1

Response to Comments Received on the April 6, 2010, 

Federal Register Proposed Rule (75 FR 17333):

Addition of National Toxicology Program Carcinogens; 

Community Right-to-Know Toxic Chemical Release

Reporting

August 12, 2010

U.S. Environmental Protection Agency

Office of Information Analysis and Access

Ariel Rios Building

1200 Pennsylvania Ave., NW

Washington, DC 20460
2

Comment Number Commenter

EPA-HQ-TRI-2010-0006-0142 Anonymous

EPA-HQ-TRI-2010-0006-0143 Steven A Paulus

EPA-HQ-TRI-2010-0006-0144 Jeff Brubaker

EPA-HQ-TRI-2010-0006-0145 Richard Cogliano

EPA-HQ-TRI-2010-0006-0146 Chemical Products Corporation

EPA-HQ-TRI-2010-0006-0147 International Institute of Synthetic Rubber 

Producers, Inc.

EPA-HQ-TRI-2010-0006-0148 OMB Watch

EPA-HQ-TRI-2010-0006-0149 Gretchen Brewer, PT AirWatchers

EPA-HQ-TRI-2010-0006-0150 Darlene Schanfald
3

Commenter: Anonymous[EPA-HQ-TRI-2010-0006-0142]

PUBLIC SUBMISSION

As of: July 22, 2010

Received: April 07, 2010

Status: Posted

Posted: April 09, 2010

Tracking No. 80ad2918

Comments Due: June 07, 2010

Submission Type: Web

Docket: EPA-HQ-TRI-2010-0006

Addition of National Toxicology Program Carcinogens; Community Right-to-Know 

Toxic Chemical Release Reporting

Comment On: EPA-HQ-TRI-2010-0006-0001

Addition of National Toxicology Program Carcinogens; Community Right-to-Know 

Toxic Chemical Release Reporting

Document: EPA-HQ-TRI-2010-0006-0142

Anonymous public comment

Submitter Information

General Comment

For your non-chemist audience, the list of chemicals is difficult to discern. Please 

consider adding 'shelf name' trade names, or names of products these chemicals are in, 

and the possible side effects if known. Thanks.

EPA Response: Most of the chemicals being proposed for listing do not have simple 

trade names or “shelf names” as they are not commonly used in consumer products. EPA 

uses the specific chemical names so that facilities that manufacture, process, or otherwise 

use them can readily identify if they have them. In some cases, where there is a common 

less technical name, EPA will include that name as well. EPA does maintain a document 

of common synonyms that contains other names for the chemicals included on the Toxics 

Release Inventory. The commenter requested additional information on the chemicals 

proposed for listing which isn’t relevant to the current rulemaking. EPA’s Substance 

Registry Services 

(http://iaspub.epa.gov/sor_internet/registry/substreg/home/overview/home.do) contains 

information on other EPA programs, as well as non-EPA sources, that may have 

additional information about the chemicals.
4

Commenter: Steven A Paulus [EPA-HQ-TRI-2010-0006-0143]

Comment:

Name: Steven A Paulus

Addition of National Toxicology Program Carcinogens;

Community Right-to-Know Toxic Chemical Release Reporting

After reading this listing of chemical that needs to be added into the National 

Toxicology Program Carcinogens and the side effects of the chemical themselves toward 

human health I Steven A Paulus supports this proposed ruling. This ruling provided a 

new addition of chemical that the EPA (Environmental Protection Agency) proposed to 

be added into the NTPC (National Toxicology Program Carcinogens) based on the 

EPCRA (Emergency Planning and Community Right-to-Know Act of 1986) and the PPA 

(Pollution Prevention Act of 1990). This National Toxicology Programs Carcinogens 

listed the entire chemical that has the ability to trigger a cell mutation in human in turn 

caused cancer. In order to be listed in the NTPC the chemical have to fulfill a certain 

requirement based on the EPCRA section 313(d)(2) in which states that the chemical is 

known to cause a significant adverse acute human health effects at concentration level. 

Secondly the chemical is known to cause variation of mutations such as cancer, tumor, 

and other irreversible mutations.

Asides from being a carcinogen, the EPA needs also to inform the public whether 

the chemical that they proposed to be listed in the EPCRA or already listed can 

contaminated the environments, and also from where does the production of the chemical 

comes into being. The EPA also needs to list a potential contamination into the public 

drinking water and also food source before the chemical is listed. For example the EPA 

need to include the uses of Phenolphthalein, for century the chemical that is known as 

Phenolphthalein was used as a laxative medicine, only just recently (2003) it is removed 

from being used as a laxatives due to the side effect it has such as diarrhea and skin 

rashes. This side effect may not be much but still important enough to be listed, after all 

according to the EPCRA section 313(d)(2) a chemical that shown to cause a significant 

adverse acute human health effects at concentration level deserve to be listed along as its 

possibility of causing cancer. The EPA also needs to include what other uses of the 

chemical so that the public understand what the possible causes of their illness and also 

the contamination of the environment around them. What it is meant by other uses, is that 

for vinyl fluoride one form of the chemical is used to make rain coats, while 

phenolphthalein is used for a pH testing in a chemistry lab. Although this other 

information is not included during the formation of this ruling, I highly insist that the 

EPA also include them in the NTPC listing, that the public may be better informed on 

what chemicals are around them. And also the EPA need to stop labeling their status as a 

possible caused for cancer and start labeling them as a caused for cancer, not just a half 

answer. Also EPA needs to make the list available to the public and made them an easy 

access, right now just to find the list you need to look all over the place and if you don’t 

know what word you use you won’t be able to find them. As for now the list can be found 
5

at http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E7FCE50709CB4C932

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory. The commenter’s suggestions for 

additional information on the 16 NTP carcinogens or for changing how carcinogens are 

categorized are outside of the scope of this rulemaking. EPA notes that some of the 

requested information may be available through other EPA programs 

(http://iaspub.epa.gov/sor_internet/registry/substreg/home/overview/home.do) or in the 

economic analysis document prepared for this rulemaking. The economic analysis 

document contains information on the uses of the chemicals and the types of facilities 

that may manufacture, process, or otherwise use the chemicals.
6

Commenter: Jeff Brubaker [EPA-HQ-TRI-2010-0006-0144]

Comment:

Jeffery Brubaker

<jsbrubaker@gmail.com>

04/12/2010 06:22 PM

To Docket OEI@EPA

cc

bcc

Subject

Comment on Docket ID No. EPA-HQ-TRI-2010-0006; FRL-9134-1

I am submitting this comment as an individual citizen. I support the proposed rule, 

because disseminating information to the public about chemicals that may be carcinogens 

is important to public health. Firms that release these chemicals should be encouraged to 

develop alternatives that are found to be of less risk to the public.

Jeff Brubaker

Carrboro, NC

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory.
7

Commenter: Richard Cogliano [EPA-HQ-TRI-2010-0006-0145

Comment:

PUBLIC SUBMISSION

As of: July 22, 2010

Received: April 18, 2010

Status: Posted

Posted: April 20, 2010

Tracking No. 80adad2d

Comments Due: June 07, 2010

Submission Type: Web

Docket: EPA-HQ-TRI-2010-0006

Addition of National Toxicology Program Carcinogens; Community Right-to-Know 

Toxic Chemical Release Reporting

Comment On: EPA-HQ-TRI-2010-0006-0001

Addition of National Toxicology Program Carcinogens; Community Right-to-Know 

Toxic Chemical Release Reporting

Document: EPA-HQ-TRI-2010-0006-0145

Comment submitted by R. Cogliano

Submitter Information

Submitter's Representative: Richard Cogliano

General Comment

Adding these 16 chemicals to the list of toxic chemicals subject to reporting under section 

313 of the Emergency Planning and Community Right-to-Know Act (EPCRA) is 

warranted and will result in the safety of United States Citizens. Adding chemicals to the 

list based on the years of research by the National Toxicology Program. Of the sixteen 

proposed chemicals, all of them are “reasonably anticipated to be a human carcinogen” 

and are used currently in the United States. By adding these to the EPCRA reporting 

chemical list, firefighters in communities which have them chemicals will be better 

informed of them and their possible carcinogenic effects. Industries using these chemicals 

will now have to report their use and pay added administrative fees to states, increasing 

funding to Local Emergency Planning Commissions thus enabling better planning and 

preparedness for the communities they serve. As a firefighter and Hazmat Technician, I 

know firsthand the hazards chemicals pose and the need for increased planning and 

preparedness.

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory.
8

Commenter: Chemical Products Corporation [EPA-HQ-TRI-2010-0006-0146]

Comment:

May 21, 2010

Office of Environmental Information (OEI) Docket

Environmental Protection Agency, Mail Code : 28221T

1200 Pennsylvania Ave ., NW.

Washington, DC 20460

Re : Docket I .D . No . EPA-HQ-TRI-2010-0006

Classification by NTP as "reasonably anticipated to be a

human carcinogen" is not an adequate scientific justification

for the addition of 16 chemicals to EPA's list of toxic

chemicals subject to the reporting requirements of section

313 of EPCRA

Dear Sir or Madam;

The following comments are submitted by Chemical Products Corporation (CPC), 

a Georgia corporation located at 102 Old Mill Road SE, Cartersville, Georgia.

EPA has proposed the addition of 16 chemicals to its list of toxic chemicals 

subject to the reporting requirements of section 313 of EPCRA as a result of 

classification by the National Toxicology Program (NTP) of these chemicals as 

"reasonably anticipated to be a human carcinogen". NTP's classification of these 16 

chemicals is shown in the 75FR65 notice to be primarily based upon evidence from 

animal studies presented in NTP technical reports. CPC will demonstrate below that NTP 

technical reports cannot be relied upon to reflect sound science and, therefore, should not 

be the basis for EPA to add these 16 chemicals to its list of toxic chemicals subject to the 

reporting requirements of section 313. 

Only 2 of the 16 chemicals proposed for addition by EPA are included in the 

International Agency for Research on Cancer (IARC) Group 2A list (Probably 

Carcinogenic to Humans); we suggest that EPA should rely upon the IARC Group 2A list 

and add only these 2 chemicals - Glycidol (CAS No . 556-52-5) and Vinyl Fluoride (CAS 

No . 75-02-5). 

This letter will document the failure of the National Institute of Environmental 

Health Sciences (NIEHS) and the NTP to assure research integrity in the preparation of 

NTP technical reports. Classification of the 16 chemicals as "reasonably anticipated to be 

a human carcinogen" in NTP's Report on Carcinogens is based to a large extent on NTP 

technical reports according to the information provided for each chemical in EPA's 

proposed rule published in 75FR65 (April 6, 2010, 17333). The deficiencies documented 
9

below in one technical report - NTP Technical Report 494 (the only one evaluated 

exhaustively by CPC) demonstrate that NTP technical reports cannot be relied upon to 

represent sound science and should not be the basis for EPA listing proposals. 

Factually incorrect information was presented to the NTP Board of Scientific 

Counselors Technical Reports Review Subcommittee on December 9, 2004 to achieve 

acceptance of the conclusions presented in NTP Technical Report 494 (TR494). 

Animal studies were conducted in the mid-1990's on the TR494 test article, 

Anthraquinone produced by the nitric acid oxidation of anthracene (a production method 

that is no longer used). Contamination of the non-mutagenic anthaquinone with the 

potent mutagen 9-nitroanthracene was discovered several years after completion of the 

TR494 animal studies . The 9- nitroanthacene contamination of the test article confounds 

interpretation of the animal studies in which cancers were observed. TR494 contains 

factually incorrect information which hides the biological significance of the potent 

mutagenic contamination in the TR494 test article, thus the conclusions presented in 

TR494 do not represent sound science. 

NTP scientists stated that "Sample A07496" was an aliquot of the TR494 

Anthraquinone test article, "Lot 5893" at the December 9, 2004 TR494 peer review and 

cited a negative mutagenicity assay of "Sample A07496" as a definitive demonstration 

that contamination of the TR494 test article by the potent mutagen 9-nitroanthracene had 

not confounded interpretation of the TR494 studies. CPC determined, through FOIA

requests, that NTP had no records associating "Sample A07496" with the TR494 test 

article, "Lot 5893". CPC submitted a Request for Correction of TR494 following the 

Department of Health and Human Services Information Quality Guidelines on May 31, 

2006 (see "a. Request for Correction (RFC)" at "28. NTP - Technical Report 494 

[Anthraquinone]", http://aspe.hhs.gov/infoQuality/reguests.shtml). 

After CPC submitted its Request for Correction of TR494 on May 31, 2006, a 

false Bulk Chemical Shipment Report was generated by NTP in June 2006 purporting to 

demonstrate that the TR494 test article, labeled "Anthraquinone Lot 5893", had been 

shipped from the repository for all retained TR494 test article, Battelle Columbus 

Laboratories, to BioReliance Testing Laboratories on June 1, 2004 (for mutagenicity 

assay). Months later, through a FOIA appeal, CPC obtained a copy of the BioReliance 

Testing Laboratories (BTL) Test Article Receipt and Transfer Report showing that the 

sample in question, received by BioReliance on June 2, 2004, was labeled only "A07496 

store at RT No Exp Date given Sieved 8 mesh" upon arrival - not "Anthraquinone Lot 

No. 5893" as shown on the false Bulk Chemical Shipment Report (see the attachment to 

"c.2 Amended RFR" under "28. NTP - Technical Report 494 [Anthraquinone]" at 

http://aspe.hhs gov/infoQualitly/requests.shtml ). Yet NIEHS ignored this information in 

its final response to CPC's Request for Reconsideration which states in part, "The 

samples were labeled by lot number, the standard information that is included on 

samples. BioReliance received the materials on June 2, 2004. You were sent this record 

previously. Battelle sent NTP the Bulk Chemical Shipment Report dated June 22, 2004 

verifying it had shipped samples of the 4 anthraquinone lots to BioReliance on June 1, 
10

2004. This document also was provided by NTP to you in NTP's Response to the Request 

for Correction. BioReliance confirmed assignment of each test article aliquot number to 

the correct lot of anthraquinone." (underline added, the response letter from Dr. Joyce 

Martin at NIEHS is available at "d.9 HHS response to RFC" under "28. NTP - Technical 

Report 494 [Anthraquinone]", http://aspe.hhs .gov/infoQuality/requests.shtml). 

NTP's only evidence that "Sample A07496" is an aliquot of the TR494 test article 

"Lot 5893" is an email from the project manager at BioReliance giving a positive 

response to an NTP staff member's request that BioReliance "please confirm that Sample 

A07496 is Lot 5893". Thus, NIEHS contends that BioReliance confirmed "assignment of 

each test article aliquot number to the correct lot of anthraquinone" - for a sample which 

was not labeled with a lot number when received by BioReliance. Further evidence that 

NTP fabricated a Bulk Chemical Shipment Report in June 2006 in response to CPC's 

Request for Correction of TR494 is provided by the final response to CPC's September 

30, 2008 FOIA request (dated October 27, 2008) which states that the Office of 

Management and the National Toxicology Program searched their files and no records of 

any parcels sent from Battelle Columbus Laboratories or Battelle Columbus Operations 

during the period May 24, 2004 through June 4, 2004 related to NTP activities were 

found (FOI Case No . 35487). 

NTP Technical Report 494 also misrepresents the scientific record regarding 

mutagenicity assay results for Anthraquinone's primary metabolite, 2-

hydroxyanthraquinone. In attempting to defend TR494, NTP has cited its own 

preincubation assay purporting to show that metabolite 2-hydroxyanthraquinone is a 

strong mutagen for Salmonella typhimurium strain TA98 in the absence of metabolic 

activation (see "d.9 HHS response to RFC" at "28. NTP - Technical Report 494 

[Anthraquinone]", http://aspe.hhs.gov/infoQuality/requests.shtml). The existence of a 

conflicting mutagenicity assay for 2-hydroxyanthraquinone which was negative for TA98 

in the absence of metabolic activation is omitted from TR494. TR494 states at page 91 

that Tikkanen et al. (1983) did not perform testing in the absence of S9 metabolic 

activation ; in fact, negative preincubation assays of 2- hydroxyanthraquinone in strains 

TA98, TA100 and TA2637 in the absence of S9 activation were reported by Tikkanen et 

al. (Tikkanen, L.; Matsushima, T.; Natori, S.; Mutagenicity of anthraquinones in the 

Salmonella preincubation test; Mutation Research; 116[3-4]:297-304; March 1983).

A negative assay of 2-hydroxyanthraquinone in TA98 without metabolic 

activation has also been reported by Butterworth et al . (Butterworth, B.E ., Mathre, O.B., 

and Ballinger, K .E., Adalsteinsson, O.; Contamination is a Frequent Confounding Factor 

in Toxicology Studies with Anthraquinone and Related Compounds; Int a Toxicol; 23; 

No. 5; 335-344; 2004). 

A lengthy and involved investigation was required to determine that TR494 does 

not represent sound science and to expose possible coordinated misconduct on the part of 

NTP scientists Dr. Richard Irwin, Dr. John Bucher, and Dr. Cynthia Smith; an 

investigation of this magnitude is far beyond the capabilities of a NTP peer review panel 

or a NTP Report on Carcinogens review panel, so the number of other NTP technical 
11

reports which do not represent sound science is unknown - and the number of subsequent 

scientifically unsound classifications of substances as "reasonably anticipated to be a 

human carcinogen" in NTP's Reports on Carcinogens is also unknown. 

Fortunately, in the case of NTP Technical Report 494, the broader scientific 

community has recognized that the report is deficient and the scientific record is being 

corrected . Professor Alan R. Boobis et al. recently stated in the journal Toxicologic 

Pathology , "The data for anthraquinone {in NTP Technical Report 494} are 

considered suspect because other carcinogenicity studies were negative, and the 

NTP carcinogenicity study used a batch of anthraquinone contaminated with the 

potent mutagen 9-nitroanthracene at a level of 1,200 ppm (Butterworth, Mathre, 

and Ballinger 2001). (A purified sample was negative in the Ames test.) Certainly, it 

can be said that the material used by the NTP was mutagenic" [Alan R . Boobis, 

Samuel M. Cohen, Nancy G. Doerrer, Sheila M. Galloway, Patrick J. Haley, Gordon C. 

Hard, Frederick G. Hess James S. Macdonald, Stephane Thibault, Douglas C. Wolf and 

Jayne Wright; A Data-Based Assessment of Alternative Strategies for Identification of 

Potential Human Cancer Hazards; Toxicol Pathol; 37; 714-732; 2009 - see page 719] . 

Professor Boobis of Imperial College London, the first-named author, received an OBE 

for his work on the risk assessment of pesticides in 2003. He is an Honorary Member of 

EUROTOX, a Fellow of the British Toxicology Society and a Fellow of the Institute of 

Biology. It is this broader scientific community represented by the IARC that EPA should 

reply upon for a determination that a substance is probably carcinogenic to humans. 

As demonstrated above, NTP technical reports cannot be relied upon to represent 

sound science. EPA should rely upon IARC inclusion of a substance on its Group 2A list 

("Probably Carcinogenic to Humans") as the basis for addition to EPA's list of toxic 

chemicals subject to the reporting requirements of section 313 of EPCRA. 

Of the 16 chemicals proposed by EPA for addition to EPA's list of toxic 

chemicals subject to the reporting requirements of Section 313, 14 have been evaluated 

by IARC and only 2 have been included on IARC's Group 2A list (Probably carcinogenic 

to humans) - these are Glycidol (CAS No. 556-52-5) and Vinyl Fluoride (CAS No . 75-

02-5) . 1-Amino-2,4-Dibromoanthraquinone (CAS No. 81-49-2) and Methyleugenol

(CAS No . 93-15-2) have not yet been evaluated and classified by IARC. 

CPC submits that a sound scientific basis exists for the addition of only 2 of the 

16 substances proposed by EPA for addition to its list of toxic chemicals subject to 

reporting under section 313 of EPCRA and section 6607 of the Pollution Prevention Act 

of 1990 (PPA); these are Glycidol (CAS No . 556-52-5) and Vinyl Fluoride (CAS No. 

75-02-5) because these chemicals are included in IARC's Group 2A listing. 

In summary, the only NTP technical report carefully scrutinized by CPC 

(Technical Report 494) has been documented to contain factual errors underpinning the 

conclusions presented in this report . The demonstration that this NTP technical report 

presents scientifically untenable conclusions, coupled with NIEHS's refusal to correct the 

scientific record, brings the scientific validity of all NTP technical reports into question. 
12

Not only has NIEHS refused to correct the scientific record for Anthraquinone, the 

TR494 test material, but the Office of Research Integrity has also stated that it lacks 

authority to investigate possible misconduct on the part of NTP scientists related to 

TR494; Dr. John E . Dahlberg stated in a letter to CPC dated January 16, 2009 that "ORI 

does not have the authority, to conduct the investigation you request. Our role is limited 

by departmental policy to conducting oversight review of investigations conducted by the 

institutions where the alleged misconduct took place." . We submit that the above 

illustrates that NTP technical reports, the primary basis for NTP classification of the 

chemicals addressed in the 75FR65 proposed rule as "reasonably anticipated to be a 

human carcinogen", should not be relied upon by EPA to make decisions regarding 

addition of chemicals to its list of toxic chemicals subject to reporting under section 313 

of EPCRA. We suggest that EPA rely instead upon the IARC Group 2A list and add only 

those chemicals which appear on the IARC Group 2A list - Glycidol (CAS No. 556- 52-

5) and Vinyl Fluoride (CAS No . 75-02-5). 

If I can answer any questions about this letter or provide any further information, 

please email me at icook@cpc-us.com or phone me at 770-382-2144 Ext. 272. 

Sincerely, 

Jerry A . Cook 

Technical Director 

EPA Response: EPA notes that the commenter is questioning the validity of an NTP 

technical report that is unrelated to any of the chemicals that EPA proposed for listing. 

The report in question concerns anthraquinone, a chemical that was not the subject of the 

proposed rule, is not on the EPCRA section 313 list of toxic chemicals, and is not 

classified as a carcinogen in the NTP’s 11th Report on Carcinogens. The commenter 

believes that the scientific validity of all of the NTP technical reports is questionable 

because of problems they have with one of the NTP technical reports. As this report is 

outside the scope of the proposed rule, EPA is not addressing the specific issues the 

commenter has with the report or the NTP’s responses to the commenter. EPA does not 

believe that issues raised about one NTP technical report mean that the scientific validity 

of all NTP technical reports should be in question. As EPA discussed in the proposed 

rule, the NTP review process for the Report on Carcinogens is extensive and includes 

both peer review and public comment (75 FR 17335, April 6, 2010). In addition, as 

discussed in the proposed rule (75 FR 17336, April 6, 2010), EPA reviewed the NTP 

chemical profiles and supporting materials for each chemical proposed for listing. The 

commenter has provided no data that would suggest that the NTP reports for the 16 

chemicals being added to the EPCRA section 313 list are flawed or any data that would 

suggest the chemicals do not meet the EPCRA section 313(d)(2)(B) listing criteria. The 

Agency finds no specific basis to question any of the NTP documents used to support the 

listing of the 16 chemicals included in this rule based on these comments.

Regarding the commenter’s suggestion that EPA only add those chemicals that 

have been classified as Group 2A (probably carcinogenic to humans) by the International 
13

Agency for Research on Cancer (IARC), EPA notes that the scientific data for a number 

of chemicals classified as Group 2B (possibly carcinogenic to humans) under IARC has 

been found to be sufficient to support listing under EPCRA section 313 (see for example, 

59 FR 1788, January 12, 1994). These determinations were the result of a case-by-case 

analysis of the available cancer data, they were not based solely on the IARC cancer 

classification. Thus, EPA would not limit the listing of carcinogens to only chemicals 

with IARC Group 2A classifications and even for IARC 2A classified chemicals EPA 

would review the available cancer data before making a listing determination. 
14

Commenter: International Institute of Synthetic Rubber Producers, Inc. 

[EPA-HQ-TRI-2010-0006-0147]

Comment:

Office of Environmental Information Docket 1 June 2010

US Environmental Protection Agency

Mail Code: 28221T

1200 Pennsylvania Ave. N.W.

Washington, DC 20460

Sent via email to oeidocket@epa.gov

RE: Docket ID No. EPA-HQ-TRI-2010-0006

Thank you for the opportunity to provide comments on the listing of isoprene in the list 

of substances subject to reporting under Section 313 of the Emergency Planning and 

Community Right-to-Know Act of 1986. These comments are being made on behalf of 

the members of the International Institute of Synthetic Rubber Producers, Inc. (IISRP), a 

non-profit trade association representing the interest of the synthetic rubber industry. Our 

members, who produce and/or consume isoprene, have a keen interest in this notice. We 

have conducted significant scientific research on this substance and have provided the 

findings to governments and/or regulatory bodies.

The IISRP has reviewed the toxicology summary and overall there are no factual 

inaccuracies however there are interpretations of the data we believe should be noted plus 

there are certain environmental data which should be included in the record.

First the text refers to similarities between isoprene and butadiene. I should also point out 

that isoprene differs from 1,3-butadiene in that for isoprene, there has been no elevations 

in thymic lymphoma in exposed mice at any concentrations tested (Placke et al 1996). 

While not necessarily ascribing to the view of Melnick & Sills (2001) to the relevance of 

lymphomas induced in mice to lymphatic/hematopoetic cancers in humans, the absence 

of this response in mouse with isoprene is noteworthy since the basis of butadiene's 

International Agency for Research on Cancer (IARC) Group1 classification is all 

hemolytic organs (which would include lymphomas).

The various other tumor types occurring with isoprene or butadiene in mice are not seen 

in epidemiology studies of butadiene exposed populations. Further, there were no 

elevations in tumors found in mice at the lowest exposure tested (10 ppm; 28 mg/m3) and 

this together with the fact that isoprene is produced endogenously in humans suggests 

that there is a threshold for such a response. Based on the above, this supports the IARC 

2B categorization of isoprene as a "possible" human carcinogen rather than the 

"reasonably anticipated" categorization by NTP, which triggers the TRI listing.
15

Next we point to the omission of environmental data which should be included in the 

record. The International Agency for Research on Cancer notes that isoprene occurs in 

the environment as emissions from vegetation, particularly from deciduous forests. In the 

United States the total emission rate of isoprene from deciduous forests has been 

estimated to be 4.9 tonnes per year, with the greatest emissions in the summer. The 

global annual emission of isoprene in 1988 was estimated to be 285 000 thousand tonnes.

Also, a paper by Sharkey et al., states with citations isoprene is the dominant 

hydrocarbon released by vegetation in most ecosystems (Guenther et al. 1994, Geron et 

al. 1994). Isoprene release by vegetation, particularly trees (Rasmussen1970), exceeds 

anthropogenic hydrocarbon release to the atmosphere (Lamb et al. 1987, 1993).

Isoprene is produced endogenously in humans. It has also been found in tobacco smoke, 

gasoline, turbine and automobile exhaust and in emissions from wood pulping, biomass 

combustion and rubber abrasion (United States National Library of Medicine 1997).

Thank you again for providing the opportunity for our comments. I will be pleased to 

address any questions you may have and can contact me at the address below.

Sincerely,

Sent via email

James L. McGraw

Managing Director & CEO

IISRP

2077 S. Gesner Road # 133

Houston, TX 77063

Phone: 713.783.7511 ext 222

jlmcgraw@iisrp.com

References:

M.E. Placke, L. Griffis, M. Bird, J. Bus, R.L. Persing, & L. A. Cox (1996) Chronic 

Inhalation study of isoprene in B6C3F1 mice Toxicology, 110 (1-3), 253 - 262

R.L.Melnick & R.C.Sills (2001) Comparative carcinogenicity of 1,3- butadiene, isoprene 

and chloroprene in rats and mice.

Chemico-Biological Interactions 135 -136, 27-42

IARC Monograph (Vol 71, p1016, 1999)

Sharkey et al., Tree Physiology 16, 649--654, 1996
16

EPA Response: EPA disagrees with the IISRP that EPA should use the IARC "possible" 

human carcinogen classification for isoprene rather than the "reasonably anticipated" 

categorization by NTP. Since isoprene is an analog of 1,3-butadiene, the NTP provided 

data on 1,3-butadiene under the section on “Additional Information Relevant to 

Carcinogenicity” (NTP, 2005. National Toxicology Program. 11th Report on 

Carcinogens—Isoprene Substance Profile. Released January 31, 2005. U.S. Department 

of Health and Human Services, Public Health Service, National Toxicology Program, 

Research Triangle Park, NC 27709). The commenter pointed out differences between 

isoprene and butadiene, however, the NTP also recognizes that there are differences in 

the data for isoprene and 1,3-butadiene as evidenced by the NTP’s classification of 1,3-

butadiene as a “known to be a human carcinogen” 

(http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s025buta.pdf). For isoprene, the NTP 

found evidence of tumor formation at multiple organ sites in multiple species of 

experimental animals (see NTP isoprene profile). Nothing in the commenter’s statements 

leads EPA to believe that isoprene is not correctly classified by NTP as “reasonably 

anticipated to be a human carcinogen” or that the data underlying that classification 

suggests the isoprene does not meet the EPCRA section 313(d)(2)(B) listing criteria.

EPA also disagrees with IISRP’s characterization that the NTP classification is a 

trigger for TRI listing. According to EPCRA § 313(d)(2), a chemical may be added to 

the TRI list if it “is known to cause or can reasonably be anticipated to cause in humans 

cancer.” Particular listings by scientific bodies, such as the NTP, are useful in 

determining whether that standard has been met but are not necessarily triggers for listing 

under EPCRA. EPA does not take an IARC Group 2B classification to automatically 

mean that a chemical would not meet the EPCRA section 313 listing criteria. EPA again 

notes that in previous EPCRA section 313 listing decisions, the scientific data for a 

number of chemicals classified as Group 2B (possibly carcinogenic to humans) under the 

IARC has been found to be sufficient to support listing under EPCRA section 313 (see 

for example potassium bromate, sodium o-phenylphenoxide, and other chemicals in 59 

FR 1788, January 12, 1994). These determinations were the result of a case-by-case 

analysis of the available cancer data; they were not based solely on the IARC cancer 

classification. Thus, EPA would not limit the listing of carcinogens to only chemicals 

with IARC Group 2A classifications. Even for IARC 2A classified chemicals, EPA 

would review the available cancer data before making a listing determination.

The environmental data that the commenter suggests in missing from the 

rulemaking record actually is discussed in detail in the supporting documents cited in the 

proposed rule. For example, reference number 13 in the proposed rule (NTP, 2005. 

National Toxicology Program. 11th Report on Carcinogensbv – Isoprene Substance 

Profile. Released January 31, 2005. U.S. Department of Health and Human Services, 

Public Health Service, National Toxicology Program, Research Triangle Park, NC 

27709) contains the following discussion:

“Exposure

Isoprene is formed endogenously in humans and is generally the major hydrocarbon (up 
17

to 70% in human breath) (Gelmont et al. 1981). Concentrations in blood range from 15 to 

70 nmol/L (1.0 to 4.8 μg/L) (Cailleux et al. 1992). Humans produce isoprene 

endogenously at a rate of 0.15 μmol/kg/h, equivalent to approximately 17 mg/day for a 

150-lb (70-kg) person (Taalman 1996). Endogenous production rates reported for rats and 

mice are 1.9 and 0.4 μmol/kg/h, respectively (Peter et al. 1987). Ambient air 

concentrations of isoprene are generally less than 10 ppb or approximately 0.03 mg 

isoprene/m3. Based on estimated human intake of 15 to 20 m3 air per day, ambient air 

would contribute less than 0.45 to 0.6 mg/day to daily isoprene exposure.

NIOSH collected data on potential exposure to isoprene in the National 

Occupational Hazard Survey (NOHS) from 1972 to 1974 (NIOSH 1976) and in the 

National Occupational Exposure Survey (NOES) from 1981 to 1983 (NIOSH 1990). The 

first survey (NIOSH 1976) indicated that 58,000 employees in over 30 different 

industries were potentially exposed to isoprene. The more limited later survey of six 

industries showed that approximately 3,700 workers were potentially exposed to isoprene 

between 1981 and 1983 (NIOSH 1990). Isoprene is emitted from plants and trees and is 

widely present in the environment at low concentrations (Taalman 1996). Isoprene global 

emissions, estimated at 175 to 503 million Mg per year, represent approximately 44 to 

51% of total global natural volatile organic compound emissions (Guenther et al. 1995). 

The average biogenic emission rate factor for isoprene in the United States is 

approximately 3 mg/m2/h. Isoprene concentrations in biogenic emissions range from 8% 

to 91% of total VOCs, with a 58% average. Since isoprene biosynthesis is associated with 

photosynthesis, isoprene emissions are negligible at night (Guenther et al. 1994). The 

south central and southeastern areas of the United States have the highest biogenic 

emissions. Summertime isoprene emissions are highest in each region and account for 

more than 50% of annual biogenic emissions (Lamb et al. 1993). 

Sources of anthropogenic releases of isoprene to the atmosphere include ethylene 

production by cracking naphtha, wood pulping, oil fires, wood-burning stoves and 

fireplaces, other biomass combustion, tobacco smoking (3,100 μg/cigarette), gasoline, 

and exhaust of turbines and automobiles (HSDB 2000). 

Reported U.S. ambient air concentrations of isoprene range from 0.003 to 0.06 

mg/m3 (1 to 21 ppb), with isoprene representing less than 10% of NMHCs (Arnts and 

Meeks 1980, Altschuller 1983, Lawrimore and Aneja 1997, Hagerman et al. 1997). 

During stagnation conditions, biogenic hydrocarbons may contribute more to total 

atmospheric hydrocarbons (Altschuller 1983). 

Foods of plant origin would be expected to be a source of daily exposure to 

isoprene since it is emitted by agricultural crops and is the basic structural unit in 

countless natural products found in foods such as terpenes and vitamins A and K (IARC 

1994). Its occurrence has been reported in the essential oil of oranges, in the fruit of hops, 

and in the root of carrots (Duke 1992). 

The primary source of isoprene in indoor air is environmental tobacco smoke. 

Isoprene was found to be the major component of hydrocarbons in the air of a smoky café 
18

(10 smoking patrons, 10 not smoking) (16.7%) and sidestream smoke (29.2%) (Barrefors 

and Petersson 1993). A monitoring survey in November 1992 in homes and workplaces 

in the greater Philadelphia area found mean isoprene concentrations in personal air 

samples of 4.65 μg/m3 in nonsmoking homes (n = 60), 18.15 μg/m3 in smoking homes (n 

= 29), 5.29 μg/m3 in nonsmoking workplaces (n = 51), and 22.80 μg/m3 in smoking 

workplaces (n = 28). Differences in isoprene concentrations in personal air between 

nonsmoking and smoking sites were highly significant (Heavner et al. 1996). Another 

survey reported median summertime isoprene concentrations of 2.90 μg/m3 in indoor air 

(n = 3; no information on whether occupants were smokers or nonsmokers) compared to 

0.40 μg/m3 in outdoor air (n = 1) in the Lower Rio Grande Valley of Texas (Mukerjee et 

al. 1997).”

As the text above clearly shows, information on environmental data was not omitted from 

the rulemaking record. However, as this information was not directly related to the 

hazard determination for isoprene being used as a basis to list the chemical, it was not 

included in the text of the Federal Register notice for the proposed rule.
19

Commenter: OMB Watch [EPA-HQ-TRI-2010-0006-0148]

Comment:

June 7, 2010 

Office of Environmental Information (OEI) Docket 

Environmental Protection Agency 

Mail Code: 28221T 

1200 Pennsylvania Ave. NW 

Washington, DC 20460

Re: OMB Watch Comments on Docket ID No. EPA–HQ–TRI–2010–0006 

"Addition of National Toxicology Program Carcinogens; Community Right-toKnow Toxic Chemical Release Reporting" 

Dear Sir/Madam: 

OMB Watch is submitting these comments on the proposed rule that would add 16 

chemicals to the list of toxic chemicals subject to reporting under section 313 of the 

Emergency Planning and Community Right-to-Know Act (EPCRA) and section 6607 of 

the Pollution Prevention Act of 1990 (PPA), 75 Fed. Reg. 17333–17349 (April 6, 2010).1

OMB Watch is a nonprofit research and advocacy organization whose core mission is to 

promote government accountability and improve citizen participation. Public access to 

government-held information has been an important part of our work for more than 15 

years, and we have both practical and policy experience with disseminating government 

information. For example, in 1989, we created the Right-to-Know Network (RTK NET), 

an online service providing public access to environmental data collected by the 

Environmental Protection Agency (EPA). Ever since, defending and enhancing the 

public's right to know about environmental and public health threats has been a leading 

cause at OMB Watch. Additionally, we are engaged in agency regulatory processes and 

encourage agency rules to be sensible and more responsive to public needs. The Toxics 

Release Inventory (TRI) has long been a prominent feature of RTK NET and the work of 

OMB Watch. 

OMB Watch strongly supports EPA's proposal to add to the TRI 16 chemicals classified 

by the National Toxicology Program (NTP) as reasonably anticipated to be human 

carcinogens. An expansion of the list of chemicals covered by the TRI program has been 

needed for years. The chemicals EPA has selected for this expansion are appropriate, and 

their inclusion will strengthen the TRI program. However, the agency is taking a very 

small step toward enhancing a vital right-to-know program, and additional steps should 

be taken to expand the number of chemicals reported to TRI and the types and number of 

industries covered by the program.

According to the Government Accountability Office (GAO), approximately 700 new 

chemicals are introduced into commerce each year.2 However, no chemicals – old or new 
20

– have been added to the TRI program since 1999 (for reporting year 2000).3 Therefore, 

in the last ten years, approximately 7,000 new chemicals have been introduced into 

commerce, and not one is reported to the TRI program. 

Obviously, not every chemical is dangerous enough to merit being tracked in the TRI 

program. But with numerous new chemicals being introduced and new facts about the 

toxicity and risks of existing chemicals being discovered all the time, a ten-year freeze on 

expanding TRI seems rather indefensible. 

PREVIOUS TRI EXPANSIONS MAY SERVE AS MODEL

At the time of the last expansion of TRI in 1999, only five years had passed since the 

previous expansion. In 1994, with one rulemaking, EPA added 286 chemicals and 

chemical categories to the TRI.4 In the 1994 proposed rule, EPA stated, "EPA and State 

regulatory agencies have integrated TRI information as a critical component in their 

environmental decisionmaking and in many cases are constrained by the lack of similar 

information on chemicals of concern not covered by the TRI."5 There is strong reason to 

believe such constraints continue to hinder the environmental decision making of state 

and federal agencies today.

The 1994 rulemaking involved a comprehensive review of possible additions to the TRI 

chemical list. The agency examined chemicals regulated under ten different federal or 

state statutes, such as the Clean Air Act, the Clean Water Act, the Comprehensive 

Environmental Response, Compensation, and Liability Act (CERCLA), the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and 

Recovery Act (RCRA), and the Toxic Substances Control Act (TSCA). In addition, EPA 

reviewed chemicals that were possible, probable, or known carcinogens according to the 

International Agency for Research on Cancer (IARC) and the sixth NTP Report on 

Carcinogens (RoC). To prioritize chemicals, EPA obviously first excluded all chemicals 

that were already on the TRI list, and then "applied a human health and ecotoxicity 

screen and a production volume screen." The toxicity screen involved a limited review of 

available toxicity data. For the production volume screen, EPA used production volume 

data primarily from the TSCA Inventory Update Rule reports (section 8) and FIFRA 

section 7. 

EPA recognized the need for the TRI to evolve and change as changes in industry and 

advances in scientific knowledge warranted. The comprehensive review and evaluation 

process that EPA undertook for the 1994 rulemaking is a strong example of the kind of 

analysis that should be a regular feature of the agency's implementation of the TRI 

program. 

The state of California's chemical right-to-know law, commonly known as Proposition 

65, offers another strong example of a regular process for evaluating chemicals.6

Proposition 65 adds chemicals to its list of substances known to the state to cause cancer, 

birth defects, or other reproductive harm every year. The program also updates toxicity 

information for numerous listed chemicals each year. Proposition 65 draws on chemical 
21

data supplied by the EPA, U.S. Food and Drug Administration, National Institute for 

Occupational Safety and Health, NTP, IARC, and other experts. 

OTHER CRITERIA FOR EVALUATING ADDITIONS TO TRI 

EPCRA Section 313(d)(2) lists several criteria by which a chemical may be added to 

TRI. The known or reasonably anticipated carcinogenicity of a chemical is just one 

criterion. The EPA may also add a chemical to TRI if it is known to cause or may be 

reasonably anticipated to cause birth defects, reproductive dysfunctions, neurological

disorders, heritable genetic mutations, or other chronic health effects. The EPA may also 

add a chemical if it is known to cause or reasonably anticipated to cause a significant 

adverse effect on the environment because of the chemical's toxicity. EPA need only 

demonstrate that a chemical meets just one of these criteria to be considered for addition 

to the TRI list.

In its first proposed addition of chemicals to the TRI program in ten years, the EPA has 

chosen to focus on just one of the criteria it is authorized to use to evaluate chemicals for 

addition to TRI. Although the agency's evaluation is sound and the 16 proposed 

chemicals are entirely appropriate for inclusion in the TRI, we believe that EPA should 

also review chemicals based on every other criterion, as well. For example, EPA should 

evaluate non-TRI chemicals for their reproductive toxicity, genotoxicity, or their adverse 

environmental impacts. Chances are high that among the tens of thousands of chemicals 

in commerce today, a significant number would meet at least one of the Section 313(d)(2) 

criteria for inclusion in the TRI. 

EPA NEEDS A REGULAR TRI REVIEW 

OMB Watch recommends that EPA establish a regular, periodic process for the agency to 

review and identify chemicals for possible addition to the TRI. Currently, the program 

allows the public and state governors to petition for the addition or removal of specific 

chemicals. But that process is too passive. Many in the public trust the EPA to be the 

expert voice on the issue of toxicity or risk from chemicals. A regular review will prevent 

the excessive, ten-year-long dearth of activity we just experienced. 

The regular review process we are recommending should draw on data and expertise 

possessed by states, other nations, other federal and international authoritative bodies, 

and EPA's own experts. EPA should also consider the results of biomonitoring studies, 

such as those conducted by the Centers for Disease Control and Prevention's (CDC) 

National Biomonitoring Program.7 Biomonitoring measures the presence of specific 

contaminants in human bodies. Such data could be used both to broaden the universe of 

chemicals under consideration for addition to the TRI program and to identify priority 

chemicals. 

Given the vast number of chemicals worthy of evaluation for inclusion in TRI, and the 

extreme resource constraints afflicting the EPA, it is incumbent upon the agency to work 

with public stakeholders to develop a system for prioritizing specific chemicals or classes 
22

of chemicals for review. EPA has taken an important and deliberate first step toward 

prioritizing chemicals by selecting certain chemicals in the NTP's most recent RoC. 

However, this step is a very small one. The addition of only 16 chemicals and no new 

industry sectors after so many years of stagnation in the TRI program is a miniscule step 

in relation to the potential new and additional threats faced by citizens from toxic 

releases. The agency should now be working to identify additional chemicals, without 

waiting for the publication of the final rule regarding the NTP carcinogens. 

SUMMARY 

OMB Watch, although highly supportive of the agency's proposal, encourages the EPA to 

expand its review of new chemicals to include the resources consulted in the 1994 

rulemaking and any additional resources the agency identifies. EPA has the authority to 

evaluate chemicals for inclusion into TRI based on several criteria, in addition to a 

substance's carcinogenicity. All criteria should be applied. The EPA should establish a 

regular process for the this review that will also set priorities that recognize the agency's 

limited staff and funding resources and the scale of the review. We also encourage the 

agency to regularly analyze whether new industry sectors warrant addition to the list of 

covered industries. Finally, as the agency develops these processes, it should work with 

public stakeholders in a transparent and participatory manner. 

We appreciate your consideration of our comments on this issue. Please do not hesitate to 

contact us at (202) 683-4840 if you have any questions. 

Respectfully, 

Brian Turnbaugh 

Policy Analyst, Environmental Right-to-Know 

1

http://www.epa.gov/tri/lawsandregs/ntp_chemicals/NTPchemicals_proposed%20Rule040

62010.pdf. 2

GAO. Options for Enhancing the Effectiveness of the Toxic Substances Control Act. 

GAO-09-428T. http://www.gao.gov/new.items/d09428t.pdf. 3

EPA added seven chemicals and two chemical compound categories, known as 

persistent, bioaccumulative toxics, for reporting year (RY) 2000. 64 Fed. Reg. 58665–

58753, October 29, 1999, http://www.epa.gov/fedrgstr/EPA-WASTE/1999/October/Day29/f28169.htm. 4

59 Fed. Reg. 61432–61502. 

http://www.epa.gov/tri/archive/dialogues/natdiagphase1_oct02/phase2/chemicalexpfrule.

pdf. 5

59 Fed. Reg. 1788–1859. http://www.epa.gov/tri/lawsandregs/trichemical/59fr1788.pdf. 6

Proposition 65 (Safe Drinking Water and Toxic Enforcement Act of 1986) is 

administered by California's Office of Environmental Health Hazard Assessment 

(OEHHA), http://oehha.ca.gov/prop65.html. 7

http://www.cdc.gov/biomonitoring/index.html. 

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory. Regarding the comments that are not 
23

directly related to the addition of the 16 NTP carcinogens, EPA will take these comments 

under consideration as the Agency reviews other possible expansions of the EPCRA 

section 313 chemical list or covered industry sectors.
24

Commenter: Gretchen Brewer [EPA-HQ-TRI-2010-0006-0149]

Comment:

PTAW <ptairwatchers@mailhaven.com> 

06/07/2010 09:03 PM

To Docket OEI@EPA

cc

bcc

Subject Docket ID No. EPA-HQ-TRI-2010-0006; FRL-9134-1

Docket ID No. EPA-HQ-TRI-2010-0006; FRL-9134-1

Re: addition of 16 chemicals to TRI reporting

EPA should include the proposed 16 chemicals among EPA's regulated TRI chemicals. 

Reducing use of carcinogenic and hazardous chemicals such as these and knowing when 

and where they are being emitted is essential to environmental and public health. 

However, do so with the knowledge that it's a stop-gap within a larger problem. For every 

few that can be scrutinized for regulation, modern industry creates thousands of new 

chemicals annually, often slightly modifying some chemical structures in order to avoid 

regulation, which means that despite our best attempts we will necessarily lose ground on 

this front in the quest to protect health and the environment. EPA should regulate TRI 

chemicals vigorously, but in order to progress faster than the addition of new chemicals 

to our total chemical exposure load, EPA must also develop strategies that address entire 

classes of compounds. More pointedly, EPA should require that before any given 

chemicals can be used or emitted, they must be proven a meaningful form and degree of 

“safe”, that processes for handling them through entire lifecycle be well-defined, and that 

meaningful financial protections be built into the usage of the chemicals: pre-emptively 

putting the onus for safety on the industry.

Thank you,

Gretchen Brewer

PT AirWatchers

PO Box 1653, Port Townsend WA 98368

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory. Regarding the evaluation of new industrial 

chemicals, under the Toxics Substances Control Act, EPA evaluates new chemicals 

before they are manufactured.
25

Commenter: Darlene Schanfald [EPA-HQ-TRI-2010-0006-0150]

Comment:

Darlene Schanfald <darlenes@olympus.net> 

06/07/2010 03:49 PM To

Docket OEI@EPA

cc

bcc

Subject RE: adding 16 chemicals to the TRI list of reportable chemicals

I have just general comments.

Of course the list should be expanded, particularly so that they are "reasonably 

anticipated to be a human carcinogen" and are released into the environment. This gives 

the public even more information through the TRI.

The amount of carcinogenic compounds, not to mention what the synergy of these 

together mean, are ruining the public health and our natural resources. Anything steps to 

control these compounds and any steps to daylight what these are should be taken.

Respectuflly,

Darlene Schanfald

481 Holgerson Rd

Sequim WA† 98382

EPA Response: EPA appreciates the commenter’s support for listing the 16 NTP 

carcinogens on the Toxics Release Inventory.