Toxicological Sciences 62, 155-165 (2001)
Copyright © 2001 by the Society of Toxicology
SAFETY EVALUATION |
Subchronic Inhalation Toxicity of the Chlorinated Propane 1,1,1,3,3,3-Hexachloropropane (HCC-230fa)
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* E. I. DuPont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714;
Pfizer Inc., Central Research Division, Eastern Point Road, Groton, Connecticut 06340;
Vulcan Chemicals, Birmingham, Alabama 35238; and
Unilever Research, SEAC Toxicology Unit, 45 River Road, Edgewater, New Jersey 07020
Male and female rats were exposed by inhalation (whole body) to HCC-230fa (1,1,1,3,3,3-hexachloropropane) for 6 h/day, 5 days/week over a 15-week period. Concentrations of 0, 0.50, 2.5, and 25 ppm were studied. A total of eight groups/sex were exposed. Four groups of male and four groups of female rats were used to measure clinical signs and growth, clinical pathology, and tissue pathology. The remaining four groups of male rats were used for immunotoxicological and sperm assessment evaluations, and the remaining four groups of female rats were used for immunotoxicological evaluation. Following the exposure period, surviving male rats were kept for a 1- or 3-month recovery period. Male and female rats exposed to 25 ppm had lower mean body weights, mean body weight gains, and food consumption during the exposure period. Male and female rats exposed to 25 ppm and sacrificed immediately after the exposure period had minimally decreased total leukocyte and lymphocyte counts. These changes were considered to be marginally adverse. Pathologic examination revealed hepatocellular hypertrophy in 0-day recovery males and an increased incidence and/or severity in chronic progressive nephropathy in 0-day, 1-month recovery, and 3-month recovery males at 25 ppm. No other pathological changes, including the testis, epididymis, and other accessory sex organs, were noted in rats during the study. Evaluation of sperm parameters at the end of the exposure period showed statistically significant decreases in epididymal sperm number per cauda epididymis, percent motile sperm, and percent normal sperm morphology at 25 ppm. The biological significance of the slight changes observed in the sperm parameters in the absence of histopathological changes is unclear. After a 1-month recovery period, no biologically significant differences in sperm parameters were noted at 25 ppm compared with controls. Exposure to HCC-230fa did not significantly alter the primary humoral immune response to sheep red blood cell (SRBC). Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 2.5 ppm.
Key Words: halogenated hydrocarbons; chlorinated alkanes; inhalation; repeated exposure; immunotoxicity; hepatotoxicity.
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  W. J. Brock, S. M. Munley, M. S. Swanson, K. M. McGown, and M. E. Hurtt Developmental Toxicity and Genotoxicity Studies of 1,1,1,3,3,3-Hexachloropropane (HCC-230fa) in Rats Toxicol. Sci., October 1, 2003; 75(2): 448 - 457. [Abstract] [Full Text] [PDF]
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