## DuPont Chemicals & 

## Fluoroproducts [ April IS 2013 U.S

. Environmental Protectio n Agency Office ofAir and Radiat ion Stratospheric Protection Divi sio n 

### Attention: Margaret Sheppard 1310 L Street · Nw, 10th Floor (Room 1029) Washington, DC 20005 Dear Ms Shepp ard: 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 ofTwo-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 concentra ti ons in the main two-generation reproduction test in rodents. This s tudy was li sted in Attachment 27 (FEA-1100 Toxicity Testing (CAS RN 692-92-2 )) of the s ubject PMN among the ongoing studi es being conducted on the PMN substance P

- 11 -0549 (see letter dated 19 March 2013). Finalization ofthi s study is ongoing. The estimated com pletion date for this final report is May 2013

. [

] Groups of 30 male and 30 (nulliparous and non-pregnant) female Cr l :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 weig h ts and f ood consumption were measured weekly, and clinical observations were evaluated daily. After approximately 2 weeks of exposure, body weight, weight gain, food consum ption, and/or food efficiency were s tati stica lly s ignificantly 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 (hyp er reactive on multiple days (3/30), l et h argic on 2 days (2/30), convuls ion s 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 femal es exposed to 

### Bsoo ppm, or in mal es or females exposed to 1500 ppm. Exposures for animals in the Ssoo ppm group were terminated on test day 15

.

Chestn ut Run Pl aza 702/1276-E, W ilmi ngton, DE 19805 E. I. duPont de Nemours a nd Company 

## 1Based 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 male s only from the original study. All of the female rats and 8500 ppm male rats from the origina l study were discontinued, a nd 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 p er week. Ten males per group from the original1500 and 5000 ppm groups were r etained 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 a

bove. There were no clinical s igns of toxicity at any exposure concentration in the pilot study. Please contact me ifyou have any questions about this submission or need further clarification. Sincerely, [ 

### 1 Via Federal Express