p.1 

CBIC Control Number 

357421 

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

December 17,2013 

BY HAND 

Document Control Office 

Office of Pollution Prevention and Toxics 

Room 6428 

U.S. Environmental Protection Agency 

1200 Pennsylvania Ave., N.W. 

Washington, DC 20460 

Re: Testing Consent Order for Ethylene Dichloride: 

Request for Modification of Enforceable Consent 

Agreement and Amendment to Study Plan (Docket No. OPPT2003-0010) 

Dear Sirs: 

The HAP Task Force requests 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), as further amended by Addendum Modification provided by 

letter dated November 23, 2011 from Maria J. Doa, and as further amended by Addendum 

Modification provided by letter dated July 22, 2013 from Maria J. Doa (the "ECA"). Six 

copies of this submission are enclosed. 

Pursuant to the ECA and the Study Plan for an extended one-generation drinking 

water reproductive toxicity study of ethylene dichloride in rats, submitted July 2, 2012, and 

amended July 16, 2012, August 7, 2012, May 24, 2013, and July 24, 2013, the experimental 

start date was September 1, 2013, and the final report, unless a second generation study was 

triggered, was due September 15, 2014. 

The study began on schedule, but was terminated on November 14, 2013 after the 

Task Force was notified that the number of litters from the F0 generation \* is lower than 

expected in controls as well as in the three treated groups. Although the el ect was not doserelated, the number of litters was insufficient to continue the study. WIL1. is agreed to 

conduct a study to determine the cause of the low litter survivability, as described in the 

Task Force 

7 2013 

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DEC 11 2013 
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Document Control Office 

December 17,2013 

Page 2 

enclosed summary. The variables WIL will be investigating are: 

(1) Harlan Teklad 2016CM vs. PMI LabDiet 5002: to assess the effect of the Harlan 

low-phytoestrogen diet on pup viability. 

(2) Harlan Teklad 2016CM (Meal) vs. Harlan Teklad 2016CM (Pellets): to assess 

whether the particle size of Harlan low-phytoestrogen diet has an effect on pup viability. 

(3) Harlan Teklad 2016CM vs. PMI Casein LabDiet 5k96: to assess another lowphytoestrogen diet as a possible candidate for use on reproductive toxicity studies that 

require low-phytoestrogen diet per guideline. 

(4) Aspen Bedding vs. Standard Corn Cob bedding (Bed O'Cobs): to assess the 

effect, if any, of the use of Aspen bedding for reproductive toxicity studies where the 

guidelines discourage use of corn-cob bedding due to its endocrine disruption potential. 

(5) Glass bottles (Teflon capped) vs. Automatic Water System (Lixits): to assess the 

effect, if any, of the use of water bottles. 

The schedule is as follows: 

Animal Receipt: 07 January 2014 

First Anticipated GD 0: 21 January 2014 

First Anticipated LD 0: 11 February 2014 

First Anticipated LD10: 21 February 2014 

WIL anticipates that it will be able to provide complete data from this study by 

February 28, 2014. 

In light of this unfortunate and unforeseeable development, the Task Force seeks EPA 

approval of a modification of the ECA and amendment to the Study Plan to provide for an 

experimental start date for the extended one-generation drinking water reproductive toxicity 

study of March 31, 2014 and a final report deadline (unless a second generation study is 

triggered) of April 14, 2015. The Task Force also seeks modification of the ECA to provide 

a new deadline of July 14, 2015 for route-to-route extrapolation of the dose-response data 

from this and extant studies. 
Document Control Office 

December 17, 2013 

Page 3 

We look forward to hearing from EPA. 

Sincerely, 

Peter E. Voytek, Ph.D. 

Manager 

Enclosure 

cc: John E. Schaeffer 

W. Caffey Norman, Esq. 

4819-6034-2036.1. 
||WIL RESEARC H 

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Page: 1 of 1 

An Investigative Study to Determine Possible Causes for Low Neonatal Survival on WIL-417005 

Compliance: non-GLP 

Group Diet 

Variables 

Bedding Water 

No. of 

Females 

1 Harlan 2016CM (Meal) Aspen Bed Glass Bottles 10 

2 Harlan 2016CM(Meal) Bed O'Cobs Glass Bottles 10 

3 Harlan 2016CM (Pellet) Aspen Bed Glass Bottles 10 

4 PMI LabDiet 5002 (Meal) Aspen Bed Glass Bottles 10 

5 PMI LabDiet 5002 (Meal) Bed O'Cobs Glass Bottles 10 

6 PMI Casein Diet 5k96 (Meal) Aspen Bed Glass Bottles 10 

7 Harlan 2016CM (Meal) Aspen Bed Lixits 10 

Objective: 

Animals: 

Groups: 

Viability Observations: 

Clinical Observations; 

Body Weights: 

Food Consumption: 

Water Consumption: 

F0 Assessments: 

F1 Assessments: 

Quality Assurance: 

Reports: 

To determine possible causes for low neonatal survival on WIL-417005. 

Sexually Mature Adult Sprague Dawley Female Rats 

70 females on study, 80 females ordered. Untreated sexually mature 

males of the same strain and source will be used to induce pregnancies. 

1 control group (mimic WIL-417005) and 6 Variable-Controlled groups. 

Twice daily observations for moribundity and mortality. 

Once daily and all females observed 3-4 times daily during the period of 

anticipated parturition and during the first 10 days of neonatal life. 

Twice weekly from receipt through LD10. 

Twice weekly from receipt through LD10. Stock male rats will receive the 

diets specified for the on-study females during the mating period. 

Twice weekly from receipt through LD10. 

Gestation lengths, live litter size; offspring sex ratio. 

Evaluation of physical abnormalities; postnatal survival; body weights 

through PND 10. 

The study will be not be monitored by the Quality Assurance Unit. 

A summary report will be generated and archived according to WIL 

Research's SOPs for in-house studies. 

Variables Assessed: 

(1) Harlan Teklad 2016C/W vs. PMI LabDiet 5002: to assess the effect of the Harlan low-phytoestrogen 

diet on pup viability. 

(2) Harlan Teklad 2016CM (Meal) vs. Harlan Teklad 2016CM (Pellets): to assess whether the particle size 

of Harlan low-phytoestrogen diet has an effect on pup viability. 

(3) Harlan Teklad 2016CMvs. PMI Casein LabDiet 5k96: to assess another low-phytoestrogen diet as a 

possible candidate for use on reproduction studies that require low-phytoestrogen diet per guideline. 

(4) Aspen Bedding vs. Standard Corn Cob bedding (Bed O'Cobs): to assess the effect, if any, of the use 

of Aspen bedding for reproduction studies where the guidelines discourage use of corn-cob bedding 

due to its endocrine disruptive potential. 

(5) Glass bottles (Teflon capped) vs. Automatic Water System (Lixits): to assess the effect if any of the 

use of water bottles on this study. 

Group 1 would be treated exactly the same as all groups on WIL-417005. The remaining 6 groups include 

one (or two) variables to help identify a possible cause for low pup viability, if it was related to these 

variables. 

CONFIDENTIAL 

We have listening down to a science.