Abstract
Objectives: The present study was conducted in order to investigate the reproductive toxicity in rats exposed to 1,4-dichlorobutane. Methods: The test chemical was administered orally at 0, 8.3, 50 and 300 mg/kg/day. Males were administered daily for 10 weeks prior to the mating period. Females were administered from between two weeks before mating to the 21stday of lactation. Results: In both sexes, a decrease in body weight and an increase in the weights of the liver and kidneys were observed. In males, discoloration of the liver, hepatocyte hypertrophy and mineralization in the kidneys were observed. In females, animal deaths, dystocia and pup deaths due to maternal dysfunction were observed. In F1 animals of both sexes, a decrease in body weight was observed at 300 mg/kg/day. An increase in the weights of the liver in both sexes, mineralization in the kidneys of males, animal deaths, hepatocyte hypertrophy and pup deaths due to maternal dysfunction were observed at 50 mg/kg/day. Mineralization in the kidneys of males was observed at 8.3 mg/kg/day. Therefore, the no-observed-adverse-effect levels (NOAELs) of 1,4- dichlorobutane were considered to be under 8.3 mg/kg/day for males, 8.3 mg/kg/day for females, more than 300 mg/kg/day for fertility in both sexes, 8.3 mg/kg/day for maternal functions and 50 mg/kg/day for F1 offspring. The absolute toxic dose was believed to be 8.3 mg/kg/day for males, 50 mg/kg/day for females, 50 mg/kg/day for maternal functions and 300 mg/kg/day for F1 offspring. However NOAEL for fertility could not be determined since there were no treatment-related changes. Conclusions: Under the present experimental conditions, 1,4-dichlorobutane is a Category 1B Reproductive Toxicant (presumed human reproductive or developmental toxicant).