The effect of dose and vehicle on early tissue damage and regenerative activity after chloroform administration to mice.

The relationship between the acute toxicity of orally-administered chloroform and its long-term tumorigenic potential was studied in male mice of the CFLP outbred Swiss albino mouse strain. A single dose of approximately 18 mg CHCl3/kg had no detectable acute toxic effect on the liver or kidneys and did not stimulate regenerative activity, whereas both toxicity and subsequent tissue regeneration were observed with single doses of about 60 mg/kg or higher. The severity of the toxic effects and regenerative changes was greater when corn oil was used as a vehicle for chloroform than when the vehicle was a toothpaste base. In earlier long-term studies in mice of the same strain, kidney tumours occurred in males given 60 mg/kg/day throughout life but not in mice given 17 mg/kg/day. The tumour response was greater when the 60-mg/kg/day dose was given in an oily vehicle than when it was given in toothpaste. The findings are consistent with the hypothesis that early acute toxic change and subsequent repair are a sine qua non for tumorigenesis in the kidney and liver in response to chloroform.