Warning about use of pesticides containing inpyrfluxam for suicide

Acute Medicine & SurgeryVolume 10, Issue 1 e834 Letter to the EditorOpen Access Warning about use of pesticides containing inpyrfluxam for suicide Yasuhito Irie, Corresponding Author Yasuhito Irie yukibiyukibi@gmail.com orcid.org/0000-0002-1628-9262 Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, Akita City, JapanCorresponding: Yasuhito Irie, MD, Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan. E-mail: yukibiyukibi@gmail.comSearch for more papers by this authorHajime Nakae, Hajime Nakae Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, Akita City, JapanSearch for more papers by this author Yasuhito Irie, Corresponding Author Yasuhito Irie yukibiyukibi@gmail.com orcid.org/0000-0002-1628-9262 Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, Akita City, JapanCorresponding: Yasuhito Irie, MD, Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan. E-mail: yukibiyukibi@gmail.comSearch for more papers by this authorHajime Nakae, Hajime Nakae Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, Akita City, JapanSearch for more papers by this author First published: 14 March 2023 https://doi.org/10.1002/ams2.834AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Dear Editor, Succinate dehydrogenase inhibitor (SDHI) has been developed for use in the agricultural industry. However, as mitochondrial electron transport complex II, the target of SDHI, is essential for energy metabolism in nearly all extant eukaryotes, the effects of SDHI-containing fungicides are not species-specific, causing toxicity to nontarget organisms and the environment.1 Inpyrfluxam is a new domestically produced SDHI with a broad spectrum registered as an agrochemical (KANAME, 37% inpyrfluxam flowable formulation, 67% water and surfactants, etc.; Sumitomo Chemical Co., Ltd., Tokyo, Japan) used in the fruit tree and horticultural sectors that has been commercially available since March 2020. We experienced a case of a male patient aged in his 30s who had been attending a mental health clinic for depression for the past 2 months. The patient was having problems at work. However, for reasons unknown, he self-discontinued taking medications for approximately 1 month. The patient's wife found him in the work area, having ingested a full 125 ml container of KANAME. The patient was collapsed and vomiting, and his wife called for emergency services. On arrival at the hospital about 1 h later, the patient had a Glasgow Coma Scale rating of E1V1M1, was drooling, and experiencing cold sweat. Electrocardiogram showed coved-type ST segment elevation in the anterior thoracic guidance and slight QT shortening. There was lactic acidosis on blood gas analysis (pH 7.02, pCO2 43 mmHg, pO2 123 mmHg, HCO3− 13.3 mmol/L, lactate 68 mg/ml). Laboratory tests showed an elevated white blood cell count of 21,100/μl, but neither thrombocytopenia (platelet count of 230,000/μl) nor coagulopathy (international normalized ratio of prothrombin time, 1.10; activated partial thromboplastin time, 21.2 s; fibrinogen, 263 mg/dl). Intubation was performed; a gastric tube was inserted, 70 ml of white drainage fluid was aspirated (Fig. 1), and gastric lavage was performed. Activated charcoal was subsequently administered and continuous hemodialysis was performed due to high anion gap metabolic acidosis. However, the patient did not regain consciousness and his blood pressure gradually decreased, resulting in progressive respiratory and organ damage. Spontaneous respiration was no longer observed, so continuous electroencephalogram was performed on day 3 after admission, which showed flat waves in all inductions. The patient died that evening. At the time of autopsy, stored blood samples from days 1 to 3 were submitted to the police. Although inpyrfluxam was detected in all samples, it was unclear how effective this treatment was; as the sample volume was small, it was not possible to confirm the blood concentration. Fig. 1Open in figure viewerPowerPoint KANAME (37% inpyrfluxam flowable formulation, 67% water and surfactants) undiluted solution recovered from a male patient aged in his 30s. The LD50 value for oral administration of inpyrfluxam in rats is 50–300 mg/kg. Assuming that 70 ml of 125 ml (containing 50,000 mg inpyrfluxam) was recovered as undiluted solution and the remaining approximately 50 ml was 80% recovered by gastric lavage, simple calculation suggests that 10 ml, or approximately 4,000 mg, remained in the body. When SDHI binds to its target site, it inhibits eukaryotic cell respiration such that cells eventually become energy-deficient and perish.2, 3 The mechanisms of cyanide and arsenic poisoning are similar. However, there is no specific antagonist for inpyrfluxam. To our knowledge, this is the first report of inpyrfluxam poisoning and, at present, only standard treatment options are available. As inpyrfluxam is being promoted worldwide as a promising pesticide, efforts are needed to elucidate its effects on the human body and toxicity so that appropriate measures can be taken in such cases. ACKNOWLEDGMENTS Sumitomo Chemical Company, Limited provided pharmaceutical information. CONFLICT OF INTEREST None. REFERENCES 1Yanicostas C, Soussi-Yanicostas N. Sdhi fungicide toxicity and associated adverse outcome pathways: What can zebrafish tell us? Int. J. Mol. Sci. 2021; 22: 12362. 2Sierotzki H, Scalliet G. A review of current knowledge of resistance aspects for the next-generation succinate dehydrogenase inhibitor fungicides. Phytopathology 2013; 103: 880– 7. 3Avenot HF, Michailides TJ. Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi. Crop Prot. 2010; 29: 643– 51. Volume10, Issue1January/December 2023e834 FiguresReferencesRelatedInformation