Assessment of butadiene exposure in synthetic rubber manufacturing workers in Texas using frequencies of hprt mutant lymphocytes as a biomarker

Jonathan B. Ward, Sherif Z. Abdel-Rahman, Rogene F. Henderson, Thomas H. Stock, Maria Morandi, Judah I. Rosenblatt, Marinel M. Ammenheuser

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    20 Scopus citations


    1,3-Butadiene (BD), which is used to manufacture synthetic rubber, is a mutagen and carcinogen. Because past occupational exposures have been associated with an increased risk of leukemia, there has been a dramatic reduction in workplace exposure standards. The health benefits of these reduced levels of occupational exposure to BD will be difficult to evaluate using relatively insensitive traditional epidemiological studies; however, biomarkers can be used to determine whether there are genotoxic effects associated with recent exposures to BD. In past studies of BD-exposed workers in Southeast Texas, we observed an increase in the frequency of lymphocytes with mutations in a reporter gene, hprt. Frequencies of hprt mutant cells correlated with air levels of BD and with the concentration of a BD metabolite in urine. Average exposures to 1-3 parts per million (p.p.m.) of BD were associated with a threefold increase in hprt variant (mutant) frequencies (Vfs). We now report results from a follow-up study of workers in a synthetic rubber plant in Southeast Texas. Thirty-seven workers were evaluated on three occasions over a 2-week period for exposure to BD by the use of personal organic vapor monitors and by determining the concentration of a BD metabolite in urine. The frequency of hprt mutants was determined, by autoradiography, with lymphocyte samples collected 2 weeks after the final exposure measurement. Based on their work locations, the study participants were assigned to high-exposure (N = 22) or low-exposure (N = 15) groups. The BD exposure, ±standard error, of the workers in the high-exposure group (1.65 ± 0.52 p.p.m.) was significantly greater than the low-exposure group (0.07 ± 0.03 p.p.m.; P < 0.01). The frequency of hprt mutant lymphocytes was also significantly different in the two groups (high, 10.67 ± 1.5 × 10-6; low, 3.54 ± 0.6 × 10-6; P < 0.001). The concentration of the urine metabolite was greater in the high-exposure group, but the difference was not significant. The correlation coefficient between hprt Vf and BD exposure levels was r = 0.44 (CI95, 0.11-0.69; P = 0.011). This study reproduced the findings from a previous study at this plant. Although studies of butadiene-exposed workers in other countries have not detected an effect of exposure on frequencies of hprt mutant lymphocytes, we have repeatedly observed this result in our studies in Texas.

    Original languageEnglish (US)
    Pages (from-to)465-483
    Number of pages19
    JournalChemico-Biological Interactions
    StatePublished - Jun 1 2001


    • Biomarker
    • Butadiene
    • Human study
    • Lymphocytes
    • hprt mutation

    ASJC Scopus subject areas

    • Toxicology


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