title: Bioassay of a solution of b-nitrostyrene and styrene for possible carcinogenicity.
abstract: A bioassay of a solution of 30 percent b-nitrostyrene and 70 percent styrene for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. The solution of the two test materials in corn oil was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. The high and low dosages utilized in the study were, respectively, 300 and 150 mg/kg for male rats; 150 and 75 mg/kg for female rats; and 175 and 87.5 mg/kg for mice of both sexes. These dosages are expressed in terms of the b-nitrostyrene contained in the styrene solution. Twenty animals of each species and sex were placed on test as controls, and were gavaged with corn oil on the same schedule as dosed animals. A 79-week period of chemical administration was followed by an additional observation period of 29 weeks for rats, and a 78-week period of chemical administration was followed by an additional 14-week observation period for mice. There was no significant difference between the survival of rats dosed with the test solution and that of their controls, and there was no significant association between dosage and mortality among female mice. There was a significant positive association between dosage and mortality among male mice; however, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. There was distinct mean body weight depression when high dose female mice or male rats were compared to their controls, indicating that the dosage administered to these animals may have approximated the maximum tolerated dosage. Since no distinct mean body weight depression, no significantly accelerated mortality, and no other toxic effects were associated with the administration of b-nitrostyrene and styrene to female rats or male mice, it is possible that these animals may have been able to tolerate a higher dosage. There were no significant positive associations between administration of the solution and increased tumor incidence in rats of either sex. When those male mice having either alveolar/bronchiolar carcinomas or alveolar/bronchiolar adenoma were combined and the resulting tumor incidences for each group were statistically analyzed, the low dose to control Fisher exact comparison was significant. The Cochran-Armitage test and the high dose to control comparison, however, were not. No other tests for tumors of any site in either male or female mice were significant. Under the conditions of this bioassay, there was no convincing evidence for the carcinogenicity of a solution of b-nitrostyrene and styrene in Fischer 344 rats or in B6C3F1 mice.