Absence of Carcinogenic Activity in Fischer Rats and B6C3F1 Mice Following 103-Week Inhalation Exposures to Toluene

Abstract

Toluene, methylbenzene, is used to back-blend gasoline, as a chemical intermediate, and as a solvent; more than 7 million tonnes are produced each year in the United States. Following 14–15-week toxicity studies to estimate appropriate exposure concentrations for the carcinogenesis bioassays, toxicology and carcinogenesis studies of toluene (>99% pure) were conducted by whole-body inhalation exposures of F344/N rats and B6C3F1 mice of each sex for 15 months or two years. Toluene levelswere 0 (chamber controls), 600, and 1,200 ppm for rats and 0, 120, 600, and 1200 ppm for mice. Exposures were 6.5 hr/day 5 days/wk. Genetic toxicology studies using Salmonella typhimurium, mouse L5178Y lymphoma cells, and Chinese hamster ovary cells were negative. No chemically related neoplasm was found in male rats, and one nasal, two kidney, and two forestomach neoplasms observed in female rats were considered not to be associated with the toluene exposure. For mice, no biologically important increase was observed for any nonneoplastic or neoplastic lesion. Studies by others had reported carcinogenicity of toluene, especially for total malignant tumors.

Keywords:

• benzene
• carcinogenesis bioassay
• dimethylbenzene
• longterm studies
• methylbenzene
• National Toxicology Program
• toluene
• xylene