Mutagenicity at the Hprt locus in T cells of female mice following inhalation exposures to low levels of 1,3-butadiene

A study was conducted to test the hypothesis that repeated low level exposu res to 1,3-butadiene (BD), approaching the OSHA occupational threshold for this chemical, produce a significant mutagenic response in mice. Female B6C 3F1 mice (4-5 weeks of age) were exposed by inhalation for 2 weeks (6 h/day , 5 days/week) to 0 or 3 ppm BD, and then necropsied at 4 weeks after the c essation of exposures to measure the frequency of mutations (MF) at the Hpr t locus using the T-lymphocyte clonal assay. At necropsy, T cells were isol ated from spleen and cultured in the presence of mitogen, growth factors, a nd a selection agent. Cells were scored for growth on days 8-9 after platin g to determine cloning efficiencies (CEs) and Hprt MFs. There was a margina l but significant reduction in the growth of splenic T cells from mice expo sed to 3 ppm (n=27) compared with control mice (n=24) (P=0.004), suggesting the occurrence of BD-induced cytotoxicity at this low exposure concentrati on. In addition, the average Hprt MF in mice exposed to 3 ppm BD [1.54 +/-0 .82 (S.D.) x 10(-6)] was significantly increased by 1.6-fold over the avera ge control value of 0.96 +/-0.51 (S.D.) x 10(-6) (P=0.004). Comparisons of these data to earlier Hprt mutagenicity studies of mice exposed to high con centrations of BD (where significant mutagenic but not cytotoxic effects we re observed) indicate that the ability to detect the cytotoxic and mutageni c responses of T cells to low levels of BID was enhanced by using a much la rger sample size than usual for both the control and treatment groups. Addi tional analyses of the quantitative relationships between CE and NIF demons trated that CE had no significant effect upon NIF values in sham-exposed co ntrol mice or mice exposed to low-level BD. Furthermore, the approaches for assessing the impact of CE and clonality on Hprt MFs in these control and BD-exposed mice were applied with the same rigor as in in vivo Hprt mutagen icity studies in human children. The overall study results support the conc lusion that short-term low-level BD exposure is mutagenic in the mouse. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.