Resistance synthetic pyrethroids

Resistance to insecticides has drawn global attention since the Korean War in 1950 when the mass use of organic synthetic insecticides, such as DDT and BHC, against agricultural pests and sanitary pests became common. Organophosphorus compounds and carbamates were used thereafter, but invited problems of safety concerns and insect resistance. Synthetic pyrethroids were watched with keen interest as alternatives and have become used widely not only for sanitary pests but also agricultural pests. The development of resistance to synthetic pyrethroids is also not a rare phenomenon and has spread all over the world. 

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). 

Keywords Cross resistance Natural pyrethrins Safety Synthetic pyrethroid... 

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. 

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. 

While the mechanism of resistance to various synthetic pyrethroids in flies has been elucidated in terms of physiology, biochemistry, and genetics, it seems that the resistance mechanism is mostly common to mosquitoes. 

It is said that the action site of pyrethroids in flies is on the neuroaxonal excitatory membrane, similarly to that of DDT. Moreover, DDT-resistant M. domestica is known to show high cross-resistance to synthetic pyrethroids and the kdr gene is involved in the onset of the resistance. It has also been shown that such resistant flies exhibit high cross-resistance to many synthetic pyrethroids developed to date. 

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

Against the above background, the development and perspective of cross-resistance to synthetic pyrethroids should be discussed as follows. 

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. 

Insects have developed resistance to cyanide, chlorinated hydrocarbons, organophosfiiates, carbamates, synthetic pyrethroids, and other insecticides ( ). This is not surprising vrtien considering the same complex of detoxifying enzymes, mainly r resented by hydrolytic, conjugative, and oxidative enzymes 9) is capable of detoxifying natural toxins as well as man-made materials. This ability is due to apprcpriate enzymes and/or isozymes that results in broad-substrate capabilities. For insects that feed on a wide variety of hosts (polyphagy), the spectrum of toxins that can be dealt with is truly remarkable. 

Insect resistance and environmental pollution due to the repeated application of persistent synthetic chemical insecticides have led to an Increased interest in the discovery of new chemicals with which to control Insect pests. Synthetic insecticides, including chlorinated hydrocarbons, organophosphorus esters, carbamates, and synthetic pyrethroids, will continue to contribute greatly to the increases in the world food production realized over the past few decades. The dollar benefit of these chemicals has been estimated at about 4 per 1 cost (JJ. Nevertheless, the repeated and continuous annual use in the United States of almost 400 million pounds of these chemicals, predominantly in the mass agricultural insecticide market (2), has become problematic. Many key species of insect pests have become resistant to these chemicals, while a number of secondary species now thrive due to the decimation of their natural enemies by these nonspecific neurotoxic insecticides. Additionally, these compounds sometimes persist in the environment as toxic residues, well beyond the time of their Intended use. New chemicals are therefore needed which are not only effective pest... 

Only countries with political clout and political sense about DDT, notably South Africa, China, and India, still use it. South Africa had stopped using DDT in 1996 under pressure to join the world s Green community and switched to the next best alternative, the synthetic pyrethroids, which are three times the price and are effective over a shorter time span. Four years later, in 2000, South Africa decided to resume DDT spraying after malaria cases jumped by 1,000 percent because of mosquito resistance to the synthetic pyrethroids. 

A large number of synthetic pyrethroids with a variety of aromatic and aliphatic fluorine substituents have been commercialized, and will be discussed in the sections on fluorinated ether, aromatic fluorine, and fluorinated aliphatic groups, respectively. Fluvalinate (Mavrik ) [50] is a trifluoromethylphenyl pyrethroid, initially introduced by Zoecon (later Zandos Ag) and later replaced by tau-fluvalin-ate, which contains two of the four isomers of fluvalinate. Tau-fluvalinate (Apistan ) is a synthetic pyrethroid used for the topical treatment of honeybees against the parasitic mite Varroa jacobsoni. Mite resistance to tau-fluvalinate has been reported [51],... 

Chapman, R.B. and Penman, D.R., Negatively correlated cross-resistance to a synthetic pyrethroid in organophosphorus-resistant Tetranychus urticae, Nature, 281, 298,1979. 

Agricultural pesticides were found to be effective insect resist agents when applied in emulsion form to wool dyebaths. Dieldrin (Fig. 16.2a), one of the original nerve poisons, is also highly toxic to mammals and aquatic life and its use has been banned in most countries. Products based on permethrin (Fig. 16.2b), a synthetic pyrethroid, are very effective against moth larvae, but have less effect on Anthrenus beetles. To overcome this disadvantage, combination products of permethrin and hexahydropyrimidine derivatives (Fig. 16.2c) have been introduced. 

Fore recently a comparable enhanced inhibition in resistant strains has been observed with aryloxadiazolone anticholinesterases (38). A second promising example is the discovery that some natural and synthetic isobutylamides are selectively toxic against houseflies that carry the super-kdr resistance trait (39). This gene causes an alteration in the sensitivity of the site of action for DDT and pyrethroids and is a major threat to the continued efficacy of synthetic pyrethroids in many of their applications. 

This is a target site for very few current insecticides, and resistance to compounds acting there has not been developed. This discovery gave additional momentum to the synthesis program. Eventually compounds with activity comparable to the synthetic pyrethroids were discovered (50) and investigations in this area continue. 

In view of the importance attached to the synthetic pyrethroids as "end of the line" conventional insecticides, some recent significant developments in resistance to this group are considered separately in this section. 

In fact, only two new classes of insecticides have been developed for commercial use in the last 30 years. Both the synthetic pyrethroids and the avermectins have excellent mammalian saftety. However, both are encumbered by previously evolved target site resistance, selected by over-use of DDT and cyclodiene insecticides, respectively. Thus, the remaining importance of the OPs and the carbamates is obvious. 

The two Heliothis species that have most commonly developed resistance are Heliothis virescens and armigera. The loss of the organophosphorous insecticides (OP s) to resistance in the 1970 s literally pushed the synthetic pyrethroids into the marketplace. Since their introduction in 1978, it was clear that these highly cost effective and environmentally compatible insecticides would be heavily relied upon to replace the OP s. The synthetic pyrethroids have become the most widely used chemicals for the control of insect pests on cotton, representing about 48% of all the insecticides applied worldwide ( ). Most applications are directed toward controlling Heliothis spp. 

Table I. Documented Cases of Synthetic Pyrethroid Resistance on Heliothis spp.

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