Quantification of the mercapturic acids of acrylonitrile and its genotoxic metabolite cyanoethylene-epoxide in a pilot human biomonitoring study

摘要

Background: Acrylonitrile is one of the most important monomers in plastic production worldwide with an enormous production volume. Acrylonitrile is a known animal carcinogen and also a major constituent of tobacco smoke, which is the main source of exposure for the general population. Aims: The metabolic conversion of acrylonitrile to its genotoxic metabolite cyanoethylene-epoxide in humans by liver cytochromes is mainly responsible for the carcinogenic properties of acrylonitrile. Therefore, our research was aimed to elucidate this metabolic pathway in humans. Methods: Based on previous works, we have developed a highly sensitive and specific LC/MS/MS-method to simultaneously quantify the specific mercapturic acids of acrylonitrile (N-acetyl-S-(2-cyanoethyl)cysteine, CEMA) and its oxidative metabolite cyanoethylene-epoxide (N-acetyl-S-(1-cyano-2-hydroxyethyl)cysteine, CHEMA) in human urine. The limit of quantification for both metabolites was 1 μg/L urine. In a pilot study we applied this method to spot urine samples of 47 non-smoking and 36 smoking persons of the general population with no occupational exposure to acrylonitrile. Results: Median levels for CEMA and CHEMA in urine samples of non-smokers were 1.9 and ＜ 1 μg/L urine. CHEMA was quantified only in 4 of the 47 samples. In contrast, both metabolites were quantifiable in more than 94 % of the smokers' urine samples. Excretion of CEMA was highly correlated to anamnestic information about daily smoked cigarettes. Median levels of CEMA and CHEMA were 184 and 29 μg/L urine, respectively. The mean relationship between CHEMA and CEMA in these samples was 13 %, but showed high variability, which was potentially caused by individual susceptibility. Conclusions: Our method is highly suitable for human biomonitoring of exposures to acrylonitrile and the future derivation of risk-based biological guidance values.