Comparison of acute neurobehavioral and cholinesterase inhibitory effects of N-methylcarbamates in rat.
While the cholinesterase-inhibiting N-methyl carbamate pesticides have been widely used, there are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (RBCs) as well as motor activity (both horizontally and vertically directed) and clinical signs of overt toxicity. The chemicals tested were carbaryl, carbofuran, formetanate, methiocarb, methomyl, oxamyl, and propoxur. All were administered orally, and rats were tested in 20-min activity sessions beginning 15 min after dosing; tissues were collected immediately after activity sessions. In general, motor activity was a sensitive measure of ChE inhibition for all these carbamate pesticides, and vertical activity showed the greatest magnitude of effect at the highest doses compared to either horizontal activity or ChE inhibition. Brain and RBC ChE activities were generally affected similarly. Pearson correlation coefficients of within-subject data showed good correlation between the behavioral and biochemical end points, with brain ChE inhibition and horizontal activity showing the highest correlation values. Determination of benchmark dose levels for 10% change in each end point also revealed that these two measures produced the lowest estimates. Thus, motor activity decreases are highly predictive of ChE inhibition for N-methyl carbamates, and vice versa.
McDaniel
Katherine L
KL
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Padilla
Stephanie
S
Marshall
Renée S
RS
Phillips
Pamela M
PM
Podhorniak
Lynda
L
Qian
Yaorong
Y
Moser
Virginia C
VC
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002219:Carbamates / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases