Chlorobenzene

Carcinogenicity

Description of key information

In a 2-year cancer study on male and female F344/N rats and B6C3F1 hybrid mice, groups of 50 males and 50 females were given chlorobenzene doses of 60 or 120 mg/kg/day by gavage for 103 weeks (5 days/week); male B6C3F1 mice received 30 or 60 mg/kg/day.
Increased mortality was statistically significant for male rats (p = 0.033, high dose), but not for female rats and mice. A statistically significant positive trend in the incidence of hepatocellular neoplastic nodules was observed in male rats (4/50, 2/50, 4/49, and 8/49 for untreated controls, vehicle controls, low and high dose groups, respectively). There were no increases in hepatocellular neoplastic nodules for female rats and mice, and there were no increases in hepatocellular or other site-specific tumours for either species. 

Justification for classification or non-classification

No classification is required

Additional information

In a 2-year cancer study on male and female F344/N rats and B6C3F1 hybrid mice, groups of 50 males and 50 females were given chlorobenzene doses of 60 or 120 mg/kg/day by gavage for 103 weeks (5 days/week); male B6C3F1 mice received 30 or 60 mg/kg/day. Due to the fact that neither in rats nor in mice chlorobenzene-related toxic effects were observed, the NOAEL for non-neoplastic effects was considered to be the highest doses tested120 mg/kg/day and 60 mg/kg/day in rats and mice, respectively, leading to the overall NOAEL. to be 60 mg/kg bw/day. Despite the relative closeness of the doses in the subchronic and chronic studies, non-neoplastic lesions clearly attributed to chlorobenzene were not observed in the chronic study. The failure of chlorobenzene to elicit toxic responses in the kidney, liver or haematopoetic system in the chronic study indicates at the most a slight potential for progressive toxicity with continued chlorobenzene administraton beyond 13 weeks.

Regarding the neoplastic effects, the NTP concluded that "under the conditions of these studies, chlorobenzene administration increased the occurrence of neoplastic nodules of the liver in high-dose male F344/N rats, providing some, but not clear evidence of carcinogenicity of chlorobenzene in male rats. Carcinogenic effects of chlorobenzene were not observed in female F344/N rats or in male or female B6C3F1 mice (NTP 1985). In an additional evaluation of this carcinogenicity study extensive statistical calculations led to the conclusion that chlorobenzene cannot be assessec as a carcinogen on the basis of the data determined (Roe, 1987) This was also confirmed by the authors of the study (Kluwe 1987).

Based on inadequate/equivocal evidence of carcinogenicity in experimental animal data, in combination with predominantly negative genetic toxicity data and the absence of epidemiological data, the EPA has rated chlorobenzene in Group D: inadequate evidence of human carcinogenicity.