A sex‐balanced rodent model for evaluating phosphine inhalation toxicity

Exposure to phosphine (PH 3 ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH 3 poisoning is thought to target oxidative respiration, the exact mechanism of action remains largely unknown, resulting in limited treatment options. In our study, the effects of PH 3 on female rats were assessed to elucidate potential sex‐specific differences and obtain a more comprehensive understanding of PH 3 toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH 3 (13,200–26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration‐time (LCt 50 ) and time of death ( t TOD ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH 3 were also of comparable magnitude, although temporally, respiratory responses occurred earlier and cardiovascular variations manifested later in female rats. Behavioral observations corroborated physiological findings and indicated a response to hypoxic conditions and low cardiac output. Together, these results provided insights on the toxic mechanisms of PH 3 , in particular, its potential interference with oxygen transport and circulation.