scope:

Abstract

In the mouse lymphoma forward mutation assay, in vitro treatments of the mouse lymphoma cell line, L5178Y, with API #83-05 induced significant Increases in the mutant frequency at the thymidine kinase (TK) locus only in the presence of metabolic activation. The cells were exposed to API #83-05 for four hours In the presence and absence of rat liver S9 metabolic activation. The test material was soluble at the concentrations tested. Under nonactivation conditions, the test material was assayed from 5.25 nl/ml to 100 nl/ml and low to moderate toxicities were induced without inducing significant, dose-dependent increases above the background mutation frequency. Treatment with 150 nl/ml was excessively toxic and not analyzable. In the presence of metabolic activation, the test material was converted to a more active form or forms. Treatments from 18.8 nl/ml to 200 nl/ml induced repeatable Increases in the mutant frequency that ranged from 2,1-fold to 4,2-fold above the background mutant frequency. API #83-05 was therefore evaluated as active in the mouse lymphoma cell system only in the presence of metabolic activation.