symptoms and pyrethroid exposure seemed likely or could not be ruled out. No evidence of irreversible peripheral or central nervous system lesions was found in any case.

Experimental Data

Neurotoxic Effects

Type I and type II pyrethroids cause different acute symptoms in rats, the animal species in which most toxicity studies of pyrethroids have been conducted (Aldridge, 1990; Vijverberg and van den Bercken, 1990). Type I pyrethroids, such as those used in the Gulf War, do not have the α-cyano moiety and cause what is called the T syndrome. The T syndrome is characterized in rats by aggressive sparring, hypersensitivity to external stimuli, whole-body tremor, and prostration. Type II pyrethroids, which contain an α-cyano group, cause the CS syndrome. The CS syndrome is characterized by burrowing behavior, profuse salivation without lacrimation, coarse tremors, clonic seizures, and sinuous writhing (choreoathetosis). Type II pyrethroids are also known to increase cardiac contractility (Forshaw and Bradbury, 1983). Some pyrethroids, such as fenproponate, cause mixed or intermediate T and CS motor syndromes (Lawrence and Casida, 1982; Wright et al., 1988). Some other pyrethroids, such as fenproparthrin, produce an intermediate TS syndrome characterized by tremors and salivation.

Acute near-lethal and lethal doses of type II pyrethroids cause axonal swelling and demyelination in the sciatic nerve of the rat (FAO/WHO, 1980; Parker et al., 1985). Near-lethal doses of both type I and II pyrethroids have also been reported to cause sparse axonopathy of rat sciatic and posterior nerves (Aldridge, 1980, 1990; Vijverberg and van den Bercken, 1990).

Chronic neurotoxicity has been reported after pyrethroid exposure in some animal experiments, but the toxicity was usually either low or absent. Little or no chronic neurobehavioral or neurohistologic toxicity has been reported after administration of pyrethrins and pyrethroids, including permethrin (Aldridge, 1990; Bainova et al., 1986; Extoxnet, 1994; Thomson, 1985; Vijverberg and van den Bercken, 1990). Axonal swelling and myelin degeneration have been reported only after repeated or high doses of permethrin, cypermethrin, or fenvalerate (Extoxnet, 1994; FAO/WHO, 1980; Rose and Dewar, 1983). Increased brain concentrations of β-glucuronidase, β-galactosidase, and alkaline phosphatase have also been seen (Dewar, 1981; Dewar and Moffett, 1979).

Carcinogenicity

Chronic application of most pyrethroids tested, including permethrin, rarely and inconsistently caused cancer (DuPont de Nemours Corp., 1989; Extoxnet, 1994; Hallenbeck and Cunningham-Burns, 1985; Ray, 1991; US EPA, 1988, 1989; Waters et al., 1982). One exception is cypermethrin, which was reported to cause benign lung tumors in female mice (US EPA, 1989). Shukla and colleagues (2001) demonstrated that deltamethrin has tumor initiating, but not tumor promoting, activity for skin tumorigenesis in mice.

Mutagenicity and Genotoxicity

One type II pyrethroid, cypermethrin, was tested and found to have no mutagenic or genotoxic effects (FAO/WHO, 1980; Pluijmen et al., 1984; Waters et al., 1982). It was reported, however, to increase polychromatic red cells with micronuclei in bone marrow in



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