Toxicology of Industrial Compounds

Mercapturic acids in human studies
Mercapturic acids, S-substituted N-acetyl-L-cysteine S-conjugates, in urine
can be used as biomarkers of internal dose of electrophilic xenobiotics.
Mercapturic acids are metabolic end products of GSH-conjugation of
various potentially electrophilic chemicals (Figure 2.6). The first
mercapturic acids were identified in 1879 as sulphur containing
metabolites after administration of bromobenzene to dogs (see references in
Vermeulen, 1989). Since then mercapturic acids from many chemicals have
been identified and these types of urinary metabolites have been used in
biotransformation, biological monitoring and toxicological studies
(Vermeulen, 1989; Van Welie et al., 1992).
Commercial availability of reference compounds and the development of
a number of different analytical techniques attributed to the popularity of
mercapturic acids in biological monitoring studies during the last few
years. Urinary excretion of the stereoisomeric mercapturic acids of Z- and
E-1,3-dichloropropene, a soil fumigant frequently used in agriculture,
proved to be a suitable biomarker for the exposure to both isomers in man.
Strong correlations were observed between 8-h time weighted average
exposure to Z- and E-DCP and complete cumulative excretion of N-acetyl-
S-(Z- and E-3-chloropropenyl-2)-L-cysteine in urine. N-acetyl-S-
(cyanoethyl)-L-cysteine was proposed as biomarker of exposure to
acrylonitrile. The best correlation between uptake of acrylonitrile via the
lungs and excretion of the cyanoethyl mercapturic acid in urine was
obtained in samples collected between the sixth and the eighth hour after
the beginning of exposure (Jakubowoski et al., 1987). The phenyl
mercapturic acid of benzene was regarded as a useful biomarker of
exposure below 1 ppm of workers in a chemical production plant
(Stommel et al., 1989). The use of certain foodstuffs and drugs may also
give rise to the excretion of mercapturic acids. Consumption of cabbage
and horse radish for example gave rise to increased thioether excretion.
Consumption of garlic and onions resulted in the excretion of N-acetyl-S-
(allyl- and 2-carboxypropyl)-L-cysteine in urine (Van Welie et al., 1992).
The hypnotic drug ( α-bromo-isovalerylurea
also gave rise to the excretion
of two diastereomeric α-bromoisovalerylurea
mercapturic acid conjugates
in urine (Mulders et al., 1993). S-Phenyl mercapturic acid was present in
urine of groups of smokers and non-smokers, not exposed to benzene, in
concentrations of 4.0±4.0 µg g −1 creatinine (Stommel et al., 1989).
Toxicokinetics
N.P.E.VERMEULEN ET AL. 23
Knowledge about the toxicokinetics of mercapturic acids is necessary to
develop optimal sampling strategies in occupational studies. Urinary
excretion rates of mercapturic acids theoretically may reflect the rates of