CHEMICALS ASSOCIATED WITH DECREASES IN THE INCIDENCE OF MONONUCLEAR CELL LEUKEMIA IN THE FISCHER RAT

A significant treatment-related decrease in the incidence of mononucle ar cell leukemia (MCL) was identified in Fischer-344/N rats for 20 che micals tested in the National Toxicology Program's 2-yr carcinogenicit y bioassay. Fourteen of the 20 chemicals caused decreases of MCL in bo th male and female rats; 6 of the 20 caused a significant decrease onl y in males and a marginal or no decrease in female rats. Seventeen of the chemicals associated with a decrease in MCL had a free aromatic am ine or nitro functional groups that could be metabolized to free amine s. With 1 exception, all 14 chemicals causing a decrease in MCL in bot h sexes produced spleen toxicity in the 13-wk studies. Reduced body we ight and decreased survival, related either to toxicity or to an incre ase in other types of lethal neoplasms, did not contribute to the decr eases in MCL observed in chemical exposure groups. Thirteen of the 20 chemicals were positive in Salmonella tests, and 15 were associated wi th increases in neoplasms at other sites in rats and/or mice, suggesti ng that different metabolites could be responsible for these varied bi ological effects.