MONITORING OF EXPOSURE TO ACRYLONITRILE BY DETERMINATION OF N-(2-CYANOETHYL)VALINE AT THE N-TERMINAL POSITION OF HEMOGLOBIN

A selected ion monitoring gas chromatography-mass spectrometry (GC-MS) procedure was developed to determine the interaction product formed b y acrylonitrile (ACN) with the N-terminal amino group in haemoglobin, The product, N-(2-cyanoethyl)valine (CEV), was analysed following its release from the protein by a modified Edman degradation procedure, Qu antitation was achieved using N-(2-cyanoethyl)-[H-2(8)]Val-Leu-Ser as internal standard, The limit of detection of the assay was 1 pmol CEV/ g globin, A close to linear dose-response relationship was found for a dduct formation in rats treated with ACN by gavage, On the basis of a linear extrapolation, a dose of 1 mg/kg body wt yielded 248 pmol CEV/g globin, Two groups of workers who were exposed to ACN contained 1984 +/- SD 2066 (n = 9) and 2276 +/- SD 1338 (n = 7) pmol CEV/g globin res pectively, These values were highly significantly greater (P < 0.01 fo llowing a one-way analysis of variance with a logarithmic transformati on of the data) than those in a group of control workers in the same f actory (31.1 +/- SD 18.5 pmol CEV/g globin, n = 11), The concentration s of N-terminal CEV in globin samples from 13 smoking and 10 non-smoki ng mothers and from their newborns were determined, Adduct levels in t he smokers averaged 217 +/- 85.1 pmol CEV/g globin, significantly high er than the levels in non-smokers, which were undetectable, Individual values in the mothers were very highly correlated with the levels in their babies (which averaged 99.5 +/- 53.8 pmol CEV/g globin), which d emonstrates that transplacental transfer of ACN occurs, Significant co rrelations were also found between the number of cigarettes smoked per day by the mother and the CEV levels in both the mothers' and newborn s' globin, There was, however, no correlation between the CEV levels a nd those of the ethylene oxide adduct N-(2-hydroxyethyl)valine in samp les from either the mothers or babies.