Resistance development carbamates

A newer class of insecticides is the pyrethroids. These are synthetic derivatives of pyrethrins, which are natural extracts from chrysanthemums. Pyrethroids have been developed to be more stable (and thus more effective as insecticides) than the pyrethrins, which are particularly instable in light. Pyrethroids are frequently used as broad-spectrum insecticides. They have high insect toxicity, but lower mammalian toxicity than their organophosphate or carbamate counterparts. Pyrethroids are still limited in effectiveness due to their environmental lability, their high cost, and their potential for resistance development. 

With the introduction of the carbamate insecticides in 1956, resistance to carbaryl appeared between 1963 and 1966 in an orchard leafroller in New Zealand, in the cotton leafworm (Spodoptera) of Egypt, and in Heliothis virescens (the so-called tobacco bud-worm) on American cotton (Table VI). Resistance developed to OP compounds had already given some cross-tolerance to carbamates... 

The existence of multiple AChE isoenzymes has several consequences. First, it increases the chances of an insect having one that is, or by a minor genetic change can be rendered, insensitive. The molecular redundancy combined with a selection pressure in the form of persistent insecticide applications would facilitate target site resistance development. Second, it could be a factor in the frequent lack of target site cross resistance between OPs and carbamates, and even between different OPs. Third, it would facilitate the disappearance of the insensitive form(s) in the absence of a selection pressure. This would especially easily explain observed instability of resistance if the form(s) with decreased affinity for the inhibitors also have decreased affinity for the neurotransmitter. Insensitivity to the inhibitor may be accompanied by a reduced rate of neurotransmitter hydrolysis (56. 28), but this is not always the case. It seems that the reduced rate of neurotransmitter hydrolysis does not impair survival, at least in laboratory cultures of insects. It is unclear what impact such reduced rates have in field populations. 

One of the major pest Insects in rice fields is the green rice leafhopper (Nephotettix cincticeps). Recently acquired resistance to carbamate insecticides has greatly complicated control of this insect. Resistance can develop by a number of different mechanisms such as cuticle thickening to Impede transport, enhanced metabolic degradation or molecular changes within the target enzyme (AChE) (1 ). In the case of carbamate insecticides, resistance occurs mainly at the target enzyme which expresses reduced sensitivity to the inhibitors (2). 

Insects have acquired resistance to organochlorine compounds, such as DDT and BHC, developed as agricultural and hygienic insecticides after World War II. This insect resistance was also acquired to subsequent organophosphorus compounds and carbamate insecticides. Photostable pyrethroids have been developed for outdoor use because pyrethroids were found to be effective against these resistant pests. As a matter of course, these pyrethroids are also effective against sanitary pests however, problems associated with safety and chemical residues indoors must be resolved. 

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. 

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. 

It should be clear to us that the development of resistance is always to be expected to any insecticide we may choose to apply, but it is not inevitable. DDT stayed effective against the European corn borer for at least 15 years (Table VIII) and there are several other examples, including diazinon and the western corn rootworm in Nebraska. Some of the species of beneficial insects which formerly suffered from insecticide damage, such as braconid parasites, lady beetles, mayfly nymphs and honeybees, have now developed certain tolerances, while several of the Phytoseiid mites which feed on the plant-feeding spider mites are becoming as resistant as their prey to OP s and carbamates. 

The development of resistance by certain insect species to chlorinated hydrocarbon insecticides aroused research into alternative chemical classes of compounds. This research led to the development of the carbamates as useful broad-spectrum insecticides. The best known of this class is carbaryl (Sevin), which has emerged as one of the most extensively used insecticides. 

So far, no serious resistance against pyrethroids has been recorded in vectors or pest populations, although there is an indication that it may be developing in some species. At present, 14 anopheline malaria vector species have developed resistance to organochlorine insecticides, eight to organophosphorus compounds and three to carbamates, and three species have reduced susceptibility to permethrin. 

Cross-resistance refers to a situation in which a strain that becomes resistant to one insecticide automatically develops resistance to other insecticides to which it has not been exposed. For example, selection of a strain of Spodoptera littoralis with fenvalerate resulted in a 33-fold increase in tolerance to fenvalerate. The resistant strain also showed resistance to other pyrethroids (11- to 36-fold) and DDT (lower than for the pyrethroids). Exposure of Cidex qninquefasciatus to fenitrothion resulted in the development of resistance to the carbamate insecticide propoxur. Similarly, selection of a housefly strain with permethrin resulted in a 600-fold increase in resistance to permethrin. The resistant strain also showed resistance to methomyl, DDT, dichlorvos, and naled (Hassall, 1990). 

The stability characteristics of various (V-acylated oxazolidines were also studied in an attempt to develop approaches which may solve the stability problems associated with the use of oxazolidines as prodrug forms. The (V-acylated oxazolidines, including a carbamate derivative, were in fact found to be highly stable in an aqueous solution, but they also proved to be resistant to hydrolysis by plasma enzymes. The latter limits the use of (V-acylated oxazolidines in prodrug design.64... 

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 major difference between OPs and carbamates is in their metabolic fate. This strongly indicates that metabolism and detoxification are the most important factors in resistance evolution. The current emphasis on target site interactions and their associated resistance mechanisms reflects their perceived practical importance, the importance of their study for the development of new insecticidal molecules, and the fundability of such research. But detailed studies of the biochemical characteristics and physiological behavior of the enzymes involved in insecticide metabolism and detoxification are still very important. 

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