Monitoring of exposure to acrylonitrile by determination of N-(2-cyanoethyl)valine at the N-terminal position of haemoglobin

A selected ion monitoring gas chromatography-mass spectrometry(GC-MS) procedure was developed to determine the interactionproduct formed by acrylonitrile (ACN) with the N-terminal aminogroup in haemoglobin. The product, N-(2-cyanoethyl)valine (CEV),was analysed following its release from the protein by a modifiedEdman degradation procedure. Quantitation was achieved usingN-(2-cyanoe-thyl)-²H₈]Val-Leu-Ser as internal standard. Thelimit of detection of the assay was 1 pmol CEV/g globin. A closeto linear dose-response relationship was found for adduct formationin rats treated with ACN by gavage. On the basis of a linearextrapolation, a dose of 1 mg/kg body wt yielded 248 pmol CEV/gglobin. Two groups of workers who were exposed to ACN contained1984 ± SD 2066 (n = 9) and 2276 ± SD 1338 (n =7) pmol CEV/g globin respectively. These values were highlysignificantly greater (P < 0.01 following a one-way analysisof variance with a logarithmic transformation of the data) thanthose in a group of control workers in the same factory (31.1± SD 18.5 pmol CEV/g globin, n = 11). The concentrationsof N-terminal CEV in globin samples from 13 smoking and 10 non-smokingmothers and from their newborns were determined. Adduct levelsin the smokers averaged 217 ± 85.1 pmol CEV/g globin,significantly higher than the levels in non-smokers, which wereundetectable. Individual values in the mothers were very highlycorrelated with the levels in their babies (which averaged 99.5± 53.8 praol CEV/g globin), which demonstrates that transplacentaltransfer of ACN occurs. Significant correlations were also foundbetween the number of cigarettes smoked per day by the motherand the CEV levels in both the mothers‘ and newborns’globin. There was, however, no correlation between the CEV levelsand those of the ethylene oxide adduct N-(2-hydroxyethyl)valinein samples from either the mothers or babies.