Académie royale de Médecine de Belgique

|

Prix Dr Monique Govaerts (2012-2014) - Lauréat Vincent Haufroid (Présentation + Résumé)

Résumé par V. Hautfroid: The biological monitoring of exposure as a tool to prevent intoxications in occupational settings

 

In complement to atmospheric measurements, biological monitoring of exposure to toxic substances present in the working environment provides a useful tool for the risk assessment process in occupational medicine. The most frequent biomarkers of exposure are classically represented by the mother substance, or one of its metabolites, measured in a biological medium, mostly urine which implies the least invasive and therefore the best tolerated sampling strategy. In the field of occupational toxicology, it is particularly important to provide occupational physicians and/or hygienists with reliable biomarkers allowing to assess exposure to substances of health concern, specifically those with carcinogenic, mutagenic and/or reprotoxic properties. As most of these substances are electrophilic compounds, an endogenous detoxification pathway uses their conjugation with glutathione to produce specific mercapturic acids excreted in urine. The development and validation of analytical methods allowing the quantification of these mercapturic acids in urine represents, therefore, an interesting approach for the development of new tools in biological monitoring.
The objective of the studies published in the present report is to document the interest of the urinary measurement of mercapturic acids specific for the exposure to substances considered as carcinogenic to humans and classified by the IARC (International Agency for Research on Cancer) in category 1. Among these substances, ethylene oxide and benzene have been selected as examples and the interest of the measurement of their respective mercapturic acids (2-hydroxyethyl mercapturic acid or HEMA and S-phenyl mercapturic acid or SPMA) in occupationally exposed workers is discussed.
This approach could be generalized to other toxic substances and this is the reason why we have developed and validated other new biomarkers from the mercapturic acid group to assess respective exposure to:
•    propylene oxide (IARC 2B) by measuring 2-hydroxypropyl mercapturic acid (2-HPMA)
•    acrolein by measuring 3-hydroxypropyl mercapturic acid (3-HPMA)
•    1,3-butadiene (IARC 1) by measuring 3,4-dihydroxybutyl mercapturic acid (DHBMA) and monohydroxy-3-butenyl mercapturic acid (MHBMA)
The assessment of another biomarker specific for exposure to N-methyl-2-pyrrolidone (reprotoxic category 1b, H360) has been also included in view of the increasing importance of this substance as a substitution solvent in various occupational settings. The measurement of 2-hydroxy-N-methylsuccinimide (2-HMSI) before next shift is of value to estimate occupational exposure to NMP. This biomarker explains about 70% of the variance observed in atmospheric exposure.