Absence of carcinogenic activity in Fischer rats and B6C3F1 mice following 103-week inhalation exposures to toluene.
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 levels were 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.
Huff
James
J
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. huff1@niehs.nih.gov
D000280:Administration, Inhalation; D000818:Animals; D001681:Biological Assay; D001837:Body Weights and Measures; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D051379:Mice; D023421:Models, Animal; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009382:Neoplasms, Unknown Primary / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D012486:Salmonella typhimurium / Q000235:genetics; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D014050:Toluene / Q000008:administration & dosage / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
D002273:Carcinogens; D012997:Solvents; D014050:Toluene