Biomonitoring of epichlorohydrin by hemoglobin adducts

A gas chromatographic mass spectrometric method for monitoring exposure to epichlorohydrin (ECH) by means of quantitative analysis of N-(2,3-dihydroxypropyl)valine in hemoglobin has been developed. The analysis is based on the modified Edman method for measurement of adducts to the N-terminal valine, one of the reactive sites of the globin chains. The presence of two hydroxyl groups in the adduct to be analyzed required special precautions to be introduced into the method, such as acetylation of the Edman derivative. An in vitro treated globin with [2H5]N-2,3-dihydroxypropyl adducts was used as internal standard. The limit of detection achieved is 4 fmol in analysis by tandem mass spectrometry. Adduct levels found in smokers (15 to 20 cigarettes per day) were between 6.5 and 11.2 pmol/g globin and for nonsmokers the adduct levels were close to the detection limit (about 2 pmol/g globin). In two rats, treated ip with 40 mg ECH/kg body wt and sacrificed after 30 days, the average adduct level was 44 pmol/g globin and that for two nonexposed rats was close to the detection level. The method will be useful for monitoring of exposure and for cancer risk estimation of ECH.