Subchronic inhalation toxicity and reproductive assessment in rats of three chlorinated propenes

Abstract

Croups of 15 male and 15 female Sprague‐Dawley rats were exposed to 1 of 3 chloropropene (2,3‐Di = DCP; 1,2,3‐Tri = TRCP; and 1,1,2,3‐Tetra ‐ TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 hid, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (∼15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP‐treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes.

Additional groups of 10 male and 20 female Sprague‐Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10‐wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21‐d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP‐treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment‐related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals.