Pyrethroids toxicity animals

Mechanism of action can be an important factor determining selectivity. In the extreme case, one group of organisms has a site of action that is not present in another group. Thus, most of the insecticides that are neurotoxic have very little phytotoxicity indeed, some of them (e.g., the OPs dimethoate, disyston, and demeton-5 -methyl) are good systemic insecticides. Most herbicides that act upon photosynthesis (e.g., triaz-ines and substituted ureas) have very low toxicity to animals (Table 2.7). The resistance of certain strains of insects to insecticides is due to their possessing a mutant form of the site of action, which is insensitive to the pesticide. Examples include certain strains of housefly with knockdown resistance (mutant form of Na+ channel that is insensitive to DDT and pyrethroids) and strains of several species of insects that are resistant to OPs because they have mutant forms of acetylcholinesterase. These... 

Adverse effects of fenvalerate on survival of terrestrial arthropods were observed at 0.002 to 0.015 pg whole-body topical application, O.llkg/ha aerial application, 5.4 mg/kg in the soil, 50 mg/kg in the diet, and 1.4 g/ant mound (Table 20.4). Synthetic pyrethroids are more effective in biological systems at low temperatures. The relative sensitivity of insects when compared with mammals is attributed in part to this negative temperature coefficient. Thus, warm-blooded animals are less affected than insects and other poikilotherms (Klaassen etal. 1986). Fenvalerate, for example, showed a negative correlation between temperature and toxicity to crickets (Acheta pennsylvanicus), being up to 1.9 times more toxic at 15°C than at 32°C (Harris etal. 1981). A similar case is made for honey bees (Apis mellifera) (Mayer et al. 1987) and for many species of aquatic invertebrates and fish (Mayer 1987). 

Second, meanwhile, no international guidelines have been provided for the manufacture, marketing, and distribution of household insecticides on such a level as those of agricultural chemicals, and not even manufacturing registration is required in some countries. Of course, the minimal required toxicity studies are conducted with synthetic pyrethroids for household insecticides to examine absorption, distribution, metabolism, and genotoxicity in animals. 

Blood and various organs of humans and other animals contain esterases capable of acetylsalicylic acid hydrolysis. A comparative study has shown that the liver is the most active tissue in all animal species studied except for the guinea pig, in which the kidney is more than twice as active as the liver. Human liver is least active the enzyme in guinea pig liver is the most active. The relatively low toxicity of some of the new synthetic pyrethroid insecticides appears to be related to the ability of mammals to hydrolyze their carboxyester linkages. Thus mouse liver microsomes catalyzing (+)-/runs-resin e 111ri n hydrolysis are more than 30-fold more active than insect microsomal preparations. The relative rates of hydrolysis of this substrate in enzyme preparations from various species are mouse > > milkweed bug > > cockroach > > cabbage looper > housefly. 

Mammalian toxicity levels to pyrethroid pesticides are extremely low, and chances for poisoning would be almost nonexistent unless animals ingested formulations that had not yet been mixed for application. 

Although certain pyrethroids exhibit striking neurotoxicity in laboratory animals whenadminista edby intravenous injection, and some are toxic by the oral route, systemic toxicity by inhalation and dermal absorption is low. There have been very few systemic poisonings of humans by pyrethroids. Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian Uver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney. 

The manifestations of neurologic disorder seen in laboratory animals given the more toxic pyrethroids in large doses are salivation, irritability, tremors, ataxia, choreoathetosis (writhing convulsions), fall in blood pressure, and death. Severe metabolic acidosis is characteristic. 

Fenvalerate has low toxicity in mammals due to its rapid metabolic breakdown. It acts directly on nerve axons by prolonging sodium channel opening in cell membranes. Insects exposed to fenvalerate are quickly paralyzed exposure causes quick insect knockdown. In small animals, type II pyrethroids cause salivation, chewing, burrowing, choreoathetosis, and seizures. They also cause lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. Fenvalerate is likely to act both on peripheral and central nervous system. It is also a potent inhibitor of calcineurin (protein phosphatase 2B). 

The toxic effects of some pesticide mixtures are additive, particularly when their toxic mechanisms are identical. The additive effects of the organophosphates chlorpyrifos and diazanon were demonstrated in one study. T Another study found the s-triazine herbicides atrazine and cyanazine to show additive toxic effects. Not all mixtures of similar pesticides produce additive effects, however. In one study, mixtures of five organophos-phate pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion) were shown to produce greater than additive effects when administered to laboratory animals. Another article discusses nonsimple additive effects of pyrethroid mixtures. Despite the similarities in their chemical structure, pyrethroids act on multiple sites, and mixtures of these produce different toxic effects. 10 ... 

Functionally, pyrethroids are a group of insect growth regulators that act as neurotoxins resisting the development of insect larvae. They are especially effective against insects that are destructive in the adult stage. They are considered non-toxic to animals and humans. Pyrethrum consists of dried flower heads of chrysanthemum. The plant is a native of Dalmatia (Yugoslavia-Balkans) and is now widely cultivated in Kenya, East Central Africa, Japan, Brazil, Ecuador, and India. 

Our preliminary results with fish brain preparations suggest that ion flux techniques may be valuable in studies of target site differences between species. We have demonstrated veratridine-stimulated, tetrodotoxin-sensitive sodium uptake in a vesicular preparation from fish brain, thus confirming the presence of functional sodium channels in this preparation. Our results with , -DDT in this system also agree well with the action of DDT analogs and pyrethroids in mouse brain assays. Further studies wih both preparations should allow the exploration of target site differences between mammals and fish that have been inferred from whole animal toxicity studies. 

With the above discussion in mind, it may be assumed that chiral xenobi-otics are likely to be present in various foodstuffs, as human food comprises the meat of fish, birds and terrestrial animals, and of course vegetables. Many chiral pesticides are used to control insects in vegetables and cereals, and hence the presence of these pesticides in the food products is to be expected. Only a few reports are available dealing the presence of chiral pesticides in various foodstuffs. The cholinesterase inhibition activity of chiral organophosphorous pesticides, as well as that of toxic organophosphorous pesticides nerve gases, are enantioselective in nature. Scientists at the Microbiological and Chemical Exposure Assessment Research Division of NERL in Cincinnati, USA, have found the chiral insecticide permethrin, a pyrethroid insecticide, in spinach. Similarly, malathion has been observed in blackberry extract [146]. 

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