Chloracetamide-N-metholol: an example of an in vitro and in vivo clastogen which is non-mutagenic to Salmonella.
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.[1]References
- Chloracetamide-N-metholol: an example of an in vitro and in vivo clastogen which is non-mutagenic to Salmonella. Ashby, J., Richardson, C.R., Lefevre, P.A., Callander, R.D., Styles, J.A. Mutat. Res. (1985) [Pubmed]
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