Formation of 1,2:3,4-diepoxybutane-specific haemoglobin adducts in 1,3-butadiene exposed workers

1,3-Butadiene (BD) is an important industrial chemical that is classified as a human carcinogen. BD carcinogenicity was attributed to its metabolites. Several reactive epoxide metabolites and the formation of the highly mutagenic 1,2:3,4-diepoxybutane (DEB) was hypothesised to drive mutagenesis and carcinogenesis at exposures experienced in humans. In this study, the authors report the formation of DEB-specific N,N-(2,3-dihydroxy-1,4-butadiyl)valine (pyr-Val) in BD-exposed workers as a biomarker of DEB formation. Pyr-Val was detected in BD monomer and polymer plant workers that had been previously analysed for several other biomarkers of exposure and effect. Pyr-Val was detected in 68 of 81 (84%) samples ranging from 0.08 to 0.86 pmol/g globin. Surprisingly, pyr-Val was observed in 19 of 23 administrative control subjects not known to be exposed to BD, suggesting exposure from environmental sources of BD. The mean ( SD amounts of pyr-Val were 0.11 ( 0.07, 0.16 ( 0.12, and 0.29 (0.20 pmol/g globin in the controls, monomer, and polymer workers, respectively, clearly demonstrating formation of DEB in humans. The amounts of pyr-Val found in this study suggest that humans are much less efficient in the formation of DEB than mice or rats at similar exposures. Formation of pyr-Val was more than 50-fold lower than has been associated with increased mutagenesis in rodents. The authors concluded that the based on the findings, formation of DEB relative to other epoxides is significantly different in the highest exposed polymer workers compared with controls and BD monomer workers. Whether this is due to saturation of metabolic formation or increased GST-mediated detoxification could not be detected.

Authors: Boysen, Gunnar; Georgieva, Nadia I.; Bordeerat, Narisa K.; Sram, Radim J.; Vacek, Pamela; Albertini, Richard J.; Swenberg, James A. ;Toxicological Sciences [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][online computer file] 2012, 125(1), 30-40 (Eng) ;

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