O,O,S-Trimethyl phosphorothioate induces hypothermia in Fischer 344 rats in a manner dependent on both doses and housing temperatures

We explored the effects of O,O,S-trimethyl phosphorothioate (OOS-TMP) on body temperatures in Fischer 344 female rats. The 7-day LD₅₀ p.o. for Fischer 344 female rats was found to be 11.8 mg/kg. OOS-TMP induced long-lasting (more than 48 h) and extensive hypothermia at doses > 14 mg/kg at a typical laboratory temperature (22° C) while it produced typical symptoms at 10 mg/kg without hypothermia. In contrast, pair-fed (to 20 mg/kg rats) rats (n=4) did not become hypothermic, negating any role of hypophagia in OOS-TMP associated hypothermia. We next investigated the effects of housing temperatures on toxicities at a LD₅₀ dose (12 mg/kg). At 30° C (n=11) and 22° C (n=13), rats did not have hypothermic bouts but at 15° C, eight out of ten rats had. Evidence that changes of housing temperatures neither modified clinical symptoms nor changed mortality rates discards a possibility of hypothermia being involved in delayed toxicity. A novel result of the present study suggests that thermoregulation may be heavily impaired by a special class of organophosphorus compounds.