Barrier to insecticide

Work in our laboratory on various parameters in R and S fish has investigated the factor(s) responsible for resistance. The results have indicated that resistance is multifactorial, involving a barrier to insecticide penetration, insecticide storage, insecticide metabolism, and an apparent "insensitivity" at the target site to the toxic effects of the insecticide. The present report concentrates on two of these factors insecticide disposition and metabolism. 

From the data presented, there is obviously a more effective barrier to insecticide penetration in R fish than in S fish. Further, this barrier apparently operates over a wide range of exposure levels. For example, when the tissue concentration in brains from R fish exposed to 10 yg/1 are compared to tissue concentrations in brains of R fish exposed to 314 yg/1 endrin, there is a 10-fold increase in endrin concentration in brain tissue (from 6.91 to 73.8 ng endrin equivalents/mg wet weight of tissue), although this represents a 30-fold increase in the insecticide exposure level. However, in S fish, the level of insecticide in brain tissue increased 355-fold (from 0.5 to 192.2 ng endrin equivalents/mg wet weight of tissue) when the insecticide exposure level was raised 17-fold (from 0.6 to 10 yg/1) (submitted for publication). It should be pointed out that the 314 yg/1 exposure levels in the R fish represents the 48-hr LC50 value while the 0.6 yg/1 exposure level is the 48-hr LC50 value for S fish. Therefore these data represent comparisons of the S and R populations at both equitoxic and equal exposure levels of endrin. 

The uptake and distribution of organochlorine insecticides has been studied under a variety of conditions. Although the results indicate that further study is needed on a characterization of extraneous factors that affect disposition, the studies clearly demonstrate the presence of a membrane barrier to insecticide penetration in the R population. This membrane barrier would aid in the protection of target sites in the R fish from the insecticide. This barrier is felt to be an important factor in resistance to organochlorine insecticides in mosquitofish. 

Barriers to insecticide penetration undoubtedly contribute to chlorinated alicyclic resistance. However, we are led to conclude that these extremely high levels of resistance are the result of a postulated insensitivity of the target site which allows these fish to tolerate elevated internal levels of these toxicants. 

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

Once the medicinal properties of I and II were appreciated, the inevitable synthesis of carbamate analogs followed. The anticholinesterase activity of physostigmine- and eserine-related synthetics suggested their possible use as Insecticides but tests of early compounds failed, due to the quaternary ammonium barrier to penetration of the insect cuticle present in them. 

Pesticides can be complexed with CyD to reduce their volatility. The interaction of the guest with the CyD produces a higher energy barrier to volatilization. Szente and Szejtli [32] prepared the inclusion complex of the volatile insecticide DDVP with yS-CyD obtaining a crystalline substance with a much more persistent contact effect than free DDVP. 

Despite their environmentally desirable qualities, pheromones account for less than 1% of the 6 billion worldwide market for insect control products (5). The two major factors that relegate pheromones to only a few minor market niches are, perversely, their high target specificity, which makes them relatively unattractive in crop systems requiring the control of multiple pest species, and their high cost of synthesis compared to insecticides. The latter factor represents a significant market barrier even in the best of circumstances where only a single pest species predominates. 

Another important factor is defining the pesticide distribution coefficients for oil and water, which affect both their ability to enter the body by penetrating skin and cell membranes and their eventual location in the system. A high distribution coefficient (characteristic of many organophosphorus and organochlorine insecticides) means these substances can easily penetrate the skin, travel via the blood-brain barrier to the central nervous system and enter intracellular formations (Kagan 1985, Kundiev 1975). 

The use of insect repellents is part of an integrated approach to prevent bites from nuisance and vector mosquitoes and other biting arthropods. This chapter reviews some of the strategies that have been used for personal protection against vectors, especially mosquitoes and discusses basic engineering, repellents in combination with impregnated clothing, insecticide-treated nets, and chemical barriers to insect vectors. 

Some studies in the late 1980s investigated the use of permethrin-treated materials as barriers to the entry of Anopheles mosquitoes to huts and houses. In some countries, sisal was treated with permethrin and placed as an insecticide-treated barrier in windows and other areas where Anopheles mosquitoes entered the houses. 

Several studies to evaluate the effectiveness of combinations of repellent and insecticide-treated clothing have been undertaken and are discussed here. The protection of an individual is enhanced by reducing the amount of skin exposed to biting insects and arthropods. In most human communities, clothes are worn, and provide a physical barrier to arthropod bites. In many tropical countries, fewer clothes may be worn, as the use of long sleeves and long trousers may not be necessary, allowing more skin to be exposed to arthropods. 

Thus nicotinoids that have the highest insecticidal action have the highest piC and, consequently, exist largely in the ionized form at physiological pH. This produces the anomaly that the compounds that are most highly ionized react most rapidly with the receptor protein, yet they are less able to penetrate through the ionic barrier surrounding the insect nerve synapse. 

This barrier can be further illustrated by comparing tissue insecticide ratios between the S and R populations. Radioactivity accumulated in major organs following exposure to 10 yg/1 l C-endrin is greater in S fish than in R fish for all organs studied except kidney (Table III). Similarly, S fish accumulate more aldrin, dieldrin and DDT in their brains than do R fish. 

When comparisons are made between populations, both the effectiveness of the membrane barrier in R fish and the sensitivity of the target site can be demonstrated (Table V). When endrin Ss/Rs ratios are compared, the ratio is less than 1 this suggests that more insecticide is required to elicit symptoms in the R than in the S fish. 

Although the CNS is protected from a number of xeno-biotics by the blood-brain barrier, the barrier is not effective against lipophilic compounds, such as solvents or insecticides (Fig. 7.1). Similarly, the peripheral nervous system is protected by a blood-neural barrier. The barriers are less well developed in the immature nervous system, rendering the fetus and neonate even more susceptible to neurotoxicants. Neural tissue susceptibility is due in large part to its high metabolic rate, high lipid content, and for the CNS, high rate of blood flow. 

In spite of the smaller ratio of nicotinic to muscarinic receptors in the brain, nicotine and lobeline (Figure 7-3) have important effects on the brainstem and cortex. The mild alerting action of nicotine absorbed from inhaled tobacco smoke is the best-known of these effects. In larger concentrations, nicotine induces tremor, emesis, and stimulation of the respiratory center. At still higher levels, nicotine causes convulsions, which may terminate in fatal coma. The lethal effects on the central nervous system and the fact that nicotine is readily absorbed form the basis for the use of nicotine as an insecticide. Dimethylphenylpiperazinium (DMPP), a synthetic nicotinic stimulant used in research is relatively free of these central effects because it does not cross the blood-brain barrier. 

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