Subchronic inhalation toxicity of the chlorinated propane 1,1,1,3,3,3-hexachloropropane (HCC-230fa)

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 per iod, Concentrations of 0, 0.50, 2.5, and 25 ppm were studied. A total of ei ght groups/sex were exposed. Four groups of male and four groups of female rats were used to measure clinical signs and growth, clinical pathology, an d tissue pathology. The remaining four groups of male rats were used for im munotoxicological and sperm assessment evaluations, and the remaining four groups of female rats were used for immunotoxicological evaluation. Followi ng the exposure period, surviving male rats were kept for a 1- or 3-month r ecovery period. Male and female rats exposed to 25 ppm had lower mean body weights, mean body weight gains, and food consumption during the exposure p eriod. Male and female rats exposed to 25 ppm and sacrificed immediately af ter the exposure period had minimally decreased total leukocyte and lymphoc yte counts. These changes were considered to be marginally adverse. Patholo gic examination revealed hepatocellular hypertrophy in 0-day recovery males and an increased incidence and/or severity in chronic progressive nephropa thy in 0-day, 1-month recovery, and 1-month recovery males at 25 ppm. No ot her pathological changes, including the testis, epididymis, and other acces sory sex organs, were noted in rats during the study. Evaluation of sperm p arameters at the end of the exposure period showed statistically significan t decreases in epididymal sperm number per cauda epididymis, percent motile sperm, and percent normal sperm morphology at 25 ppm. The biological signi ficance of the slight changes observed in the sperm parameters in the absen ce 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 (N OAEL) was considered to be 2.5 ppm.