An Assessment of the Toxicological Properties of Pyrethroids and Their Neurotoxicity

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Abstract
1. Most pyrethroids can be divided into two classes on the basis of differences in the signs of toxicity (T- orCS-syndromes). Since these syndromes also correspond to particular aspects of their chemical structure and since the order of appearance of the signs of poisoning is the same in each class, it is concluded that these syndromes originate from a single primary action of the pyrethroid. 2. Pyrethroids cause morphological changes in peripheral nerves of rats when given in high doses. The production of these minor lesions are correlated with a dose of the pyrethroid that causes death in some of the treated rats. Lower doses do not cause these effects. Therefore, the morphological changes are produced as a secondary consequence of the primary action of pyrethroids and are not due to a different form of toxicity. 3. Pyrethroids have been shown to cause functional changes (behavioral) in rats shown as a deficit in performance on an inclined plane. Increases in peripheral nerves of β-glucuronidase and β-galactosidase have also been demonstrated. These increases are a late finding and are considered to be associated with repair processes. As with the morphological changes these enzyme changes are correlated with doses that cause death in some of the animals. There is no firm evidence that the behavioral changes are correlated with either the morphological or biochemcial changes. 4. Available information indicates that all the above changes described in 2 and 3 are reversible or repairable. 5. Many pyrethroids cause an effect in humans termed parasthesia. It seems probable from structure-activity relationships that parathesia, as for their systemic toxicity, is brought about by an action of pyrethroids on sodium channels of the sensory nerves. 6. Studies have been carried out on human volunteers and a guinea pig model has been developed. Subjective human experience and some experimental work indicates that the effects are reversible and result in no permanent change. 7. There is no conclusive evidence that pyrethroids have neurotoxic actions other than those originating from their primary action on sodium channels, through a dissociable interaction with macromolecular component(s). 8. Further research is recommended to extend knowledge of pyrethroids as a class rather than for individual compounds. 9. All available evidence indicates that, at doses of pyrethroids likely to be encountered in working practice, when serious poisoning does not occur, neurotoxicity due to the pyrethroids will not occur except as a reversible transient effect on the skin. This minor warning response is due to the primary action of pyrethroids on sodium channels, a reversible interaction.