1-Hexene, 3,3,4,4,5,5,6,6-octafluoro-6-iodo-

Endpoint summary

Description of key information

A repeat dose inhalation toxicity study was conducted on IOFH.  The result of the study was: 
The No Observed Adverse Effect Concentration (NOAEC) was 55 ppm (0.79 mg/L, vapor) when tested according to OECD 412.

Additional information

The repeat-dose inhalation toxicity potential of the test article (Clear and colorless to pale pink liquid, Purity 98.6%, Lot 2) was evaluated in a 1-week screening study in Sprague-Dawley rats. The study was conducted in compliance with GLP regulations. The test method was based on OECD 412 (2009). Rats (6/sex/dose) were exposed nose-only to 0, 55, 257, or 993 ppm (0, 0.79, 3.72, 14.38 mg/L) of the test article vapor 6 hours/day for 7 consecutive days. Clinical observations (prior to exposure, at exposure midpoint, once daily thereafter) and body weights (Days 0, 3, 6, 10, 13, and 14) were noted. Hematology, serum chemistry, and serum hormone levels were analyzed for all rats (3/sex/group) at the primary (Day 7) and recovery (Day 14) necropsies. Complete necropsies were conducted on all animals and the adrenals, kidneys, liver, lungs, testes (males) thymus and thyroids were examined in control and 993 ppm group animals at necropsy. Gross lesions and target tissues were examined from all animals at primary and recovery necropsies. A single animal in the 55 ppm group was found dead but the death was not considered test article related. There were no test substance-related effects on survival. Test substance-related clinical observations for the 993 ppm group males and females included vocalization upon handling and intermittent tremors beginning 1 hour post-exposure on Day 1, yellow material on body surfaces (dorsal rump, ventral, dorsal or lateral trunk and urogential area) generally throughout the exposure period, and unkempt appearance and thin body condition on Day 6. Low or single incidences of vocalization upon handling and yellow material on dorsal rump or dorsal trunk were also noted in the 55 and/or 257 ppm group females. Lower body weight gains or body weight losses were noted in the 257 ppm group males and 993 ppm group males and females throughout the exposure period and in the 55 ppm group males from Day 3 to 6 when compared to the control group. At the end of the exposure period, mean body weights were 13.7% and 17.1% lower in the 257 and 993 ppm group males, respectively and 8.8% lower in the 993 ppm group females when compared to the control group. During the recovery period, lower body weight gains were noted in the 993 ppm group males from Day 6 to 10 when compared to the control group. The 257 ppm group males and 993 ppm group females recovered from the body weight effects. Lower food consumption was noted for the 257 ppm group males and the 993 ppm group males and females throughout the exposure period and in the 257 ppm group females from Day 0 to 3 compared to the control group. Food consumption was similar or higher than controls in all exposure groups during the recovery period. Test substance-related alterations in hematology parameters consisted of lower absolute reticulocyte counts in the 257 ppm group males and 993 ppm group males and females, higher absolute neutrophil counts in the 993 ppm group males, and lower absolute eosinophil counts in all test substance-treated male groups on study day 7. Following the recovery interval, absolute neutrophil counts remained higher in the 993 ppm group males and females. Test substance-related alterations in serum chemistry parameters included higher alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase values in the 993 ppm group males and females, higher sorbitol dehydrogenase values in the 257 ppm group males and 993 ppm group males and females on Day 7. Alterations in these enzymes were not noted after the recovery interval. On Day 7, cholesterol values were below the lower limit of detection for all males and females at 993 ppm and in 1 male at 257 ppm. Cholesterol values were lower than controls in the 55 and 257 ppm group males and the 55 and 257 ppm group females. On Day 14, mean cholesterol values were higher than controls in the 993 ppm group males and females. Test substance-related lower total protein and albumin values were noted in the 993 ppm group males on Day 7. On Day 14, mean total protein, albumin, and globulin values were slightly higher and the albumin to globulin ratio was slightly lower than controls in the 993 ppm group males. Mean total protein and globulin values were slightly higher than controls in the 257 ppm group males. Total T3 values were lower than controls in all test substance-treated male and female groups on Day 7. On Day 14, mean total T3 values were higher than controls in the 993 ppm group males. Total T4 values were higher than controls in all test substance-treated male and female groups on Day 7. On Day 14, T4 values were higher than controls in the 993 ppm males and females. Mean TSH values were higher in the 993 ppm group males and females on Day 7. Individual TSH values were higher than the upper limit of instrument evaluation for all males at 257 ppm and for one male at 55 ppm. Exposure to 993 ppm of the test article was associated with pallor in the liver and yellow matting of the skin in males and females. Exposure to 257 and 993 ppm was associated with enlargement and dark red discoloration of the adrenal glands in males and females. Microscopically, enlargement correlated with adrenal cortical hypertrophy and dark red areas correlated with hemorrhage. Pallor of the liver was also observed after a 7 day recovery period. Exposure to 257 and 993 ppm test article was associated with higher liver and adrenal gland weights and lower thymus weights in males and females and lower testes weights in males. Exposure to 993 ppm was associated with higher kidney weights in males and females. The adrenal gland and kidney weight changes were reversible after a 7-day recovery (non-exposure) period. The liver, thymus and testes weight changes were not completely reversible after recovery. Exposure to all dose levels was associated with midzonal hepatocellular vacuolation, single cell necrosis, and increased mitoses in the liver. Exposure to 257 and 993 ppm was associated with hypertrophy, hemorrhage, necrosis and acute inflammation in the adrenal cortex; lymphoid depletion in the thymus; and germ cell degeneration in the testes. Hepatocellular vacuolation, single cell necrosis, and subacute inflammation were observed in livers from males and females at all exposure levels (except single cell necrosis at 55 ppm) after a 7-day recovery period, indicating a lack of reversibility in this time period. Adrenal cortical hemorrhage and seminiferous tubular degeneration of the testes were also observed at the recovery necropsy with exposure to 993 ppm and thymic lymphoid depletion was observed at the recovery necropsy with exposure to 257 ppm and 993 ppm.  Based on the results of the study, the No Observed Adverse Effect Concentration (NOAEC) was 55 ppm (0.79 mg/L, vapor) for the test article.

Justification for classification or non-classification

IOFH meets the CLP classification criteria for a Category 2 (STOT RE 2) target organ toxicant.