Brain tissue, insecticide

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. 

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. 

Researchers were also able to establish the link between declines of other predatory species such as the European sparrowhawk and the use of organo-chlorine pesticides other than DDT. For instance, the cyclodiene insecticides aldrin, dieldrin, and he-ptachlor used as seed treatments caused massive mortality of both seed-eating species and their predators. All of the insecticides had the following points in common they were highly soluble in fats and refractory to metabolism. The impacts on the predatory species typically take place in periods of food stress when fat soluble residues are released from fat stores and returned into general circulation. In a food-stressed individual, the brain remains as the most lipid rich tissue and this is where contaminants move to. Toxicity results when threshold values in brain tissue are exceeded. At sublethal levels, documented effects of cyclodiene insecticides in birds have included changes in their reproductive, social, and avoidance behaviors. 

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. 

Still another experimental route to introducing otherwise excluded molecules into the brain is to chemically modify them so that they are lipophilic and therefore can passively diffuse. The brain, just as most other organs and tissues of the body, has enzymes to metabolize or biotransform metabolites in order to use and then get rid of them. Many of these pathways are oxidative. A reduced species or derivative which is lipophilic can enter the brain by simple passive diffusion there to be oxidatively transformed into an active state. Compounds which have been tested in animals include derivatives of 2-PAM (an antidote for organophosphate insecticide poisoning) and phenylethylamine (similar to amphetamine type molecules). Figure 5 illustrates the general concept behind this method. 

The body tissues are generally submitted to a toxicological laboratory in sufficient quantities hence these specimens are better suited for quantitative analysis. The detection and determination of the unchanged insecticide in the stomach, intestine, liver, kidney, spleen, lungs, brain, and in other tissues and body fluids are useful indicators of direct insecticide action. 

The amount of the pesticides present in different autopsled tissues received from fatal cases of poisoning have been estimated quantitatively in our laboratory. In accidental poisoning cases where vapors of insecticides are inhaled, no insecticide is likely to be detected in the stomach or intestine but considerable amounts may be detected in the lungs, brain, and blood. 

Insecticide Sex Age Time period before death Mode of ingestion Concentration (milligram per cent of tissue/material) StomachlIntestine 1LiverlKidneylSpleenlLung 1 Heart 1 Brain Stomach Wash ... 

The data presented above show clearly that GABA receptors of mammalian brain are targets for the toxic action of cyclodiene, yBHC and pyrethroids. Although, the binding and flux assays, used so sucessfully to study interactions of these insecticides with mammalian brain, have had limited success when applied to insect tissues, there is ample evidence to suggest that GABA receptors of insects are targets for AVM (7, 21) cyclodienes and pyrethroids (17, 22). 

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