title: A comparison of cholinesterase activity after intravenous, oral or dermal administration of methyl parathion.
abstract: Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30-48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37 degrees C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (> or =6 h) and was prolonged (> or =48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. rkramer@pharmacology.umsmed.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kramer
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wellman
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Robin W
authors.initials: RW
authors.lastname: Rockhold
authors.forename: Rodney C
authors.initials: RC
authors.lastname: Baker
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D004333:Drug Administration Routes; D005260:Female; D007275:Injections, Intravenous; D007306:Insecticides / Q000008:administration & dosage* / Q000494:pharmacology; D007700:Kinetics; D008743:Methyl Parathion / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008743:Methyl Parathion; D002802:Cholinesterases