Chlorfenapyr poisoning: a systematic review

Abstract

Introduction

Chlorfenapyr, a N-substituted halogenated pyrrole, is a broad-spectrum insecticide. The insecticidal activity of chlorfenapyr depends on its biotransformation by hepatic cytochrome P450 monooxygenases to tralopyril, which uncouples mitochondrial oxidative phosphorylation and disrupts adenosine triphosphate production. Neither the metabolism of chlorfenapyr nor the mechanism of tralopyril is completely elucidated. Acute human chlorfenapyr poisoning is not well characterized, and best practice in management following acute exposure is unclear. The purpose of this review is to characterize acute human chlorfenapyr poisoning by its clinical course, laboratory investigations, and imaging findings and propose a management plan for acute human chlorfenapyr exposure.

Methods

We systematically searched PubMed, Web of Science, Google Scholar, and EMBASE from inception to April 2024 across all languages for human chlorfenapyr and tralopyril cases, with descriptions of exposure, clinical manifestations, and clinical course included. Only manuscripts and abstracts from scientific conferences with sufficient clinical data following acute human exposures were included. In vitro studies, animal studies, agricultural studies, environmental impact studies, and non-clinical human studies were excluded. We then reviewed citations of included studies for additional eligible publications. Non-English publications were translated using Google Translate or primarily translated by our authors. The study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews.

Results

We identified 3,376 publications of which 48 met study inclusion criteria, describing 75 unique cases of human poisoning from ingestion, inhalation, dermal exposure, and intra-abdominal injection of chlorfenapyr. No cases of tralopyril exposure were identified. The median time from exposure to symptom onset was six hours (interquartile range 1–48 hours). The most frequent initial or presenting signs/symptoms included diaphoresis, nausea and/or vomiting, and altered mental status. While hyperthermia (≥38 degrees centigrade) was less common at presentation, hyperthermia developed in 61 percent of all patients and was temporally associated with clinical deterioration and death. Most common laboratory abnormalities included elevated blood creatine kinase activity, hepatic aminotransferase activities, and lactate concentration. Imaging studies of the central nervous system often showed extensive symmetrical white matter abnormalities with swelling. Case fatality was 76 percent, and survivors commonly experienced sustained neurological sequelae. Management strategies were highly varied, and the effectiveness of specific medical interventions was unclear.

Discussion

Acute human chlorfenapyr poisoning is characterized by a latent period as long as 14 days, deterioration over hours to days, and can result in serious morbidity and mortality. Development of hyperthermia, likely driven by oxidative phosphorylation uncoupling by tralopyril, is an ominous clinical sign and is temporally associated with clinical decompensation and death. Laboratory abnormalities, particularly elevated creatine kinase activity, hepatic aminotransferase activities, and lactate concentration, were common, but only creatine kinase activity differed amongst survivors and fatalities. Best clinical practice in the management of patients exposed to chlorfenapyr is unclear, and we opine that a conservative approach with close clinical monitoring and supportive care is prudent.

Limitations

The limitations of all reviews include their inherent retrospective and observational nature as well as publication bias that emphasizes severe outcomes, thus impacting the spectrum of illness and skewing mortality percentage. In addition, we interrogated a finite number of databases for publications on human chlorfenapyr exposure and there were limited cases with laboratory testing to confirm chlorfenapyr poisoning. Analysis of our systematic review was not powered to detect differences between groups, comparative statistics were not performed, and significance is not reported.

Conclusions

Acute human chlorfenapyr toxicity is characterized by a latent period following exposure, development of new or progression of established signs/symptoms, potential for critical illness, rapid deterioration, serious morbidity, and mortality. A conservative approach to patient management is prudent.

Keywords:

• Chlorfenapyr
• insecticide
• pesticide
• poisoning
• tralopyril

Acknowledgements

Jason Yang for his primary translation of multiple Chinese language publications into English.

Authors’ contributions

GC, HN, and LY are responsible for the conception and design of this project. GC, HN, AB, and LY contributed to the literature review. All authors contributed to drafting the manuscript, critical revisions, and final approval of the version to be published. GC takes responsibility for the paper as a whole.

Disclaimer

For HN: The work and thoughts herein are those of the author and do not reflect the official policy or position of the United States Air Force, the US Department of Defense, or the US Government.

Disclosure statement

No conflicts with the content of this paper are declared by any author.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this review.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.