A sex-balanced rodent model for evaluating phosphine inhalation toxicity

Exposure to phosphine (PH₃ ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH₃ 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 PH₃ on female rats were assessed to elucidate potential sex-specific differences and obtain a more comprehensive understanding of PH₃ toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH₃ (13,200-26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration-time (LCt₅₀ ) and time of death (t_TOD ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH₃ 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 PH₃ , in particular, its potential interference with oxygen transport and circulation.