MUTAGENICITY EVALUATION STUDIES IN THE IN THE RAT BONE MARROW CYTOGENETIC ASSAY IN THE MOUSE LYMPHOMA FORWARD MUTATION ASSAY VACUUM RESIDUM API Sample 81-13
ABSTRACT Chromosome aberrations were determined in the bone marrow cells of Sprague-Dawley rats subchronically exposed per os to API #81-13 (five daily doses). Three dose levels were employed: 3 g/kg/day@ 1 g/kg/day and 0.3 g/kg/day. Bone marrow was sampled six hours after the last dose. Ten male and ten female animals were exposed to each dose and control level. The structural aberration frequency in bone marrow cells of rats exposed to API #81-13 did not differ significantly from the negative control at any tested dose. The percentages of cells showing one or more structural aberrations or two or more structural aberrations were likewise similar to the negative controls@ as was the frequency of numerical aberrations. These results were the same whether males or females or both sexes pooled were evaluated by the Student t-test. A concurrent positive control substance@ triethylenemelamine@ showed a significant increase in structural aberration frequency. For in vitro treatments of the mouse lymphoma cell line@ L5178Y@ the mutant frequency at the thymidine kinase (TK) locus was significantly increased only in the presence of metabolic activation. The cells were exposed to API #81-13 for four hours both in the presence and absence of rat liver S9 metaboic activation. API #81-13 was assayed at an applied concentration range of 62.5 ug/ml to 1000 pg/ml which was well into the insoluble range of concentrations. The toxicities were in the low to moderate range even at insoluble concentrations of test material. Without metabolic activation@ no significant increases in the mutant frequency were induced. However@ the activation mix converted API #81-13 to a weakly active form or forms. Small@ but significant increases in the mutant frequency were induced in two trials. API #81-13 was therefore evaluated as weakly active in the mouse lymphoma cell system.