Biomedical subjects
M F Wooder
Publications and source records attributed to M F Wooder.
The chemical and biochemical reactivity of dichlorvos.
The chemical structure, reactivity and metabolic fate of the insecticide dichlorvos (2,2-dichlorovinyl dimethyl phosphate) are discussed in relation to the possible genotoxicity of this and other methyl phosphate triesters. Recent attempts to demonstrate the methylation of DNA following exposure of bacteria and animals to dichlorvos are reviewed. On the basis of comparative data relating mutagenesis to methylation reactions, it seems entirely appropriate to conclude that the mutagenicity of dichlorvos to bacteria is due solely to methylation of the bacterial DNA under the conditions of these tests. However, the methylation of mammalian DNA could not be demonstrated under realistic exposure conditions (when the alkylating mutagen methyl methanesulphonate afforded clearly measurable methylation). The failure to detect methylation by dichlorvos in vivo is attributed to the operation of highly efficient enzyme-catalysed biotransformations which rely largely on the phosphorylating reactivity of dichlorvos. The biotransformation pathways, characterised mostly in the rat, appear to be common also to pig, mouse, hamster, and man.
In vivo alkylation studies with dichlorvos at practical use concentrations.
Twenty male CFE rats were exposed to atmospheres containing 0.064 microgram/l of [Me-14C] dichlorvos (113 Ci/mol) for 12 h. Analysis of the DNA and RNA from the total soft tissues of these rats revealed no methylation of the N7 atom of guanine moieties. The limits of detection of methylation were one methyl group per 6.0 X 10(11) and per 2 X 10(9) nucleotide units for DNA and RNA, respectively. Only 0.000001% of the administered dose would have needed to react with DNA in order to produce detectable methylation of this macromolecule. The exposure period employed in this study (12 h) constituted a significant fraction of the half-life of 7-methylguanine moieties in DNA (3 days). On the basis of this information and the extremely rapid metabolism of dichlorvos in a wide range of mammalian tissues and species it was concluded that dichlorvos does not methylate the nucleic acids of mammalian tissues when it is inhaled continuously at practical use concentrations.
Studies on the interactions of dieldrin with mammalian liver cells at the subcellular level.
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