Most insecticides derived from plants (eg, rotenone from Derris and pyrethrins from Chrysanthemum or Pyrethrum) have traditionally been considered safe for use on animals.
Rotenone is present in a number of plants (Derris, Lonchocarpus, Tephrosia, and Mundulea). It is used worldwide because it has broad-spectrum insecticidal, acaricidal, pesticidal, and fish-killing properties.
Its formulations include crystalline preparations (concentration, approx 95%), emulsifiable solutions (approx 50%), and dust (0.75%). Rotenone dust is used for insects, lice, and ticks on animals. Rotenone emulsions are used for eliminating unwanted fish in the management of bodies of water.
In insects, rotenone is both a contact and a systemic insecticide. Rotenone's toxicity in humans, animals, and fish is via inhibition of mitochondrial respiratory chain complex I, with cell death by apoptosis due to excess generation of free radicals. Following chronic exposure to rotenone, fatty acid synthesis is altered in the mitochondria, resulting in fatty changes in the liver and kidney. The oral LD50 of rotenone is approximately 60–135 mg/kg in rats and 350 mg/kg in mice. In rabbits, the LD50 for rotenone following IV, oral, and dermal routes are 0.35–0.65, 1.5, and 100–200 mg/kg, respectively.A no observed adverse effect level (NOAEL) of 0.4 mg/kg/d has been determined in rats and dogs.
In poisoned animals, clinical signs may include pharyngitis, nausea, vomiting, gastric pain, clonic convulsions, seizures, muscle tremors, lethargy, incontinence, and respiratory stimulation followed by respiratory depression. The cardiovascular effects include tachycardia, hypotension, and impaired myocardial contractility. In rats and dogs, experimental inhalation of rotenone dust produced onset of signs earlier than after oral ingestion. Toxicity is greater if the particles are smaller in size. Death occurs due to cardiorespiratory failure. Rotenone has the potential for reproductive toxicity and teratogenicity.
Selective toxicity of rotenone to insects and fish in comparison to mammalian species is due to greater absorption from the GI tract and formation of large quantities of highly toxic metabolites.
Diagnosis of rotenone poisoning is based on detection of rotenone residue in blood, liver, urine, feces, and vomitus.
There is no specific antidote for rotenone poisoning, so treatment is supportive.
Pyrethrins and Pyrethroids
Pyrethrins are insecticides obtained from the flowers of Chrysanthemum cinerariaefolium. Natural pyrethrins (pyrethrin I, pyrethrin II, jasmolin I, jasmolin II, cinerin I, and cinerin II) have been used as insecticides for decades. However, these compounds are very unstable in the body, so pyrethroids are preferred.
Pyrethroids are synthetic derivatives of natural pyrethrins. Type I pyrethroids, which lack an alpha-cyano substituent, include pyrethrin I, allethrin, tetramethrin, kadethrin, resmethrin, phenothrin, and permethrin. Type II pyrethroids, which contain a stabilizing alpha-cyano-3-phenoxybenzyl component, include cyfluthrin, cypermethrin, fenpropanthrin, deltamethrin, cyphenothrin, fenvalerate, and fluvalinate.
Currently, the type II pyrethroid flumethrin is commonly used against ectoparasites (ticks Ticks Ticks are obligate ectoparasites of most types of terrestrial vertebrates virtually wherever these animals are found. Ticks are large mites and thus are arachnids, members of the subclass Acari... read more , lice Overview of Lice Numerous species of lice parasitize domestic animals. Lice are largely host specific, living on one species or several closely related species. Lice are obligate ectoparasites and depend on... read more , and mites) on cattle, sheep, goats, horses, and dogs as a spray or dip and as a 1% solution pour-on treatment. Flumethrin is also used in combination with imidacloprid in collars against fleas and ticks on cats.
The toxicity of type II pyrethroids is greater than that of the type I pyrethroids. In general, the cis-isomers are usually more toxic than the trans-isomers. The oral LD50 of pyrethrin I, allethrin, tetramethrin, resmethrin, and permethrin in rats are 900, 680, 4,640, 100, and 2,000 mg/kg, respectively. The corresponding LD50 for bifenthrin, cypermethrin, deltamethrin, fenvalerate, and fluvalinate are 70, 500, 31, 450, and 1,000 mg/kg, respectively. Among pets, cats appear to be more sensitive to pyrethroid toxicity.
Following oral ingestion, pyrethrins and pyrethroids are rapidly hydrolyzed in the GI tract. Approximately 40%–60% of an orally ingested dose is absorbed. Being lipophilic compounds, pyrethroids distribute to the tissues with high lipid content such as fat and nervous tissue, in addition to liver, kidney, and milk.
Synergists (eg, piperonyl butoxide, sesamex, and piperonyl cyclonene) are added to pyrethrins and pyrethroids to increase their stability and effectiveness. This is accomplished by inhibiting mixed function oxidases, enzymes that detoxify pyrethrins and pyrethroids. Unfortunately, this also potentiates toxicity in mammals.
In dogs, cats, and large animals, the clinical signs of pyrethroid poisoning are similar for both type I and II pyrethroids. Clinical signs include salivation, vomiting, hyperexcitability, tremors, seizures, dyspnea, weakness, prostration, and death. Type II pyrethroids may also elicit signs such as choreoathetosis or salivation syndrome.
The molecular targets of the pyrethrins and pyrethroids are similar in mammals and insects. These targets include voltage-gated sodium, chloride and calcium channels, GABA-gated chloride channels, nicotinic acetylcholine receptors (nAChRs), and intracellular gap junctions. Pyrethrins and pyrethroids slow the opening and closing of the sodium channels, resulting in hyperexcitation of nerve cells. Mammals are less susceptible to pyrethroid toxicosis than insects because they have faster metabolic clearance, higher body temperatures, and at least 1,000 times less sensitive sodium channels.
Diagnosis of pyrethrin or pyrethroid poisoning is based on history of exposure, clinical signs, and determination of insecticide residue in body tissues and fluids. These insecticides do not produce characteristic pathological lesions.
There is no specific antidote for pyrethrin or pyrethroid poisoning in animals. Generally, supportive treatment is required after ingestion of a dilute pyrethrin or pyrethroid preparation. Toxicity may also be due to the solvent. Induction of emesis may be contraindicated. A slurry of activated charcoal at 2–8 g/kg may be administered, followed by a saline cathartic (magnesium or sodium sulfate [10% solution] at 0.5 mg/kg).
In the case of dermal exposure, the animal should be bathed with a mild detergent and cool water. The area should be washed gently so as not to stimulate the circulation and enhance skin absorption. Shampoos containing insecticides should not be used. Initial assessment of the animal’s respiratory and cardiovascular status is important. Further treatment involves continuing supportive care. Atropine sulfate can be used to control excess salivation or gastrointestinal hypermotility. Seizures should be controlled with either diazepam (0.2–2 mg/kg, IV, to effect) or methocarbamol (55–220 mg/kg, IV, not exceeding 200 mg/min). Phenobarbital or pentobarbital (IV, to effect) can be used if diazepam or methocarbamol are too short-acting.