Toxicology and Carcinogenesis Studies of 1,2-Dichloropropane (Propylene Dichloride) (CAS No. 78-87-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
Chemical Formula: C3H6Cl2
1,2-Dichloropropane is a chemical intermediate widely used in the production of tetrachloroethylene and carbon tetrachloride. It is an oil and fat solvent in certain furniture finishes, dry cleaning fluids, and paint removers and has been used to fumigate grain and soil and to control peach tree borers. Approximately 77 million pounds of 1,2-dichloropropane were produced in the United States in 1980. The current 8-hour time-weighted-average concentration to which workers may be exposed to is 75 ppm.
Carcinogenesis studies of 1,2-dichloropropane (>99% pure) were conducted by administering the chemical in corn oil by gavage to groups of 50 female F344/N rats and 50 male and 50 female B6C3F1 mice at doses of 125 or 250 mg/kg body weight and to groups of 50 male F344/N rats at doses of 62 or 125 mg/kg body weight. Doses were administered five times per week for 103 weeks. Vehicle control groups of 50 rats and 50 mice of each sex received an equivalent amount of corn oil by gavage on the same dosing schedule.
Survival was reduced for high dose female rats (P<0.001) and for high dose female mice (P<0.05) relative to controls; 16/50 high dose female rats and 26/50 high dose female mice survived to the end of the experiment. Survival in the other groups was comparable to the control groups. In female mice, ovarian, uterine, or multiple organ infections may have contributed to the deaths of 5/11 vehicle control, 9/14 low dose, and 14/22 high dose animals that died before the end of the study. There was no evidence of an adverse effect on survival in male rats or in male mice.
Mean body weights of high dose male (-14%) and high dose female (-24%) rats were lower than those of the controls. Low dose rats and all groups of mice had mean body weights comparable to the controls.
High dose female rats had increased incidences of both clear-cell changes and necrosis of the liver; but there was no increase in the incidence of liver tumors in the female rats. There was no treatment-related effects observed in the male rats, other than decreased body weights.
Dose-related increases were observed for adenomas of the liver in both male (control, 7/50; low dose, 10/50; high dose 17/50) and female (1/50, 5/50, 5/50) mice. The increase in the frequency of liver carcinomas supported the evidence that there was a neoplastic response in the mouse liver for both sexes (males: 11/50, 17/50, 16/50, females: 1/50, 3/50, 4/50). Hepatocytomegaly and hepatic necrosis were increased in male mice, but not in female mice.
A dose related increase in adenocarcinomas of the mammary gland was observed in female rats (control, 1/50; low dose, 2/50; high dose, 5/50) with the majority of these tumors being found at the end of the study (1/37, 3%; 2/43, 5%; 4/16, 25%). The incidence of mammary adenocarcinomas was increased when compared to the historical controls for this laboratory (3/150, 2.0%) and for all laboratories combined (11/895, 1.2%). Mammary fibroadenomas were decreased in the high dose treated female rats (15/50, 20/50, 7/50).
The mutagenic activity of 1,2-dichloropropane was marginal. The compound was tested in strains TA100, TA98, TA1537, and TA1535 of Salmonella typhimurium in the presence or absence of S9 and no clearly positive response was obtained. Chromosomal aberration and sister chromatid exchange data showed that 1,2-dichloropropane caused increases in both in the absence or presence of S9.
Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenicity for male F344/N rats receiving 62 or 125 mg/kg. For female rats there was equivocal evidence of carcinogenicity in that 250 mg/kg 1,2-dichloropropane caused a marginally increased incidence of adenocarcinomas in the mammary gland; these borderline malignant lesions occurred concurrent with decreased survival and reduced body weight gain. There was some evidence of carcinogenicity for male and female B6C3F1 mice exposed to 1,2-dichloropropane, as indicated by increased incidences of hepatocellular neoplasms, primarily adenomas.
Synonym: propylene dichloride
Report Date: August 1986