Haemoglobin adducts as biomarkers of occupational exposure to 1,3-butadiene

Abstract

Adducts of 1,2-epoxy-3-butene (EB) with haemoglobin were monitored in 17 workers from the 1,3-butadiene (BD) production unit of a petrochemical plant and in nine referents employed at the same factory but not exposed to BD. The air concentrations of BD were determined using stationary and personal monitoring. The ambient level of exposure of the plant workers handling butadiene containers (sampling and voiding) was on average 11.2 +/- 18.6 (mean +/- SD) mg/m3. Maintenance and laboratory workers were exposed to levels < or = 1.2 mg/m3. The particular haemoglobin adduct measured was 2-hydroxy-3-butenylvaline, formed by reaction of N-terminal valine with carbon 1 in EB. The adduct levels were increased (0.16 +/- 0.099 pmol/g; n = 10) in plant workers compared with the levels in maintenance and laboratory workers and controls (approximately 0.05 pmol/g; seven laboratory workers and nine controls evaluated). Thus, the method used for adduct determination--derivatization of 200-300 mg globin samples with penta-fluorophenyl isothiocyanate according to the N-alkyl Edman method and detection of the thiohydantoin derivatives by tandem mass spectrometry--is sufficiently sensitive to allow monitoring of exposure to BD down to the p.p.m. level.

Biomonitoring of 1,3-butadiene and related compounds.

“…Albrecht et al (48) exposed mice and rats at 0, 50, 200, 500, and 1300 ppm and showed a nonlinear dose response in mice at concentrations above 200 ppm and a linear dose response for rats. The adduct data are in general agreement with concentrations of epoxybutene measured in blood and tissues that were lower in rats than in mice exposed to butadiene (42)(43)(44)50 (47). The workers, all nonsmokers, were divided into two groups on the basis of work location.…”

“…Male B6C3F1 mice and Sprague-Dawley rats were exposed to 0, 2, 10, and 100 ppm butadiene (6 hr/day, 5 days/week for 4 weeks) (47). The adducts were detectable after 1 week of exposure at all butadiene exposure concentrations (unpublished observation).…”

“…The dose response for formation of adducts of epoxybutene with N-terminal valine in hemoglobin has been investigated in butadiene-exposed mice and rats (45,47,48) using the N-alkyl Edman method (49) and GC-MS or GC and MS-MS (tandem mass spectrometry) for adduct determination. Male B6C3F1 mice and Sprague-Dawley rats were exposed to 0, 2, 10, and 100 ppm butadiene (6 hr/day, 5 days/week for 4 weeks) (47).…”

“…Blood samples from 26 employees at a butadiene manufacturing plant in Portugal were analyzed for N-(2-hydroxy-3-butenyl)valine using tandem mass spectrometry for adduct detection (52,53). The subjects included smokers and nonsmokers.…”

“…kHB can be determined in in vitro experiments and, accordingly, the relationship between AUC and resulting adduct levels can be established. Table 1 presents data on hemoglobin adduct levels from exposure to butadiene and some related compounds (styrene, ethylene, ethylene oxide, and acrylonitrile) in nonsmokers, smokers, and subjects with occupational exposure (52,53,(78)(79)(80)(81)(82). The HBI of butadiene, on the order of 1 x 10-3 pmol/g globin per ppm x hr, is low when compared to the value calculated for rats (50x 10-3), indicating a lower overall efficiency of butadiene in humans than in rats.…”