MUTAGENICITY EVALUATION STUDIES IN THE RAT BONE MARROW CYTOGENETIC ASSAY IN THE MOUSE LYMPHOMA FORWARD MUTATION ASSAY HYDRODESULFURIZED MIDDLE DISTILLATE (D) API SAMPLE 81-10
Abstract Chromosome aberrations were determined in the bone marrow cells of Sprague-Dawley rats acutely exposed intraperitoneally to API #81-10 (single dose). Three dose levels were employed: 3 g/kg@ 1.0 g/kg and 0.3 g/kg. Bone marrow was sampled at various times after treatment ((6@ 24 and 48 hr). Ten male and ten female animals were exposed to each dose and negative control level. The structural aberration frequency in bone marrow cells of rats exposed to API #81-10 did not differ significantly from the negative controls at any kill time or at any dose tested. 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 significant increases in structural aberration frequency at two dose levels. 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 #81-10 for four hours in the presence and absence of rat liver S9 metabolic activation. API #81-10 was assayed at an applied concentration range of 3.91 nl/ml to 62.5 nl/ml. The toxicities were in the moderate to high range. Without metabolic activation no significant increases in the mutant frequency were induced@ However@ the activation mix converted API #81-10 to a more active form or forms and significant increases in the mutant frequency were induced. API #81-10 was therefore evaluated as weakly active in the mouse lymphoma cell systems.