These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.
Thirteen-week studies were conducted to investigate potential differences in rat strain susceptibility to 1,2-dichloroethane toxicity. F344/N rats, Sprague Dawley rats, Osborne-Mendel rats, and B6C3F1 mice (10 animals of each sex) were exposed to 1,2- dichloroethane in drinking water at 0, 500,1,000, 2,000, 4,000, or 8,000 ppm for 13 weeks. In addition, groups of 10 F344/N rats of each sex were administered 1,2-dichloroethane in corn oil by gavage to compare toxicity resulting from bolus administration with that of continuous exposure in drinking water. Gavage doses of 1,2-dichloroethane were within the range of daily doses resulting from exposure in drinking water.
No compound-related deaths occurred in any of the rat strains exposed to1,2-dichloroethane in drinking water. Weight gain depression was common in each sex of all three rat strains in the 4,000 and 8,000-ppm groups throughout the studies. Water consumption was decreased by 50%-60% with increasing dose for all exposed male and female rats regardless of strain. Kidney and liver weights were increased in dosed rats of all three strains. No chemical-related lesions were observed except for a dose- related incidence of renal tubular regeneration in female F344/N rats.
Nine of 10 female mice exposed to 8,000 ppm 1,2-dichloroethane in drinking water died before the end of the study. Mean body weights of males at 500 ppm or more and females at 1,000 ppm or more were lower than those of controls throughout most of the studies. Kidney weights were significantly increased for dosed males and females. Renal tubular cell regeneration was seen in males at 8,000 ppm; at 4,000 ppm, minimal regeneration was present in 8/10 male mice.
All male F344/N rats that received 240 or 480 mg/kg and 9/10 females that received 300 mg/kg 1,2-dichloroethane by gavage died before the end of the studies. Mean body weights of the highest dose males and females were lower than those of vehicle controls throughout the studies. Liver and kidney weights were increased for dosed males and females; however, no compound-related lesions were observed. Necrosis of the cerebellum, hyperplasia, inflammation, and mineralization of the forestomach, and necrosis of the thymus were seen in animals that died or were killed in moribund condition.
Rat strain differences in susceptibility to 1,2-dichloroethane toxicity were not apparent at the drinking water concentrations used in these studies; only female F344/N rats exhibited mild chemical related renal lesions. Male B6C3F1 mice appeared to be more susceptible than rats to toxicity of 1,2-dichloroethane administered in drinking water; renal tubule regeneration was observed in male mice in the 4,000- and 8,000-ppm groups. The higher toxicity in mice was likely due to higher water consumption, resulting in up to tenfold higher doses to mice than to rats. 1,2-Dichloroethane administered in drinking water resulted in less toxicity to F344/N rats than administration of similar doses by gavage.