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Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides
MOSER, V. C. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides. Presented at Neurobehavioral Teratology Society (NBTS) Meeting, San Diego, CA, June 26 - 29, 2011.
In this study, we directly compared dose-response data using brain and RBC ChE measurements, along with motor activity, for four previously untested OPs: mevinphos, monocrotophos, dicrotophos, and phosphamidon.
Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinesterase (ChE)-inhibiting pesticides have been studied for some organophosphorus (OP) and N-methyl carbamate pesticides, many of which have widespread use in agriculture and around the home. Much of this literature, however, has focused on a relatively few pesticides that clearly demonstrate greater effects in the young compared to adults. In this study, we directly compared dose-response data using brain and RBC ChE measurements, along with motor activity, for four previously untested OPs: mevinphos, monocrotophos, dicrotophos, and phosphamidon. Adult and postnatal day 17 (PND17) Long-Evans hooded male rats were tested; PND11 pups were also tested with dicrotophos only. Test chemicals were administered via oral gavage and tests were conducted at times intended to span peak behavioral and ChE effects. These OPs tested produced a rapid onset and recovery from the behavioral effects. There were age-related differences in the inhibition of brain, but not necessarily RBC, ChE. Mevinphos was clearly more toxic, up to 4-fold, in the young rat. On the other hand, monocrotophos, dicrotophos, and phosphamidon were somewhat more toxic, but the magnitude of the differences was lower, mostly below 2-fold. Motor activity was consistently decreased in adults for all chemicals tested; however, there was more variability with the pups and clear age-related differences were only observed for mevinphos. These data may be compared to previous, comparable studies that we have conducted with other OPs and carbamates. Overall, while some pesticides show markedly increased sensitivity for ChE inhibition in the young, many others show little or no difference. Motor activity is a good reflection of ChE inhibition in adults, but does not have as good a correlation in the young, perhaps reflecting immaturity of the neural systems. These data support conclusions that age-related differences in pesticide toxicity are highly chemicalspecific. This is an abstract of a proposed presentation and does not reflect US EPA policy
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION