BIOMONITORING OF EPICHLOROHYDRIN BY HEMOGLOBIN ADDUCTS

A gas chromatographic mass spectrometric method for monitoring exposur e 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 t he N-terminal valine, one of the reactive sites of the globin chains. The presence of two hydroxyl groups in the adduct to be analyzed requi red special precautions to be introduced into the method, such as acet ylation of the Edman derivative. An in vitro treated globin with [H-2( 5)]N-2,3-dihydroxypropyl adducts was used as internal standard. The li mit of detection achieved is 4 fmol in analysis by tandem mass spectro metry, Adduct levels found in smokers (15 to 20 cigarettes per day) we re between 6.5 and 11.2 pmol/g globin and for nonsmokers the adduct le vels 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 da ys, the average adduct level was 44 pmol/g globin and that for two non exposed rats was close to the detection level. The method will be usef ul for monitoring of exposure and for cancer risk estimation of ECH. ( C) 1996 Academic Press, Inc.