# <6>A

**~** Task 

# Force

Document Control Office Office ofPollution Prevention and Toxics Room 6428 U.S. Environmental Protection Agency 1200 Pennsylvania Ave., N.W. Washington, DC 20460 P. O . Box 33 1 , Millwoo d , VA 22646 (540) 837 -1 602
October 27 , 2014

Re: 

### Testin& Consent Order for Ethylene Dichloride;
Dear Sirs: 

### Analysis of Data for Determination ofSecond Generation Study (Docket 

### No. OPPT-2003-0010)



# . The extended one-generation drinking water reproductive toxicity study for ethylene dichloride in rats has reached the stage to decide whether there is a need to go further with a second generation analysis based on the triggers defined in the OECD guideline. We have already provided the available unaudited data to EPA to review which includes: behavior data, developmental landmarks and survival to weaning data, nipple/areola and anogenital distance data, balanopreputial separation, summary of organ weight data for males and females, individual organ weight data for males and females, most current body weight and body weight changes for males and females 

### (F 1 ), necropsy findings for pups, the draft pathology report with FO pathology tables, historical control summary ofreproductive performance, pup survival indices, pup body weights, pup organ weights, developmental landmarks, male and female organ weights, sperm concentration and morphology. We observed a noticeable difference between the experimental control (45.4+/-2 .55) and high dose (47.1+/- 2.54) mean balanopreputial separation time. However, this was not statistically significant, it was less than two days , and when compared to mean historical controls (45.6 +/-1.59) the high dose value was closer to the historical mean value than the experimental dose value . Additionally, there appeared to be a trend in decrease body weight with dose which was not statistically significant. This was was likely attributed to decreases in water consumption due to possible palatability issues, as well as a decrease in food consumption, and not rela ted to developmental toxicity . There was also a noticeable difference between mean anogenital distance in males (control 4 .05+/- .467) and high dose (4.25+/- .164) and females (controls 2.11 +/-. 239) and high dose (2.20+/- .148) which were not statistically significant. The high dose experimental means were also closer to historical control values (males 4.17+/- .374) (females 2. 25+/-.210).There were no significant/relevant dose-related differences found with regard to the other toxicological data examined. , Furthermore, balanopreputial separation is not assessed in the typical second generation because the pups are sacrificed before sexual maturation. Based on these data there are no meaningful dose-related effects and a second generation would not likely contribute to the assessment ofthe developmental toxicity of ethylene dichloride. Ifyou have questions regarding our interpretation ofthe data, a teleconference should be scheduled immediately, since the cut-off date for initiating the second generation study is October 31 81• Sincerely,

Peter E.Voytek, Manager HAP Task Force cc: Jim 

### Lamb Jacque Maurisson Jeff Char lap John 

### E. Schaeffer Jim Bus Caffey Norman, Esq