The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity.
Fifteen organic phosphate pesticides were tested by computer tracking for their acute behavioral toxicity with the nematode Caenorhabditis elegans. Thirteen of these 15 chemicals are used as insecticides and are anticholesterase agents. The other two chemicals are used as herbicides. EC50 values for each chemical were compared to the corresponding LD50 acute lethality value in rats and mice. Order of toxicity was found to be significantly correlated in comparisons of C. elegans to both rats and mice. Mechanistic investigations were conducted by assaying 8 of the 15 chemicals for anticholinesterase activity in C. elegans. Significant cholinesterase inhibition was confirmed for five chemicals that had displayed high behavioral toxicity, while three chemicals of low behavioral toxicity showed no significant decrease in cholinesterase activity. Toxicity for two chemicals that do not inhibit cholinesterase in mammals was linked to pH effects. Detailed comparison of individual chemicals and metabolic issues are discussed. These results have positive implications for the use of C. elegans as a mammalian neurological model and support the use of C. elegans in early rounds of chemical toxicity screening.
Cole
Russell D
RD
Department of Environmental Health Science, The University of Georgia, Athens, GA 30602-2102, USA.
Anderson
Gary L
GL
Williams
Phillip L
PL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002802:Cholinesterases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology* / Q000523:psychology; D009943:Organophosphorus Compounds; D014176:Protein Biosynthesis
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds; D002802:Cholinesterases