Pyrethrin toxicity

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Pyrethrins are a common toxin affecting cats, with mortality rates following intoxication, of between 5 and 35%[1]. The majority of poisonings occur due to administration of canine products (Linnett, 2008).

They are naturally occurring compounds derived from a combination of insecticidal esters (pyrethrins, cinerins, and jasmolins) that are isolated from the flowers of Tanacetum (Chrysanthemum) cinerariaefolium and related species. Their chemical derivatives, known as synthetic pyrethroids (SPs) were developed to improve stability and spectrum of activity as a pesticide[2].

Initially used on production animals from the early 1970s, their use has since gained acceptance in small animal products, and spot-on insecticides containing pyrethrins are a common treatment for fleas and flea allergy dermatitis. A wide range of products is available, many of which can be purchased without veterinary advice.

Permethrin contains various cis-trans ratios ranging from 40:60 to 25:75. The insecticidal effect and mammalian toxicity are related to the cis isomer content. Permethrin is a very effective insecticide with low toxicity to most mammals, and has a wide safety margin when used appropriately. It is a fat-soluble compound that is subject to rapid metabolism and excretion after absorption (oral, dermal or via the lungs). Permethrin is metabolised by ester hydrolysis in the plasma and liver, followed by hydroxylation, and glucuronide and sulfate conjugation. These products are then almost completely eliminated from the body in urine within 12 days. Enterohepatic circulation does not readily occur. Synergists (e.g. piperonyl butoxide) are often combined with pyrethrin and pyrethroid insecticides to delay their metabolism, increasing their toxicity to insects and, potentially, to mammals.

Permethrin acts as a neuro-intoxicant by interfering with the axonal sodium gate. It decreases sodium movement through cell membranes, thus suppressing potassium conduction, which inactivates the action potential, resulting in repetitive nerve firing because depolarisation does not occur. These actions on the presynaptic nerve endings lead to adverse clinical signs seen in permethrin toxicosis. The development and severity of clinical signs is proportional to the concentration of the chemical in nervous tissue. Onset of clinical signs can be within hours of exposure, but may be delayed up to 24 hrs or longer[3].

While SPs are relatively non-toxic in most mammals, cats are noted for their inability to metabolise and biotransform certain compounds and as a species are very sensitive to adverse reactions to this drug[4]. The specific reason for increased sensitivity of cats to permethrin is probably complex, but thought to be associated with a deficiency in glucuronidase, which is necessary for permethrin metabolism via glucuronidation. Further, the hydrolytic enzymes that degrade pyrethroid esters have a slow rate of hydrolysis in cats, compared with other species, thus increasing their susceptibility[5].

Products containing permethrins, such as spot-ons, flea sprays, collars and flea shampoos, are generally intended for exclusive use in either dogs or cats and toxicity or adverse reactions can occur when label instructions are not followed. A number of preparations contain 45-65% permethrin and are intended for use in dogs only, and cats may be adversely affected after oral ingestion, topical application of concentrated products, off-label usage, or by grooming dogs that have been treated.

Clinical signs

Signs of permethrn toxicity often occur within hours of intoxication and can range from mild to severe. Minor signs such as ear twitching, restlessness and ptyalism are sometimes reported, as well as repeated contractions of cutaneous muscles (distinct to muscle fasciculation), vomiting, diarrhoea, anorexia and lethargy. In more severe cases, disorientation, confusion, hyperesthesia, ataxia, temporary blindness, head tilt, pyrexia, mydriasis, tachypnoea, cardiac arrhythmias and collapse occur[6].

There appears to be no correlation between dose of permethrin applied and the severity of clinical signs. Even small quantities of permethrins have been reported to cause serious reactions in cats[7].


Diagnosis of pyrethrin toxicosis can generally be made from a history of exposure and typical clinical signs.

Laboratory isolation of permethrin compounds in the blood is often costly and usually unwarranted.

Differential diagnoses to consider include other causes of seizures, such as lead toxicity, encephalitis, idiopathic epilepsy, hypoglycaemia, hepatic encephalopathy, strychnine toxicity[8].


Treatment of cats affected by permethrin toxicity involves stabilisation, dermal decontamination, tremor and seizure control and supportive care. Although tremors and seizures can be treated using similar methods (diazepam and propofol), seizures related to permethrin toxicity are generally refractory to diazepam in the long term. Diazepam is generally a good initial choice (given as a constant rate infusion IV), and may be beneficial when used as a part of a combination, especially with low-dose propofol administration.

Intravenous crystalloids are indicated for maintenance of intravascular fluid volume and hydration, and although permethrin appears to have no direct effect on the liver or kidneys, crystalloid therapy protects the kidneys from myoglobulin breakdown products that may be produced during tremors. Bladder care is important, given that cats affected by permethrin toxins generally have a lower-motor-neuron bladder because of the anticholinesterase activity of the permethrin toxin

Atropine is not an antidote for permethrin toxicity. A test dose of atropine (0.01-0.02 mg/kg IV) can help to distinguish organophosphate and carbamate toxicity from pyrethrin toxicosis, with a low-dose of atropine reducing/reversing the cholinergic signs (hypersalivation, bradycardia, miosis) induced by organophosphate or carbamate overdose. Low doses of atropine administered eith IM or SQ, however, can be used to control hypersalivation associated with pyrethrin exposure, but will not control nicotinic signs, tremors, seizures and ataxia. Atropine also causes tachycardia, which can be detrimental.

Gastric decontamination using emetics and activated charcoal has not been shown to decrease treatment time and is probably not indicated.

There have been no reports of long-term effects after recovery, including trauma, hypoxia or prolonged hyperthermia during seizure activity. Certain situations lead to a worse prognosis despite aggresive therapy; for example, prolonged uncontrolled seizures can cause cerebral oedema, irreversible brain damage, and traumatic damage and breakdown of muscle tissue can lead to myoglobinuria-induced nephropathy.

Misuse of permethrin spot-on products on cats can lead to severe morbidity and mortality; however, with prompt, effective treatment the prognosis is generally good.

Recommendations for management of feline permethrin toxicity[9]

1. Seizure control

  1. Diazepam: 0.25 - 0.5 mg/kg IV, repeated as needed every 3-5 min
  2. Midazolam: 0.3 mg/kg IV/IM, repeated as needed every 3-5 min. If ongoing seizures after benzodiazepine bolus x 2, then consider:
  3. Propofol: 4-6 mg/kg slow IV as a bolus, then 0.05 - 0.3 mg/kg per min IV as constant rate infusion
  4. Alfaxan: 2-3 mg/kg slow IV bolus
  5. Phenobarbital: 2-4 mg/kg slow IV, diluted 1:10 with 0.9% NaCl. Repeat as needed every 2 hrs. Total dose < 20 mg/kg/day

2. Muscle fasciculation control

  1. Methocarbamol: 55-200 mg/kg IV/PO tid, up to 330 mg/kg/day
  2. Midazolam: 0.002-0.005 mg/kg per min IV as constant rate infusion
  3. Propofol: 0.05-0.3 mg/kg/min as constant rate infusion

3. Ensure patent airway - swab.suction pharynx if ptyalism. Oxygen supplementation if required

4. Skin decontamination - warm nath with mild detergent, towel, warm dry

5. Temperature monitoring - maintain at 38.0 - 39.00C

6. IV crystalloids - aim for 1.5 x maintenance. Monitor packed cell volume / total plasma protein, electrolytes, urine SG when available

7. Ocular lubrication - every 4 hours, e.g. lacrilube

8. Bladder expression - check every 6-8 hrs

9. Darkened environment - avoid sensory stimulation


  1. Sutton, NM, Bates, N & Campbell, A (2007) Clinical effects and outcome of feline permethrin spot-on poisonings reported to the Veterinary Poisons Information Service (VPIS), London. JFMS 9:335-339
  2. Bates, N (2000) Pyrethrins and pyrethroids. In Campbell, A Chapman, M (Eds) Handbook of poisoning in dogs and cats. Blackwell Science, London. pp:42-45
  3. Dymond, NL & Swift, IM (2008) Permethrin toxicity in cats: a retrospective study of 20 cases. AVJ 86(6):219-222
  4. Anadon, A, Martinez-Larranaga, MR & Martinez, MA (2009) Use and abuse of pyrethrins and synthetic pyrethroids in veterinary medicine. Vet J' 182:7-20
  5. Malik, R et al (2010) Permethrin spot-on intoxication in cats: Literature review and survey of veterinary practitioners in Australia. JFMS 12:5-14
  6. Linnett, PJ (2008) Permethrin toxicosis in cats. Aust Vet J 86:32-35
  7. Richardson, JA (2000) Permethrin spot-on toxicoses in cats. J Vet Emerg Crit Care 10:103-106
  8. Boland, LA & Angles, JM (2010) Feline permethrin toxicity: retrospective study of 42 cases. JFMS 12:61-71
  9. Adapted from Protocols, ARH, Strathfield South NSW, Australia
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