A case of human poisoning with a flufenoxuron-containing insecticide

Abstract

Introduction. Flufenoxuron is a recently introduced insecticide. The compound is known to exert its insecticidal activity by inhibiting chitin synthesis in insects. However, its toxic effects on humans are unknown. Case report. A 72-year-old woman was brought to the emergency department by ambulance. The person accompanying her brought an empty 100-mL bottle of an insecticide (Cascade™), which was found at the scene. The active ingredient of the product is flufenoxuron and the other components include surfactants and solvents. A detailed composition obtained from the manufacturer was flufenoxuron, ethoxylated nonylphenol phosphate, polyoxyethylene nonylphenol, N-methyl-2-pyrrolidone, and cyclohexanone. Upon arrival at the intensive care unit (ICU), her arterial pH was 7.093, her bicarbonate level was 7.4 mEq/L, and the anion gap was 33.8 mEq/L. Her lactic acid concentration was 16.5 mmol/L. Lactic acidosis was not considered to be a consequence of circulatory shock, because there was no clinical sign of shock other than lactic acidosis, and cardiac output was never below 4.5 L/min. Her acid–base status began to improve and returned to near normal on the next day. Conclusion. It can be hypothesized that the toxicity of the product includes inhibition of the oxygen utilization mechanism at the cellular level. The product is composed of a number of components, similar to many other herbicide products. It is not possible to identify which of the ingredients was specifically responsible for the toxic effects in this case.

Keywords:

• Insecticides
• Acid–base disorders
• Lactic acidosis
• Pesticide toxicity

Flufenoxuron (Cascade(™), 1-[4-(2-chloro-α-α-α-trifluoro-p-tolyloxyl)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, is a recently introduced insecticide. It has been registered in more than 20 countries including South Korea, Japan, China, France, Italy, Spain, Latin American countries, and African countries for its application to fruits, vegetables, flowers, and beans.¹ The compound is mainly a larvicide, and it is known to exert its insecticidal activity by inhibiting chitin synthesis in insects, which causes abortive molting and death.² However, its toxic effects on humans are unknown. We report a case of intoxication with a flufenoxuron-containing insecticide characterized by severe lactic acidosis.

Case report

A 72-year-old woman was brought to the emergency department by ambulance. The person accompanying her brought an empty 100 mL-bottle of Cascade^™ that was found at the scene. The active ingredient of the product is flufenoxuron and the other components include surfactants and solvents. The detailed composition obtained from the manufacturer included flufenoxuron (5.3%), ethoxylated nonylphenol phosphate (10.0%), polyoxyethylene nonylphenol (8.0%), N‐methyl-2-pyrrolidone (20.0%), and cyclohexanone (56.7%). When she presented to the emergency department, she was comatose with a Glasgow coma scale score of 3, and there was foam around her mouth. Her heart rate was 83 beats/min; blood pressure 120/70 mmHg; respiratory rate 20 breaths/min; and pulse oximetry indicated 94% saturation on supplemental oxygen given with a face mask. Her arterial pH was 7.34, plasma sodium concentration 141 mEq/L, potassium 3.5 mEq/L, chloride 105 mEq/L, and anion gap 18 mEq/L upon presentation. Her blood alcohol concentration was 0.5 mg/dL and methemoglobin level was 0.1%. She was intubated and connected to a mechanical ventilator. Gastric lavage was performed, and 50 g of activated charcoal was given through a nasogastric tube. A drug profiling assay using the REMEDi-HS system (Bio-Rad Laboratories, Hercules, California, USA) identified chlorodiazepam in her blood and urine and cimetidine in her urine. Her caregiver said that the drugs had been prescribed by her primary care physician. She was known to have longstanding diabetes and depression, but was not taking any antihyperglycemic agent or antidepressant at the time of presentation. She was transferred to the intensive care unit about 3 h after her arrival at the emergency department.

Upon arrival at the intensive care unit, her arterial pH was 7.09, the partial pressure of carbon dioxide (pCO₂) was 23.8 mmHg, her bicarbonate level was 7.4 mEq/L, sodium concentration was 147 mEq/L, potassium concentration was 3.7 mEq/L, chloride concentration was 105 mEq/L, and the anion gap was 34 mEq/L. Her lactic acid concentration was 16.5 mmol/L, explaining the widened anion gap. Lactic acidosis was not considered to be a consequence of circulatory shock, because there was no clinical sign of shock other than lactic acidosis. Also, cardiac output measured by impedance cardiography was never below 4.5 L/min. Co-ingestion with cyanide was considered, as she had unexplained lactic acidosis, and sodium thiosulfate was given empirically. Laboratory confirmation of cyanide poisoning was unavailable. Other supportive measures were continued, and 40 mL of 8.4% sodium bicarbonate solution was given only once when her blood pH was below 7.1. Her acid–base status began to improve, and returned to a near-normal balance the next day (Fig. 1). Aspiration pneumonia developed in her right lung and antibiotic treatment was started.

Fig. 1. Change in the patient's acid–base status.

She was extubated on the fifth hospital day and was fully conscious. She remembered the self-intoxication event and denied ingesting anything other than the insecticide. She was transferred to a community hospital on the eighth hospital day for prolonged care.

Discussion

A PubMed search using the keyword flufenoxuron yielded no result regarding the toxic effects of flufenoxuron on humans. According to the factsheet from the U.S. Environmental Prevention Agency,³ the rat LD₅₀ after acute oral exposure to flufenoxuron is over 5,000 mg/kg, much greater than the amount ingested in this case. The surfactants contained in the product are not known to produce lactic acidosis. There is a report of coma and acidosis caused by cyclohexanone, the solvent used in the product.⁴ The victim was reported to have suffered coma, circulatory shock with severe hypotension, metabolic acidosis, and eventually rhabdomyolysis. Hydrocarbons are known to exert cardiotoxicity and shock,⁵ and circulatory shock can cause lactic acidosis. Our case is different from the previous report in that there was lactic acidosis without any evidence of circulatory shock. It can be hypothesized that the toxicity of the product includes inhibition of the oxygen utilization mechanism at the cellular level. It is unclear whether sodium thiosulfate had any effect on our patient's course. The anion gap narrowed after the sodium thiosulfate was given, but this could have been a coincidence. We believe this is the first report of human toxicity from a flufenoxuron-containing insecticide. The product is composed of a number of components, similar to many other herbicide products. It is not possible to identify which of the ingredients was specifically responsible for the toxic effects in this case. However, the surfactants and solvent used in the product have a relatively long history of use and there are a number of reports on human toxicity, but there is no report of lactic acidosis without circulatory shock. Subsequent observations could help better clarify the toxic effects of flufenoxuron on humans.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.