Genetic Toxicity of Malathion: A Review
by Dr. Peter Flessel
California Department of Health Services
|Directly Quoted from:
Environmental & Molecular Mutagenesis, 22:717, 1993
Genetic Toxicity of Malathion: A Review
Dr. Peter Flessel, University of California, Berkeley
"The available evidence indicates that technical grade or other than pure malathion has the potential to produce genotoxic effects in mammalian systems. The results of the available studies on the genotoxicity of malathion can be summarized as follows:
In test animals, technical grade malathion appears to have the potential to produce chromosomal changes including chromosomal aberrations and micronuclei.
In humans, the genotoxic effects of malathion have not been adequately studied. In human and animal cells in culture, both technical grade and purified malathion appear to produce cytogenetic damage, including chromosomal aberrations and Sister Chromatid Exchanges.
Malathion does not appear to produce point mutations in standard gene mutation assays in bacteria, but its metabolite malaoxon (94% pure) was positive in mammalian cell mutation tests.
The interaction of malathion with DNA has not been adequately studied; published studies suggest a weak interaction.
The human health implications of these data are unclear. Agents such as malathion, which cause mutations in in vitro or in vivo test systems, are not now regulated by health agencies as human hazards (EPA, 1986). They may, however, have the potential to cause cancer or adverse reproductive outcomes in humans. A large body of evidence links mutations with these health outcomes. Because mutations, especially those resulting in the loss of tumor supressor genes, are implicated as important mechanisms of human cancers (Cavenee et al., 1986; Gallie and Worton, 1986; Weinberg, 1989), data on mutational mechanisms becomes relevant. Several recent articles discussed the important role of chomosomal damage in cancer, and the possible underlying mutational mechanisms, such as mitotic recombination. Among adverse reproductive outcomes, spontaneously aborted abnormal embryos and fetuses frequently carry chromosomal abnormalities (Boue et al., 1985). Chromosomal aberrations have long been known to be associated with various types of mental retardation and morphological abnormalities in man. For example, chromosomal imbalance (e.g. trisomy) is a cause of Down's Syndrome (Smith and Berg, 1976) and congenitial cardiac malformations (Rowe and Uchida, 1961). In a recent study of mechanisms, a chromosomal translocation which accompanies a form of muscular dystrophy was shown to cause a deletion mutation in a specific gene locus that in turn causes the aberrant phenotype (Love and Davies, 1989). These observations which stress the importance of chromosomal damage may indicate that exposure to malathion (and perhaps other organophosphates) has the potential for genetic damage in humans. It should be emphasized that genotoxic effects observed with malathion may in fact arise from impurities in the technical grade mixtures.
Additional support for the significance of the findings about malathion reviewed in this manuscript is also provided by studies recently reviewed by Garrett et al. (1992) showing that other organophosphates like malathion have similar cytogenetic effects. Dimethoate, for example, has many similar effects as well as structural similarity.
In conclusion, although the genotoxic effects observed with malathion may arise from impurities, including malaoxon in the technical grade mixtures, it should be emphasized that humans are exposed to the technical grade. To resolve the ambiguities related to the major causative agent(s) of the genotoxicity observed in impure mixtures, it is recommended that the composition of the technical grade malathion be determined and the components be tested individually for genotoxicity. Finally, since dermal exposure is a primary means of exposure in humans, it is important to observe that positive results were obtained in animals dermally exposed to technical grade malathion."
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