Toxicology and carcinogenesis studies of cumene (CAS No. 98-82-8) in F344/N rats and B6C3F1 mice (inhalation studies).

Background: Cumene occurs naturally in petroleum and is used as a solvent, in gasoline and diesel fuels, and as the principal chemical in the production of phenol and acetone. We studied cumene to determine if it caused cancer in rats or mice.

Methods: We exposed groups of 50 male and female rats and mice to air containing cumene 6 hours per day for 2 years. Rats and male mice were exposed to concentrations of 250, 500, or 1,000 parts per million (ppm) of cumene in air, and female mice were exposed to concentrations of 125, 250, or 500 ppm. Similar groups of 50 animals were exposed to clean air in the same inhalation chambers 6 hours per day as the untreated control groups. Tissues from more than 40 sites were examined for every animal.

Results: All groups of animals exposed to cumene exhibited hyperplasia of the epithelial tissues of the nose, and exposed male and female mice experienced metaplasia and hyperplasia of the lung. Male mice also had nonneoplastic lesions in the forestomach and liver. Adenomas of the respiratory epithelium of the nose were observed in male and female rats, and male rats had increased incidences of renal tubule adenoma or carcinoma (combined) and interstitial cell adenoma of the testis. Adenomas and carcinomas of the lung were markedly increased in male and female mice exposed to cumene. The rate of liver neoplasms was also increased in exposed female mice, and a few hemangiosarcomas of the spleen and follicular cell adenomas of the thyroid gland were seen in male mice exposed to the highest concentration of cumene.

Conclusions: We conclude that the increased occurrences of adenomas of the epithelium of the nose in male and female rats, of renal tubule adenoma or carcinoma (combined), of adenomas and carcinomas of the lung in male and female mice, and of liver neoplasms in female mice were caused by exposure to cumene. The occurrence of interstitial cell adenoma of the testis in male rats and hemangiosarcomas of the spleen and follicular cell adenomas of the thyroid gland in male mice may also have been associated with exposure to cumene.