DuPont Chemicals & Fluoroproducts 

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April IS 2013 

U.S. Environmental Protection Agency 

Office of Air and Radiation 

Stratospheric Protection Division 

Attention: Margaret Sheppard 

1310 L Street ·Nw, 10th Floor (Room 1029) 

Washington, DC 20005 

Dear Ms Sheppard: 

DuPont Chemicals & Fluoroproducts 

Chestnut Run Plaza 702 1276-E 

4417 Lancaster Pike 

Wilmington, DE 19805 

USA 

MAY 2 8 i3 

Reference: DuPont SNAP Information Notice 

(Z)-t,1,1,4,4,4-hexafluoro-but-2-ene (CAS RN 692-49-9) 

Interim Results of Two-Generation Reproduction Tolerability Study 

This letter is to inform you of interim results of a recently conducted two-generation reproduction 

tolerability study on the PMN substance. The tolerability study will serve as the basis for test 

concentrations in the main two-generation reproduction test in rodents. 

This study was listed in Attachment 27 (FEA-1100 Toxicity Testing (CAS RN 692-92-2)) of the 

subject PMN among the ongoing studies being conducted on the PMN substance P-11-0549 (see 

letter dated 19 March 2013). Finalization of this study is ongoing. The estimated completion date 

for this final report is May 2013. 

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Groups of 30 male and 30 (nulliparous and non-pregnant) female Crl:CD(SD) rats were exposed 

by whole body inhalation for 6 hours per day, 7 days per week to o, 1500, sooo or 8500 ppm of 

the test substance diluted in air for. Body weights and food consumption were measured weekly, 

and clinical observations were evaluated daily. After approximately 2 weeks of exposure, body 

weight, weight gain, food consumption, and/or food efficiency were statistically significantly 

reduced in males at 1500 ppm and above, and in females at sooo ppm and above. Clinical signs 

of toxicity were observed in males exposed to Ssoo ppm during the second week of exposure 

(hyper reactive on multiple days (3/30), lethargic on 2 days (2/30), convulsions on 1 day (1/30), 

and stained fur on multiple days (4/30)). Stained fur was also observed in 3/30 males and 3/30 

females exposed to sooo ppm. No clinical signs of toxicity were observed in females exposed to 

Bsoo ppm, or in males or females exposed to 1500 ppm. Exposures for animals in the Ssoo ppm 

group were terminated on test day 15. 

Chestnut Run Plaza 702/1276-E, Wilmington, DE 19805 

E. I. duPont de Nemours and Company 

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Based on observed effects, the study was continued as a pilot study on approximately test dayt8 

(which was considered to be test day o of the pilot study) using males only from the original 

study. All of the female rats and 8500 ppm male rats from the original study were discontinued, 

and 3 additional male groups were added. Ten control males were re-assigned to be exposed to 

500 ppm, and 10 control males were re-assigned to a 3000 ppm group. Ten males from the 

original 5000 ppm group were re-assigned to a 5000 ppm group that was exposed 5 days per 

week instead of 7 days per week. Ten males per group from the original1500 and 5000 ppm 

groups were retained for the pilot study. 

For the pilot study 10 males per group were exposed to o, 500, 1500, 3000, 5000 ppm for 6 

hours per day, 7 days per week, and one group of sooo ppm males exposed for 5 days per week 

for 24 days. Body weights and food consumption were measured twice weekly, and clinical 

observations were evaluated daily. Statistically significantly reduced body weight and weight gain 

occurred at 1500 ppm and above. Food consumption was significantly reduced at 3000 ppm and 

above. There were no clinical signs of toxicity at any exposure concentration in the pilot study. 

Please contact me if you have any questions about this submission or need further clarification. 

Sincerely, 

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Via Federal Express