HPRT MUTANT LYMPHOCYTE FREQUENCIES IN WORKERS AT A 1,3-BUTADIENE PRODUCTION PLANT

1,3-Butadiene is a major industrial chemical that has been shown to be a carcinogen at multiple sites in mice and rats at concentrations as low as 6.25 ppm. Occupational exposures have been reduced in response to these findings, but it may not be possible to determine by using tr aditional epidemiological methods, whether current exposure levels are adequate for protection of worker health. However, it is possible to evaluate the biological significance of exposure to genotoxic chemical s at the time of exposure by measuring levels of genetic damage in exp osed populations. We have conducted a pilot study to evaluate the effe cts of butadiene exposure on the frequencies of lymphocytes containing mutations at the hypoxanthine-guanine phosphoribosyl transferase (hpr t) locus in workers in a butadiene production plant. At the same time, urine specimens from the same individuals were collected and evaluate d for the presence of butadiene-specific metabolites. Eight workers fr om areas of the plant where the highest exposures to butadiene occur w ere compared to five workers from plant areas where butadiene exposure s were low. In addition, six subjects with no occupational exposure to butadiene were also studied as outside controls. All of the subjects were nonsmokers. An air sampling survey conducted for 6 months, and en ding about 3 months before the study, indicated that average butadiene levels in the air of the high-exposure areas were about 3.5 +/- 7.5 p pm. They were 0.03 +/- 0.03 ppm in the low-exposure areas. Peripheral blood lymphocytes from the subjects were assayed using an autoradiogra phic test for hprt mutations. The weighted mean variant (mutant) frequ ency (Vf) (+/- SE) in the eight exposed subjects was 3.84(+/-0.70)10(- 6) per evaluatable cell, as compared to 1.16(+/-0.27)x 10 in the low-e xposed and 1.03(+/-0.07)x10(-6) in the outside controls. The Vf of the low-exposed controls and the outside controls were not significantly different, but the mean frequency of mutant lymphocytes in the seven e xposed subjects was significantly higher when compared to the mean Vf of the nonexposed controls (p<0.01) and the low-exposed controls (p<0. 05). A single metabolite of butadiene, 1,2-dihydroxy-4-(N-acetlylcyste inyl-S) butane, was detected in the urine of all subjects. The concent ration in the urine of the workers in the high-exposed group was signi ficantly greater than in the low-exposed or nonexposed groups. The cor relation between the level of the metabolite in urine and the frequenc y of hprt mutants was r = 0.85. The observation of an elevated Vf in t he exposed subjects and the strong correlation of Vf with the level of excreted metabolite suggests that butadiene exposures under these con ditions were sufficient to induce somatic cell mutations. This degree of increase in Vf is similar to what we have observed in cigarette smo kers. The results available at this time indicate that current levels of occupational exposure to butadiene may not be sufficiently low to p rotect workers from the adverse effects that may result from exposure to mutagens.