Toxicokinetics of agricultural chemicals and its applications to the forensic toxicology

Research Project

Project/Area Number	63570273
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Legal medicine
Research Institution	Kumamoto University
Principal Investigator	TSUNENARI Shigeyuki Kumamoto Univ. Medical School, Dept. of Forensic Med., Professor, 医学部, 教授 (80040202)
Co-Investigator(Kenkyū-buntansha)	YONEMITSU Kosei Kumamoto Univ. Medical School, Dept. of Forensic Med., Assistant, 医学部, 助手 (10128332)
Project Period (FY)	1988 – 1989
Project Status	Completed (Fiscal Year 1989)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000) Fiscal Year 1988: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords	Forensic toxicology / Agricultural chemicals / Paraquat / Malathion / Methomyl / Toxicokinetics / Pharmacokinetic parameters / Compartment model / 中毒 / 薬動力学的パラメ-タ- / 薬動力学的パラメーター / コンパートメントモデル
Research Abstract	Toxicokinetic studies of paraquat, malathion and methomyl were performed using dogs as experimental animals and their results of pharmacokinetic parameters were discussed from the points of practical applications to forensic toxicology. The plasma profile of paraquat following its intravenous administration to the dog was fitted to a 3-exponential function of pharmacokinetic analysis, and the distribution and elimination of paraquat in the dog could be analyzed on the bases of a 3-compartment open model system. While a 1- or 2-exponential function was needed to express the pharmacokinetics of malathion and methomyl. The half lives in the elimination phases of these three chemicals after intravenous administrations were about 10 hrs for paraquat, 2-3 hrs for malathion and 2-3 hrs for methomyl, respectively. The bioavailabilities of paraquat after oral administrations were calculated to be about 5%. These low availabilities were thought to be caused by the low absorption rates of paraquat from the stomach and intestines. The low availabilities were also observed in the experiments of malathion and methomyl. Rapid decompositions of these chemicals in the intestines and the liver were thought to be the main reason for the low availabilities. After large oral doses of malathion and methomyl, no significant changes were observed in their pharmacokinetic parameters. The present pharmacokinetic data are not enough to evaluate either an unknown dose or the time of ingestion on an actual poisoning case, but they will be useful fundamental data for the forensic toxicology and for the therapy of the patient poisoned of these three chemicals.