ABSTRACT
Dichlorvos has been in widespread use as an insecticide for over 40 years, during which time its carcinogenicity and genotoxicity have been evaluated extensively. In vitro genotoxicity assays--have shown dichlorvos to be a direct acting genotoxicant at high concentrations, consistent with its known chemical reactivity. This activity is greatly reduced in the presence of S9-mix providing auxiliary metabolic activation, again consistent with its known chemistry and metabolism. Dichlorvos has been examined in a number of in vivo genotoxicity assays using a range of cell types and endpoints, and whilst there are some reports of activity, a critical evaluation has shown that there is no convincing evidence that dichlorvos has significant genotoxic activity in vivo under exposure conditions relevant to potential human exposures. In combination with the extensive carcinogenicity database for dichlorvos, the weight of evidence indicates that dichlorvos is not genotoxic under exposure conditions relevant to those that might occur in humans.
Subject(s)
Dichlorvos/metabolism , Dichlorvos/toxicity , Animals , Carcinogenicity Tests/methods , Carcinogenicity Tests/statistics & numerical data , Dichlorvos/chemistry , Humans , Hydrolysis , Insecticides/chemistry , Insecticides/metabolism , Insecticides/toxicity , Molecular Structure , Mutagenicity Tests/methods , Mutagenicity Tests/statistics & numerical dataABSTRACT
Aniline has been reported to be positive in the mouse bone marrow micronucleus test. This finding is inconsistent with its lack of carcinogenicity in this species. Micronuclei can arise by mechanisms that do not involve direct interaction with DNA, e.g. induction of aneuploidy or stimulation of erythropoiesis. However, clastogenic materials would be expected to demonstrate an increased level of chromosomal damage in dividing precursor erythroblasts. In the present study we have investigated the ability of aniline HCl to induce chromosome aberrations in bone marrow metaphase cells. No evidence of clastogenicity was observed in this study. This suggests that the activity seen in earlier micronucleus assays may have arisen by a mechanism not involving direct DNA interaction. Aniline is known to be toxic towards the erythropoietic system and the possibility exists that micronuclei may be produced as a result of this toxicity.
