Pyrethrins and synthetic pyrethroids

Pyrethrins and synthetic pyrethroids are among the safest of the topically applied ectoparasiticides, because of their selective toxicity for insects (mam-malian-to-insect toxic dose ratio is greater than 1000, compared with 33 for organophosphates and 16 for carbamate insecticides). In contrast to the very wide margin of safety for mammalian species, pyrethroids are toxic to fish. The synergistic action of pyrethrins and piperonyl butoxide (in combination preparations) is due to the inhibition by piperonyl butoxide of the microsomal enzyme system of some arthropods. Preparations of synthetic pyrethroids (permethrin, cypermethrin) often contain a mixture of drug isomers in varying proportions. 

PRO (Fig. 9.1) is an economically important, widely used synergist of natural pyrethrins and synthetic pyrethroid insecticides with ait excellent record of human health anti safety over the 40 years or so since its introduction. Most pynelhnoids have a good record of environmental and human safety in the absence of PBO. a much greater tonnage of more potent, synthetic insecticides would be required to achieve the same levels of insect control, with potential adverse consequences for the natural environment. 

Anadon A, Martmez-Larranaga MR, Martinez M (2009) Use and abuse of pyrethrins and synthetic pyrethroids in veterinary medicine. Vet J 182 7... 

Pyrethrins and synthetic pyrethroids have antiparasitic activities, but in general, pyrethroids have a broader spectrum than pyrethrins. The widespread and uncontrolled use of pyrethrins and pyrethroids might lead to environmental damage, insecticide and acaricide resistance in infected population, and a possible exacerbation of insect and arcari-bome population. The development of insect resistance can appear as a result of increased potency and especially increased persistence in the environment [33]. 

It is estimated that 45-50 billion mosquito coils are used annually by approximately 2 billion people worldwide, mainly in Southeast Asia, but with a growing market in South America and Africa. Mosquito coils were traditionally made with finely groundpyrethrum daisy Chtysanthemum cinerariaefolium) flowers mixed with coconut husks or sawdust. Synthetic pyrethroids, based on the molecular structure of the pyrethrins contained in the pyrethrum daisy, have outstripped natural pyrethrins for use in household pesticides because they are far more photo stable, although both chemical groups possess rapid insecticidal and repellent action. Nonetheless, 17,000 tons of natural pyrethrum are produced in Kenya, Tanzania, Rwanda, and Australia annually to supply the household insecticide market. There is ample evidence that mosquito coils made from both natural pyrethrins and synthetic pyrethroids effectively repel mosquitoes. ... 

Natural and synthetic pyrethroid insecticides have been reviewed,100 and the synthesis of pyrethrins related to bioresmethrin has appeared (cf. Vol. 5, p. 16) 101 the fluorinated pyrethroid fluorethrin has been synthesized and is superior to bromethrin and resmethrin as an insecticide 102 the metabolism of cis- and trans-resmethrin in rats has been reported.103 Further papers report the synthesis104 and... 

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... 

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

The compounds featured in Table 1.1 are considered briefly here. Pyrethrins are lipophilic esters that occur in Chrysanthemum spp. Extracts of flower heads of Chrysanthemum spp. contain six different pyrethrins and have been used for insect control (Chapter 12). Pyrethrins act upon sodium channels in a manner similar to p,p -DDT. The highly successful synthetic pyrethroid insecticides were modeled on natural pyrethrins. 

These synthetic pyrethroids mimic natural counterparts, of which the most important is pyrethrin 1 (10.265). Unfortunately, the natural products lack the photochemical and hydrolytic stability necessary for use as wool insect-resist agents. The synthetic products have the required stability, yet retain the low mammalian toxicity and low environmental retention of the natural products. Permethrin, however, is toxic to aquatic life and is therefore subject to increasingly severe discharge limits. There is some evidence that permethrin is less effective against larvae of a certain beetle. This can be compensated for by using a combination of permethrin with the hexahydropyrimidine derivative 10.264. Some possible alternative pyrethroids have been mentioned [517] as development products (10.266-10.269). 

As described in the section on Cross-resistance in this chapter, it was found that some insect species showed extremely low cross-resistance to three ingredients, pyrethrins as well as d-allethrin and prallethrin, although they developed resistance to photostable synthetic pyrethroids. The latter two compounds of d-allethrin and prallethrin have quite similar chemical structures and the same configuration as cinerin I (an ingredient of pyrethrins). It is considered preferable to develop pyrethroids retaining the characteristics of natural pyrethrins and household insecticides containing them in the perspectives of safety and low cross-resistance. 

Pyrethrum became the main source of household insecticides in sprays in the USA (1919) and mosquito coils (1895) as well as oil-based preparations (1924) in Japan. Thereafter, the insecticidal ingredients shifted from pyrethrins to various synthetic pyrethroids, but mosquito coils have been used worldwide for more than 110 years without changing in shape. 

After World War II, the production of pyrethrum in Japan fell markedly and declined to only 1,000 tons in terms of dried flowers in 1965. At present, pyrethrum is not cultivated in Japan and the main producers are Kenya, Tanzania, Tasmania, and China, with worldwide production in 2010 amounting to around 10,000 tons of dried flowers. Dried flowers are extracted and purified at pyrethrum-extracting factories on the spot, producing 25-50% pyrethrin extracts. While pyrethrum extracts have been replaced with various synthetic pyrethroids, they are still used in houses, food factories, gardens, and organic farms, all of which emphasize the importance of safety. Katsuda [1] reported that natural pyrethrins showed a low development of resistance by flies and mosquitoes compared with many synthetic pyrethroids, against which a high development of cross-resistance was observed. 

Although pyrethroids consist of natural pyrethrins and many photostable synthetic pyrethroids, they must be discriminated when discussing cross-resistance. 

Cross-resistance to pyrethroids for outdoor use has developed markedly in M. domestica, mosquitoes, cockroaches, and so on however, it has also been found that natural pyrethrins as well as d-allethrin and prallethrin (ETOC ), which have very similar chemical structures and the same configuration as natural pyrethrins, show an extremely low degree of cross-resistance development by these highly-resis-tant sanitary pests compared to photostable pyrethroids. Many novel synthetic pyrethroids recently developed as household insecticides have tended to pursue efficacy improvements in terms of rapid knock-down effects, residual efficacy or volatility. 

Natural pyrethrins are a neurotoxin and repel, knock down, and kill by contact with insects at a low concentration. On the other hand, they have ideal features for household insecticides because of their quite low dermal and oral toxicides to warm-blooded animals. Neither plants other than pyrethrum nor synthetic insecticides have been reported to have such properties. Numerous synthetic pyrethroids have been developed by chemists since the complicated chemical structure of natural pyrethrins was elucidated in the middle of the twentieth century. Allethrin was the first synthetic pyrethroid put into practical use. 

Natural pyrethrins, insecticidal ingredients occurring in the flowers of Tanacetum cinerariaefolium (also known as Chrysanthemum cinerariaefolium or Pyrethrum cinerariaefolium), have been modified for higher stability in the environment as well as better biological performance for more than 40 years, and consequently more than 30 synthetic pyrethroids have been marketed and used worldwide for controlling indoor and agricultural pest insects [1,2]. 

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