Toxicity and carcinogenicity of rotenone given in the feed to F344/N rats and B6C3F1 mice for up to two years.

ABSTRACT

Toxicity and carcinogenicity studies of rotenone were conducted in F344/N rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were given rotenone in their diet for up to 103 weeks. The doses were 0, 38, and 75 ppm for rats and 0, 600, and 1,200 ppm for mice. Reduction in body weight gain occurred in male and female mice given rotenone. No effects on survival were observed for rats of either sex or female mice. Survival of male mice at 1,200 ppm was significantly greater than that of controls (47/50 vs. 29/50). There were no observed nonneoplastic effects due to rotenone, and for male and female mice no neoplasms were induced by rotenone. Parathyroid adenomas occurred at a higher incidence (4/44) in male rats at 75 ppm than in the controls (1/41). Because these tumors are rare (historical rate in NTP studies is 0.3%), the increase in the incidence of these benign tumors may have been related to rotenone administration. Hepatocellular neoplasms were reduced (p less than 0.01) in males receiving 1,200 ppm 1/50 relative to controls 12/47. Because this low rate of liver tumors is unusual in male B6C3F1 mice, this decrease was considered to be related to rotenone administration.