title: Monitoring of exposure to acrylonitrile by determination of N-(2-cyanoethyl)valine at the N-terminal position of haemoglobin.
abstract: A selected ion monitoring gas chromatography-mass spectrometry (GC-MS) procedure was developed to determine the interaction product formed by 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. Quantitation was achieved using N-(2-cyanoethyl)-[2H8]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 adduct 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 respectively. These values were highly significantly greater (P < 0.01 following a one-way analysis of variance with a logarithmic transformation of the data) than those in a group of control workers in the same factory (31.1 +/- SD 18.5 pmol CEV/g globin, n = 11). The concentrations of N-terminal CEV in globin samples from 13 smoking and 10 non-smoking mothers and from their newborns were determined. Adduct levels in the smokers averaged 217 +/- 85.1 pmol CEV/g globin, significantly higher 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 demonstrates that transplacental transfer of ACN occurs. Significant correlations were also found between the number of cigarettes smoked per day by the mother and the CEV levels in both the mothers' and newborns' globin. There was, however, no correlation between the CEV levels and those of the ethylene oxide adduct N-(2-hydroxyethyl)valine in samples from either the mothers or babies.
authors.affiliation: MRC Toxicology Unit, University of Leicester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Tavares
authors.forename: H
authors.initials: H
authors.lastname: Borba
authors.forename: M
authors.initials: M
authors.lastname: Monteiro
authors.forename: M J
authors.initials: MJ
authors.lastname: Proença
authors.forename: N
authors.initials: N
authors.lastname: Lynce
authors.forename: J
authors.initials: J
authors.lastname: Rueff
authors.forename: E
authors.initials: E
authors.lastname: Bailey
authors.forename: G M
authors.initials: GM
authors.lastname: Sweetman
authors.forename: R M
authors.initials: RM
authors.lastname: Lawrence
authors.forename: P B
authors.initials: PB
authors.lastname: Farmer
mesh_terms: D000181:Acrylonitrile / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D004784:Environmental Monitoring; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D016273:Occupational Exposure; D051381:Rats; D011916:Rats, Inbred F344; D014633:Valine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D006454:Hemoglobins; C091192:N-(2-cyanoethyl)valine; D014633:Valine; D000181:Acrylonitrile