Toxicokinetics, Metabolism and Distribution

SM is a lipophilic compound that is absorbed readily by the skin, eyes, respiratory tract and gut. There is a substantial literature database for SM kinetics in animals, as well as some data obtained from either accidental or deliberate human exposures. There appear to be differences in the pattern of distribution of SM between humans and other animals, although whether this is 

SM is rapidly absorbed from the site of administration in all species, whereupon it either reacts rapidly with macromolecules (alkylation) or is metabolised, the major metabolites being thiodiglycol and GSH adducts. 

Toxicologically relevant doses of SM rapidly penetrate the surface layers of the skin (stratum corneum) and there is evidence that a depot is formed in the skin during absorption, although the location and toxicological relevance of this depot are not certain. 

When S-labelled SM was applied to the skin of rats under occlusion, 90% of the applied dose was absorbed within 6 hours. Uptake increased linearly with the applied contamination density in the range of 3-605 g cm , reaching a maximum of approximately 7 pg cm min at 955 pg cm . After 6 hours, approximately 75% of the applied radioactivity had passed through the skin and distributed systemically, 25% was retained in the skin, up to 30% was excreted in the urine and 5-8% remained in the blood. The half life of the radioactivity in the plasma was 2.4 days, but detectable radioactivity remained bound to haemoglobin 40 days after application. 

Measurement of radiolabel cannot distinguish between parent compounds and metabolites, so no conclusions can be drawn about the identity of distributed and excreted material from these studies alone. 

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