Poisoning due to Pyrethroids

Abstract

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give alpha-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the alpha-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inh...

Evidências neuroquímicas e comportamentais do efeito ansiogênico da deltametrina em ratos

“…Exposure to pyrethroid insecticides can induce neurobehavioral effects in rodents and other species, including humans 7,8,9,10 . Aspects of open field behavior and catalepsy 11,12 , conditioned behavior 12,13,14 , motor activity 15,16 , anxiety 11,17 and aggressive behavior 11 .…”

Pyrethrin and pyrethroid exposures in the United States: A longitudinal analysis of incidents reported to poison centers

“…Pyrethroids alter the gating characteristics of neuronal sodium channels, delaying their closure and resulting in a lowered action potential threshold and repetitive firing [9,10]. Although the mechanism of action of pyrethrins has not been as thoroughly investigated as pyrethroids, a review concluded that pyrethrins are also considered sodium channel toxins that possess a similar toxicodynamic effect as pyrethroids [11].…”

“…Although the mechanism of action of pyrethrins has not been as thoroughly investigated as pyrethroids, a review concluded that pyrethrins are also considered sodium channel toxins that possess a similar toxicodynamic effect as pyrethroids [11]. Pyrethrins and pyrethroids have a lower degree of mammalian and human toxicity than insects because insects have increased sodium channel sensitivity, a smaller body size, and lower body temperature [9].…”

Safety of Permethrin and Pyriproxyfen in Dogs Treated With VetGuard Plus®

“…Evidence suggests that the mechanism of action differs in toxicity of type I and type II pyrethroids [22,24]. In humans, dermal exposure to permethrin can cause irritation, itching, and paresthesia, while ingestion may cause nausea, vomiting, sore throat, abdominal pain, coma, convulsions and death [25][26][27]. Studies have shown that dermal exposure of permethrin has caused irritation in rabbits, and ingestion of the product has caused transient signs in dogs, including tremors [18,28].…”