Mercapturic acids as metabolites of aromatic aldehydes and alcohols

After administration of substituted (CH3, OH, OCH3, F, CL, Br, NO2) benzaldehyde or benzyl alcohols in the rat an enhanced urinary thioether excretion was found in some cases. With p-substituted benzaldehyde only occasionally a slight increase could be shown, but with o-substituted aldehydes and alcohols thioether excretions amounted up to 13% of the dose. Mercapturic acids were isolated and identified by synthesis, mass-, and n.m.r.-spectrometry as the arylmethyl thioethers of N-acetylcysteine. Steric hindrance by o-substituents must be the main cause of a relative decrease in oxidation to the carboxylic acid and an increase of the importance of both the reduction of the aldehydes and the reaction of the alcohols, presumably to sulphuric acid esters, as intermediates for the alkylation of glutathione. Consequently, previous administration of pyrazole, an inhibitor of alcohol dehydrogenase, caused an even larger thioether excretion after injection of o-chlorobenzyl alcohol.