Pyrethrins neurotoxicity

Clark JM (1995) Effects and mechanisms of action of pyrethrins and pyrethroid insecticides. In Chang LW, Dyer RS (eds) Handbook of neurotoxicity. Marcel Dekker, New York, NY, pp 511-546... 

Pyrethrins are absorbed orally and by inhalation, but only slightly across intact skin. They are very effectively hydrolyzed to inert products by mammalian liver enzymes. This rapid degradation combined with relatively poor bioavailabiUty probably accounts in large part for their relatively low mammalian toxicity. Dogs fed extraordinary doses exhibit tremor, ataxia, labored breathing, and salivation. Similar neurotoxicity rarely, if ever, has been observed in humans, even in individuals who have used pyrethrins for body lice control (extensive contact) or pyrethrum as an anthelmintic (ingestion). 

Pyrethroids. Pyrethroids, such as natural pyrethrins and synthetic analogs, allethrin, permethrin, and others, are well known for their neurotoxicity (48-59). However, as a major class of insecticide, they have a remarkable safety margin for mammals, principally because of the rapid metabolic degradation of pyrethroids in mammalian species (48-50). The acute toxicity of pyrethroids involves two distinct syndromes in rats and mice (49-51). The first one, T syndrome or tremor (Type I), is characterized by a rapid onset of tremor, initially in the limbs and gradually extending over the whole body. Death is associated with clonic seizures. The second... 

Crotamiton is available as a 10% cream for the treatment of scabies, although it is less effective than pyrethrins or permethrin (81,82). Because crotamiton may need to be applied a second time for successful treatment of scabies but the pyrethrins or permethrin require a single application, poor patient compliance with crotamiton may reduce its effectiveness. The advantage of crotamiton over lindane comes from the fact that lindane has potential neurotoxicity if absorbed especially in infants and children, whereas crotamiton has less systemic neurotoxicity. The most common side effect reported for crotamiton is skin irritation. 

Some published data are difficult to interpret. For example, 26 men were exposed in tanks and holds of two merchant vessels being painted (solvents) and sprayed with mala-thion 20% and pyrethrin 1.5%, with piperonyl butoxide in toluene. They showed losses of concentration, unawareness of danger and unconsciousness at toluene levels estimated as 10,000 to 12,000 ppm and up to 30,000 ppm below waist level. Additive effects of the neurotoxic insecticides were not discussed. 

In the last century, the development of organophosphorus, carbamate, and organochloride insecticides was followed by synthetic pyrethroids. As a result, pyrethroids are now used frequently in the domestic milieu. Pyrethroid insecticides are synthetically derived from the molecular structure or sharing the same mechanism of action of natural pyrethrins that have broader spectmm of activity, more stability, and residual activity (persists longer than that of natural pyrethrins) and include the following allethrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, flumethrin, fluvalinate, tau-fluvalinate, and permethrin (see structure in Fig. 137.2). They are lipophilic compounds and generally of low acute oral toxicity to mammals but are very toxic to aquatic organisms. When synthetic pyrethroids are administered to mammals parenterally, the synthetic pyrethroids are neurotoxic. 

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