Pyrethrins are naturally occurring compounds obtained from the flowers of Tanacetum cinerariaefolium (also called Chrysanthemum cinerariaefolium or Pyrethrum cinerariaefolium). Given the poor stability of pyrethrins in air, light and heat, synthetic analogues, called pyrethroids, have been produced. These latter can be administered together with synergistic compounds, such as piperonyl butoxide, in order to increase their potency.
Following the Second World War, the pyrethrin-based insecticides were replaced by the more stable and cheaper organochlorines, organophosphates and carbamate, but because of the environmental pollution and toxicity of these latter groups of compounds, there has been a return to the use of pyrethrins, with the synthesis of every more effective compounds.
There are six naturally occurring pyrethrins: pyrethrin I and II, jasmolin I and II and cinerin I and II.
The synthetic compounds are classified into first- and second-generation compounds.
- First generation: these are esters of chrysanthemic acid containing a furan ring (pyrethrin I, allethrin, tetramethrin, cadethrin, resmethrin, phenothrin, permethrin).
- Second generation: the addition of a α-cyano-3-phenoxybenzyl group increases the potency of effect against insects (cypermethrin, fenpropanthrin, deltamethrin, cyphenothrin, fenvalerate, fluvalinate).
SOURCES
Contamination of running water or still water with these substances occurs following accidental or deliberate treatment, for example for mosquito disinfestation. Dogs can be exposed to the products by drinking contaminated water.
Antiflea solutions for topical use can contain pyrethrin, allethrin, fenvalerate, resmethrin, sumithrin and permethrin; likewise there are sprays for the environment containing cyfluthrin, tetramethrin and prallethrin. These products can be water-based, alcohol-based or petroleum-based to increase their toxicity.
KINETICS OF TOXICITY
The pyrethrins and pyrethroids are lipophilic substances and are rapidly absorbed by the oral, cutaneous and inhalatory routes. They are distributed into lipid-rich tissues (adipose tissue, nervous system tissue, liver, kidney and milk).
They are rapidly hydrolysed by plasma, hepatic and intestinal esterases into less toxic metabolites. Following the action of mixed function oxidases and conjugation with glycine, glucuronic acid or sulphates, these pesticides are excreted in the urine.
MECHANISM OF ACTION
Pyrethrins and pyrethroids have a high affinity for the voltage-dependent sodium channels of nerves, causing drastic changes in the kinetics of channel opening, thereby blocking repolarisation of the cell membrane at the end of the action potential.
As far as concerns the type I pyrethroids, these changes are not accompanied by marked depolarisation and the neurones, therefore, fire repeatedly.
In contrast, the type II pyrethroids cause a greater delay in closure of the sodium channels with consequent depolarisation of the membrane in which a conduction block occurs. Furthermore, they have an inhibitory effect on the receptors for gamma-amino butyric acid (GABA), thereby causing convulsions.
TOXICITY
The LD50 values (mg/kg) for pyrethrin I and various pyrethroids in the rat are:
TYPE I
- pyrethrin I: per os → 900 mg/kg
- allethrin: per os → 680 mg/kg
- tetramethrin: per os → 4640 mg/kg
TYPE II
- cypermethrin: per os → 500 mg/kg
- fenvalerate: per os → 450 mg/kg
- deltamethrin: per os → 31 mg/kg
Pyrethrin and pyrethroids are unlikely to cause chronic effects in humans and animals, given that these species have efficient systems for degrading and detoxifying such pesticides. Cats, however, are an exception because of their lesser capacity of glucuronation of these compounds. Acute toxicity is more common following the use of type II pyrethroids when these are administered in association with synergistic compounds capable of inhibiting the mixed function oxidases and esterases of insects, but also of increasing the toxicity of pyrethroids to mammals.
CLINICAL SIGNS
The signs are relatively non-specific and include:
- depression
- hypersalivation
- muscle tremors, loss of motor co-ordination, clonic convulsions
- stiffness of the hind quarters
- mydriasis (cat)
- aggressiveness (cat)
- vomiting
- diarrhoea
- ataxia
- dyspnoea
- cyanosis
- loss of appetite
- tachycardia, possibly with fibrillation (cat)
DIFFERENTIAL DIAGNOSIS
- decompensated cardiomyopathy
- thyroid/adrenal neoplasms
- poisoning by organophosphates and carbamates: total blood cholinesterase levels are reduced following exposure to organophosphates and carbamates, but normal after exposure to pyrethrins and pyrethroids.
TREATMENT
There is no specific antidote.
It is very important to maintain the body temperature, since hypothermia increases the toxicity of these compounds.
In order to limit absorption:
- Following ingestion: induce vomiting (if the ingestion has occurred less than 2 hours previously, but NOT for petroleum-based products)
- Gastric lavage
- Apomorphine: 0.05-0.1 mg/kg s.c., i.m.
- Xylazine: 1 mg/kg s.c.
- Following contact: wash with neutral soap to remove the substance; do not use water that it too hot in order to avoid peripheral vasodilatation.
In order to enhance elimination:
- NaCl [4]0.9% or Ringer’s lactate solution for infusion
- Activated charcoal (within 3-4 hours): 2g/kg
For the treatment of convulsions:
- Diazepam: 0.2-2 mg/kg i.v.
- Pentobarbital: 4-20 mg/kg i.v.
- Methocarbamol: up to 200 mg/kg i.v. in cats
Administer electrolyte solutions to maintain hydration and preserve urinary excretion.
PROGNOSIS
In most animals pyrethrin poisoning resolves within 24-48 hours; the period can be longer for pyrethroids. Death of the animal is rare, but possible.
Suggested readings
- Bradberry SM, Cage SA, Proudfoot AT, Vale JA. Poisoning due to pyrethroids. Toxicol Rev 2005;24:93-106.
- Dymond NL, Swift IM. Permethrin toxicity in cats: a retrospective studyof 20 cases. Aust Vet J 2008;86:219-23.
- Malik R, Ward MP, Seavers A, et al. Permethrin spot-on intoxication of cats. Literature review and survey of veterinary practitioners in Australia. J Feline Med Surg 2010;12:5-14.
- Miller TA, Adams ME. Mode of action of pyrethroids. In: Insecticide Mode of Action. Academic Press 1982;3-25.
- MountME, Moller G, Cook J, et al. Clinical illness associated with a commercial tick and flea product in dogs and cats. Vet Hum Toxicol 1991;33:19-27.
- Valentine WM. Toxicology of selected pesticides, drugs, and chemicals. Pyrethrin and pyrethroid insecticides. Vet Clin North Am Small Anim Pract 1990;20:375-82.
Useful links
Pesticide database, Pyrethrin I
Pesticide Database, Pyrethrin II