Barrier to insecticide penetration

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. 

Hydrocarbons comprise a majority of the cuticular lipids while wax esters, sterol esters, alcohols and non-esterified fatty acids are also common components. In addition to preventing desiccation, insect waxes also function to prevent abrasion, to act as a barrier against microbial penetration to reduce the absorption of toxic environmental chemicals (including insecticides) and in some cases some components may act in chemical communication (Jackson and Blomquist, 1976). 

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). 

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. 

Important solvent properties are volatility, viscosity, surface tension, and lipid solubility. The first three determine the area over which a given volume of solvent spreads the larger the area of contact between insecticide and outer cuticle layers, the larger its total penetration rate will be. Acetone does not spread very far from the site of application, because it is so volatile. Lipid solubility affects the dissolution of the wax components of the epicuticle. By disrupting this layer, e.g., depositing a drop of acetone, the insecticide could bypass the epicuticular barrier. All these effects together may explain why an optimal balance of solvent properties is necessary to obtain maximal penetration rates (Welling and Patterson, 1985). 

The polarity of insecticides has been regarded as an important factor for cuticular penetration. As mentioned earlier, the typical insect cuticle should be considered a two-phase system, the outer layer (epicuticle) having hydrophobic properties and the inner layers (procuticle) having hydrophilic properties. Thus, whether the insecticide is lipid soluble or water soluble, its tendency to move through the cuticle as a whole depends on whether it can pass through the hydrophobic or hydrophilic barrier, whichever the case may be. The efficiency of such movement will probably depend on the oil-water partition coefficient of the insecticide, the nature of the surfactant or solvent—which may be a part of the insecticide formulation—and the nature of the cuticle itself (Terriere, 1982). 

Table 6.3 shows penetration rates of four insecticides dimethoate, paraoxon, dieldrin, and DDT, through cockroach cuticle. It is seen that the rates of penetration are inversely related to their partition coefficient in the olive oil-water system. In other words, the compound with the best solubility in water, as indicated by its partition coefficient, moved through the cuticle most rapidly. In this experiment, the insecticides were applied to the cuticle as acetone solutions, and it was suggested by the authors that this may have neutralized or canceled any barrier presented by the epicuticle. Thus, the data indicate the... 

The arthropods, especially the insects, exhibit probably the greatest ability to synthesize and utilize alkanes of any class of the Animal Kingdom. Their external surfaces are covered with cuticular waxes that provide a barrier which is impervious to water and prevents invasion by micro-organisms as well as providing general protection. This barrier may also effect (both positively and negatively) the penetration of insecticides. The waxes contain a wealth of hydrocarbons with n-alkanes sometimes predominating. Over one-hundred hydrocarbons have also been isolated and characterized from internal... 

The annual cost of termite treatments to the U.S. consumer is about 1.5 billion, and each year, as many as 1.5 million homeowners will experience a termite problem and seek a control option. From the 1940s until 1995, the nearly universal treatment approach for subterranean termite control involved the placement of large volumes of insecticide solutions into the soil surrounding a structure to create a chemical barrier through which termites could not penetrate. 

Xenobiotics of agronomical interest are very often applied to plants as post-emergence treatments and have therefore to pass through the cuticle lipophilic barrier in order to reach plant cells. Some of these products are highly lipophilic and the cuticle does not impede their penetration [1]. However, several other products are sufficiently hydrophilic to be severely limited in their penetration by the cuticle barrier. It is the case of mineral nutrients, of several insecticides,and endotherapic fungicides and of some herbicides such as glyphosate, paraquat, aminotriazole...[2]. 

---