse 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

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- 2009

- 047 7

- 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 con ducted 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 produ ce 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+%. Emergen cy 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 hazar dous species. The pre

- treated waste water is then discharged toEPA

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Page 185 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 cau stic 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 ha s 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 Tr eatment 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 de dicated 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
iss uance 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 t o 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 Ac t Chemicals (USEPA, 2012a ) that is being published simultaneously with this comment response document

.EPA

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Page 186 

### EPA Comment Code: 1070 Increase Transparency

General Response: The agency has reevaluated the list a nd 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 Incl udes 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 wh en conducting hazard identification and dose

- respo nse 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 with in this document, or other EDSP

- related support documents

Please s ee E PA Comment Code: 1020 Continue U se 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.EPA

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Page 187 EPA Document ID: EPA

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Comment Part: 19
EPA Comment Code: 1070

Comment: A confounding factor in assessing the “added value” of EDSP s creening 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: P lease see general response to c omment under EPA Comment Code: 1070 Increase Transparency.

Commenter Name: Richard Becker Commenter Organization: American Chemistry Council
EPA Document ID: EPA

- HQ

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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 c riteria 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 oc curring 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 o f 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 D raft 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 high ly 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 c omment under EPA Comment Code: 1070 Increase Transparency.EPA

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Page 188 Commenter Name: Richard Becker Commenter Organizati on: American Chemistry Council
EPA Document ID: EPA

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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 Te sting 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. Thes e 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 develop ing 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 c omment 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 Procedure s for Screening Safe D rinking 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

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- 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

in terpret 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, and rogen, 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. H owever, 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 developm ent and
validation of Tier 2 tests.EPA

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Page 189 Response: Please see general response to c omment under EPA Comment Code: 1070 Increase Transparency.

Commenter Name: Michael White Commenter Organization: Chemical Producers and Distributors Association
EPA Document ID: EPA

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- 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 c omment under EPA Comment Code: 1070 Increase

Trans parency. 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: Mi chael White Commenter Organization: Chemical Producers and Distributors Association
EPA Document ID: EPA

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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 Li st 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 t he 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, stron gly acidic or basic, solubility, vapor pressure molecular weight).EPA

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Page 190 Response: Please see general response to c omment 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 do cument

.

Commenter Name: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

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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

m ight 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 naturall y 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 pos itive 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 Contin ue use of Qualifying Language an d 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, p lease see general response to comment under EPA Comment Code: 1070 Increase Transparency.EPA

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Page 191 

### EPA Comment Code: 107 5 Request for Formal Response

General Response: EPA previously stated in the November 17, 2010, F ederal Register for the S econd 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 commen t, even though t his action is not a rulemaking. EPA hopes that this response to comment document will help to provide more

tran sparency for the EDSP process. In finalizing the list, EPA considered all comments and information received from the public conce rning 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

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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 EDS P 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 contami nant 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 r elevant 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 rel ieve 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

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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 rulemakingEPA

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Page 192 proceeding on whether the substances that EPA has decided to include on t he 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 si mply 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

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- 0024.1; EPA

- HQ

- OPPT

- 2009

- 0477

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Response: Please see general response s 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

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- 2009

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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 comment s 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 n otice 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.

R esponse: Please see general response to comment under EPA Comment Code: 1075 Request for Formal Response.

Commenter Name: Richard BeckerEPA

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Page 193 Commenter Organization: American Chemistry Council
EPA Document ID: EPA

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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 inconsi stent 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 f or 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 ha d 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 th at “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 publi c 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 E DSP 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 challen ged (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: 107 5 Request for Formal Response. Please also see Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening Safe Drinking Wate r Act Chemicals (USEPA, 2012a ) that is being published simultaneously with this comment response document

.EPA

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Page 194 Commenter Name: Gregory Watson Commenter Organization: Acetochlor Registration Partnership
EPA Document ID: EPA

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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

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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 Manag ing 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 Doc ument ID: EPA

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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 hasEPA

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Page 195 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 a nd 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 Organiz ation: Consumer Specialty Products Association
EPA Document ID: EPA

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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 conce rned 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 th e 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 resul ts 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 f urther. 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 ProgramEPA

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Page 196 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

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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 comme nt 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 o f 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

a cting 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 : 1075EPA

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Page 197 Comment: January 18, 2010

Steve A. Owens,
Assistant Administrator Office of Chemical Safety and Polluti on 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

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Dear Assista nt 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 Pol icy 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 Prog ram.] 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 o rder 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

F ederal 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 respo nse 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 numbe r 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 othe r 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 wer e 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 t o reconsider the compounds included on the list and provide responses to publicEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 198 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 lis t. 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 proce ss 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 membe rs 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 I nformation 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 Orga nization: Acetaldehyde Working GroupEPA

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Page 199 EPA Document ID: EPA

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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 Janu ary 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
identi fied 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 b e 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 Agenc y 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 t he 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 th at 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: Ple ase see general response to comment under EPA Comment Code: 1075 Request for Formal Response.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 200 Commenter Name: Gregory Watson Commenter Organization: Monsanto Company
EPA Document ID: EPA

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Comment Part: 3
EPA Comment Code : 1075

Com ment: * 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.

Respo nse: 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 L ist 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 ind ustry. 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 th e EPA should adhere to the requisite notice andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 201 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 Agen cy:

* 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 wi th 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 t o 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: 3EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 202 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 regu latory 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 Vel sicol 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 D ocument 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 gene ral 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 E DSP 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 203 E PA 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 Agen cy 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 transparen t 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

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- 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 204 

### EPA Comment Code: 2005 Pesticides as a Group

General Resp onse: EPA acknowledges that for some of the chemicals listed on the second EDSP list there may be existing data re levant to the Tier 1 screening. For test orders requirin g Tier 1 screening assays, the a gency 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 orde r. Test orders specifically provide recipients the opportunity to provide “other

scien tificall y 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 makin g its determinations public. Future test order recipients may obtain the se determination s from the EPA W eb 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

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- 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. Simi larly, 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 h igher 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 as says 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,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 205 toxicogenomic data, and reproductive toxicity tests", as well as testin g 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, uterot rophic, 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 mecha nistic 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 c omment under EPA Comment Code: 2005 Pesticides as a Group. Also, please see gener al 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

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- 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, p lease 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 approv ed 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

-EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 206 chronic and chro nic 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 endocrin e

- 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, ute ri, 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 bett er 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, ru minant 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 Program s 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 inc lude 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 appropriat e 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 t he 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 emph asis 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:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 207 2100 Pesticide Registration Review Issues. Also, p lease 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, i n response to a petition from several States.

Response: Please see general response to comment under EPA Comment Code: 2100 Pesticide Registration Review Issues. Also, p lease see general response to comment under EPA Comment Code:
2005 Pesticides as a Gro up.

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 ch emicals 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

reg istering 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 outcom es, 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, i t 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 pes ticides 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 208 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 chemi cals, 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 expos ure 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 c hemicals 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 screenin g. 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 bo th 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. P lease see general response s to comment under EPA Comment Code s : 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 pes ticide 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 hav e 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: P lease see general response to comment under EPA Comment Code s : 1050 Evaluation
Criteria review

, 2100 Pesticide Registration Review Issues , and 2005 Pesticides as a Group

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 209 

### 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 be nzyl chloride, cumene hydroperoxide (CHP), oxirane, methyl

- (propylene oxide or PO), and triethylamine (TEA).

EPA received comments chlorodifluoromethane ( HCF C

- 22 ) and toluene diisocyanate (TDI) should also be removed from the list due to testability is sues. 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 g lycol. 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 met amorphosis 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 pred icted 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 neces sary 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 aro matase 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?EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 210 Propylene glycol produced from the spontaneous conversion of p ropylene 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. cryopreservatio n 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 endocr ine 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 (Herschberg er 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 metho ds. 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 a bove 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 f or 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 in formation, 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 p ropylene 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) Quant itative Structure

- Activity Relationship for the Acute Toxicity of Some Epoxy Compounds to the Guppy. Aquatic Toxicology.
13:195

- 204.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 211 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 epoxid es 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, butyl ene 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 bioaccumulatio n 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

carc inogen. 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 condu cted for the EDSP must be based on “validated test systems and other scientificallyEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 212 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 (

- 4 0.8 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 Pla stics 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 c omment 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 proto cols 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 scientif ically 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 213 Response: Please see general response to comment under EPA Comment Code: 2010 Contam inants 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: Triethylamin e Acute Toxicity To Rainbow Trout (Oncorhynchus Mykiss) Under Flow

Through 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 pr ior 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 th e corrosive nature and strong alkalinity of TEA.

Response: Please see general response to c omment 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, 201 0 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 ba sic, 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 pro perties. 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 c omment under EPA Comment Code: 2010 Contaminants Identified by Commenters as Being or Potentially Incompatible with Test Assays.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 214 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 eli mination 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 C omment 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

- c hemical 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 EP A Comment Code: 2010 Contaminants Identified by Commente rs 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

- adduc ted species occurring in these in vitro assays would not be expected to reflect theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 215 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 216 

### 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 banne d, no longer manufactured or imported, or are cancelled pesticides and should therefore be
exclu ded from the second EDSP list. The a gency 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 p lease 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 f or scabies and lice treatment. Lindane has been detected in sources of drinking water. See EPA ’s W eb site for more information on linda ne: http://www.epa.gov/ttn/atw/hlthef/lindane.html

. 2. Polychlorinated biphenyl (PCB) : This chemical remain s on the list so that orders can be issued

should a manufacturer be identified or someone begin s 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 b anning or limiting the use of MTBE, with effective dates ranging f

rom 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 wat er wells is likely to continue because of existing soil and ground

water contamination and continued MTB E

- contaminated plume movement. The production andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 217 importation of MTBE in the United States was over 1 billion pounds for all IUR repor ting cycles

from 1 986 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

– T richloroethane : 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 bei ng 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 Po llution 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 af filiated 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 Endocrin e 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 theEPA

- 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 conta ined 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 importer s. 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 oppor tunity 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/tes ting.

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 the se 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 wo uld 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 contact ed 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 your s,

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

- O PPT

- 2009

- 0477

- 0019EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 219 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 s ulfosate ) 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 chemic als 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 quest ion 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 non

agricultural (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 le vels 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 f enamiphos 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 t he 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 Decemb er 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 Comment Response Document

Page 220 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 fena miphos), 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.
Toler ances 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 w hether 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 th at 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 Ethica l 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 r egistration 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

Sulfo sate, 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 regist ration maintenance fees, and a notice was published in the Federal Register on October 27, 2004 titled “Cancellation of pesticides for non

- paymentEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 221 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). A lso, 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 pest icide 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 activit y 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 agricul tural 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 wi th 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 pharmaceutica l 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 ve ry 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, th ere 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: 12EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 222 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 bec ause 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 th at can rem ove 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 detectio n 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. Therefo re 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 Manufact ured 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

- D G 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 b e 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: Pat ricia Casano Commenter Organization: General Electric Company
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0023
Comment Part: 1
EPA Comment Code: 2020EPA

- 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 c hemicals 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 th at 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 th e 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 a lso 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 atEPA

- 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 conti nually 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 ha ve 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 env ironment, 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 adip ose 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 decrease d 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
unint entional 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 backgr ound population PCB serum levels peaked in 1979, and have declined since that time.

Including PCBs In The EDSP Is UnnecessaryEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 225 The point of the EDSP is to screen chemicals for possible endocrine effects, but EPA already is assessing the potential noncance r 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 EP A'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 repro ductive 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 endo crine 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 determine s 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 te sting 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
info rmation.

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 Co urt recently stated:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 signi ficant 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 o ption"); 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
determin ing 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 gene rally 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). S ee 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 EP A 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 e ffort 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 endo crine 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 a ctivities 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. T here 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 EP A 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 b een 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 Beck er 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 w ho 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 so me instances, may be found as contaminants of drinking water, are not covered by the 1996 endocrine
amendments to the SDWA.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 228 Response: Please see general response to comment under EPA Comment Code: 2020 Contaminants No Longer Manufactured or Imported, or U sed 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 followi ng 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 inte nds 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 d rinking 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 incl usion 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 Ac t 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

- O PPT

- 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 noEPA

- 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 mater ial 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 op posed 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 toxap hene.

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 subs ection, 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 order s 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 discon tinue 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 Procedur es”).]

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 Organiz ation: Hercules, a wholly owned subsidiary of Ashland Inc.
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0030
Comment Part: 4
EPA Comment Code: 2020EPA

- 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 resour ces.

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 Prot ocol (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 allowanc es 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 protec tion 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.

Even tual 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 Indu stry 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

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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. To xicol. 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

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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 th e 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 t he 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.

Resp onse: 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

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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

- trichloroethan e drinking water exposure has declined effectively toEPA

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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

- trich loroethane 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 r esulting 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 Co mprehensive 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

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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 Un ited 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). T here 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 tet rachloride 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.

Commente r Name: Robert Simon Commenter Organization: American Chemistry CouncilEPA

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Page 233 EPA Document ID: EPA

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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 act ions 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 ph ase

- 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 homolo gue 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 D ecember 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 TSC A 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 Associatio n EPA Document ID: EPA

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Comment Part: 9
EPA Comment Code: 2020EPA

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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 FFDC A 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 manufacture d 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 no t 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 Nam e: Wendelyn Jones Commenter Organization: CropLife America and Endocrine Policy Forum
EPA Document ID: EPA

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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 al igned 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 awa re 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 ra pid 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 Na me: Frank Sanders Commenter Organization: Bayer CropScience LPEPA

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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: Plea se 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

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- 2009

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- 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

w ould 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, hept achlor 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

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- 2009

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Comment Part: 5
EPA Comment Code: 2020EPA

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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

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- 2009

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- 0068
Comment Part: 10
EPA Comment Code: 2020

Comment: IV. EPA Sh ould 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, heptach lor 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 an d, 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 Ag ency 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 su bsection, 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 chemi cal 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

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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 ("Draf t 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, 2 009 ("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 respons e 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 re ceive 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 implem entation 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 propose d 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 w ho 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 EDS P List 2 that will not be tested within the EDSP. Rather than attempting to list those substances, EPA should direct itsEPA

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Page 238 resources to determining whether substances that might be tested are found in sources of drinking water to which a substantial populati on 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
Co mmenter Organization: Velsicol Chemical LLC (Velsicol)
EPA Document ID: EPA

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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 Ma nufactured 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
manufacture rs 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 implic itly 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,

c ontinuing 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: E PA 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 manufac tures 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

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Page 239 • 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 equit able.

• 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

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- OPPT

- 2009

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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
th ese 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 I ncludes 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

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- 0073
Comment Part: 4
EPA Comment Code: 2020

Commen t: In addition, EPA asked whether chlordane, heptachlor or endrin were manufactured for non

pesticide 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 onlyEPA

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Page 240 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. Qui ll Enc. (one CD)

Attachments [See PDF Docket ID EPA

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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 wit h Cancelled Registrations.EPA

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Page 241 

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

General R esponse: EPA received several comments requesting that chemicals be excluded from the
second EDSP list based on information tha t 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

r emain 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 b een 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 A ssays

.

EPA has identified and reviewed production and/ or release data for these chemicals ; EPA believes th at
these data are reliable for determining that these chemicals “may be found in sources of drinking water”
to which a “substanti al 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 a gency 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 recommen ds 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 lin k (pathway) to drinking

water. The Toxics Release Inventory (TRI) database

, which includes informa tion 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 lin k (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. EP A 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 use s 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

Co mmenter Name: Marcy Banton Commenter Organization: LyondellBasell Industries
EPA Document ID: EPA

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Comment Part: 2
EPA Comment Code: 2030

Comment: 2. Propylene oxide is not expected to be found or persist in water.

As noted above, p ropylene oxide is readily biodegradable in aquatic environments (MITI, 1988); hence it is not expected to be persistent in the environment. Furthermore, propylene oxide spontaneouslyEPA

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Page 242 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 oxid e 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 res ponse s to comment under EPA Comment Code s : 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 hel p 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 a nd wildlife.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 243 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 C ode : 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)
Off ice 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;

Se cond 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 post

emergence herbicidal active ingredient.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 244 Pursuant to EPA's request for comments on List 2, DAS is providing specific rema rks 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 co ncerns: 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 Regi ster 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 Wa ter 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 include s 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 populati on 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 mo ving 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 in formation 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 (Cal ifornia, 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 quantif ication 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 an alyzed 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.e r.usgs.gov/apex/f?p=HBSL:HOME:0]

Ground WaterEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 245 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 response s to comment under EPA Code s : 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 se e 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 listin g:

- 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 Jan uary 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 cri terion 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 sub stance 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 Asse ssment Report (SIAR)EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 246 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

- wo rld 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 1 21].]

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 relea sed 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 on

site 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 ini tiator 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 ex posure 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 temperatur e 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 s heets 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 temper ature 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 article s 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 phy sical 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 requiremen t that “such substances may occur in sources of drinking water to which a substantial population may be exposed.” [75 FR 70250]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 247 Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants Unlikely to Persist in Drinking Wate r

.

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 Attachme nt 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 seve n 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 solubilit y 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 groundwater

monitoring wells were below the analytical detection limit. [FN2: See, “Groundwater Issues Relating to

Alask an 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 follo wing 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 o fficials found that the discharge into the Kanawha River did not result in any reports of fish kills or other environmental
effects.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 248 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 response s under EPA Comment C ode s : 2040 Natu rally Occurring
contaminants

. Also see general response to comment under EPA C omment C ode : 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 D rinking 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 Disr uptor 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 d rinking water chemicals as authorized by the Safe Drinking Water Act (SDWA) section 1457. Among the compounds on List 2 is isoxaben, a selective pre

emergence herbicidal active ingredient.

Pursuant to EPA’s request for comments on the Draft EDSP List 2, D AS 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 emph asize 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 Wat er 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 is oxaben, 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 solubi lity 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.usg s.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: 2030EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 250 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 wate r 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 hav e 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. Sinc e 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
relea sed 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 th e 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 Contaminan ts 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 HCFC

22 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 wentEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 251 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” inclu des 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 mult iple 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 com ponent 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” appar ently 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 s cores 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 surfac e 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 w ater”. 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 sh ould 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 re sponse to comment under EPA

Comment Code: 1060 SDWA 1457.

Commenter Name: Rebecca Bernstein Commenter Organization: Arkema Inc.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 252 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 H 2NNH2 • 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 polyureth ane 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 r eleased into reservoirs from power plants is further diluted and has a very short half

life in surface water, again, reacting with dissolved oxygen to form nitrogen and water.

Government reports cite literature indicating "Hydrazine is rapidly removed fro m 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 2 009 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 dr inking 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.] Final ly, 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 p opulation would be exposed to hydrazine by this

route.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 253 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 In c. 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, whic h 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 ; Diisop ropylamine; 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 accumu late 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

- 003 3
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 L ist 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 wa ter were reported.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 254 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 t o 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 di etary 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 req uiring 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: Degradatio n 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 e stimated 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 exp osed.

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 Produce rs 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 pr esence 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 ofEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 255 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

- 1 21]] 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 e nvironmental 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 i ndicates 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, ove r 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 r aw 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 ma ny 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)EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 256 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 Substa ntial 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 explaine d 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 refrigerat ion 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.

R esponse: 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. 20460EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 257 Attention: Docket ID Number EPA

- HQ

- OPPT

- 2009

- 0477 Submitted via Federal eRulemaking Portal: http://w ww.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 commit ted 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 bil lion 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 an d 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 com munication, 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 MD I: 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 hydrophob ic 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 re sponse to comment under EPA Comment Code: 2030 Con taminants Unlikely to Persist in Drinking Water.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 258 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, environ mental 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 e ffluents 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 c ars 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 a nd 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 c ontrolled 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., SW

846, 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 (LC

MS).

Response: Please see general response to comment under EPA Comment Code: 2030 Contaminants
Unlikel y to Persist in Drinking Water.

Commenter Name: Sahar Osman

- Sypher Commenter Organization: American Chemistry Council
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0 477

- 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 ma y be exposed to TDI. The Panel appreciates the opportunity to provide comments to theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 inf ormation/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 c omment 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 prima ry 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 san dy 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 t he 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, althoug h 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 de tections of ethylene glycol in water. Further, in the penultimate stage of the Universe

- to

- Preliminary CCL (PCCL) screeningEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 260 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 reli ance 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 shou ld 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 response s to comment under EPA Comment C ode s : 2030 Contaminants Unlikely to Persist in Drinking Water and 2040 Naturally Occurring Contaminants.

Commenter Name: Jean Kasakevich Commenter Organization: The Dow Chemical Compan y (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:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 261 Second List of Chemicals for Tier I Screening" [75 FR 70248; 11/17/2010; EPA

- HQ

- OPPT2009

- 0477; FRL

- 8848

- 7], specifically concerning Propylene Oxid e.

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 eval uation 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 ris k 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 keepin g 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 surfa ce 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 s to commen t under EPA Comment C ode s : 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 a s 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 emissio ns 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, thi s 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 reporte d emissions toEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 262 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

ge neral 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
C omment C ode : 2030 Contaminants Unlikely to Persist in Drin king 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 Screen ing 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 CORPORAT ION

January 18, 2011EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 26 3 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. R eg. 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 Contaminan t 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 Drinkin g 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 foun d 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, C hemicals 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, Hazard ous 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 co ntrols 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 e xposed 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: 2030EPA

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Page 264 Comment: Exhibit 3 attached hereto summarizes the information that EPA used to list benzy l 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 i n 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

w ere "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 important ly, 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 publi c 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 t he 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: U nited 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 reactio n. [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 chlor ide 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 con tainment 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. Seco ndary 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 qualif ied 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 A gency did not investigate, however, whether such a determination was actually made (it was not)EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 265 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 requi ring 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 populat ion 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 pl ants, 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 l ikely 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) o f 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 benzy l 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 t ypical 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 th e 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 20 04 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 infe r 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 wate r. 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 w idely distributed precipitation of benzyl chloride from the atmosphere to surface water in 2004, where any precipitation would have hydrolyzedEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 266 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 an d 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 significa nt 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. F erro 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 sa tisfy 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 satisf y 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 p lease see gener al response to comment under EPA Comment
Code: 20 80 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 (S IRC)
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.EPA

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Page 267 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 w ater 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 bein g 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 concentra tions 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 re lated 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 o bserved 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 t o 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 ca ses 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

prese nt at concentrations which would cause endocrine related effects on aquatic populations. Levels of styrene in groundwater also have been found to be very low.

SummaryEPA

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Page 268 The environmental fate properties of styrene are well documented, and indicate an overal l 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 resp onse to comment under EPA Comment C ode : 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 highl y 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 photodegra ded 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

presen ted 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 hexachloro cyclopentadiene 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, 3 71

- 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 Pr oject No. 482428, Report No.4 Laboratory Report.]EPA

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Page 269 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
hex achlorocyclopentadience 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 a lso 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

- lif e 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

f actor 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 d ays 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 gro und 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 unlike ly 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 Enviro nmental 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 Indus trial 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 partic ulates 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.EPA

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Page 270 Response: Please see general response to comment under EPA Comment C ode : 2030 Con taminants 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 a re 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 drinki ng 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, o r 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

R eview 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 32 5, 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.EPA

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Page 271 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 serv ing 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 Oc currence 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 p opulation 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 prese nt 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 positi ves. 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

repor ted 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 appreci ates 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 shou ld
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 O rganization: The Dow Chemical Company (DOW)
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0069EPA

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Page 272 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 Sc reening" [75 FR 70248; 11/17/2010; EPA

- HQ

- OPPT

2009

- 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 p roduction 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 partic ipated 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 an d 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 drinki ng 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 doe s not persist in surface water or groundwater environments.

Response: Please see general response to commen t under EPA Comment Code : 2030 Contaminants Unlikely to Persist in Drinking Water. Also, please see general response to comment under EPA

Comment C ode: 1060 SDWA 1457.

Commenter Name: Jean Kasakevich Commenter Organization: The Dow Chemical Company (DOW)
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0069EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 273 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 su bstances 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 D ow 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 dischar ge, 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 sourc e. 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 d etected 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: E pichlorohydrin 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 drinki ng 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 ge ographies, 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 Tie r 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, Mat erial Safety Data Sheets, and other US regulations).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 274 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 wate r, 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 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, 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 mut agens 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 275 John, J.A., et al. (1983b). Teratologic evaluation of inhaled epichlorohydrin and allylchloride in rats and

r abbits. 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., Sella kumar, 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). Cytog enetic 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 Du uren, 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
bill ion 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 commen t under EPA Comment Code: 2030 Contaminants Unlikely to Persist in Drinking Water. Also, please see general response s to comment under EPA
Comment Code s : 2080 Contaminants with Low or No Compre hensive Occurrence Data and Therefore Do Not Meet SDWA 1457 Requirements and 1060 SDWA 1457.EPA

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Page 276 

### 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 possib ility 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 Relea se 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 25,0 00 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 perc hlorate on CCL 3 can be found at http://water.epa.gov/scitech/drinkingwater/dws/ccl/upload/Final

- CCL

- 3

- Contaminant

- Information

Sheets.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. Environmenta l 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 m anufacturer 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.EPA

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Page 277 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 electro chemical 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 busine ss 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 conta mination. 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 perchlora te 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, E PA 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) li st (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).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 278 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. C hemicals 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 weig ht). 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, ag ricultural, 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 is otopes, 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 fe rtilizer, 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 photoc hemical 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 perchlo rate 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 (R ajagopalan 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 relea se 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).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 279 • 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 consiste ntly 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 scru blands, 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 response s to co mment under EPA Comment Code s : 2040 Naturally Occurring Contaminants and 1050 Evaluation Criteria Review

.

Commenter Name: Gregory Dolan Commenter Organization: Methanol Institute
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 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 dat a 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 chromatograp hy 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: Inter tox, Inc. on behalf of Perchlorate Study Group
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0039
Comment Part: 2
EPA Comment Code: 2040EPA

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Page 280 Comment: The purpose of this document is to examine the Agency’s inclusion of perchlorate on the

November 17th list. The foll owing 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 conce rn 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 a ddition 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 p recipitation.

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 byp roduct 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 s ee 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, radionuclid es).

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 sta ble 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).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 281 • The average perc hlorate 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 mini mal 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 samp les 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 zone s 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 gl obally. 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 fertili zer is natural, it can be distinguished from perchlorate deposited in the US. Some examples from publicly available literature include:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 282 • 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 so urce 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 8,0 00 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 i n 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

e xclusion 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 re sponse s to comment under EPA Comment Code s : 2040 Naturally Occurring Contaminants and 2020 Contaminants No Longer Manufactured or Imported, or Used in the US, also Includes Pesticid es 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 nat urally 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

Occurr ing Contaminants.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 283 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 preci pitation.

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 byproduc t 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 Administrat ion (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 DirectorEPA

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Page 284 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., BA SF, 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 cla ss 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

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- 0042
Comment Part: 5
EPA Comment Code: 2040

Comment: NAPPA also notes th at 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 “n aturally

occurring 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 environment al 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 acr ylamide 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.EPA

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Page 285 Commenter Name: Andrew Jaques Commenter Organization: North American Polyelectrolyte Producers Association
EPA Document ID: EPA

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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, inor ganics, 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. Chem icals 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 mor e 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 “natural ly

- 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 ED SP 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/ p olyacrylamide 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 acrylamid e. 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 Nation al 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
th at 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:EPA

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Page 286 The greatest source of exposure of the g eneral 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, includin g 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.

Respons e: Please see general response s to comment under EPA Comment Code s : 2040 Naturally Occurring Contaminants and 1050 Evaluate Criteria Review

.

Commenter Name: Robert Fensterheim Commenter Organization: Acetaldehyde Working Group
EPA Document ID: EPA

- HQ

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- 2009

- 0477

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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 statuto ry 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 comparis on 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. Additiona lly, 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 Organizat ion: Acetaldehyde Working Group
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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Comment Part: 8
EPA Comment Code: 2040

Comment: II. Drinking Water is a De Minimis Contributor to the Public Exposure to AcetaldehydeEPA

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Page 287 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 fin ally 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 bei ng 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 (in cluding 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.EPA

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Page 288 

### 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 relev ant 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 Relevan t Information (OSRI) as part of their initial response to re ceiving 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 (U SEPA, 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 Pesticide s with Cancelled Registrations. Several
contaminants mentioned in this section have been removed from t he 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
Commente r 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 activitiesEPA

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Page 289 (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 st udies 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 C ode : 2060 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints and general response to comment under EPA Comment C ode : 2020 Contaminants No Long er 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 littl e 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 exp osures 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 regulati on 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 l eads 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 CC l4 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,EPA

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Page 290 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 alcohol

induced cirrhosis (Van Thiel, Gavaler et al. 1980; Sundari, Wilfred et al. 1 997; 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 semi niferous 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 v alue 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 t he 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 Tox ic 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 stre ams. 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% chl orine 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 prod uce 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.EPA

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Page 291 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 r eduction 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. Ef fects 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 parti cularly 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 estrog en 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, di srupts 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 injecti ons 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 anti

thyroid 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 an d 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 ex tremely 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 thi s 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 remediati on 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 regulato ry 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 endocrineEPA

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Page 292 activity of these chemicals, these data render further testing redundant and there is therefore no reason for including these chemicals i n 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
2007 f). 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 a ffected 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 methoxychl or 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).

Respon se: Please see general response to comment under EPA Comment Code: 20 60 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 Ani mals (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 (Ande rsen, 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 (Kum ar, 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

- androgen ic fungicide known to inhibit testosterone binding (Kelce, Monosson et al. 1994) and was used as a control in validation of the fish short

- termEPA

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Page 293 reproduction, Hershberger, steroidogenesis, and male pubertal assays. In validation studies for the fish
short t erm 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 o f 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 a nd 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 and rogen 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 w ith Cancelled Registrations.

Commenter Name: Catherine Willett Commenter Organization: People for the Ethical Treatment of Animals (PETA), et al.
EPA Document ID: EPA

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- OPPT

- 2009

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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 toxicolo gical 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 se veral 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 “po tent” 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 exposure

induced mutagenicity (Ghana yem, 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 neuro toxicity 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 obser ved reproductive impacts (which predominantly affect males), multigenerational
studies in rats have identified additional mechanisms that contribute to the chemical’s cumulativeEPA

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Page 294 toxicity profile. Acrylamide increases Leydig cell death and perturbs gene exp ression 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 specifi c 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 fo r 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 commen t under EPA Comment Code: 20 60 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

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- 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 excl uded 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 Agenc y 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 Tie r 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, pe rchlorate 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).EPA

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Page 295 According to the research reviewed, perchlorate is not a carcinog en, 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 fir st 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 syst ems 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; FRL

8848

- 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 rev isions 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 t he science regarding perchlorate.

Response: Please see general response to comment under EPA Comment Code: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

.

Commenter Name: Howard Feldman
C ommenter Organization: American Petroleum Institute
EPA Document ID: EPA

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- 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

- 0001EPA

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Page 296 Re: Comments on Specific Chemicals (Benzene and MTBE) for the “Endocrine Disruptor Screening Program: Seco nd List of Chemicals for Tier 1 Screening” [75 FR 70248; 11/17/2010; EPA

- HQ

- OPPT

2009

- 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,

trans portation, 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 eff ects 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 resource s.

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 repro duction 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, developm ental 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 l ife 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 determi ned 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

Wa ter 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 Early

life 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 toxic ity test with the cladoceran (Daphnia magna), is proposed for EDSP Tier 2. EPA shouldEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 297 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 Character ization 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 to xicological effects’ end

points. 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 epidemiolog ical 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: 20 60 C hemicals 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

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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). T he 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 genotox icant. 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: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

.

Commenter Name: Rebecca Bernstein Commenter Organization: Arkema I nc. EPA Document ID: EPA

- HQ

- OPPT

- 2009

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Comment Part: 9
EPA Comment Code: 2060

Comment: c. TPTH Has Already Been Tested in Higher Tier StudiesEPA

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Page 298 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: 20 60 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

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- 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 the se 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: 20 60 Chemicals with Toxicity Data Indicating Endocr ine Disruption or Other Reproductive Developmental Endpoints

.

Commenter Name: Andrew Jaques Commenter Organization: North American Polyelectrolyte Producers Association
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 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 shrim p, 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 acr ylamide does not cause significant harm to aquatic organisms at low concentrations” (Environment Canada 2009) and concluded that:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 299 [A]crylamide is not entering the environment in a quantity or concentration or under conditions that have or may have an imm ediate 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 bioaccumulatio n.

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 c onducted 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
chan ges, 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 repr oductive 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
end point 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: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

.

Commenter Name: Andrew Jaques Commenter Organization: North American Polyele ctrolyte Producers Association
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 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/UCEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 300 M200349.pdf] outlines its research accomplishments and ongoing work on acrylamide (this is summarized in Attachment 2). The NCTR is evaluating both the chroni c 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 expecte d 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 bey ond 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 populatio n” 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). Additiona l 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 healt h 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 dat abase 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 d oes 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 t he 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 As sessment for the Challenge Program: 2

- Propenamide (Acrylamide) CAS 79

- 06

- 1. August 2009EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 301 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/Existing

Chemicals/ 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: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

. Also, see general response s to comment under EPA Comment Co de s : 2090 Contaminants with MCLG of zero
and 1065 EPA’s Authority to Require Testing.

Commenter Name: Robert Simon
Commenter O rganization: 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. PF OA 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

con ducted 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 non

human primate species. Additional human health and env ironmental 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 th e 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 302 b. Chronic Toxicity Studies i n 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 a s 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 triio dothyronine, 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 fluoropolym er 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 provide d 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 long

term (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 priorit y 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 303 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 endpoin ts, 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 activiti es 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 pathw ay 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 chemical s 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 Long

Chain 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 informa tion 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

ReferencesEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 304 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 ra ts. 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 m innow (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. Toxico genomic 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 do cument

.EPA

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Page 305 Commenter Name: Kathleen Roberts Commenter Organization: Methyl Tertiary Butyl Ether (MTBE) Consortium
EPA Document ID: EPA

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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 f

or 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 ba ttery 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 b e 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 Availab ility 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 c ollect 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 CytosolEPA

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Page 306 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 baculovirus

infected insect cells (Mose r 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 in dicated 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 th e 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.

Estr ogen 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 mammalian

based transfection assay using human liver HepG2 cells. Changes in acti vation 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 t o

- 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 Comm ittee 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 t he 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, fi ndings, 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 m etabolites 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 bee n 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 laborat ories have independently conducted 28

- day gavage studies of MTBE and looked at effects on male rat prostate andEPA

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Page 307 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 a ndrogen

- 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 t hose 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 rode nt 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 w ould 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 t hese 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 screen ed 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 Peyst er 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 s erum 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
bioas says.

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 progre ss). Although analysis of data is not quite complete, it is clear that liver and testicular microsomal aromatase activity continue to show dose

- related decreasingEPA

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Page 308 trends in this high

- dose MTBE in vivo rat model. Final results for other related endpoints ar e 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 physiolo gical 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 o thers 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 effec t 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 E R

-- 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 rea sons 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 tol erated 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 we re 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.EPA

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Page 309 No clear, cons istent 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 subcuta neous 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 th e 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 endocrin e effects that have not
received as much attention.

Hershberger (Rat)

This assay uses gonadectomized adult male rats and is designed to detect androgenic and anti

androgenic 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 pu blication, 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 weig hts 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, an d 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 org an 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 not ations 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)EPA

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Page 310 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
al ter pubertal development. No generally comparable studies have been reported to date. Endocrine

related 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 co nducted 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

ma le 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 pube rtal 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
incre ase 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. Essentiall y 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 ass ay.

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 typica l 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 isEPA

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Page 311 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 i ndicative 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 lar vae/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 zebra fish (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 t o 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.

Ther e 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 measure s (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

conc entration 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 def ined. 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

appa rently 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 analyse s of MTBE concentrations were going to be performed, then the authors should have made some general statements about the observed relationshipsEPA

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Page 312 between nominal and measured concentrations and reported all results based upon nominal
concentrations.

* The a uthors 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 e xposure 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 protei n 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 sugg est 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 22 0 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 conce ntrations 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 t o 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 concentr ations 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 experime nts. 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 measur es are highly susceptible to timing with significant losses in velocity occurring within seconds after activation of the sperm (Kime etEPA

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Page 313 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, ar e 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 2 20 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 o n 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 concentratio ns 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 t he 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 analys is of the estrogenicity of MTBE was determined using the medaka fish vitellogenin assay. As a positive reference substance 17β

estradiol 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 250EPA

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Page 314 nanogram 17β

- estradiol per liter. This last level was a nominal level and was not checked by chemical analysi s.

The level of aromatase m

- RNA in the liver did not change by exposure to MTBE or exposure to 17β

estradiol. 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 rene wal. 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 Me daka (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 (NO AEL) 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 demonstra ted 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 result s 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 l evels 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 an d 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 Requ irements 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 s ubstance 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.EPA

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Page 315 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 prof

ile 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 en compass 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 assessme nts, 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 th e 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 e xposure. 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 tha t 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 ha ve 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 extr eme 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 a re 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 mechanistical ly

- 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 experimentsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 316 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 not ed 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 EP A 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

Alme ida 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 o f 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 Toxicolo gy 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, Rod riguez 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 toxi city 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 An drogen 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, Rura ngwa 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, Yuf eng 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 dem onstration. 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 repr oductive 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 methyl

tert

- 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 estrogen

sensitive t issues 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) Co mpetitive 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 111:8 3

- 88.

Williams TM, Cattley RC and Borghoff SJ. (2000). Alterations in endocrine responses in male Sprague

Dawley 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: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 319 

### 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 relev ant 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 r esponse 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 Ta sk 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: P lease see general response to comment under EPA Comment Code: 20 70 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, NWEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 320 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 w hich 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 therefo re 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 m ay 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 no t 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, tera tology 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

- 34 4 rats as test subjects. Although not expressly stated, it appears that this study was conducted according to test guidelines in use at the time.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 321 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 mal e 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 paren tal 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 stu dy. The no

- observed

- effect

level (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 conce ntration (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 va riable 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 avail able 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 (C ERHR) 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 p hases 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 ecotoxici ty 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 re s ponse to comment under EPA Comment Code: 2010 Contamin ants Identified by Commenters as Being Potentially Incompatible with Test Assays. Also, p lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: John Jachetta
Commente r Organization: Dow AgroSciences LLCEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 322 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. Endocrine

related effects have never been found in any study.

In short

- term dietary repeat

- dose rat s tudies (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 NO EL 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 non

carcinogenic 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 s alivation 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 NOEL s 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 le sions 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 par ental 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, piclora m 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);EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 323 * Daphnid, 21

- d NOEC = 6.79 ppm (picloram acid) (21); * Daphnid, 21

- d NOEC = 11.8 ppm (picloram ac id) (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/o r 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 therefor e 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: P lease see gener al response to comment under EPA Comment Code: 20 70 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 demons trates 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 expos ure (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 o r 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 ur ine, 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 car cinogenicity (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

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 324 Response: P lease see general response to comment under EPA Comment Code: 20 70 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

- media ted 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. Fu rthermore, 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 Affa irs

Response: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Catherine Willett Commenter Organization: People for the Ethical Treatment of Animals (PETA), e t 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 long

term 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 325 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 act ivation 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) u sing 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 hE R 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 po tent 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 s ignificant 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 carcinogenici ty 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 th at 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 we re more refractory to the induction of thyroid follicular cell tumors than rats (EPA 2006a). An epidemiological study thatEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 326 evaluated >1000 alachlor manufacturing

- plant employees showed no evidence of increased incidence of thyroid tumors or any other hormo nally

- 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 experi mentally 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: P lease see general response s to comment under EPA Comment Code s : 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect and 2060 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Develop mental 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. Eviden ce 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 ca se

control 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 c ombined with proven lack of endocrine activity should exempt alachlor from further testing.

Response: P lease see general response to comment under EPA Comment Code: 20 70 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 ofEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 327 pesticides with suspected residues in vegetables and fruits by using the cell proliferation of estrogen

dependent 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
bin ding 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. P lease see general response to
comment under this EPA Comment Code: 20 20 Contaminants No Longer Manufactured or Imported, or used in the US, also Includes Pesticides with Cancelled Registrations. Also, p lease see general response to comment under EPA Comment Code: 20 70 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 chroni c 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 conf irmed 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 th e 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 1 967; 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 e ffects (ATSDR 2007). Inhibition of benzene’s metabolism consequently reduces benzene’s toxicity (Andrews, Lee et al. 1977).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 328 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 expos ure 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 typ ically 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 fur ther 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 (follo wing 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

- amino phenol, 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 nitro

and 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 tar get 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; E PA 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 rel atively 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 (Bo nd, 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

- wee k 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).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 329 Although n o 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: t wo 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 nitr oarenes, 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 ant ioxidants 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 hepatotoxi city 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 biochemic al, 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 gluta thione 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 notEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 330 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 rem oved 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 chemotherapeuti c 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 ED SP 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 e t 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 organ s, 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 oxid e (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

- li fe 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/da y 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 wa s 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 o nly to body weight changes and methemoglobinemia with its associated hematologic effects (Ellis, Hong et al. 1984).EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 331 Although GTN has not been examined for its capacity to bind estrogen, androgen or thyroid hormone receptors in in vitro assays, reproducti ve 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 attrib uted to an increase in interstitial cell tissue and consequently decreased spermatogenesis in males (NovaDel Pharma Inc. 2004). An additional three

generation reproductive toxicity study in rats showed no effects on fertility, viability, growth, or develop ment 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 injecti on 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 adminis tered 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 studie s 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 dini trate, 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 d egeneration 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 as sessment 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 al so 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 332 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 manu factured 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 pr ovided such arguments for several chemicals that would warrant their removal from the second list.

Response: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect

. Please also see gen eral responses to comment under EPA
Comment Code s : 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 Organiz ation: 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
vi a 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 prior ity for endocrine screening.

Response: P lease see general response to comment under EPA Comment Code: 20 70 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 includin g 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 Ma rch 30, 2006 the American Chemistry Council Benzene, Toluene and Xylene (BTX) VCCEP ConsortiumEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 333 submitted data for several chemicals, including benzene. That submission included an exposure assessment as well as data on reproductive and developmental toxici ty.

- 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 systemi c (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
ai r 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 substanc es 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 ava ilable 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 to xicity 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 mal e 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, immunotoxi city 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 blo od” 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 effect s 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 to xicity 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 databas e 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. TheseEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 334 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 activi ty. 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 effecti ve 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 : P lease see general response to comment under EPA Comment Code: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

. Also,

p lease see general response to comment under EPA Comment Code: 20 70 Cont aminants 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 conce rns 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 i s 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: P lease see general response to comment under EPA Comment Code: 20 70 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 pro duced 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 endocrineEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 335 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 I ndustry 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 HCFC

22 toxicity studies have been conducted us ing 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: P lease see general response to comment und er EPA Comment Code: 20 70 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: P lease see the general r esponse to comment under this EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Rebecca Bernstein Commenter Organization: Arkema Inc.
EPA Document ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0033EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 336 Comment Part: 15
EPA Commen t 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, Novem ber 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 c onducted 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 Pharmaco logy 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 sin gle 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 ro ute 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 h erein, 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 337 Phone: (215

- 419

- 5415)
Email: rebecca.bemstein@arkema.com

Response: P lease see general response s to comment under EPA Comment Code s : 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect and 2030 Contaminants Unlikely to Persist in Drinking

W ater

.

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
endocrin e 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 For ce 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: P lease see general response to comment under EPA Comment Code: 20 70 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 f ound 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. AtEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 338 1350 ppm, reductions in body weights, weight gain, food efficiency and water consum ption 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 we re 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 hatchabil ity 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 Orga nisms, 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 w ere 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 drinki ng 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 lo w 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 201 1. 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 re levant 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 lact ation, 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 Reproducti on 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 concentra tions 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 th e 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).]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 339 An aquatic study examined the effects ofEDC on the early life stage of the fathea d 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 rangin g 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: P lease see general response to comment under EPA Comment Code: 20 70 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 development al 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) Tox icity 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

- TrichloroethaneEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 340 As shown in the enclosed summary ta ble, 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, th e 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 re

mated 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. W ith 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 w ere 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.

Th e 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 devel opmental 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 associ ations 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 dr inking water. In fact, these dataEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 341 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 pro duce 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 t he 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: P lease see general response to comment under EPA Comment Code: 20 70 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
hu mans 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 simi lar to the effect of a naturally occurring estrogen.

Response: P lease see general response to comment under EPA Comment Code: 20 70 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.] essen tially supports the summary of the data presented:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 342 "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 com plete 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 endocrine

related ef fects 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, gona ds, 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 prior ity 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 Info rmation 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 durat ion, 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 employin g dose levels up to 1,000 mg/kg

day 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, indicat ing 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 befo re 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 orEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 343 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 i n 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 (19 95).] 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 t wo

generation 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. [F N21: 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 w eight 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: P lease see general response to comment under EPA Comment Code: 20 60 Chemicals with Toxicity Data Indicating Endocrine Disruption or Other Reproductive Developmental Endpoints

. Also,

p lease see ge neral response to comment under EPA Comment Code: 20 70 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 andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 344 common sense for EPA to impose expensive and animal

- intensive Tier 1 screening when th e study requirement for which the screening is done has already been filled.

Response: P lease see general response to comment under EPA Comment Code: 20 70 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

W e 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 anthropog enic 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 a ffect 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:EPA

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Page 345 • 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 metabolize d, 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

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- 0039.1]

a Source: Wikimedia Commons
b Sou rce: 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 li st 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: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Intertox, Inc.
Com menter Organization: Intertox, Inc. on behalf of Perchlorate Study Group
EPA Document ID: EPA

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Comment Part: 12
EPA Comment Code: 2070

Comment: • Additionally, US EPA is justified as other chemicals, such as nitrate, that do not mimi c 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 346 Response: P lease see general response to comment under EPA Comment Code: 20 70 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

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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 ha s 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 methemog lobinemia (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 a nd then excluded from the November
17th list.

The same two criteria listed by the Agency that would exclude perchlorate, would also exclude nitrate.

Response: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected t o Produce Estrogen

- like Effect.

Commenter Name: Stephen Longacre Commenter Organization: FMC Corporation
EPA Document ID: EPA

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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:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 347 Page 4: "The Agency believes that previously completed human health assessments are adequate and there is no dietary risk that exceed s 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 populat ion 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 i ncident 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 co mplete. 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 concer ns 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: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Anthony Wagner Commenter Organization: American Chemical Council
EPA Document ID: EPA

- HQ

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- 2009

- 0 477

- 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 pro posed substances to be subject to Tier 1 screening under the EDSP. Ethylbenzene has already been subject to a full range of toxicityEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 348 testing that is relevant to endocrine mediated pathways, including a 2

- generation reproductive effects study.

Response: P l ease see general response s to comment under EPA Comment Code s : 20 70 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

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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 VCC EP 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. Importa ntly, 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
endocri ne

- mediated responses of concern for health evaluations of either human or environmental species.

Response: P lease see general response s to comment under EPA Comment Code s : 20 70 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

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Comment Part: 14
EPA Comment Code: 2070

Comment: Adequate data ar e already available for Acetochlor and its degradates:EPA

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Page 349 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 prod ucts 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 batter y 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 deve lopmental 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 bi rds. 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 thyroid

sensitive 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 lev els 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 potent ial 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 haza rd 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: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect. Also, please see general response s to c omment under EPA
Comment Code s : 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

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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 acetoc hlor and a closely

- related herbicide, alachlor. In addition to staff from "Toxicology Excellence for Risk Assessment" (TERA), the panel included the following experts:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 350 * 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: Ga dagbui, 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 re lated 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: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Anthony Wagner
Commenter Organization: American Chemistry Council
EPA Document ID: EPA

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- OPPT

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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: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect.

Commenter Name: Anthony Wagner Commenter Organizatio n: 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 theEPA

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Page 351 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 glyco l 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 repro ductive, 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 cau se 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 o r 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 substa nces 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 reproducti ve/developmental effects.EPA

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Page 352 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. Th e 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 or der 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 effec ts 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 ethy lene 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: P lease see general response s to comment under EPA Comment Code s : 20 70 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

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- 0046EPA

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Page 353 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 three

generation reproductive rat s tudy 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 endoc rine 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 s tudies 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.EPA

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Page 354 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 metabolis m 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) dose

rate 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 d aily, 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 al terations) 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 pharma cokinetics 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, e mbryo, 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 whi ch 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 glyc ol 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 a nd 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 l itters 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 high

dose

- treated mice and an examination for skeletal defects demonstrated a pattern including reduction in

t he size of bones in the skull, fused ribs, and abnormally shaped sternebrae and vertebrae in the high

dose

- 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 waterEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 355 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

- gen eration 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 re production 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 domina nt 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 triethy lenemelamine (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 Rep roduction (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 Inhalati on 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 conce ntrations 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 fr om 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. Ge neva. 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. 5EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 356 BASF AG (19 96). Pruefung der biologischen Abbaubarkeit von Ethylenglykol im DOC

- Abnahme (Die

Away) 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 a nd 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: P lease see general response s to comment under EPA Comment Code s : 20 70 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 degradate s: 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 en docrine 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 en docrine

- 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 r abbits, as well as reproduction studies in rats evaluate a wide array of estrogen

- , androgen

- and/or thyroid

sensitive tissues. Data were obtained on potential endocrine

- mediated responses such as reproductive parameters (e.g. mating, fertility, and gestat ional 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 ass essed 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 toEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 357 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 equival ent 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
Alac hlor 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 othe r 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 nec essary 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.] s ubstantial 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 developm ental 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 da ta 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 (4 3919

- 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.

Respo nse: P lease see general response s to comment under EPA Comment Code s : 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect and 2100 Pesticide Registration Review Issues

.

Commenter Name: Stephen RisottoEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 358 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 determ ination 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,

Decem ber 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 viv o studies
include an ER

- mediated luciferase (luc) reporter assay in mice, an Utherotrophic assay in Sprague

Dawley 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 rela ted 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 51 7 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 co nducted 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 stimu late 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 Bonefield

Jorgenson did not observe activity in MVLN cells (MCF

- 7 human breast cell line transfected with the firefly luciferase gene) and after the administrati on 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 ofEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 359 environmenta lly 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 unabl e 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 u terine 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 uterotro phy 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 ant iandrogenic 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

- bod y 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 t he 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

– prepara tion 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/strat egy/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 popula tion 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 estrog enic 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 a bout 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 RisottoEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 360 Senior Director, Phthalate Esters

Response: P lease see general response to comment under EPA Comment Code: 20 70 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 d emonstrates no specific targeted effects on reproductive or developmental endpoints, along with additional chronic da ta that support this
conclusion

.

3) PDC has no structural alerts for estrogen

- or androgen

- receptor binding activity (Serfimova et al.,

20 07).

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: P lease see general response to comment under EPA Comment Code: 20 70 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 o f 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 an d 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 r at 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 obviousEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 361 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 OEC D 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 targe ting 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 po ssess 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 reproduc tive 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 availa ble for PDC, one which evaluates most of the Tier 2 endpoints, to indicate that PDC does not demonstrate endocrine disruption effects.

Response: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estro gen

- 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 362 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

mi xtures, 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. Two

Generation Reproduction Study in Sprague

- Dawley Rats. Unpublished report from The Dow Chemical Company, Midland, MI.

Moran, MJ, Lapham, WW, Rowe, BL and Zogors ki, 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 interpreta tion 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: P lease see general response to comment under EPA Comment Code: 20 70 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 363 3) PO is rapidly hydrolyzed to propylene glycol (PG), especially under acidic conditions such a s 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 respons e 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 C omment 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 tw o

- 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 stu dy 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 org ans (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 E PA, 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 inEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 364 Tier 2

- equivalent tests such a s 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

. P lease also see general response to comment under EPA
Comment Code: 20 70 Contaminants Not Expec ted 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 Protect ion 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 in tends 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 te sts 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 styreneEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 365 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 remove d 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, two

generation reproduction with developmental neurotoxicity in rats, chronic carcinogenicity studies in two species, as well as limited evaluations of reproduction and development i n 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/eva ls/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 human s” 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 dose s 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: P lease see general response to comment under EPA Comment Code: 20 70 Co ntaminants 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 thyro id 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 366 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 two

tier ed 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 whic h 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 co mprehensively 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 effect s 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 i n 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 Ti er 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. Positiv es 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 po tential 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 wer e 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 inc entive 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 bas is 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: P lease see general response s to comment under EPA Comment Code s : 20 70 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
Comm ent Part: 5
EPA Comment Code: 2070EPA

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Page 367 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 redundanc y 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. Chron ic 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. T oxicol. 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, Co ggon 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. AEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 368 comprehensive evaluation of the potential health risks associated with occupational and environmental

e xposure 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 mic e. 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 exp osure 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; Birt h 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

- Enviro nment. 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 rein forced 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 369 Kishi R, Katakura Y, Ikeda T, Chen BQ, Miyake H. 1992. Neurochemical effects in rats followin g 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. Neur otoxicol 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, Ha gen 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: P lease see general response to comment under EPA Comment Code: 20 70 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

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- 0069EPA

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Page 370 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 co llected under EDSP and does not support
endocrine

- related effects.

Response: P lease see general response to comment under EPA Comment Code: 20 70 Contaminants Not Expected to Produce Estrogen

- like Effect

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 371 

### 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 l isted 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 chemic al 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 Ani mal 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

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- 2009

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- 0014
Comment Part: 3
EPA Commen t 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 MC LG 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 enforceme nt 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 nat ional 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 populati on 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 byprod uct 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]. TheEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 372 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 piclora m 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 thes e 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 foun d 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 prob ability 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 contaminan ts...” 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 Registratio n 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.EPA

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Page 373 EPA Documen t ID: EPA

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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 fo od 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

- yea r 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 i n 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: P lease see general response to comment under EPA Comment Code: 2080 Contamin ants 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

- 04 77

- 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 rai ses the question as to whether a substantial population is, in fact, exposed to alachlor in water and food.

Response: P lease see general response to comment under EPA Comment Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefo re Do Not Meet SDWA 1457 Requirements

.

Commenter Name: Gregory Dolan Commenter Organization: Methanol InstituteEPA

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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 Screen ing 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 Regist er 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: T his 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, an d (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 fail ed to follow OMB’s directive that EPA consider and report on experience gained with respect t o 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 Comment Response Document

Page 375 1. The Available Data Do Not Support The Conclusion That Methanol “May B e 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 contaminan t 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 m ethanol 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 Releas e 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 subs tantial 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

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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). Subseq uently in the most recent UCMR monitoring (2007

- 2010), EPA’s OGWDW did not include MTBE on the list of compounds to be monitored.

Response: P lease 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

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- 2009

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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
d eterminations, 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 unlik ely 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 CORRE SPONDING 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 PO PULATION 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: P lease see general response s to com ment under EPA Comment Code s : 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 Ch emistry Council
EPA Document ID: EPA

- HQ

- OPPT

- 2009

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- 0035
Comment Part: 1
EPA Comment Code: 2080EPA

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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 Const itution 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 mem bers 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 de signed 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, accounti ng 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 cl osely 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, Off ice 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’

- methy lenedianiline (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 assess ment and the 2001 EUEPA

- 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 assessme nt 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: P lease see general response to comment under EPA Comment Code: 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore D o 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 presente d 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 Occurr ence 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) pr ovides 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 th e Second Six

- Year Review of National Primary Drinking Water Regulations, EPA

- 815

- B

09

- 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 basi ns 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 da ta 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 19 98 and new water quality data beginning in 1999. STORET is a repository for data collected by local, state and federal agencies, Indian tribes, universities, andEPA

- 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 wate r 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 Rep orting 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 t here 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 E DSP 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 NAW QA 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 locatio ns had concentrations above the current MCL/MCLG.[FN13: Id. At 4

- 16.]

Response: P lease 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: 2080EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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
determinati ons, 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 whi ch 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 rel y 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 havi ng 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 da ta 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 tha t 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 c hloride) 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 dete rmined 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 in formation 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 no t 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 TR I release information and the USGS study finding that population density is the strongest predictor of dichloromethane occurrence.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 con taminant, 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 c hanges 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. 1 5500, 15528.]

Response: P lease 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 cas es, 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 382 Moreover, as a part of the exposure analysis, data from the National Contaminant Occurrence Datab ase (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 regulat ed 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: P lease 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
drinki ng 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 acryl amide:

...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 duringEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 residua l
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 (20 02). 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

a crylamide.

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 consu mption 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 wel l 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 dri nking 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: P lease 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 w ater 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: P lease 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 Acetochlo r, 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 st ory.[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 Fou r 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

Pr ogram," 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 con centrations (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 sat isfied 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 A

PEST/2009/SeptemberlDay

- 16/p21845.pdf.]

Response: P lease 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 Comment Response Document

Page 385 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 publ ish 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 o f 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

- ic ing 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 i ndividual 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 e levated 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 s oil, 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 per meable 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 Comment Response Document

Page 386 Response: P lease 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

- 0 051
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 C andidate 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 chem ical 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 p resented 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 Inform ation 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 th ree 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

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- 0051.2]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 387 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 g eneral 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 drin king waters sampled from Seattle, WA and Philadelphia, PA.

Response: P lease 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

.

Comment er 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 scientifica lly rigorous approach and does not necessarily correlate to human exposure.

Response: P lease see general response s to comment under EPA Comment Code s : 2080 Contaminants with Low or No Comprehensive Occurrence Data and Therefore Do Not Meet SDWA 1457 Requi rements 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 expos ure 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). D uring 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 lit er and less (detection limit 0.001EPA

- 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 H onegger, 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 Fuhr man, 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: P lease see general response to comment under EPA Comment Code: 2080 Contamina nts 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 C omment 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 deter mine 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 protect ion.] 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 per cent (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 s ubstantial 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 ex posure 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 Comment Response Document

Page 389 Response: P lease 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 c omment 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; FRL

8848

- 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

- p roducts 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 hist ory 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 ani mal 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 fac ts, 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 ofEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 390 groundwater by the US Geol ogical 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

. P lease 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

Com ment: 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 emis sions, 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. B ased 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 sourc es, 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 pr esence 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, ju st 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) conta ining no detectable PDC (limit of detection 0 .2EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 39 1 [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: P lease see genera l 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 th e 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 i s submitting the following two comments in reference to the proposed testing of p

Dichlorobenzene (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 mo lding 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 absol ute 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.

T herefore, 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 use s 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 Comment Response Document

Page 392 Response: Please see general response to comment under EPA Comment Code: 2080 Contaminants with Low or No Comprehensive Occurren ce 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 c omment 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 D raft 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

s pecific 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 MaterialsEPA

- 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 S creening 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 o f 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 A ct (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 rulemakin g.

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 o f 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
Publ ic 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 394 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 indi cate 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 inge stion 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 test ing 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 drinkin g 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 (ran ge 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 fro m 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 EDS P 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: P lease 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 395 Commenter Na me: 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

w ater 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 2 009, 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. Evaluat ing 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

- ha lf 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 396 Velsicol believes one problem with the Occurrence Data Report is EPA’s treatment of non

- detec ts. 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 contam inant 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 w as 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 non

numeric values were replaced with the national modal MR L, 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 determine d 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 quanti tation (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 Protectio n 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 an d 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 ot hers 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 analyze d 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 dat a 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 andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 397 typically fails to identify the actual concentrations of individual substances. Therefore, ECGC often results in false positive results for a particular substance. O ther 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 t his 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 under lying 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
artifa cts, 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 wh ich 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 E PA'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 comme nt 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 D ecisions (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 th at 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, theEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 398 highest measured value in a public drinking water well wa s 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: P lease 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 399 

### 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 feasi ble. 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 in form 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 infor mation 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

datab ase. 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 t he time or the data were deemed unsatisfactory).

Response: P lease 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

- 0034EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 drinkin g 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 (sub stances 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)." [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, t o 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, respective ly. 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/physi cal 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 f or EDC, establish that neither is likely to evidence endocrine effects.

Response: P lease 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 andEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 he alth 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 equa l 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

- setti ng 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, th e 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

ze ro, 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: P lease 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
exhaust ive 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 402 EPA recently determined, af ter 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 (P QL), 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, revis ions 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: P lease 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 bas ed 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 Direc tor

Enclosure [See PDF Docket ID: EPA

- HQ

- OPPT

- 2009

- 0477

- 0038.1]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 403 Response: P lease 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 Acrylam ide (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; EPA

HQ

- 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

- OPPT

2009

- 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 Co mpany.] 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 member s 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

pr oduce 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 wor ldwide. 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 “aEPA

- 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: P lease see general response s to comment under EPA Comment Code s : 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 Amer ican 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 Euro pean 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
det ail, 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 a crylamide (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 d irecting 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: P lease see general response s to comment under EPA Comment Code s : 2090 Contaminants
with MCLG of Zero and 208 0 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 Documen t 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 h ave the benefit of assisting the Agency in developing new NPDWRs, PHGs, MCLs, etc. EPA states:EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 405 SDWA section 1412(b)(9) requires the Agency to periodically review the existing NPDWRs and revise them, if appropriate. Information about the potential for end ocrine 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 scree ning 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 resu lt 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: P lease see general response s to comment under EPA Comment Code s : 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 .000 4mg/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: P le ase see general response under EPA Comment Code: 2090 Contaminants with MCLG of

Zero

.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 406 

### EPA Comment Code: 2100 Pesticide Registration Review Issues

General Response: The a gency 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 clear ance 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 a gency and pesticide registrant s.

While that process is in its early stages, the List 2 effort provides an opportunity to include the fiscal year ( FY ) 20 07 and 20 08 registration chemicals in an attempt to begin addressing the early Registration
Review chemicals. Chemicals that are ne w registrations would also be addressed when those chemicals
beco me due for re

- evaluation under Registration Review.

This being said, the a gency undertakes a comprehensive review of each new registration and, in reaching its decisions regarding registra tion eligibility

, considers a wide range of toxicity studies that provide information on endocrine

- related effects, including: the rat 2

- generation reproduction study (or
the e xtended 1

- genera tion reprod uction study) , mammalian subchronic bioassays (in rat s 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 st udies (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 (usuall y in daphnid or mysid shrimp). The a gency 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 Cosmeti c 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 p esticide 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 sour ces 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, wa ter 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 selection s 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 a gency has elected to keep the FY 2007 an d 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 SDWAEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 407 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 test ing 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 t he a gency 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 th at 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 regist ration
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

- registratio n 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

- registrati on 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 prep aring 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 Comment Response Document

Page 408 Unlike pesticide chemicals that undergo a review and approval process, many TSCA chemicals that lack
sufficient h ealth 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 chemic als 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, wh ile 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 registra tion 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 candidat es 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 int o 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 cont act 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 work s 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 impacti ng 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

- 0014EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 409 Comment Part: 1
EPA Comment Code: 2100

Comment: Dow AgroSciences LLC is providing specific comments regarding inclusion of picloram on
"Draft Endo crine 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 Pot omac 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 Lis t 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 EDS P 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 Fo od, 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 u nder 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 toEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 410 reduce the burden on the pesticide industry at this time. Lis ting 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: Nne ka 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 schedule d 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 as sessment 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 t hat 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 in gredient'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

- 0001EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 411 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 endoc rine 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 Sc reening 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 a ccording 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 est imated 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 n ot 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 inevitabl e 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 412 2) Inclusion of Clomazone on the Second List for Endoc rine 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
chemic als 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 chem icals 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 fr om 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 propo sed 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 ind icates 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 wa ter 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 Pestici de 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" whichEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 413 states: "While the initial group of pesticide active ingredients were selected for EDSP Tier 1 scre ening 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 AR P 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 coordin ated 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 potent ial endocrine disruption effects has been fully developed and validated using List 1 Chemicals.

Response: Please see general response to c omment 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: “Wh ile 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 openin g 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 414 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 cle ar, 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 en docrine 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 th at 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 sc reening 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 informati on 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 necessa ry information for upcoming re

- registrations.

Response: Please see general response to c omment 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 a ll 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 pesticide s 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 pesticide s within the existing pesticide evaluation and registration review processes.

Response: Please see general response to c omment under EPA Comment Code: 2100 Pesticide Registration Review Issues.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 415 

### 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 l ist. When compiling the second EDSP list, EPA focused on priority drinking water contaminants and pesticide s previously identified by EPA. These priority chemicals included the Contaminant Candidate List 3 (CCL 3) chemicals, chemicals with National Primary Drinking Water Standards, and R egistration Review pesticides. While the chemicals mentioned
in th e comments were not included on the current EDSP list, they may be included on future EDSP list s

. 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 select ing c hemical s for the second EDSP list , EPA did not use information on the potential for a chemical to cause endocrine e ffects as criteria for listing. For more
information p lease see general response to comment under EPA Comment Code : 1050 Evaluating
Crit eria 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 wit h 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 u se 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 t he 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 w ith 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 416 In 2009, the Endocrine Society, a highly regarded scientific org anization 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 outc omes 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, t he 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 link ed 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

- 2 009 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.[FN 3: 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 bindi ng 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://ww w.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 triclosa n 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 impac ted 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,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 417 Needham LL. (2008). Exposure of the U.S. population to bisphenol A and 4

- ter tiary

- 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 Tab le: 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 subpopul ations) 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 parti cularly 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 Tec h, 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 chromat ography

– 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 wit h 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 th ese 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

- di srupting 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 e xposure 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, U cci AA, et al (2007). Induction of mammaryEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 418 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 ute ro 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 pred ict 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, Hotch kiss 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 B PA 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 additio n, 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, Ben

Jonathan N (2009). Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptor

α

- positive and

– negative breast cancer cells. Environmental Health Perspectives, 117:175

- 180.]. Similar
low doses also affected hormones related to metabolic disorde rs, 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 pro ducts, 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 cosmet ics to hold color and scent.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 419 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 e xposed 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: Ph thalate 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 t hat 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 anog enital
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 laborato ry 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

- n

butyl phthalate exposure in reats reduces fertility and alters ovarian function during pregnancy in female Long Evans hooded rats. Toxicological Science, 93(1):189

- 95.]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 420 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 organ s.[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 pht halates 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

- est rogen 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.]

Tric losan:

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. Sp ongberg, 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 i nto 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 wit h 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 CD C data show a 40 percent jump in triclosan levels in people over a two

year period.[FN49: SCCS (Scientific Committee on Consumer Safety), Preliminary opinion on triclosan antimicrobial resistance), 23 March, 2010. European Commission, Brussels.]EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 421 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 endocri ne 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 Toxicolog y, 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

t reated 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: R eceptor

- 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 sus pected 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 o n 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 Propos ed 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.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 422 Perchlorate exposure does not occur in isolation from exposure to other goitrogens, or anti

- thyroid agents, that hav e 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 th ree 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 thiocy anates 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, Apri l 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 lit tle public health relevance.

Response: Please see general response to comment under EPA Comment Code : 4000 Chemicals Currently Not Included on the E DSP 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
di srupting 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 pr esence 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 drinkin g. Studies by the U.S. Geological Survey (USGS) have revealed a chemical soup of pharmaceuticals, steroid hormones,EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 423 unregulated pesticides, flame retardants, rocket fuel chemicals, plasticizers, detergents, fragrance ingredients and stain repellants in dri nking 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 St ates

-- 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 chemica l 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 da ily 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 Chemica ls. 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 conce rning 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 i s 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 on to the market with no toxicity information, and older chemicals
remain untested too.

Response: Please see general response to c omment under EPA Comment Code: 1050 Evaluation
Criteria. Also, please see general response to comment under EPA Comment Code : 40 00 Chemicals Currently Not Included on the EDSP List.EPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 424 

### 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 Poli cies 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 Sc reening 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

- OPPT

2009

- 0477).

Dear Mr. Owens:

CropLif e 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 membe r 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 f ood, 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 memb ers 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 thei r members in complying with the Agency’sEPA

- 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 publi shed 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 co mment 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 perio d 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 secon d 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 yo u 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 fo r the reasons described in the attached letter.

November 18, 2010 Mr. Stephen A. OwensEPA

- 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

- OPPT

2009

- 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 c omment 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 per iod 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 Wate r 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 o f 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 registran ts, 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 potentiall y 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 impl ement 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 wh ich 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 AffairsEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

Page 427 Frank San ders, 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 testin g 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 pub lished 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 Jan uary 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 HANDEPA

- OGWDW Final EDSP List 2 February 2013 Comment Response Document

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 ext ension 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 Feder al 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, su ch 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

Administr ator 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 pro duce 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 hum ans 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 occurre nce 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
Comme nter 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 reques t 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 r equest

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 Comment Response Document

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, Kl ein 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=
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Hackett AG, Gustafson DI, Moran SJ, Hendley P, van Wesenbeeck I, Simmons ND, Klein AJ, Kronenberg JM, Fuhrman J D, 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

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Kalkhoff SJ, Kolpin DW, Thurman EM, Ferrer I, Barcelo D. 1998. Degradation of Chloroacetanil ide
Herbicides: The Prevalence of Sulfonic and Oxanilic Acid Metabolites in Iowa Groundwaters and Surface Waters. Environmental Science and Technology 32: 1738

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