2-Cyanoethylmercapturic acid (CEMA) in the urine as a possible indicator of exposure to acrylonitrile.

Abstract

The aim of this study was to evaluate the efficiency of metabolism of acrylonitrile (ACN) to N-acetyl-S-(2-cyanoethyl)-L-cysteine (2-cyanoethylmercapturic acid (CEMA) in man, the kinetics of excretion of this metabolite, and the relation between the uptake of ACN and the excretion of CEMA in urine. Eleven experiments were performed on six male volunteers exposed for eight hours to ACN at concentrations of 5 or 10 mg/m3. The average respiratory retention of ACN was 52% and 21 8% of the retained ACN was excreted as CEMA in urine. Elimination approximated first order kinetics with half life of about eight hours. The best correlation between the uptake of ACN in the lungs and excretion of CEMA in urine was obtained when the concentration of CEMA in the urine fraction, collected between the sixth and eighth hours after the beginning of exposure, was adjusted to a specific gravity of 1-016 (y = 0 33x -13-3; r = 0 83). CEMA excretion, however, cannot be used as an individual index of exposure.According to the International Agency for Research on Cancer there is sufficient evidence for the carcinogenicity of Acrylonitrile (ACN) in animals.1 Though there is only limited evidence for the carcinogenicity of ACN in man it seemed worth while to investigate the absorption of ACN by all routes.Acrylonitrile may be absorbed through the respiratory tract (the retention of vapour is 46%) and liquid ACN is absorbed through the skin at the rate of 0-6mg/cm2/h.2 At present, no reliable method for evaluating internal exposure to ACN is available. Accepted 31 October 1986 showed that CEMA is the main metabolite of ACN and that in rats about 50-60% of the dose is excreted in urine in this form. Therefore, excretion of CEMA seems to have the potential to be an index of internal exposure to ACN.In preliminary studies Dramifnski and Trojanowska confirmed the presence of CEMA in the urine of workers engaged in manufacturing acryl fibres (unpublished data). The concentration of CEMA in urine collected at the end of the shift varied between 25 and 350 mg/l. The sensitivity of the method, however, did not allow for the evaluation of the kinetics of CEMA excretion in urine.The present study aimed to determine the efficiency of ACN metabolism to CEMA, the kinetics of urinary CEMA excretion, and to find a correlation between CEMA excretion in the urine and the absorbed dose of ACN.

Mercapturic acids revisited as biomarkers of exposure to reactive chemicals in occupational toxicology: a minireview

“…As for acrylamide exposure, two different MAs have been measured in human urine and should be further investigated; AA-MA which results from the direct conjugation of GSH on acrylamide and GA-MA, the MA of glycidamide which is formed by epoxidation of acrylamide (Boettcher et al 2005). In the case of acrylonitrile exposure, the measurement of 2-cyanoethylmercapturic acid (CEMA) has been assessed in a human experimental study for biomonitoring purposes but this parameter could not be used as an individual index of exposure given a very high inter-individual variability (Jakubowski et al 1987). …”

“…A possible explanation for such observations could be genetic polymorphisms in XMEs responsible for BMA and/or DPMA biosynthesis and further toxicogenetics studies should be encouraged in that way. In this context, the potential use of CEMA could be reassessed for acrylonitrile exposure (Jakubowski et al 1987).…”

“…In this minireview, we will focus on those three aspects and discuss more deeply the latest developments or Stommel et al (1989) Toluene [108-88-3] Benzylmercapturic acid (BMA) (Benzyl) Takahashi et al (1994) p-Toluylmercapturic acid (p-TMA) (p-Toluyl) Angerer et al (1998) Xylene [1330-20-7] Jakubowski et al (1987) results in relation to the points (2) and (3) with a special attention towards human studies.…”

Carcinogenicity and Other Health Effects of Acrylonitrile with Reference to Occupational Exposure Limit.

“…Exposure-response relationships for these effects have not been established yet. Jakubowski et al (1987) 106) treated six male volunteers with 2.3 or 4.6 ppm AN by inhalation exposure for eight hours, and examined urinary excretion of metabolites. None of the volunteers complained of subjective symptoms such as headache, vomiting, and weakness which had been known to occur after exposure to AN.…”

Urinary markers for measuring exposure to endogenous and exogenous alkylating agents and precursors.

“…Aringer and Lidums (14) have also drawn attention to the problems of dietary confounding in the total urinary thioether method. As a consequence, it has been recognized that the determination of individual mercapturic acids is not only desirable because of sensitivity, but also adds to the specificity of the method, as in the case of acrylonitrile (15), benzene (16) and ethylene oxide (17). Individual MAs can be determined by a number of methods including GC (15), HPLC-electrochemical detection (18), HPLCfluorescence of derivatives (17), and GC-MS (19).…”