May 7, 2oi2

U.S. Environmental Protection Agency Office of Air and Radiation Stratospheric Protection Division Attention: Margaret Sheppard 1310 L Street NW, ioth Floor (Room 1029) Washington, DC 20005 Dear Ms. Sheppard: Reference: SNAP Submission 

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2-Butene, 41,14,44-hexafluoro-, (2Z)- (CAS RN 69 2- 49
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In summary, the overall rat no-observed-adverse-effect-level (NOAEL) and lowest-observedadverse-effect level (LOAEL) in the 9o-day repeated inhalation studies are 5000 ppm and 7500 ppm, respectively. Calculations for risk assessment are typically based off of a NOAEL or LOAEL. The test substance is 2-Butene, 41,144,4-hexafluoro-, (2Z)- (CAS RN 69 2- 49

- 9)• Please contact me if you have any questions about this submission or need further clarification. Sincerely,

Via Federal Express attachmentsMay 4, 2oi2

U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics Confidential Business Information Center (CBIC) — TS74o7M Attention: Audrey Binder EPA East Building, Room 6428 1201 Constitution Avenue, NW Washington, DC 2000 4

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Dear Ms. Binder: Reference: PMN P -11- 0549

Submission Report Number —
As a follow-up to our phone call on 3o April 2012, please find below a summary of the two 9o-day inhalation toxicity studies that we discussed and which have been submitted during review of the above-identified PMN. In summary, the overall rat no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) in the 9o-day repeated inhalation studies are 5000 ppm and 75oo ppm, respectively. Calculations for risk assessment are typically based off of a NOAEL or LOAEL. The test substance is 2-Butene, 41,14,44-hexafluoro-, (2Z)- (CAS RN 692- 49

- 9)• First Study: Study Title: 9o-Day Inhalation Toxicity Study in Rats Study Completed On: August 12, 2010 Male and female rats were exposed to o, 500,1500 or io,000 ppm PMN substance via wholebody inhalation for 6 hours per day, 5 days per week for 13 weeks. Reduced body weight gain and reduced food consumption were observed at the io,000 ppm exposure level. There were no adverse effects in the clinical or anatomical pathology parameters in animals exposed to the PMN substance. The NOAEL was 1500ppm. Second Study: Study Title: 9o-Day Inhalation Toxicity Study in Rats Study Completed On: August 30, 2011 Male and female rats were exposed to o, 3000, 4000, 5000 or 7500 ppm PMN substance via whole-body inhalation for 6 hours per day, 5 days per week for 13 weeks. The NOAEL was 5000 ppm and 75oo ppm for males and females, respectively. Male rats had significantly reduced body weight in the 7500ppm exposure group, but no histopathological effects were observed in any test group. The adverse effect seen in this study was in the male rats only so the overall NOAEL/LOAEL for the study was based on that. No adverse effects were seen in the females. Please note that the second study was primarily conducted to provide a"more precise" NOAEL, since in the first study there was such a large gap between the NOAEL and the next highestconcentration (1500ppm to io,000 ppm). An in vivo micronucleus assessment was also added

onto the second study to evaluate the ability of the PMN substance to cause DNA damage. Also note that the decalcification observation was a test substance-related finding in both 9o-day studies. Thereby identifying 500 ppm as the LOEL (lowest-observed-effect-level). However, this finding is considered non-adverse as it is consistent with exposure to a fluorine-containing test substance, and it was not associated with any histopathological changes suggestive of tissue injury or any adverse functional consequences in the tissues (bone and teeth). For the purposes of riskassessment it is reasonable to focus on exposure levels associated with adverse, rather than nonadverse effects. The overall rat NOAEL and LOAEL in the 9o-day repeated inhalation studies are 5000 ppm and 7500ppm, respectively.
Please contact me if you have any questions about this submission or need further clarification.