Benzimidazolecarbamate methyl ester--evaluation of its effects in vivo and in vitro.
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Biomedical subjects
Publications and source records attributed to J A Styles.
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The industrial biocide chloracetamide-N-metholol (CAM) has been shown to be non-mutagenic to 6 strains of Salmonella using both the plate-incorporation and a pre-incubation test protocol. Its biocidal activity is unlikely to have influenced these results since Kathon 886, a more potent biocide, was concomitantly detected as mutagenic to strain TA100. In contrast, CAM was weakly clastogenic to human lymphocytes cultured in vitro and elicited a positive response in the mouse bone marrow micronucleus test when assayed using the intraperitoneal, but not the oral route of administration. A positive response was concomitantly observed for the rodent carcinogen and formaldehyde-releasing agent hexamethylphosphoramide (HMPA) in these 2 clastogenicity assays. Data are presented showing the slow hydrolysis of CAM to formaldehyde in vitro, and both [carbonyl-14C]CAM and [metholol-14C]CAM have been shown to interact covalently with calf-thymus DNA in vitro. It is concluded that CAM may be a direct-acting carcinogen to rodents, but that both the qualitative and quantitative outcome of its bioassay for carcinogenicity will be influenced critically by the bioassay protocol adopted; in particular, by the route of administration selected. These findings emphasize the need to complement the Salmonella gene-mutation assay with an in vitro assay for the induction of chromosomal aberrations if in vivo genotoxins are to be detected efficiently in vitro.
Known and proposed metabolites of shikimic acid were synthesised, characterised and tested for genotoxic activity using the Salmonella/mammalian microsome mutagenicity test, the bacterial fluctuation mutagenicity test and the BHK 21 cell transformation test. Under the conditions used, none of these compounds showed any activity. However, shikimic acid itself was active in the BHK 21 cell transformation assay. It therefore seems unlikely that shikimic acid is a carcinogenic initiating agent, but it may act as a carcinogen-promoting agent in the bracken fern (Pteridium aquilinum).