ToxCard: Pyrethrin and Pyrethroid Toxicity

Authors: Grant Gerstner, DO (EM Resident Physician, San Antonio, TX); Joseph Maddry, MD (EM Attending Physician and Toxicologist, San Antonio, TX) // Anthony Spadaro MD, (Fellow in Medical Toxicology, Rutgers NJMS); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case:

A 2-year-old female arrives to the emergency department via EMS in respiratory distress. She was playing outside unattended for a moment. She was found in the garden shed crying with brown dust covering her skin and in her oropharynx. The patient had an acute onset of fever, wheezing, tremors, and vomiting. En route, EMS administered albuterol, fluids, and ondansetron. Vitals upon arrival are: heart rate 150 beats per minute, blood pressure 102/65 mmHg, respiratory rate 55 breaths per minute, 98% SPO2 on room air, and temperature of 101.4 F. She is tremulous. Secretions are normal. Pupils are 3 mm and reactive to light. She is protecting her airway. Lungs have diffuse wheezes bilaterally and her abdomen is nontender. Her skin examination is notable for flushed and dry skin. The patient’s father arrives shortly after and reports recently treated his lawn with insecticide granules. He shows you a picture of the packaging which shows Zeta-Cypermethrin and Bifenthrin as the active ingredients.

Questions:

1. What are pyrethrins and pyrethroids?
2. How does pyrethrin/pyrethroid toxicity present?
3. What is the management of acute pyrethrin/pyrethroid toxicity?

Background:

Pyrethrins (Figure 1) and pyrethroids (Figure 2) are synthetic ester compounds, used in insecticides, and are derived from naturally occurring substances of plants such as the Dalmatian Pellitory flower (Chrysanthemum cinerariaefolium). These insecticides act as potent arthropod neurotoxins.¹ Their mechanisms of action include: agonism at voltage-gated sodium channels, prolonging neural depolarization and preventing return to resting action potential.² At high concentrations in humans, pyrethrins and pyrethroids also act as GABA receptor antagonists which may cause central nervous system excitatory effects such as hypersalivation and choreoathetosis.³ Insects have voltage-gated sodium channels that bind with higher affinity to pyrethrins and pyrethroids than mammals. The toxicity of such is approximately 2,250 times greater in arthropods than mammals.⁴ Mammals also possess gastrointestinal enzymes that rapidly hydrolyze pyrethrins, making small exposures benign.⁵ This makes pyrethrins and pyrethroids generally safe to use in yards with human and pet foot traffic. However, large concentrations of skin, respiratory, or gastrointestinal exposures may cause toxicity.⁴

According to the 2023 National Poison Data System’s Annual Report, there were 3,663 pyrethrin cases and 18,412 pyrethroid cases.⁶ Of which, 10,450 were pediatric cases. Approximately 87% of cases were unintentional exposures. 3,735 of these cases were treated at a healthcare facility. 41 had major adverse outcomes and there were no immediate deaths.⁶ Exposures to these chemicals commonly occur in homes with outdoor gardens and in agricultural settings.⁷

Clinical Presentation and Diagnosis:^8-10

Pyrethrin and pyrethroid overdoses present similarly and may present concurrently as these active ingredients are often combined in pesticide treatments. Additionally, the excipients in insecticides may cause irritation of the skin, GI tract, or respiratory system. Toxicity ranges based on route of ingestion as well as concentration. Due to the broad range of presenting symptoms, diagnosis of an undifferentiated patient may prove difficult. History will likely reveal the diagnosis.  However, with variable presenting symptoms, a differential diagnosis of potential mimics must be considered such as: serotonin syndrome, neuroleptic malignant syndrome, anticholinergic toxicity, polysubstance abuse, meningitis, encephalitis, seasonal allergies, pneumonitis, asthma exacerbation, anaphylaxis, thyrotoxicosis.

Presenting symptoms of toxicity may include:

• CNS
  • Agitation
  • Fever
  • Headache
  • Tremor
  • Seizure (rarely, in large exposures)
• Ocular
  • Lacrimation
  • Conjunctivitis
• Cardiovascular
  • Tachycardia
  • Arrhythmia
• Pulmonary
  • Rhinitis
  • Mucosa edema
  • Cough
  • Dyspnea
  • Wheezing
• Gastrointestinal
  • Nausea and Vomiting
• Dermatological
  • Flushing
  • Rash (urticaria or contact dermatitis)

Management:

Management of acute pyrethrin/pyrethroid toxicity depends on the exposed organ system and concentration ingested. A primary survey should be performed immediately to determine the stability of the patient and life-sustaining interventions required. Healthcare workers should don gowns, gloves, and masks  before providing adequate decontamination once the patient is determined stable. Treatment is primarily supportive, but some presentations may require more aggressive interventions. Early consultation with your local poison control center (1-800-222-1222) or a toxicologist at your hospital will provide recommendations for management and prognosis.

Diagnostics

Diagnostic tests, depending on the clinical scenario and concern for self-harm or alternative causes of the patient’s presentation, to consider include: CBC (cell dyscrasias), CMP (electrolyte derangements, hepatic dysfunction, renal dysfunction), TSH (thyroid storm), UA (infection, proteinuria), UDS (concomitant ingestion), ETOH (intoxication), acetaminophen (coingestion), aspirin (coingestion), EKG (toxidrome, arrhythmias), Chest XR (respiratory symptoms), head CT (if altered).

Nervous system

The nervous system is affected at high concentrations of exposure.⁴ Agitation and muscle fasciculations are the most common neurotoxic symptoms. Toxidromes from the two types of pyrethrins may manifest differently, and these effects were first reported in pharmacokinetic studies from rats in the 1970s. Type I pyrethroids were more likely to cause tremors and therefore coined “T syndrome.” Type II pyrethroids were associated with choreoathetosis and salivation, labeled “CS syndrome.” However, these syndromes are not mutually exclusive to either structure.³ Severe complications include seizures. The Environmental Protection Agency began regulating the use and concentrations of pyrethrins and pyrethroids with the Insecticide, Fungicide, and Rodenticide Act of 1972. This led to lower concentrations of pyrethrins and pyrethroids in insecticides, so seizures are unlikely to occur unless a patient is exposed to extraordinary levels.¹¹ In such case, neurotoxic symptoms may be treated with GABAergic drugs such as benzodiazepines.¹² Refractory status epilepticus may require standard treatment of status epilepticus with airway protection, antiepileptics, and continuous sedation.^13,14

Cutaneous

Cutaneous exposures may present with an insidious onset of symptoms due to slow, prolonged absorption. The initial step in treatment is decontamination to prevent further exposure to the patient and healthcare workers. Patients with pyrethrin and pyrethroid cutaneous exposure should have clothing removed and their skin washed with soap and water.¹⁵ Those with cutaneous irritation may require further washing and application of topical emollients such as steroids, calamine lotion, and/or vitamin E oil.³ Vitamin E oil may also be used for subsequent paresthesias, which should subside within 12-24 hours.^3,16

Respiratory

Inhalation of pyrethrins/pyrethroids may cause pneumonitis or respiratory distress. ^17,18 Treatment is mostly supportive. Inhaled beta-agonists may provide relief for bronchospasm. Anticholinergics such as low-dose sublingual 1% atropine solution  (1 to 2 drops every 2 to 4 hours) may be considered if copious secretions impede airway management.¹² In severe cases, securing a definitive airway takes precedence.

Gastrointestinal

Oral ingestion of pyrethrins and pyrethroids pose the greatest risk of toxicity due to concentration availability. At low levels, humans possess gastrointestinal carboxylesterases that rapidly metabolize pyrethrins and pyrethroids. Higher concentrations saturate these enzymes leading to increased insecticide absorption.⁵ Food intake may increase absorption, so the patient should be kept NPO. In the setting of large-volume consumption, activated charcoal may be considered (50 – 100g in adults) may be considered if the patient presents shortly after ingestion with low risk of aspiration. Gastric lavage is not typically recommended due to the risk of aspiration pneumonitis from insecticide solvents.³

Multisystem 

Rare cases of multiorgan dysfunction (anaphylaxis) have been reported.¹⁹ In such cases, remove the inciting agent and provide life support. Rely on standard management of anaphylaxis. Use IM or IV anaphylaxis dosing of epinephrine, antihistamines, steroids, and inhaled beta-agonists as warranted.

Case Follow-up:

The patient was decontaminated with soap and water while she received  intravenous steroids and continuous nebulized albuterol treatments. The patient was made an NPO status and given intravenous crystalloids. She was admitted for observation and did not experience any further symptoms. 12 hours after ingestion, her vitals were stable, and she was discharged home.

Clinical Pearls:

• Pyrethrins and Pyrethroids are approximately 2,250 times more neurotoxic to insects than humans; exposures are generally tolerated at low concentrations
• Mild cases can be treated with supportive therapy
• Complications are most severe after oral ingestion due to the concentration absorbed
• Severe cases are due to neuroexcitation and should be treated with neuro inhibitory drugs such as benzodiazepines 
• Address ABCs for stability and decontaminate when safe
• Activated charcoal may be indicated in large oral ingestions with short times to presentation

References:

1. Hodoșan C, Gîrd CE, Ghica MV, et al. Pyrethrins and Pyrethroids: A Comprehensive Review of Natural Occurring Compounds and Their Synthetic Derivatives. Plants (Basel). Nov 29 2023;12(23)doi:10.3390/plants12234022
2. Dong K. Insect sodium channels and insecticide resistance. Invert Neurosci. Mar 2007;7(1):17-30. doi:10.1007/s10158-006-0036-9
3. Bradberry SM, Cage SA, Proudfoot AT, Vale JA. Poisoning due to pyrethroids. Toxicol Rev. 2005;24(2):93-106. doi:10.2165/00139709-200524020-00003
4. Chrustek A, Hołyńska-Iwan I, Dziembowska I, et al. Current Research on the Safety of Pyrethroids Used as Insecticides. Medicina (Kaunas). Aug 28 2018;54(4)doi:10.3390/medicina54040061
5. Kaneko H. Pyrethroids: mammalian metabolism and toxicity. J Agric Food Chem. Apr 13 2011;59(7):2786-91. doi:10.1021/jf102567z
6. Gummin DD, B. MJ, C. BM, et al. 2023 Annual Report of the National Poison Data System® (NPDS) from America’s Poison Centers®: 41st Annual Report. Clinical Toxicology. 2024/12/01 2024;62(12):793-1027. doi:10.1080/15563650.2024.2412423
7. Malangu N, and Ogunbanjo GA. A profile of acute poisoning at selected hospitals in South Africa. Southern African Journal of Epidemiology and Infection. 2009/01/01 2009;24(2):14-16. doi:10.1080/10158782.2009.11441343
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11. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Facilities. Updated 31 January 2025. Accessed 24 April 2025, https://www.epa.gov/enforcement/federal-insecticide-fungicide-and-rodenticide-act-fifra-and-federal-facilities
12. Scheepers LD, Freercks R, Merwe Evd. Acute cypermethrin and other pyrethroid poisoning – An organophosphate-like poisoning: A case report and review. Toxicology Reports. 2023/12/01/ 2023;11:107-110. doi:https://doi.org/10.1016/j.toxrep.2023.06.013
13. Rangaraju, S., & Webb, A. (2013). Status epilepticus following inhalational exposure to Bifenthrin, a Type II pyrethroid. Clinical Toxicology, 51(9), 906. https://doi.org/10.3109/15563650.2013.824581
14. Helman A. EM Cases: Emergency Management of Status Epilepticus. Accessed 14 April 2025, https://www.emdocs.net/em-cases-emergency-management-of-status-epilepticus/
15. Ramchandra AM, Chacko B, Victor PJ. Pyrethroid Poisoning. Indian J Crit Care Med. Dec 2019;23(Suppl 4):S267-s271. doi:10.5005/jp-journals-10071-23304
16. Tucker SB, Flannigan SA, Ross CE. Inhibition of cutaneous paresthesia resulting from synthetic pyrethroid exposure. Int J Dermatol. 1984 Dec;23(10):686-9. doi: 10.1111/j.1365-4362.1984.tb01236.x. PMID: 6526564.
17. Tewari A. Respiratory system: Highly exposed yet under-reported organ in pyrethrin and pyrethroid toxicity. Toxicol Ind Health. Nov 2024;40(11):622-635. doi:10.1177/07482337241273808
18. Vorselaars ADM, van den Berg PM, Drent M. Severe pulmonary toxicity associated with inhalation of pyrethroid-based domestic insecticides (Bop/Sapolio): a case series and literature review. Curr Opin Pulm Med. Jul 1 2021;27(4):271-277. doi:10.1097/mcp.0000000000000779
19. Vanden Driessche KSJ, Sow A, Van Gompel A, Vandeurzen K. Anaphylaxis in an Airplane After Insecticide Spraying. Journal of Travel Medicine. 2010;17(6):427-429. doi:10.1111/j.1708-8305.2010.00455.x