Liver damage induced in rats by malathion impurities.
Administration of a single oral dose of the malathion impurity, O,O,S-trimethyl phosphorothioate (OOS-Me) or O,S,S-trimethyl phosphorodithioate (OSS-Me), to the rat resulted in hemostatic disorders, e.g. prolongation of blood clotting, prothrombin and thrombin time. Deficiency of coagulation Factors II, V and VII was also observed. OOS-Me and OSS-Me also caused dose-dependent increases of beta-glucuronidase in the blood with a maximum of 15- and 31-fold observed following treatment with 60 mg/kg OOS-Me and 40 mg/kg OSS-Me, respectively. Analysis of serum beta-glucuronidase by isoelectrofocusing electrophoresis showed that the liver endoplasmic reticulum was the source of this enzyme released into the blood. Co-treatment of OOS-Me with 5% O,O,O-trimethyl phosphorothioate (OOO-Me), a potent antagonist of OOS-Me-induced delayed toxicity, prevented hemostatic disorders but had no effect in reducing beta-glucuronidase levels. However, pretreatment of rats with piperonyl butoxide reduced the amount of beta-glucuronidase released into the blood. Of other O,O,S-trialkyl phosphorothioates examined, the O,O-diethyl S-alkyl phosphorothioates showed the highest activity in increasing beta-glucuronidase levels.
Keadtisuke
S
S
Department of Entomology, University of California, Riverside.
Dheranetra
W
W
Nakatsugawa
T
T
Fukuto
T R
TR
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000097:blood; D006487:Hemostasis / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008294:Malathion / Q000633:toxicity; D008297:Male; D063086:Organothiophosphates / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011517:Prothrombin Time; D051381:Rats; D011919:Rats, Inbred Strains; D013918:Thrombin Time
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C023890:O,O,O-trimethyl phosphorothioate; C019123:O,O,S-trimethyl phosphorothioate; C033125:O,S,S-trimethyl phosphorodithioate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005966:Glucuronidase; D008294:Malathion