p.1 

Task Force 

CBIC Control Number 

355333 

P.O. Box 331, Millwood, VA 22646 (540) 837-1602 

July 24, 2013 o 

BY HAND ro -x?S 

cn HfT i 

Maria J. Doa, Ph.D. oc Em 

Director ° 

Chemical Control Division £J 

Environmental Protection Agency 

1200 Pennsylvania Ave., N.W. 

Washington, DC 20460 oed&P«ceSSCllH 

Re: Testing Consent Order for Ethylene Dichloride: 

Request for Modification of Enforceable Consent 

Agreement and Amendment to Study Plan (Docket No. OPPT2003-00101 

Dear Dr. Doa: 

Thank you for your response of July 22, 2013 to our request for a modification of the 

Enforceable Consent Agreement for Ethylene Dichloride ("EDC"), 68 Fed. Reg. 33125 (June 

3, 2003), as amended, 74 Fed. Reg. 36196 (July 22, 2009), further amended by Addendum 

Modification provided by letter dated November 23, 2011 from Maria J. Doa (the "ECA"). 

The Task Force understands and shares your concerns about the unavoidable delays 

encountered by WIL Laboratories in preparing to conduct the Extended One-Generation 

Drinking Water Reproductive Toxicity Study of Ethylene Dichloride in Rats, based on 

OECD Guideline 443. The study plan submitted on May 24, 2013 included a start date of 

July 8, 2013 and a completion date of July 24, 2014. These dates were based on EPA's 

approval in advance of the start date. When this was not received, I notified the laboratory to 

postpone ordering the animals, and sent John Schaeffer the enclosed fax dated July 10 to this 

effect. 

The addendum modification you provided contains a completion date of July 28, 

2014, based on the now-inoperative start date of July 8, 2014. Mr. Schaeffer asked for a new 

schedule based on an expected acceptance date no later than August 5. I am informed by 

WIL that, due to limited vivarium space, the earliest date it can now initiate this study is 

September 1, making the completion target date September 15, 2014. In order to meet these 

dates, I need to inform WIL by August 7, 2013. The enclosed schedule reflects WIL's 
p. 2 

Maria J. Doa, Ph.D. 

July 24,2013 

Page 2 

current estimate of the time required for it to conduct the study, analyze and interpret the 

results, draw conclusions, and write a peer-reviewed report. Any shortening of this period 

could result in an incomplete study that would not be scientifically credible, would be useless 

to the Agency for assessing potential human risk, and would not conform to EPA's own 

testing guidelines and standards. 

I have signed the enclosed addendum modification and initialed new handwritten 

deadline dates of September 15,2014 for the main study (unless a second generation study is 

triggered) and December 15,2014 for the route-to-route extrapolation. I look forward to 

receiving the countersigned addendum modification from you by August 5, 2013 so that we 

can initiate and complete the study in accordance with the ECA. 

Enclosures 

cc: John E. Schaeffer 

James C. Lamb, IV, Ph.D. 

JimS. Bus,Ph.D. 

Jacques Maurissen, Ph.D. 

W. Caffey Norman, Esq. 

Document Control Office (six copies) 

4842-J657-7553.1. 

Sincerely, 

Peter E. Voytek, Ph.D. 

Manager 
p. 3 

P.O. Box 331, Millwood, VA 22646 (540) 837-1602 

Task Force 

DATE 7/10/13 

TO: John Schaeffer 

FROM: Peter Voytek 

SUBJECT: EDC Study Plan 

PAGES: 1 

The HAP Task Force submitted the study plan to EPA dated May 24, 2013 for the Extended One-Generation Drinking 

Water Reproductive Toxicity Study of Ethylene Dichloride in Rats. An experimental start date of July 8, 2013 was 

provided with a final report to be submitted to EPA on July 21, 2014. These dates were based on the assumption that 

the study plan would be approved by EPA in a timely manner in order for the animals to be ordered, acclimated, and 

clinically examined prior to the experimental start date. Since we have not received any notification from EPA I told the 

laboratory to postpone ordering the animals until we have approval of the work plan. As your are aware the animals 

need to be of a certain age at the beginning of the experimental stage as required by the protocol. 

I am puzzled by the delay. The most important and essential part of the work plan is the study protocol that has already 

been reviewed and approved by your pharmacokineticists, neurotoxicolgists, and reproductive and developmental 

toxicoiogists. If any technical issues remain i need to be informed so that changes can appropriately be made to the 

protocol and approved by the Agency before any testing is possible. The time to initiate and complete this study 

assumes that no technical issues may arise. As with all biological testing the unexpected may occur and necessary 

amendments will be required in order to achieve the objective of the study as described in the protocol and to assure 

technical quality. However, in our many previous toxicity tests on both 1,1,2-trichloroethane and ethylene dichloride 

conducted over many years, I do not recall that any technical issues arose to delay the completion dates once the study 

was initiated. 

After receiving approval of the study plan I will immediately notify the Laboratory to order the animals and the 

experimental start date will be one month after the date of receipt of the EPA letter. 

If you have any questions contact me. 
Schedule for Extended One-Generation Drinking Water Reproductive 

Toxicity Study of Ethylene Dichloride in Rats 

Date of EPA Response: 8/5/2013 

Animal Receipt 8/19/2013 

First Dose 9/1/2013 

End of FO breeding 10/12/2013 

End of FO Parturition 11/3/2013 

Last Necropsy Cohort la 2/2/2014 

Last Necropsy Cohort lb 3/3/2014 

Last Necropsy Cohort 2a 11/24/2013 

Last Necropsy Cohort 2b 1/20/2014 

Audited Draft Report to HAP Task Force 6/9/2014 

Final Report to HAP Task Force 9/8/2014 

Final Report to EPA Date 9/15/2014 

4815-9509-5316.1. 
p. 5 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C, 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Dr. Peter E.Voytek 

HAP Task Force Manager JUL 2 2 2DJ3 

P.O. Box 331 

Millwood, Virginia 22646 

Re: May 24, 2013, Request by the HAP Task Force for Modification of Enforceable Consent 

Agreement for Ethylene Dichloride (Docket No. EPA-HO-OPPT-2003-0010) 

Dear Dr. Voytek: 

EPA has completed its review of the requested modification to the "Extended OneGeneration Drinking Water Reproductive Toxicity Study of Ethylene Dichloride in Rats" that is 

based on the OECD Extended One-Generation Reproductive Toxicity Study Guideline 443 

(EOGRTS), and your email of July 11,2013, concerning the test schedule. The HAP Task 

Force/WIL Laboratories study protocol also combines a neurotoxicity testing component, and 

was approved by EPA on November 23,2011, The modification includes the requested schedule 

changes to the original study plan, including an extension to the submission date for the required 

final reports. EPA has also reviewed the protocol amendments that Were originally submitted 

with the protocol from WIL Laboratories (Protocol Amendment 1) and the additional 

amendment (Protocol Attachment 2) that contains changes to the protocol that were requested by 

EPA. EPA further acknowledges the addition of Dr. Sawhney Coder as an emergency contact for 

the study. 

You have stated in your request letter that a modification to the test schedule is needed 

because WIL Laboratories had difficulties obtaining the necessary equipment to conduct the 

study. Then, as testing was about to begin, preliminary work determined that there was an 

unforeseen problem with maintaining the needed test substance concentrations* While EPA 

understands that solving this problem took time and effort, such that an extension for submitting 

the final reports is needed, the Agency remains concerned about the delays that have occurred. In 

granting this extension, EPA also understands that the'problem with maintaining the necessary 

test concentrations is now resolved. 

Enclosed, for your signature, is the Addendum Modification to the EDC ECA. The 

Addendum Modification confirms the approved changes to the revised testing as well as the 

revised dates that the final reports are due. The Addendum also includes the WIL protocol 

amendments. 

Internet Address UJRLj • http rVwwwepa gov 

Rticycled/Recyctable • Printed with Vegetable Oil Based Inks on "100% Poslcansumer. Process Chlorine Free Recycled Paper 
p. 6 

The final report for the combined EOGRTS/neurotoxicity study is due July 28,2014. The 

final report for route-to-route extrapolation for reproductive effects and neurotoxicity is due 

October 28,2014. Note that, in accordance with the original enforceable consent agreement 

(ECA), the HAP Task Force must submit interim reports describing the status of all testing 

performed under this ECA to EPA every six months. Failure to adhere to the conditions of the 

ECA, including the ECA reporting requirements, could result in penalties as specified in 40 

C.F.R. § 790.65. While EPA appreciates the work of the HAP Task Force to bring this testing to 

a satisfactory conclusion, it is also concerned that this ECA has incurred numerous delays. 

Please sign and return the enclosed addendum to the ECA for 1,2-ethylene dichloride. 

This signed document will be submitted to the above-referenced EPA Docket for this ECA. 

Please contact John Schaeffer if you have any questions (phone: 202-564-8173; email: 

schaeffer.john@epa. gov). 

Sincerely, 

Maria J. Doa^Pfi-D. 

Director 

Chemical Control Division 

Enclosures a/s 
We the undersigned agree to the change to the Enforceable Consent Agreement for 1,2-Ethylene 

Dichloride (CAS No. 107-06-2) as described in the table below: 

Original Language (Im Modification Addendum to Table I of the EDC ECA (74 FR 36196) 

dated November 17,2011, and by approval letter of November 23,2011) 

Tier U Testing and/or Program Review 

Extrapolation Reporting 

Reproductive toxicity/Neurotoxicity 

(oral) 

Reproductive toxicity/Neurotoxicity 

route-to-route extrapolation ol*dose-response 

(oral data to inhalation, including 

Tier II testing and extant studies 

reported by Aiumoi, ct aJ., 

(1976), Rao, el aJ..(l980), and 

Lane, ctal., (1982)) 

Test Standard Deadline for Final Report 

Combined Reproductive Kffects 

/Neurotoxicity Protocol 

ECA appendix C.4 and C6 

June 28, 2013 

(New study plan due 

February 28, 2012) 

September 27, 2013 

Amended, Language (change in Table 1 of the EDC ECA as amended on July 22,2013, and 

by approval letter of July 22,2013) 

Tier (I Testing and/or Program Review Test Standard Deadline for Final Report 

Extrapolation Reporting 

Reproductive toxicity/Neurotoxicity 

(oral) 

Reproductive toxicity/Neurotoxicity 

roule-io-routc extrapolation of dose-response 

(oral data to inhalation, including 

Tier 11 testing and extant studies 

reported by Aiumoi, et ai., 

(1976). Rao, ct al., (1980), and 

Lane, et aL (1982)) 

5«*ft»v4^ lb/ 

Combined Reproductive Effects vJuly38» 2014 

/Neurotoxicity Protocol/with WIL ^£ \j 

Protocol Amendment i and WIL 

Protocol Attachment 2 

ECA appendix C.4 and C.6 October 28, 2014 

Maria J. Doa. Ph.D. Date Peter 

Director Manager 

Chemical Control Division HAP Task Force 

;erE. Voytek, f^D'. Daife 
P. 8 

July 22,2013 

Addendum Modification 

To 

Enforceable Consent Agreement 

For 

1,2-EthyIene Dichloride 

(CAS No. 107-06-2) 

Tier JiffAPs Testing 

Docket No. OPPT-2003-0010 
p. 9 

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