ORGANIC POLLUTANTS: An Ecotoxicological Perspective - Chapter 16 doc

293 16 Neurotoxicity and Behavioral Effects of Environmental Chemicals 16.1 INTRODUCTION In the previous chapters there have been many examples of environmental chemicals, both natural and human-made, that have harmful effects on the nervous system of animals. Many of these compounds are toxic both to vertebrates and invertebrates. Interestingly, ve major groups of insecticides, organochlorine insecticides (OCs), organophosphorous insecticides (OPs), carbamate insecticides, pyrethroids, and neo- nicotinoids, all owe their insecticidal toxicity largely or entirely to their action on sites in the nervous system. A few of these compounds have also been used to con- trol vertebrate pests (e.g., the cyclodiene endrin has been used for vole control, and the OP insecticides fenthion and parathion for controlling birds). Separate chapters have been devoted to the OCs (Chapter 5), OPs and carbamates (Chapter 10), and the pyrethroids (Chapter 12). Other human-made pollutants also have harmful effects on the nervous system of animals, although they are not used with the intention of doing so. Examples include the organomercury fungicides and tetraethyl lead, which has been used as an antiknock in petrol (both in Chapter 8). It would appear, therefore, that the nervous system represents an “Achilles heel” within both vertebrates and invertebrates when it comes to the toxic action of chemicals. When pesticide manu- facturers have screened for insecticidal activity across a wide diversity of organic chemicals, many of the substances that have proved successful in subsequent com- mercial development have been neurotoxic. This line of argument can be extended to natural toxins as well (Chapter 1). Thus, many plant toxins such as the pyrethrins, physostigmine, strychnine, veratridine, aconitine, etc., all act upon the nervous system. As discussed earlier, the presence of such compounds in plants is taken as evidence for a coevolutionary arms race between higher plants and the animals that graze upon them. The production of these compounds may protect the plants against grazing by vertebrates and invertebrates. Apart from plants, animals and microorganisms also produce neurotoxins that have deadly effects upon vertebrates or invertebrates or both in the living environment. For example, snakes, spiders, and scorpions all produce neurotoxins, which they inject into their prey to immobilize them (see Chapter 1, Section 1.3.1). Also, tetrado- toxin is stored within the puffer sh, and ergot alkaloids are produced by the fungus © 2009 by Taylor & Francis Group, LLC 294 Organic Pollutants: An Ecotoxicological Perspective, Second Edition Claviceps purpurea. Indeed, these natural toxins have given many useful leads in the design of new pesticides, biocides, or drugs. In earlier chapters, many examples were given of lethal effects and associated neu- rotoxic or behavioral effects or both caused by pesticides in the eld. These included effects of organomercury fungicides upon birds (Chapter 8, Section 8.2.5), organo- chlorine insecticides on birds, and both organophosphorous and carbamate insecti- cides upon birds (Chapter 10, Section 10.2.4). Also, a retrospective analysis of eld data on dieldrin residues in predatory birds in the U.K. suggested that sublethal neu- rotoxic effects were once widespread and may have contributed to population declines observed at that time (Chapter 5, Section 5.3.5.1). Lethal and sublethal effects of neu- rotoxic insecticides upon bees is a long-standing problem (see Chapter 10, Section 10.2.5). Speaking generally, it has been difcult to clearly identify and quantify neuro- toxic and behavioral effects caused by pesticides to wild populations, especially where the compounds in question have been nonpersistent (e.g., OP, carbamate, or pyrethroid insecticides), and where any sublethal effects would have been only transitory. It is very clear, therefore, that there have been many examples of neurotoxic effects, both lethal and sublethal, caused by pesticides in the eld over a long period of time. Far less clear, despite certain well-documented cases, is to what extent these effects, especially sublethal ones, have had consequent effects at the population level and above. Interest in this question remains because neurotoxic pesticides such as pyre- throids, neonicotinoids, OPs, and carbamates continue to be used, and questions con- tinue to be asked about their side effects, for example, on sh (Sandahl et al. 2005), and on bees and other benecial insects (see, for example, Barnett et al. 2007). The present account will consider, in a structured way, how neurotoxic com- pounds may have effects upon animals, and how these effects can progress through different organizational levels, culminating in behavioral and other effects at the “whole animal” level. Emphasis will be placed upon the identication and quanti- cation of these effects using biomarker assays, and upon attempts to relate these biomarker responses to consequent effects at the population level and above, refer- ring to appropriate examples. The concluding discussion will focus on the use of this approach to identify and quantify existing pollution problems and on its potential in environmental risk assessment. In the rst place, there are a number of different sites of action for toxic chemicals within the central and peripheral nervous system of both vertebrates and inverte- brates. When studying the effects of neurotoxic compounds, it is desirable to monitor the different stages in response to them using appropriate biomarker assays, begin- ning with initial interaction at the target site (site of action), progressing through consequent disturbances in neurotransmission, and culminating in effects at the level of the whole organism, including effects upon behavior. Thus, in concept, a suite of biomarker assays can be used to measure the time-dependent sequence of changes that follows initial exposure to a neurotoxic compound—changes that constitute the process of toxicity. From integrated studies of this kind should come principles and techniques that can be employed to develop and validate new approaches and assays for the purpose of environmental monitoring and environmental risk assessment. In reality, however, only a very limited range of biomarker assays are available at the time of writing, and much work still needs to be done to realize this objective. © 2009 by Taylor & Francis Group, LLC Neurotoxicity and Behavioral Effects of Environmental Chemicals 295 An overview will rst be given of the interaction of neurotoxic compounds with target sites within the nervous system before moving on to discuss disturbances caused in neurons and, nally, effects at the whole-organism level; prominent among the latter will be behavioral effects. Throughout, consideration will be given to bio- marker assays that may be used to monitor the toxic process. Examples will be given of the successful use of biomarker assays, where, by judicious use of such assays, effects observed in the eld have been attributed to neurotoxic chemicals. In conclu- sion, there will be a discussion of attempts to relate biomarker responses to conse- quent effects upon populations and above. 16.2 NEUROTOXICITY AND BEHAVIORAL EFFECTS Animal behavior has been dened by Odum (1971) as “the overt action an organ- ism takes to adjust to its environment so as to ensure its survival.” A simpler def- inition is “the dynamic interaction of an animal with its environment” (D’Mello 1992). Another, more elaborate, one is, “the outward expression of the net interac- tion between the sensory, motor arousal, and integrative components of the central and peripheral nervous systems” (Norton 1977). The last denition spells out the important point that behavior represents the integrated function of the nervous sys- tem. Accordingly, disruption of the nervous system by neurotoxic chemicals may be expected to cause changes in behavior (see Klaasen 1996, pp. 466–467). Throughout the present text, toxicity is described as a sequence of changes initi- ated by the interaction of a chemical with its site (or sites) of action, progressing through consequent localized effects and culminating in adverse changes seen at the level of the whole organism. Thus, in what follows, the description of the bio- chemical mode of action of neurotoxic compounds will be followed by an account of localized effects before concluding with effects seen at the level of the whole animal, particularly behavioral effects. By approaching neurotoxicity in this way, it should be possible, in the longer term, to develop biomarker assays that can monitor the different stages in toxicity and to produce combinations of biomarker assays that will give a quantitative in- depth picture of the sequence of changes that occurs when an organism is exposed to a neurotoxic compound or a mixture of neurotoxic compounds. In following this progression, one moves from biochemical interactions, which are particular for a certain type of compound, to behavioral effects that are far less specic. However, by following this integrated approach, it should be possible to distinguish the contribu- tion of individual members of a mixture to a common effect at a higher level of bio- logical organization, for example, an alteration in the conduction of nervous impulse or a change in behavior. Later in this account, examples will be given describing experiments that have successfully linked mechanistic biomarker assays to behav- ioral changes despite the complexity of the nervous system. Following from the above, behavioral assays, which can be relatively simple and cost-effective, can be very useful as primary screens when testing chemicals for their neurotoxicity in the context of medical toxicology (see Dewar 1983, Atterwill et al. 1991, and Tilson 1993). Where disturbances of behavior are identied, subsequent more specic tests, including in vitro assays, may then be performed to establish © 2009 by Taylor & Francis Group, LLC 296 Organic Pollutants: An Ecotoxicological Perspective, Second Edition where and how damage is being caused to the nervous system. It should be added that behavioral effects of chemicals may be very important in ecotoxicology. They may be critical in determining adverse changes at the population level (Walker 2003, Thompson 2003). Some authors have drawn attention to evidence for the greater sensitivity of early developmental stages of mammals to neurotoxins in comparison to adults (Colborn et al. 1998, Eriksson and Talts 2000). It has been claimed that neurotoxic and endo- crine-disrupting chemicals are most damaging if there is exposure during embryonic, fetal, or postnatal life stages. This is a point to be borne in mind when investigating the long-term effects of neurotoxins using biomarker strategies. 16.3 THE MECHANISMS OF ACTION OF NEUROTOXIC COMPOUNDS The principal, known mechanisms of action of some neurotoxic environmental chemicals are summarized in Table 16.1. In considering these, it needs to be borne in mind that the interactions between chemicals and the nervous system in vivo can be very complex, and there is a danger of oversimplication when arguing from mecha- nisms of action shown to occur in vitro. It is very important to relate results obtained in vitro to interactions that occur in vivo, taking into account toxicokinetic factors. The distribution of chemicals over the entire nervous system and the concentrations reached at different sites within it are critical in determining the consequent interac- tions and toxic responses. Further, any given neurotoxic compound may interact not just with one well-dened target but with contrasting target sites in different parts of the nervous system. Thus, one chemical may interact with two or more quite differ- ent receptor sites (e.g., Na + channel and GABA receptor) at the same time, albeit in different parts of the nerve network. Also, there may be different forms of the same type of active site—with contrasting afnities for neurotoxic compounds. That said, this account will attempt to focus on the principal modes of action that particular chemicals have shown to particular species of animals in vivo. Taking rst the voltage-sensitive Na + channels (Chapter 5, Figure 5.4) that are found in the plasma membranes of nerve and muscle cells of both vertebrates and invertebrates, it is seen that these are regulated by two separate processes: (1) activa- tion, which controls the rate and voltage-dependence of the opening of this hydro- phobic channel, and (2) inactivation, which controls the rate and voltage-dependence of the closure of the channel. These channels are known to exist in many different forms despite the fact that they all have the same common function, that is, the regulation of sodium currents across the plasma membrane. Three different types are recognized in rat brain, and strongly contrasting forms are recognized in differ- ent strains of the same species. Resistant strains of houseies and other insects have different forms from susceptible strains of the same species. For example, kdr and super kdr strains have forms of the proteins constituting Na + channels which are dif- ferent from those found in susceptible strains (see Chapter 5, Section 5.2.5.2), and the forms present in these resistant strains are insensitive to both DDT and pyrethroid insecticides; that is, they provide the basis for resistance to the insecticides. © 2009 by Taylor & Francis Group, LLC Neurotoxicity and Behavioral Effects of Environmental Chemicals 297 TABLE 16.1 Neurotoxic Action of Some Environmental Chemicals Sites of Action Human-Made Chemicals Notes Natural Toxins Notes Na + Channels DDT Pyrethroids Both can prolong the passage of Na + current Pyrethrins Veratridine Veratridine appears to act at a different part of pore channel from DDT or pyrethroids Nicotinic acetylcholine receptors Neonicotinoids Similar action to Nicotine Nicotine Act as agonists causing desensitization of receptor Gamma aminobutyric acid (GABA) receptors Dieldrin, endrin, gamma HCH (BHC), toxaphene Inhibitors of receptor, reducing chloride inux Picrotoxinin Inhibitor of GABA receptors Acetylcholinesterase OP and carbamate insecticides Inhibitors of enzyme causing buildup of acetylcholine in synapses Physostigmine Inhibitor of acetylcholinesterase Neuropathy target esterase Certain OP compounds including DFP, mipafox, and leptophos Aging of inhibited enzyme leads to degeneration of peripheral nerves Cause damage to CNS of vertebrates Organomercury and organolead compounds Toxicity may be connected with ability to combine with SH groups Methyl mercury Occurs naturally as well as being human made Sources: Eldefrawi and Eldefrawi (1990), Johnson (1992), Ballantyne and Marrs (1992), and Salgado (1999). © 2009 by Taylor & Francis Group, LLC 298 Organic Pollutants: An Ecotoxicological Perspective, Second Edition The Na + channel is the target for certain naturally occurring toxins (see Chapter 5, Figure 5.4). The lipid-soluble alkaloid veratridine can activate the channel by binding to it and stabilizing it in a permanently open conformation (Eldefrawi and Eldefrawi 1990). This causes a prolongation of the sodium current and disruption of the action potential—typically, repetitive ring of the action potential. The marine toxins tetro- dotoxin and saxitoxin have the opposite effect. They are organic ions bearing a posi- tive charge that can bind to the channel near its extracellular opening and thereby block the movement of sodium ions. Of the insecticides, the principal mode of action of both DDT and the pyrethroid insecticides is thought to be upon Na + channels. Rather like veratridine, they bind to the channel causing a prolongation of the Na + current, although they appear to bind to a different part of the protein than does this alkaloid (Chapter 5, Figure 5.4). Nerves poisoned by DDT typically produce multiple rather than single action potentials when they are electrically stimulated (Figure 16.1). Control A. Action Potential Passed Along Nerve following Single Voltage Stimulus + mv – mv Influx Na + B. Current Generated on Postsynaptic Membrane of Inhibitory Synapse following Stimulation with Gab + mv – mv Influx Cl – + mv – mv DDT Poisoned Nerve FIGURE 16.1 Generation of action potentials. © 2009 by Taylor & Francis Group, LLC Neurotoxicity and Behavioral Effects of Environmental Chemicals 299 The nicotinic receptor for acetylcholine is located on postsynaptic membranes of nerve and muscle cells. It is found in both the central and peripheral nervous system of vertebrates, but only in the central nervous system of insects (Eldefrawi and Eldefrawi 1990). A hydrophobic cationic channel is an integral part of this transmembrane pro- tein. With normal synaptic transmission, acetylcholine released from nerve endings interacts with its binding site on the receptor protein, and this leads to an opening of the pore channel and an inux of cations. The consequent depolarization of the mem- brane triggers the generation of an action potential by neighboring sodium channels, and so the message is passed on. The natural insecticide nicotine acts as an agonist for acetylcholine and can cause desensitization of the receptor. Neonicotinoid insecticides such as imidacloprid act in a similar way to nicotine. They are more lipophilic than the natural compound and are more effective as insecticides. Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remain- der of this description will be restricted to this form. GABA-A possesses a variety of binding sites (Chapter 5, Figure 5.4). One of them is for the natural transmitter GABA, an interaction that leads to the opening of the pore channel and the inux of chloride ions (Figure 16.1). Another, close to or in the chloride ion channel, binds the naturally occurring convulsant picro- toxinin, the cyclodiene insecticides (e.g., dieldrin, endrin), gamma HCH (lindane), and toxaphene. Convulsions accompany severe poisoning by these insecticides. The GABA-A receptor of mammalian brain is believed to be the primary target for cyclo- diene insecticides in that organ. Binding of picrotoxinin and cyclodiene insecticides to the receptor retards the inux of chloride ions through the pore channel following stimulation with GABA; that is, they inhibit the normal functioning of the receptor. Acetylcholinesterase is a component of the postsynaptic membrane of cholinergic synapses of the nervous system in both vertebrates and invertebrates. Its structure and function has been described in Chapter 10, Section 10.2.4. Its essential role in the postsynaptic membrane is hydrolysis of the neurotransmitter acetylcholine in order to terminate the stimulation of nicotinic and muscarinic receptors (Figure 16.2). Thus, inhibitors of the enzyme cause a buildup of acetylcholine in the synaptic cleft and consequent overstimulation of the receptors, leading to depolarization of the postsynaptic membrane and synaptic block. The carbamate and OP insecticides and the organophosphorous “nerve gases” soman, sarin, and tabun all act as anticholinesterases, and most of their toxicity is attributed to this property. The naturally occurring carbamate physostigmine, which has been used in medicine, is also an anticholinesterase. Some OP compounds can cause relatively long-lasting inhibition of the enzyme because of the phenomenon of © 2009 by Taylor & Francis Group, LLC 300 Organic Pollutants: An Ecotoxicological Perspective, Second Edition “aging”; the inhibited enzyme undergoes chemical modication, and inhibition then becomes effectively irreversible. A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neu- ropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphouoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2–3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). Organometallic compounds such as alkylmercury fungicides, and tetraethyl lead, used as an antiknock in petrol, are neurotoxic, especially to the central nervous system of vertebrates (Wolfe et al. 1998, Environmental Health Criteria 101, and Chapter 8, BOX 16.1 TECHNIQUES FOR MEASURING THE INTERACTION OF NEUROTOXIC CHEMICALS WITH THEIR SITES OF ACTION A central theme of this text is the development of biomarker assays to measure the extent of toxic effects caused by chemicals both in the eld studies and for the purposes of environmental risk assessment. Considering the examples given in Table 16.1, a number of possibilities present themselves. In the rst place, competitive binding studies may reveal the extent to which a toxic compound is attached to a critical binding site. For example, the convulsant TBPS binds to the same site on GABA-A receptors of rat brain as do cyclodiene insecticides such as dieldrin. In samples preexposed to dieldrin, the binding of radiolabeled TBPS will be less than in controls not exposed to the cyclodiene (Abalis et al. 1985). The difference in binding of the radioactive ligand to the treated sample in comparison to binding to the control sample provides a measure of the extent of binding of dieldrin to this target. Similarly, the competitive binding of tetrodotoxin and saxitoxin to the Na + channel may be exploited to develop an assay procedure. In cases where the mode of action is the strong or irreversible inhibition of an enzyme system, the assay may measure the extent of inhibition of this enzyme. This may be accomplished by rst measuring the activity of the inhibited enzyme and then making comparison with the uninhibited enzyme. This practice is followed when studying acetylcholinesterase inhibition by organophosphates (OP). Acetylcholinesterase activity is measured in a sample of tissue of brain from an animal that has been exposed to an OP. Activity is measured in the same way in tissue samples from untreated controls of the same species, sex, age, etc. Comparison is then made between the two activity measurements, and the percentage inhibition is estimated. © 2009 by Taylor & Francis Group, LLC Neurotoxicity and Behavioral Effects of Environmental Chemicals 301 Section 8.2.4 and Section 8.2.5 in this book). Neurotoxic effects in adult mammals include ataxia, difculty in locomotion, neurasthenia, tremor, impairment of vision and, nally, loss of consciousness and death. Necrosis, lysis, and phagocytosis of neu- rons are effects coinciding with these symptoms of toxicity. As described earlier, sub- lethal neurotoxic effects on humans and wild vertebrates have occurred and still occur as the result of environmental contamination by methylmercury. The mechanism of neurotoxic action is complex and is not well understood. There is strong evidence that methylmercury compounds can have adverse effects upon a number of proteins, including enzymes and membrane-spanning proteins involved in ion transport (ETAC 101). It seems probable that the strong tendency of these compounds to bind with—and thereby render ineffective—functional –SH groups of the proteins is the main reason for this (see, for example, Jacobs et al. 1977, who studied the inhibition of protein syn- thesis by methylmercury compounds). There is also evidence that exposure to sublethal levels of methyl mercury can cause changes in the concentration of neurochemical receptors in the brains of mammals and birds (Basu et al. 2006, Scheuhammer et al. 2008). Thus, an increase in concentration of brain muscarinic receptors for acetylcho- line and a decrease in the concentration of brain receptors for glutamate was observed Axon Dendrites Axon Pre-Synaptic Membrane Receptors Pore Channels Direction of Transmission Synaptic Cleft Post-Synaptic Membrane Vesicles with Neurotransmitter Cholinergic (Nicotinic) Synapse ACh Receptor Na Channel Direction of Transmission Synaptic Cleft Vesicles with Acetylcholine (Ach) ACh-ase FIGURE 16.2 Schematic diagram of synapse. © 2009 by Taylor & Francis Group, LLC 302 Organic Pollutants: An Ecotoxicological Perspective, Second Edition following exposure to environmentally realistic levels of methylmercury. This obser- vation was made both in mink and common loons. In summary, the toxic effects of methylmercury on vertebrates are complex and wide ranging, and with the present state of knowledge it is not possible to ascribe this neurotoxicity to one clearly dened mode of action. 16.4 EFFECTS ON THE FUNCTIONING OF THE NERVOUS SYSTEM Following combination with their sites of action, the main consequent effects of the neurotoxic compounds described here are upon synaptic transmission or propagation of action potential. In some cases (e.g., methylmercury and some OPs) there are signs of physical damage such as demyelination, phagocytosis of neurons, etc. The follow- ing account will be mainly concerned with effects of the rst kind—that is, electro- physiological effects—which may provide the basis for assays that can monitor the progression of toxicity from an early stage and thus provide a measure of sublethal effects caused by differing levels of exposure. Effects on the peripheral nervous sys- tem and the central nervous system will now be considered separately. 16.4.1 EFFECTS ON THE PERIPHERAL NERVOUS SYSTEM Electrical impulses are passed along nerves as a consequence of the rapid progres- sion of a depolarization of the axonal membrane. In the resting state, a transmem- brane potential is maintained on account of the impermeability of the nerve to ions such as Na + and K + . Were the membrane freely permeable, these ionic gradients could not be sustained. Active transport processes maintain ionic gradients in excess of those that could be achieved purely by passive diffusion. However, when Na + channels open in the axonal membrane, a very brief inwardly owing Na + current causes a transient depolarization. This is rapidly corrected by a subsequent outward ow of K + ions. The Na + current is terminated when the pore channel closes, and the succeeding K + current ows briey until the transmembrane potential returns to its resting state (Figure 16.1). The passage of action potentials along a nerve can be recorded by inserting microelectrodes across the neuronal membrane and using them to record changes in the transmembrane potential in relation to time. This has been done in a variety of ways. Microelectrodes can be inserted into nerves of living animals, or into isolated nerves, or cellular preparations of nerve cells (see Box 16.2). An important rene- ment of the technique involves “voltage clamping.” This permits the “xing” of the transmembrane potential, which restricts the movement of ions across the mem- brane. Thus, it is possible to measure just the Na + current or the K + current in control and in “poisoned” nerves, thereby producing a clearer picture of the mechanism of action of neurotoxic compounds that affect the conduction of action potentials along nerves. Measurements of this kind may be just of spontaneous action potentials or of potentials that are elicited by electrical or chemical stimulation. Chemical stimula- tion may be accomplished using natural neurotransmitters such as acetylcholine. The effects of neurotoxic chemicals upon nerve action potential have been mea- sured both in vertebrates and insects. Of particular interest has been the comparison © 2009 by Taylor & Francis Group, LLC [...]... be either free living or deployed The advantage of the latter is © 2009 by Taylor & Francis Group, LLC 316 Organic Pollutants: An Ecotoxicological Perspective, Second Edition greater experimental control Laboratory-reared fish, for example, can be deployed into polluted and clean waters and comparisons made between biomarker responses in the two cases The importance of behavioral factors in population... Ballantyne, B.C and Marrs, T.C (Eds.) (1992) Clinical and Experimental Toxicology of Organophosphates and Carbamates—A wide-ranging collection of chapters giving a broad coverage of the toxicology of these important neurotoxic compounds Eldefrawi, M.E and Eldefrawi, A.T (1991) Nervous-System-Based Insecticides—Describes the mechanisms of action of a wide range of neurotoxic compounds, both human-made and naturally... monitor changes at the level of the gene can run alongside assays to show changes at the cellular level (e.g., interaction with sites of action, electrophysiological responses) Appropriate combinations of assays can give an in-depth picture of the operation of this causal © 2009 by Taylor & Francis Group, LLC 314 Organic Pollutants: An Ecotoxicological Perspective, Second Edition chain, which can then... a point that will be returned to in Section 16. 8 © 2009 by Taylor & Francis Group, LLC 306 Organic Pollutants: An Ecotoxicological Perspective, Second Edition 16. 5 EFFECTS AT THE LEVEL OF THE WHOLE ORGANISM In the first place, severe neurotoxicity can cause gross neurophysiological disturbances at the whole organism level, such as convulsions, paralysis, and inability to walk (or, in the case of birds,... regulatory testing protocols (Thompson and Maus 2007) It is argued that any behavioral effects that are ecologically important will be picked up in field or semi-field trials © 2009 by Taylor & Francis Group, LLC 308 Organic Pollutants: An Ecotoxicological Perspective, Second Edition In medical toxicology, there have been many reports of humans showing behavioral disturbances following exposure to sublethal... potential to measure the sequence of changes that occur in animals exposed to neurotoxic compounds—changes that may lead to neurophysiological and behavioral disturbances and finally death Such an approach can give a better understanding of the phenomenon of neurotoxicity in the earlier stages of intoxication and an ability to recognize it and quantify it in the laboratory and in the field The employment... are illustrated in Figure 16. 1 In nerves poisoned by the insecticide, there is a prolongation of the sodium current and a consequent delay in returning to the resting potential This can result in the © 2009 by Taylor & Francis Group, LLC 304 Organic Pollutants: An Ecotoxicological Perspective, Second Edition generation of further spontaneous action potentials, that is, there can be repetitive action... 2001) Nicotinoids can disturb the functioning of cholinergic synapses, which are involved in the operation of the proboscis reflex as © 2009 by Taylor & Francis Group, LLC 312 Organic Pollutants: An Ecotoxicological Perspective, Second Edition well as in learning and memory in the honeybee Again, effects of this kind can have a detrimental impact on foraging Behavioral effects of pollutants may also disrupt... rhythmical changes arising from thalamic nuclei The signals recorded can be separated into frequency bands—faster waves exceeding 13 Hz, and slower ones below 4 Hz Changes in EEG patterns have been observed when humans and experimental animals are exposed to neurotoxic compounds Thus, humans occupationally exposed to aldrin or dieldrin showed characteristic changes in EEG patterns (Jaeger 1970) These changes... capsules Behavioral effects were related © 2009 by Taylor & Francis Group, LLC 310 Organic Pollutants: An Ecotoxicological Perspective, Second Edition to brain cholinesterase levels The most sensitive parameter was posture, which was found to change when brain cholinesterase activity fell below 88% of the control value Reductions in flying and singing, and increased resting were associated with inhibition . human made Sources: Eldefrawi and Eldefrawi (1990), Johnson (1992), Ballantyne and Marrs (1992), and Salgado (1999). © 2009 by Taylor & Francis Group, LLC 298 Organic Pollutants: An Ecotoxicological. to in Section 16. 8. © 2009 by Taylor & Francis Group, LLC 306 Organic Pollutants: An Ecotoxicological Perspective, Second Edition 16. 5 EFFECTS AT THE LEVEL OF THE WHOLE ORGANISM In the rst. by Taylor & Francis Group, LLC 304 Organic Pollutants: An Ecotoxicological Perspective, Second Edition generation of further spontaneous action potentials, that is, there can be repetitive