Biomonitoring of 1,3-butadiene and related compounds.

Abstract

The 1990 Clean Air Act Amendments list several volatile organic chemicals as hazardous air pollutants, including ethylene oxide, butadiene, styrene, and acrylonitrile. The toxicology of many of these compounds shares several common elements such as carcinogenicity in laboratory animals, genotoxicity of the epoxide intermediates, involvement of cytochrome P450 for metabolic activation (except ethylene oxide), and involvement of at least two enzymes for detoxication of the epoxides (e.g., hydrolysis or conjugation with glutathione). These similarities facilitate research strategies for identifying and developing biomarkers of exposure. This article reviews the current knowledge about biomarkers of butadiene. Butadiene is carcinogenic in mice and rats, which raises concern for potential carcinogenicity in humans. Butadiene is metabolized to DNAreactive metabolites, including 1,2-epoxy-3-butene and diepoxybutane. These epoxides are thought to play a critical role in butadiene carcinogenicity. Butadiene and some of its metabolites (e.g., epoxybutene) are volatile. Exhalation of unchanged butadiene and excretion of butadiene metabolites in urine represent major routes of elimination. Therefore, biomonitoring of butadiene exposure could be based on chemical analysis of butadiene in exhaled breath, blood levels of butadiene epoxides, excretion of butadiene metabolites in urine, or adducts of butadiene epoxides with DNA or blood proteins. Mutation induction in specific genes (e.g., HPRT) following butadiene exposure can be potentially used as a biomarker. Excretion of 1,2-dihydroxy-4-(N-acetylcysteinyl-S)butane or the product of epoxybutene with N-7 in guanine in urine, epoxybutene-hemoglobin adducts, and HPRT mutation have been used as biomarkers in recent studies of occupational exposure to butadiene. Data in laboratory animals suggest that diepoxybutane may be a more important genotoxic metabolite than epoxybutene. Biomonitoring methods need to be developed for diepoxybutane and other putative reactive butadiene metabolites. With butadiene and related compounds, the ultimate challenge is to identify useful biomarkers of exposure in which quantitative linkages between exposure and internal dose of the important DNA-reactive metabolites are established. Environ Health Perspect 104(Suppl 5): 907-915 (1996)

Ethylene Oxide in Blood of Ethylene-Exposed B6C3F1 Mice, Fischer 344 Rats, and Humans

“…As a result, calculated adduct levels for continuous exposures to 0.1 ppm are equal in mice and humans (see Tables 5 and 6 ). The animal-to-human differences in the ET-induced EO burdens and HEV levels are relatively small compared with the burdens by epoxides or their hemoglobin adduct levels of other small olefins such as propylene ( Filser et al , 2008 ), butadiene ( Osterman-Golkar and Bond, 1996 ; van Sittert et al ., 2000b ), or styrene ( Filser et al , 2002 ; Osterman-Golkar et al , 1995 ). For an average volunteer (this study), the ET-induced EO concentrations in blood are calculated to be 36-fold higher than those of propylene oxide at equal conditions of exposure to both olefins (computed from the present data and those given in Filser et al , 2008 ).…”

Comparison of urinary mercapturic acid excretions in users of various tobacco/nicotine products

“…The human carcinogen 1,3-butadiene is reported to form at least four MAs, 29 of these 2-MHBMA and DHBMA (chemical structures; see Table 1) are most frequently used for biomonitoring purposes. 30 From published data, 26 average releases of 1,3-butadiene of 67-100 μg/cig (CC), 0.25-0.75 μg/10 puffs (EC), and 0.21-0.40 μg/stick (HTP) can be deduced. The corresponding daily intake was calculated to amount to 863, 4.5, and 3.4 μg/day for users of CCs, ECs, and HTPs, respectively.…”

Biomarkers: Coming of Age for Environmental Health and Risk Assessment

“…Biomarker studies have been proposed as important components of the research strategy to address the potential carcinogenicity of BD and its metabolites in humans (165,177). A number of such studies have recently been conducted on occupationally exposed cohorts.…”