title: Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur.
abstract: To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.
authors.affiliation: Cellular and Molecular Toxicology Branch, Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Padilla.Stephanie@epa.gov <Padilla.Stephanie@epa.gov>
authors.forename: S
authors.initials: S
authors.lastname: Padilla
authors.forename: R S
authors.initials: RS
authors.lastname: Marshall
authors.forename: D L
authors.initials: DL
authors.lastname: Hunter
authors.forename: A
authors.initials: A
authors.lastname: Lowit
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002219:Carbamates / Q000737:chemistry / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D010575:Pesticides; D002802:Cholinesterases