The conventional scheme for arsenic methylation accounts for methylated oxyarsenical production but not for thioarsenical formation. Here, we report that in vitro anaerobic microbiota of mouse cecum converts arsenate into oxy- and thio- arsenicals. Besides methylarsonic acid (MMA(V)), arsenate was transformed into six unique metabolites: mono-, di-, and trithio-arsenic acid, monomethyldithio- and monomethyltrithio-arsonic acid, and dimethyldithioarsonic acid. Thioarsenicals were found in soluble and particulate fractions of reaction mixtures, suggesting interactions with anaerobic microbiota. Metabolism of ingested arsenate to oxy- and thio-arsenicals before absorption across the gastrointestinal barrier could affect bioavailability, systemic distribution, and resulting toxicity.

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The metabolic fate of the bacterial mutagen, environmental pollutant and potential carcinogen 1-nitropyrene (NP) has been investigated in the rat. Over half of an i.p. dose (10 mg/kg) of 1-nitro[14C]pyrene was excreted within 24 h of dosing, 15% of the dose in urine and 40% in the faeces. After 96 h greater than 80% of the dose had been recovered. The urinary and fecal metabolites of NP were separated and quantitated by h.p.l.c., then identified by high resolution gas chromatography/mass spectrometry (h.r.g.c./m.s.) and comparison with synthetic reference compounds, where available. Very little (less than 5%) of the dose was excreted unchanged. Urinary metabolites were all excreted in conjugate form, mainly with glucuronic acid. Among the principal metabolite fractions identified were 3-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene (already known as hepatic in vitro metabolites of 1-nitropyrene) and the hitherto unreported metabolites 6-hydroxy-N-acetyl-1-aminopyrene and 8-hydroxy-N-acetyl-1-aminopyrene. Mutagenic activity was detected, by means of the Ames Salmonella (strain TA 98) plate incorporation assay, in the urine of rats dosed with NP. This mutagenicity, unlike that of NP itself, required exogenous metabolic activation. It was predominantly associated with 6-hydroxy-N-acetyl-1-aminopyrene and with the nitropyrene phenols (specific mutagenicity 600 and 700 rev/nmol respectively in the presence of 0.6 mg of S9 protein per plate). The majority of the residual metabolites were polar, refractory to enzymic hydrolysis, and of low mutagenicity. The major proportion of the 14C in feces was not extractable or amenable to enzymic hydrolysis; the extractable fecal metabolites were similar in nature to those in urine.