Structure and pulmonary toxicity relationship on O,O-dimethyl S-alkyl phosphorothioate esters.
The structure-pulmonary toxicity relationship was investigated using three different O,O,S-trimethylphosphorothioate (OOS-TMP) analogues, which is known to induce a typical mortality pattern (delayed death) and pulmonary injury; O,O-dimethyl S-ethyl (OOS-DMEP), O,O-dimethyl S-propyl (OOS-DMPP), and O,O-dimethyl S-butyl (OOS-DMBP) phosphorothioates. The mortality pattern in rats dosed with OOS-DMEP was similar to the "delayed death" pattern: the LD50s in rats for OOS-DMEP decreased dramatically from more than 200 mg/kg within 24 hr to 41.1 (males) or 13.8 (females) mg/kg 7 days after treatment while the LD50s in rats for OOS-DMPP and OOS-DMBP did not. Histopathological examinations revealed that OOS-DMEP induced pulmonary oedema and bleeding at a dose of 1/2 LD50 by 72 hr after dosing while the other two compounds did not. Thus, it was concluded that OOS-DMEP induces pulmonary injury, thereby eliciting the "delayed death" mortality pattern.
Hasegawa
J
J
Department of Anesthesiology, Akita University School of Medicine, Japan.
Wada
Y
Y
Sageshima
M
M
Suzuki
M
M
Kamiyama
S
S
Abe
N
N
Koizumi
A
A
D000818:Animals; D005260:Female; D007928:Lethal Dose 50; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D063086:Organothiophosphates / Q000032:analysis / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C019123:O,O,S-trimethyl phosphorothioate