Mercapturic acids, protein adducts, and DNA adducts as biomarkers of electrophilic chemicals

The possibilities and limitations of using mercapturic acids and protein and DNA adducts for the assessment of internal and effective doses of electrophilic chemicals are reviewed. Electrophilic chemicals may be considered as potential mutagens and/or carcinogens. Mercapturic acids and protein and DNA adducts are considered as selective biomarkers because they reflect the chemical structure of the parent compounds or the reactive electrophilic metabolites formed during biotransformation. In general, mercapturic acids are used for the assessment of recent exposure, whereas protein and DNA adducts are used for the assessment of semichronic or chronic exposure. 2-Hydroxyethyl mercapturic acid has been shown to be the urinary excretion product of five different reactive electrophilic intermediates. Classification of these electrophiles according to their acid-base properties might provide a tool to predict their preference to conjugate with either glutathione and proteins or with DNA. Constant relationships appear to exist in the cases of 1,2-dibromoethane and ethylene oxide between urinary mercapturic acid excretion and DNA and protein adduct concentrations. This suggests that mercapturic acids in some cases may also play a role as a biomarker of effective dose. It is concluded that simultaneous determination of mercapturic acids, protein and DNA adducts, and other metabolites can greatly increase our knowledge of the specific roles these biomarkers play in internal and effective dose assessment. If the relationship between exposure and effect is known, similar to protein and DNA adducts, mercapturic acids might also be helpful in (individual) health risk assessment

Personal air sampling and biological monitoring of occupational exposure to the soil fumigant cis-1,3-dichloropropene

OBJECTIVES—To assess exposure of commercial application workers to the nematocide cis-1,3-dichloropropene (cis-DCP).
METHODS—The study was conducted during the annual application season, August to 15 November, in the starch potato growing region in The Netherlands. 14 Application workers collected end of shift urine samples on each fumigation day (n=119). The mercapturic acid metabolite N-acetyl-S-(cis-3-chloro-2-propenyl)-L-cysteine (cis-DCP-MA) in urine was used for biological monitoring of the cis-DCP uptake. Inhalatory exposure was assessed by personal air sampling during a representative sample (n=37) of the fumigation days. Extensive information was collected on factors of possible relevance to the exposure and the application workers were observed for compliance with the statutory directions for use. The inhalatory exposure during all fumigation days was estimated from the relation between the personal air sampling data and the biological monitoring data. Exposure levels were correlated with the general work practice. The fumigation equipment and procedures were in accordance with the statutory directions of use, with the exception of the antidrip systems. Two antidrip systems were used: antidrip nozzles or a compressed air system.
RESULTS—The geometric mean exposure of the application workers was 2.7 mg/m(3) (8 hour time weighted average); range 0.1-9.5 mg/m(3). On 25 days (21%) the exposure exceeded the Dutch occupational exposure limit (OEL) of 5 mg/m(3). This could mainly be explained by prolonged working days of more than 8 hours. The general work practice of the application workers was rated by the observers as good or poor. No difference in exposure to cis-DCP was found in the use of none, one, or two antidrip systems. Malfunctioning of the antidrip systems and lack of experience with the compressed air system were identified as possible causes for the lack of effectiveness of these antidrip systems. The use of personal protection was not always in accordance with the statutory directions of use. Dermal exposure to liquid cis-DCP was found four times during repair and maintenance, but the biological monitoring data did not suggest a significant increase in cis-DCP uptake.
CONCLUSIONS—The application of cis-DCP in the potato growing industry can be performed at exposure concentrations below the Dutch OEL of 5 mg/m(3) if the working days are limited to 8 hours. An injector equipped with either kind of antidrip system which is in good working order, as well as the consistent use of personal protection in accordance with the statutory directions of use, may ensure exposure concentrations below the Dutch OEL.


Keywords: cis-1,3-dichloropropene; occupational exposure; soil fumigation; N-acetyl-S-(cis-3-chloro-2-propenyl)-L-cystein