A Fatal Case of Chlorfenapyr Poisoning and the Therapeutic Implications of Serum Chlorfenapyr and Tralopyril Levels

Abstract

Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient’s signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

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“…In animals, dealkylation of an ethoxymethyl group on chlorfenapyr, reveals the active metabolite, tralopyril, which uncouples mitochondrial oxidative phosphorylation to disrupt ATP-production leading to death [37]. Although relatively non-toxic to HEK293 cells (EC 50 = 20.918 ± 7.337 µM), there have been poisoning cases with chlorfenapyr [38, 39, 40], likely undermining its direct repurposing potential as an anthelmintic.…”

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“…Hence, heightened vigilance is essential in cases of hyperthermia (> 39℃) associated with acute chlorfenapyr poisoning, irrespective of the onset timing. The reported minimal lethal dose for oral administration stands at 10 mL of 10% chlorfenapyr in a 13-year-old girl, with a median time to death averaging 10 days (ranging from 5 to 20 days) (26,32,33). Notably, inhalation and skin contact exposure can also result in severe poisoning.…”

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“…After 156 hours of exposure, a brief tonic seizures was followed by an increased heart rate. The patient died 157 hours after ingesting the pesticide (72). Chlorfenapyr intoxication causing dermal manifestations may be harmful.…”