The rubber accelerator,
2-mercaptobenzothiazole (MBT), has been reported to cause
allergic contact dermatitis from gloves and other rubber products, but its chemical fate when exposed to occupational
oxidants and the mechanism of its pathogenesis are not known. It was hypothesized that the
thiol group is critical to MBT's (its oxidation products or metabolites) covalent binding and/or haptenation to nucleophilic
protein residues. Oxidative transformation of MBT to the
disulfide 2,2'-dithiobis(benzothiazole) (MBTS) was observed within the glove matrix when
hypochlorous acid,
iodine, and
hydrogen peroxide were used as
oxidants.
Cysteine reduced MBTS to MBT with subsequent formation of the mixed
disulfide 2-amino-3-(benzothiazol-2-yl disulfanyl)propionic
acid which was identified and characterized. Spectrophotometry and mass spectrometry experiments demonstrated the simultaneous reduction of MBTS and
disulfide formation with Cys34 on
bovine serum albumin, suggesting a potential route of
protein haptenation through covalent bonding between
protein cysteinyl residues and the MBT/MBTS
thiol moiety. Metabolism of MBT using
isoniazid and
dexamethasone-induced rat liver microsomes, to give a
protein reactive
epoxide intermediate and provide an alternative
protein haptenation mechanism, was not observed. The data suggest that the critical functional group on MBT is the
thiol, and haptenation is via the formation of mixed
disulfides between the
thiol group on MBT and a
protein sulfhydryl group.