n-(2-cyanoethyl)valine and 2-hydroxyethylvaline

The analytical determination of hemoglobin adducts was used as an effective biomonitoring tool after a fire outbrake at a chemical plant close to Cologne/Germany in 2008. More than 1000 people (e.g. fire-men, police officers, and workers) were potentially exposed to acrylonitrile and ethylene. Air monitoring in the surrounding was performed, and acrylonitrile was measured in concentrations up to 20 ppm, the mean value being 7 ppm (time range: 8 h). As many people were concerned about their individual body burden, biomonitoring was recommended for all people involved. 816 persons took advantage of this opportunity and came for blood sampling to the occupational health department of our company. Regarding the lifespan of erythrocytes up to 3 months, it was possible to analyze hemoglobin adducts of acrylonitrile and ethylene during and after the accident. In case of acrylonitrile the hemoglobin adduct N-(2-cyanoethyl) valine and regarding ethylene, N-(2-hydroxyethyl) valine was determined. As a result, the body burden was in nearly all cases within our internal adduct reference values (CyEtVal<15 μg/L blood or <612 pmol/g globin; HyEtVal<15 μg/L blood or 646 pmol/g globin). In about 1% of the cases, the adduct concentrations were slightly above these reference values. This means that the body burden measured by biomonitoring turned out to be far lower than the one expected from the air data. Therefore, following chemical incidents, in case biomonitoring is meaningful, it is highly recommended beside of air monitoring.

Topics: Accidents, Occupational; Acrylonitrile; Chemical Hazard Release; Emergency Responders; Environmental Monitoring; Ethylenes; Firefighters; Germany; Hemoglobins; Humans; Occupational Exposure; Police; Valine

An accidental exposure of six workers to ethylene oxide (EO) provided the rationale for a biomonitoring and follow-up study, whose aim was to analyse protein adduct kinetics and examine the differentiation between accidental and environmental exposure, e.g., from tobacco smoke. For this purpose, the decrease in the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV) was followed during a five-month period after the accident, together with N-2-cyanoethylvaline (CEV) and urinary cotinine, two well-established biomarkers for smoking. The follow-up study showed that EO adduct concentrations significantly increased after a short but presumably high exposure. Initial biomonitoring revealed HEV levels above 500 pmol g(-1) globin in all cases, with a maximum of about 2,400 pmol g(-1) globin. This compares to a German EKA value (exposure equivalent for carcinogenic substances) for a daily 8-h-exposure to 1 ppm EO of 90 μg L(-1) blood (~3,900 pmol g(-1) globin). The adduct levels dropped in accordance with the expected zero-order kinetics for a single exposure. After the five-month observation interval, the HEV concentrations in blood reflected the individual background from tobacco smoking. The results of this study show that even a short exposure to ethylene oxide may result in a significant rise in haemoglobin adduct levels. Although protein adducts and their occupational-medical assessment values are considered for long-term exposure surveillance, they can also be used for monitoring accidental exposures. In these cases, the calculation of daily 'ppm-equivalents' may provide a means for a comparison with the existing assessment values.

Topics: Accidents, Occupational; Biomarkers; Carcinogens; Chemical Industry; Cotinine; Ethylene Oxide; Humans; Male; Occupational Exposure; Smoking; Valine

A cohort of 59 persons with industrial handling of low levels of acrylonitrile is being studied as part of a medical surveillance programme. Previously, an extended haemoglobin adduct monitoring (N-(cyanoethyl)valine and N-(hydroxyethyl)-valine) was performed regarding the glutathione transferases hGSTM1 and hGSTT1 polymorphisms but no influence of hGSTM1 or hGSTT1 polymorphisms on specific adduct levels was found. A compilation of case reports of human accidental poisonings had pointed to significant individual differences in human acrylonitrile metabolism and toxicity. Therefore, a re-evaluation of the industrial cohort included known polymorphisms of the glutathione transferases hGSTM3 and hGSTP1 as well as of the cytochrome P450 CYP2E1. A detailed statistical analysis revealed that exposed carriers of the allelic variants of hGSTP1, hGSTP1*B/hGSTP1*C, characterized by a single nucleotide polymorphism at nucleotide 313 which results in a change from Ile to Val at codon 104, had higher levels of the acrylonitrile-specific haemoglobin adduct N-(cyanoethyl)valine compared to the carriers of the codon 113 alleles hGSTP1*A and hGSTP1*D. The single nucleotide polymorphism at codon 113 of hGSTP1 (hGSTP1*A/hGSTP1*B versus hGSTP1*C/hGSTP1*D) did not show an effect, and also no influence was seen on specific haemoglobin adduct levels of the polymorphisms of hGSTM3 or CYP2E1. The data, therefore, point to a possible influence of a human enzyme polymorphism of the GSTP1 gene at codon 104 on the detoxication of acrylonitrile which calls for experimental toxicological investigation. The study also confirmed the impact of GSTT1 polymorphism on background N-(hydroxyethyl)-valine adduct levels in haemoglobin which are caused by endogenous ethylene oxide.

Topics: Acrylonitrile; Carcinogens; Cytochrome P-450 CYP2E1; DNA Adducts; Ethylene Oxide; Glutathione S-Transferase pi; Glutathione Transferase; Hemoglobins; Humans; Isoenzymes; Occupational Exposure; Polymorphism, Genetic; Valine