Pyrethrin and Pyrethroid Toxicity

Etiology

Little published data exists about the most common mechanisms by which patients experience toxic exposure to pyrethroids in the United States. Intentional ingestion and inhalational and dermal exposure are the most likely routes of entry into the human body. Agricultural workers and individuals spraying large volumes of insecticide are at risk for inhalation and dermal exposure. One-third of pyrethroid exposure cases reported to the Toxic Exposure Surveillance System (TESS) between 2000 and 2005 involved children younger than 6.[6] Thus, accidental exposure likely comprises a significant fraction of exposures outside of occupational settings.

Epidemiology

Poison centers documented 121,748 pyrethrin and pyrethroid exposure cases between 2000 and 2005 across the United States. During the study period, cases of pyrethrin and pyrethroid exposures reported to the TESS increased from 13,759 in 2000 to 25,949 in 2005. Roughly 33% of exposures occurred in children younger than 6. Intentional ingestions comprised less than 3% of cases, and the mortality rate was less than 0.01%.[6]

The National Poison Data System (NPDS) reported 20,123 cases of pyrethrin and pyrethroid exposure in 2022. Roughly 21% of exposures involved children younger than 6. Similar to prior data, 2.6% of exposures were cases of intentional self-harm. Approximately 17.3% of exposures were treated in a healthcare facility, with 0.2% of all cases resulting in severe toxicity. Four of the 20,123 cases resulted in fatality, resulting in a case fatality rate of 0.02%.[7]

Pathophysiology

The primary mechanism of action of pyrethrin and pyrethroids is prolonged activation and opening of voltage-dependent sodium channels, resulting in a tail current and prolonged depolarization. Type II pyrethroids are more potent, causing a more prolonged depolarization.[8] Insect voltage-dependent sodium channels have a greater sensitivity to pyrethroids, and these compounds are approximately 2000 times more toxic to insects than humans. Type I pyrethroids have a negative temperature coefficient, indicating higher potency at temperatures lower than normal human temperature. In contrast, type II pyrethroids have a positive temperature coefficient, are more potent at higher temperatures, and are thus more likely to cause toxicity in humans.[9][10]

Pyrethrins and pyrethroids also act as antagonists at γ amino-butyric acid (GABA) chloride channels within the central and peripheral nervous system. This affinity likely causes the salivation and choreoathetosis symptoms that led to the naming of the original CS syndrome caused by type II pyrethroids. This same antagonist effect at GABA chloride channels likely plays a role in the seizure activity observed after significant type II pyrethroid exposure.[11]

The clinical manifestations associated with these action mechanisms vary. Skin exposures may manifest with paresthesias and contact dermatitis. Eye exposures may result in excessive lacrimation. Pyrethroid ingestion is more likely to result in toxicity and may cause excessive salivation, nausea, vomiting, epigastric pain, altered mental status, muscle fasciculation, seizure, respiratory distress, and pulmonary edema.[12]

Toxicokinetics

Pyrethrins and pyrethroids generally have higher bioavailability by ingestion than dermal exposure. Additives in insecticides containing these substances also affect absorption, particularly piperonyl butoxide, which enhances absorption in humans and insects. Results from a prior study showed that less than 2% of cypermethrin, a type II pyrethroid, is absorbed dermally, while 19% to 50% is absorbed when ingested. Piperonyl butoxide-containing formulas increased dermal absorption rate to around 8% and gastrointestinal tract absorption to greater than 70%. Pyrethroids are rapidly cleared hepatically, though piperonyl butoxide also slows this metabolism. Nontoxic metabolites are subsequently excreted in urine.

History and Physical

Several aspects of the patient's history are paramount to proper treatment. Determining the route of exposure is critical, as it may dictate subsequent evaluation and management and the need for immediate skin decontamination. Common exposure routes include ingestion, inhalation, and dermal. The clinician should obtain as much information about the product to which the patient was exposed.

Pyrethroid types I and II present with similar rates of nausea, vomiting, and tremor. However, type II pyrethroids are more likely to present with neurotoxic manifestations, such as paraesthesias, depressed mental status, and seizures. Hypersalivation has been observed more frequently with type II than type I pyrethroids.[13] Additional compounds in pyrethroid products, such as piperonyl butoxide or hydrocarbon carriers, may increase the duration of symptoms or cause toxicity on their own.[14] Symptoms generally appear within minutes to hours of exposure, with local signs of irritation, such as dermatitis and abdominal pain, manifesting before systemic problems like altered mental status and seizures.

Pertinent examination findings, such as confusion and depressed mental status, may be seen in systemic toxicity. However, these signs are rare except in large ingestions. Muscle fasciculations may also be seen in the extremities. Crackles or rales may be heard on auscultation secondary to aspiration, typically of the hydrocarbon carrier. Patients may have abdominal pain and tenderness following ingestion. Local irritation and erythema arise from contact dermatitis. Patients experiencing an allergic response to pyrethroids may display respiratory distress, urticaria, hypotension, and oral swelling. Lacrimation and salivation may be expected in patients with ocular and oral exposures, respectively.

Evaluation

No single laboratory test exists to identify specific pyrethroid compounds. However, mass spectrometry may be utilized in some settings to detect metabolites.[15] Given the overlap of symptoms with organophosphate toxicity, cholinesterase measurement may be helpful to delineate the type of exposure further. However, such tests are not rapidly available and lack the ideal sensitivity and specificity. Thus, cholinesterase measurement should not delay treatment.

A basic metabolic panel helps evaluate for electrolyte abnormalities in patients with significant vomiting. Chest radiography should be obtained if patients develop respiratory distress or have evidence of pulmonary edema on examination. Chemical pneumonitis or pulmonary edema secondary to aspiration may be delayed several hours. For a more comprehensive discussion of the evaluation and management of hydrocarbon exposure, please see StatPearls' companion activity, "Hydrocarbon Toxicity."

Treatment / Management

The management of toxic exposure to pyrethroids or pyrethrins includes close monitoring, observation, and supportive care. Patients often fail to identify the insecticide product. Thus, other agents should be included in the evaluation, most critically organophosphates, which have overlapping signs and symptoms such as salivation, lacrimation, mental status changes, and tremors but are typically of more serious health consequences. Prior studies have identified pyrethroid toxicity cases initially misdiagnosed as organophosphate toxicity and treated with atropine, resulting in significant atropine toxicity and death.

Decontamination should be included among the first management measures in any pesticide exposure to prevent further toxicity to the patient and secondary contamination of healthcare workers. Individuals displaying evidence of anaphylaxis should receive epinephrine, antihistamine, and corticosteroids in line with usual anaphylaxis treatment. Prior case reports also highlight that hydrocarbon carriers in pyrethroid insecticide formulations can cause chemical pneumonitis, potentially leading to respiratory failure and death after ingestion. Patients in respiratory distress should receive supplemental oxygen and be closely monitored. Local irritation from contact exposure should be cleaned with soap and water. Paresthesias have been treated with topical vitamin E oil, though this symptom is generally self-limited and resolves within 24 hours.

Patients who develop seizures should be treated with benzodiazepines. Individuals requiring endotracheal intubation should receive benzodiazepines or other GABA-receptor agonists for sedation. Continuous electroencephalography must be considered if anticipating persistent seizures. Further, benzodiazepines may also be used to treat patients who present with tremors after pyrethroid exposure. Noting the time since ingestion is critical in possible pyrethroid poisoning cases. Activated charcoal may be considered if the patient presents within an hour of ingestion. However, this measure is contraindicated if the patient is vomiting or exhibiting mental status changes, increasing the risk of charcoal aspiration. Gastric lavage and bowel irrigation are not recommended. Atropine may be considered for excessive salivation or pulmonary edema but should be used cautiously, given its adverse effect profile.[16](B3)

Differential Diagnosis

Organophosphate toxicity may present with symptoms similar to those of pyrethrin and pyrethroid toxicity and should be considered in severe poisoning cases. Peripheral neuropathies should be considered when patients present with paresthesias in the absence of other toxic manifestations of exposure. Patients with altered mental status and seizures should have additional neurologic and medical assessment for other causes of their presentation, such as stroke, metabolic encephalopathy, infection, or other toxic exposures. Patients with evidence of chemical pneumonitis may have been exposed to any number of products, particularly hydrocarbons, which pose the greatest aspiration risk.

Prognosis

Patients poisoned by pyrethrins or pyrethroids have a favorable prognosis, as symptoms are generally mild and resolve with supportive care. Individuals with localized skin irritation can expect their symptoms to resolve spontaneously, typically within 24 hours. Patients with larger ingestions are more likely to develop systemic toxicity symptoms, potentially requiring hospitalization. Fatality is exceedingly rare and often associated with other toxic concomitant ingestions.

Complications

The potential complications of pyrethrin or pyrethroid toxicity include the following:

• Seizures
• Nausea
• Vomiting
• Respiratory distress
• Tremor
• Altered mental status
• Choreoathetosis
• Hyperthermia
• Skin irritation
• Hyperglycemia 

Prompt recognition and treatment are crucial to prevent significant morbidity. Clinicians should remain vigilant for symptoms and provide appropriate care to affected patients.