Toxicological Review of an Uncoupler, Chlorfenapyr

The field of forensic toxicology faces significant challenges when assessing toxic substances whose blood concentrations do not correlate proportionally with toxicity. A representative example of such substances is uncouplers, which induce apoptosis via mitochondrial dysfunction, leading to delayed toxicity. In this study, we examined domestic intoxication cases involving uncouplers, with particular focus on chlorfenapyr, a widely recognized uncoupler. Symptoms observed in poisoning cases included initial vomiting, abdominal pain, and diarrhea, followed by hyperthermic episodes, rhabdomyolysis, optic nerve damage, pancreatitis, brain damage, and, ultimately, death occurring days to weeks later. In fatal cases, the blood concentration of chlorfenapyr was found to be below 1 ppm (ranging from tens to hundreds of ppb), making it easily overlooked in routine toxicological screenings. Furthermore, due to its delayed toxic effects, chlorfenapyr may not be detected in gastric contents, necessitating careful forensic evaluation. In negative chlorfenapyr cases presenting with hyperthermic episodes and signs of cell death, exposure to other uncouplers should be considered. Clinical cases reviewed in this study suggest that ingesting as little as 20 mL of pesticide products containing chlorfenapyr can lead to death weeks later, highlighting the severe delayed toxicity of this compound. Therefore, regulatory policies governing its use should be reinforced, and the development of alternative pesticides should be considered to mitigate fatal risks.