Neurotoxicological Effects and the Mode of Action of Pyrethroid Insecticides

Abstract

Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system.Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhanced neurotransmitter release, eventually followed by block of excitation, result from a prolongation of the sodium current during membrane excitation. This effect is caused by a stereoselective and structure-related interaction with voltage-dependent sodium channels, the primary target site of the pyrethroids.Near-lethal doses of pyrethroids cause sparse axonal damage that is reversed in surviving animals. After prolonged exposure to lower doses of pyrethroids axonal damage is not observed.Occupational exposure to pyrethroids frequently leads to paresthesia and respiratory irritation, which are probably due to repetitive firing of sensory nerve endings. Massive exposure may lead to severe human poisoning symptoms, which are generally treated well by symptomatic and supportive measures.

Residential pesticide use during pregnancy among a cohort of urban minority women.

“…In addition to being an acetylcholinesterase inhibitor, propoxur has recently been shown to be a tumor promoter (39). The pyrethroids are transient neurotoxins and skin and respiratory irritants (40,41). The organochlorines DDT and chlordane are neurotoxins and have been shown to be carcinogens and endrocrine disruptors in experimental bioassays (42,43).…”

Differential Behavioral Responses of <I>Anopheles gambiae</I> (Diptera: Culicidae) Modulate Mortality Caused by Pyrethroid-Treated Bednets

“…Pyrethroids do not accumulate in the body and their excretion is rather rapid, even after repeated administrations: typically, 90% of the administered dose is excreted in urine and faeces within a week after treatment (IPCS, 1999;Aldridge, 1990;Vijverberg & van den Bercken., 1990). Studies carried out on human volunteers have shown that, after oral administration of cypermethrin doses of 0.25, 0.5, 1 and 1.5 mg/subject, about 75% of the dose is excreted in 24 hours; the rate of excretion is similar for all dosages.…”

Efecto de Dosis Única Intraperitoneal de Cipermetrina en la Corteza Cerebral Somatosensorial de Ratones CF- 1

“…Por otro lado, el estrés oxidativo a nivel del sistema nervioso, producido por cipermetrina, altera el funcionamiento normal de los receptores ionotrópicos en las membranas neuronales (Eells & Dubocovich, 1988), inhibe la actividad de la acetilcolinesterasa (Rao & Rao, 1995), retarda el cierre de los canales de sodio voltaje-dependiente (Aldridge, 1990;Vijverberg & van den Bercken, 1990) aumenta la liberación de acetilcolina de las terminaciones sinápticas, prolongando la depolarización por liberación de neurotransmisores que excitarían a neuronas vecinas (Eells et al, 1992). Estos acontecimientos producen un aumento aberrante en las concentraciones intracelulares de calcio, como un mecanismo citotóxico que puede causar su muerte mediada por la vía de la apoptosis (Jordán, 2003); y con la consecuente alteración de su citoarquitectura con una interrupción y reducción significativa de la proteína MAP2 (Abdel-Rahman et al, 2001), mostrando una alteración morfológica y, por ende, neurodegeneración (eosinofilia en soma y dendritas).…”