Biological monitoring of butadiene exposure by measurement of haemoglobin adducts

The measurement of haemoglobin (Hb) adducts is an important tool for monitoring exposures to industrial chemicals such as ethylene, ethylene oxide and propylene oxide. The aim of the present study was to use this method to monitor occupational exposure to butadiene. The methodology was evaluated with Hb samples obtained by reacting butadiene monoepoxide (BkO), the primary reactive metabolite of 1,3-butadiene, with blood and by dosing BMO to rats and mice. The Hb adducts: N-(2-hydroxy-3-buten-1-yl)valine and N-(1-hydroxy-3-buten-2-yl)valine were determined as the pentafluorophenylthiohydantoin derivatives using the modified Edman degradation procedure and gas chromatography with negative ion chemical ionisation mass spectrometry. The adducts were quantified using d(4)-N-(2-hydroxyethyl)valine as an internal reference chemical. Relatively high background signals were observed which made accurate quantitation difficult, The lower limit of detection was estimated as 10-20 pmol/g globin, The experiments have demonstrated that appropriate reference samples are required for accurate quantitation and the method requires further refinement to improve the sensitivity of the analysis.