Bioassay of 2,4,5-trimethylaniline for possible carcinogenicity.

Abstract

A bioassay of 2,4,5-trimethylaniline for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered 2,4,5-trimethylaniline at one of two doses, either 200 or 800 ppm for the rats and either 50 or 100 ppm for the mice, for 101 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical. Mean body weights of the dosed male and female rats were generally lower than those of corresponding controls; mean body weights of the dosed mice were only slightly lower in the males than in the corresponding controls and were unaffected or affected irregularly in the females. Survival was not affected significantly when the rats or mice were administered the test chemical and was 70% or greater in all dosed or control groups. Sufficient numbers of animals were at risk for late-appearing tumors. In the rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences that were dose related in both males and females (P</= 0.001), and in direct comparisons the incidences were slightly higher in the high-dose males, high-dose females, and low-dose females (P</= 0.004) than in corresponding controls (males: controls 1/19; low-dose 6/50; high-dose 20/50; females: controls 0/20; low-dose 12/49, high-dose 27/50). In addition, alveolar/bronchiolar carcinomas or adenomas occurred in the female rats at incidences that were dose related (P=0.003), and in a direct comparison the incidence was significantly higher in the high-dose group (P=0.017) than in the corresponding control group (controls 0/20; low-dose 3/43; high-dose 11/50). In the female mice, hepatocellular carcinomas occurred at incidences that were dose related (P</= 0.001), and in direct comparisons the incidences were significantly higher (P</= 0.001) in the low- and high-dose animals than in the corresponding controls (controls 0/20, low-dose 18/49, high-dose 40/50). Because historical records of this laboratory for control B6C3F1 male mice show a relatively high incidence of hepatocellular carcinomas, an increased incidence of these tumors in 2,4,5-trimethylaniline dosed male mice as compared with matched controls could not be clearly associated with administration of the test compound. It is concluded that under the conditions of this bioassay, 2,4,5-trimethylaniline was carcinogenic for male and female F344 rats and female B6C3F1 mice, inducing hepatocellular carcinomas or neoplastic nodules in the rats of each sex, alveolar/bronchiolar carcinomas in the female rats, and hepatocellular carcinomas in female mice.

• Authors: National Toxicology Program
• Journal: National Cancer Institute carcinogenesis technical report series (Natl Cancer Inst Carcinog Tech Rep Ser) Vol. 160 Pg. 1-141 ( 1979) ISSN: 0163-7185 [Print] United States
• PMID: 12799702 (Publication Type: Journal Article)