Excretion of mutagens in sweat and faeces of man, and in serum, gastric juice and urine of rats, after oral dosing of niridazole or metronidazole

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Abstract
Frameshift mutagens were isolated and concentrated from sweat and faeces of three healthy volunteers (non-smokers) of whom two received 750 mg metronidazole/person and one received 500 mg niridazole. The sweat samples were collected in a sauna a day before and 8 h after oral uptake of the medicaments. The faecal samples were those expelled 12 h before and after drug uptake. All extracts were tested for mutagenicity in the bacterial microtiter fluctuation test employing Salmonella typhimurium TA1538. No mutagenic activity was found with the samples obtained before the drugs were taken, whereas the samples collected after drug treatments were all mutagenic (P < 0.05). In an animal experiment, female Wistar rats were used to study the time-course of the excretion of mutagens in serum, urine and gastric juice after uptake of 10–20 mg niridazole by gavage. Significant mutagenic activities (P < 0.001) were found in serum 10 min after and in gastric juice 12h after treatment with niridazole. Non-significant but detectable mutagenicities were found in urine 12 h after treatment, when S. typhimurium G46 was employed as a test organism. These latter mutagenicities were significant (P < 0.05) 24 h after treatment, they reached a peak of activity (P < 0.01) 48 h post-administration and disappeared 12 h thereafter.