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3Part Further Issues and Future Prospects The rst part of this text dealt with basic principles determining the distribution and effects of organic pollutants in the living environment. The second focused on major groups of organic pollutants, describing their chemical and biological prop- erties and showing how these properties were related to their environmental fate and ecological effects. Attention was given to case histories, especially to long-term studies conducted in reasonable depth and detail, which illustrate how some of these principles work out in practice in the complex and diverse natural environment. The importance of these case studies should be strongly emphasized because, despite the shortcomings of many of them and the often only limited conclusions that can be drawn from them, they do provide insights into what happens in the “real world” as opposed to the theoretical one represented by the model systems that are necessarily employed during the course of risk assessment. Consideration of these “case histo- ries” can give valuable guidelines with regard to the development of improved new ecotoxicity tests and testing systems (e.g., microcosms and mesocosms). Since the recognition in the 1960s of the environmental problems presented by some persistent organochlorine insecticides, there have been many restrictions and bans placed upon these and other types of organic pollutants in western countries. These restrictions have been in response to perceived environmental problems posed by an individual compound or classes of compounds. As we have seen, some restric- tions/bans have been followed, in the shorter or longer term, by the recovery of populations that were evidently adversely effected by them. Such was the case with various species of predatory vertebrates following restrictions on organochlorine insecticides, or on dog whelks and other aquatic mollusks following restrictions on © 2009 by Taylor & Francis Group, LLC 242 Organic Pollutants: An Ecotoxicological Perspective, Second Edition the use of organotin compounds. Thus, in more recent times, some relatively clear- cut cases of pollution problems associated with particular compounds or classes of compounds appear to have been resolved—at least in more developed countries of the world where there have been strong initiatives to control environmental pollution. Consequently, in developed countries, there has been much less evidence for the existence of such relatively clear-cut pollution problems in recent years. On the other hand, concern has grown that there may be more insidious long-term effects that have thus far escaped notice. Interest has grown in the possible effects of mixtures of relatively low levels of contrasting types of pollutants, to which many free-living organisms are exposed. In the extreme case, it has been suggested that ecotoxicology might be regarded as just one type of stress, alongside others such as temperature, disease, nutrients, etc. (Van Straalen 2003). This third part of the book will be devoted mainly to the problem of addressing complex pollution problems and how they can be studied employing new biomarker assays that exploit new technologies of biomedical science. Chapter 13 will give a broad overview of this question. The following three chapters, “The Ecotoxicological Effects of Herbicides,” “Endocrine Disruptors,” and “Neurotoxicity and Behavioral Effects,” will all provide examples of the study of complex pollution problems. The concluding chapter will attempt to look into the future. What changes are we likely to see in pollution caused by organic compounds and in the regulatory systems designed to control such pollution? What improvements may there be in testing pro- cedures having regard for ethical questions raised by animal welfare organizations? Can ecotoxicity testing become more ecologically relevant? Can more information be gained by making greater use of eld studies? © 2009 by Taylor & Francis Group, LLC 243 13 Dealing with Complex Pollution Problems 13.1 INTRODUCTION In the second part of the text, attention was focused on particular pollutants or groups of pollutants. Their chemical and biochemical properties were related to their known ecotoxicological effects. Sometimes, with the aid of biomarker assays, it has been possible to relate the responses of individuals to consequent effects at the level of population and above. Biomarker assays provided the essential evidence that adverse effects on populations, communities, and ecosystems were being caused by envi- ronmental levels of particular chemicals. The examples given included population declines of raptors due to eggshell thinning caused by p,pb-DDE, and decline or extinction of dog whelk populations due to imposex caused by tributyl tin (TBTs). These were relatively straightforward situations where much of the adverse change was attributable to a single chemical. In other cases, as with the decline of raptors in the U.K., effects were related to one group of chemicals, in this case the cyclodienes. Since these events, there have been extensive bans on certain chemicals, and there is less evidence of harmful effects due to just one chemical or group of related chemi- cals. Interest has moved toward the possible adverse effects of complex mixtures of chemicals, sometimes of contrasting modes of action, often at low levels. Establishing the effects of combinations of chemicals in the eld is no simple mat- ter. There are many cases where adverse effects at the level of population or above have been shown to correlate with levels of either individual pollutants or combina- tions of pollutants, but the difculty comes in establishing causality, in establish- ing that particular chemicals at the levels measured in environmental samples are actually responsible for observed adverse effects. This question has already been encountered in the studies of pollution of the Great Lakes of North America by poly- chlorinated aromatic compounds and other pollutants (this book, Chapters 5, 6, and 7). A major difculty is that many factors other than the pollutants actually deter- mined by chemical analysis may contribute to population declines, including short- age of food, habitat change, disease, and climatic change—and other pollutants that have not been analyzed. Such factors may very well correlate with the measured pol- lutant levels, especially where comparison is simply being made between the popula- tions in one or two polluted areas and a “reference” population in a “clean” area. In badly polluted areas, there may be elevated levels of other pollutants in addition to those determined by chemical analysis, and these may have direct effects upon the species being studied, or indirect ones by causing changes in food supply. © 2009 by Taylor & Francis Group, LLC 244 Organic Pollutants: An Ecotoxicological Perspective, Second Edition 13.2 MEASURING THE TOXICITY OF MIXTURES As explained earlier, toxicity testing of pesticides and industrial chemicals for the purposes of statutory environmental risk assessment is very largely done on single compounds (Chapter 2, Section 2.5). For reasons of practicality and cost, only a minute proportion of the combinations of pollutants that occur in the natural envi- ronment can be tested for their toxicity. This dilemma will be discussed further in Section 13.3. A different and more complex situation exists, however, in the real world; mixtures of pollutants are found in contaminated ecosystems, in efuents discharged into surface waters, for example, sewage and industrial efuents, and in waste waters from pulp mills. The tests or bioassays employed here usually measure the toxicity expressed by mixtures, and investigators are presented with the prob- lem of identifying the contributions of individual components of a mixture to this toxicity. Simple toxicity tests/bioassays often establish the presence of toxic chemi- cals without identifying the mechanisms by which toxicity is expressed. The issue is further complicated by the possibility that naturally occurring xenobiotics, such as phytoestrogens taken up by sh, may contribute signicantly to the toxicity that is measured. In the simplest situation, chemicals in a mixture will show additive toxicity. If envi- ronmental samples are submitted for both toxicity testing and chemical analysis, the toxicity of the mixture may be estimated from the chemical data, to be compared with the actual measured toxicity. As explained earlier for the estimation of dioxin equivalents (Chapter 7, Section 7.2.4), the toxicity of each component of a mixture may be expressed relative to that of the most toxic component (toxic equivalency fac- tor or TEF). Using TEFs as conversion factors, the concentration of each component can then be converted into toxicity units (toxic equivalents or TEQs) the summation of which gives the predicted toxicity for the whole mixture. Often, the estimated toxicity of mixtures of chemicals in environmental samples falls short of the measured toxicity. Two major factors contribute to this underestimation of toxicity: rst, failure to detect certain toxic molecules (including natural xenobiotics), and second, the determination by analysis of chemicals that are of only limited availability to free-living organisms, as when there is strong adsorption in soils or sediments. In the latter case, analysis overestimates the quantity of a chemical that is actually available to an organism. Potentiation (synergism) between pollutants can also contribute to the underestimation of toxicity when making calculations based on chemical analysis (see Doi, Chapter 12 in Volume 2 of Calow 1994). Sometimes, during the course of analysis, mixtures of pollutants present in environmental samples are subjected to a fractionation procedure in an attempt to identify the main toxic components. By a process of elimination, tox- icity can then be tracked down to particular fractions and compounds. The advantages of combining toxicity testing with chemical analysis when deal- ing with complex mixtures of environmental chemicals are clearly evident. More useful information can be obtained than would be possible if one or the other were to be used alone. However, chemical analysis can be very expensive, which places a limitation on the extent to which it can be used. There has been a growing interest in the development of new, cost-effective biomarker assays for assessing the toxic- ity of mixtures. Of particular interest are bioassays that incorporate mechanistic © 2009 by Taylor & Francis Group, LLC Dealing with Complex Pollution Problems 245 biomarker responses and are inexpensive, rapid, and simple to use (see Section 13.5). These can be used alone or in combination with standard toxicity tests, and some of them identify the mechanisms responsible for toxic effects, thus indicating the types of compounds involved. 13.3 SHARED MECHANISM OF ACTION—AN INTEGRATED BIOMARKER APPROACH TO MEASURING THE TOXICITY OF MIXTURES A very large number of toxic organic pollutants, both manmade and naturally occur- ring, exist in the living environment. However, they express their toxicity through a much smaller number of mechanisms. Some of the more important sites of action of pollutants were described earlier (Chapter 2, Section 2.3). Thus, a logical approach to measuring the toxicity of mixtures of pollutants is to use appropriate mechanistic biomarker assays for monitoring the operation of a limited number of mechanisms of toxic action and to relate the responses that are measured to the levels of individual chemicals in the mixtures to which organisms are exposed (Peakall 1992, Peakall and Shugart 1993). Such an approach can provide an index of additive toxicity of mixtures, which takes into account any potentiation of toxicity at the toxicokinetic level (Walker 1998c). Mechanistic biomarkers can be both qualitative and quantita- tive; they identify a mechanism of toxic action and measure the degree to which it operates. Thus, they can provide an integrated measure of the overall effect of a group of compounds that operate through the same mechanism of action. Where the mechanism of action is specic to a particular class of chemicals, it can be related to the concentrations of components of a mixture which belong to that class. Four examples will now be given of such mechanistic biomarker assays that can give integrative measures of toxic action by pollutants, all of which have been described earlier in the text. Where the members of a group of pollutants share a common mode of action and their effects are additive, TEQs can, in principle, be estimated from their concentrations and then summated to estimate the toxicity of the mixture. In these examples, toxicity is thought to be simply related to the proportion of the total number sites of action occupied by the pollutants and the toxic effect additive where two or more compounds of the same type are attached to the binding site. 1. The inhibition of brain cholinesterase is a biomarker assay for organophos- phorous (OP) and carbamate insecticides (Chapter 10, Section 10.2.4). OPs inhibit the enzyme by forming covalent bonds with a serine residue at the active center. Inhibition is, at best, slowly reversible. The degree of toxic effect depends upon the extent of cholinesterase inhibition caused by one or more OP and/or carbamate insecticides. In the case of OPs administered to verte- brates, a typical scenario is as follows: sublethal symptoms begin to appear at 40–50% inhibition of cholinesterase, lethal toxicity above 70% inhibition. 2. The anticoagulant rodenticides warfarin and superwarfarins are toxic because they have high afnity for a vitamin K binding site of hepatic microsomes (Chapter 11, Section 11.2.4). In theory, an ideal biomarker would © 2009 by Taylor & Francis Group, LLC 246 Organic Pollutants: An Ecotoxicological Perspective, Second Edition measure the percent of vitamin K binding sites occupied by rodenticides. However, the technology is not currently available to do that. On the other hand, the measurement of increases in plasma levels of undercarboxylated clotting proteins some time after exposure to rodenticide provides a good biomarker for this toxic mechanism. 3. Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3b4,5b-tet- rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4). They have high afnity for the thyroxin-binding site on transthyretin (TTR) in plasma. Toxic effects include vitamin A deciency. Biomarker assays for this toxic mechanism include percentage of thyroxin-binding sites to which roden- ticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A. 4. Coplanar PCBs, PCDDs, and PCDFs express Ah-receptor-mediated tox- icity (Chapter 6, Section 6.2.4). Binding to the receptor leads to induction of cytochrome P450 I and a number of associated toxic effects. Again, toxic effects are related to the extent of binding to this receptor and appear to be additive, even with complex mixtures of planar polychlorinated com- pounds. Induction of P4501A1/2 has been widely used as the basis of a biomarker assay. Residue data can be used to estimate TEQs for dioxin (see Chapter 7, Section 7.2.4). In addition to the foregoing, three further examples in this list (numbers 5–7) deserve consideration. These are (5) interaction of endocrine disrup- tors with the estrogen receptor, (6) the action of uncouplers of oxidative phosphorylation, and (7) mechanisms of oxidative stress. Until now only the rst is well represented by biomarker assays that have been employed in ecotoxicology. 5. Interaction with the estrogen receptor (ER) has been important in the devel- opment of biomarker assays for endocrine disrupting chemicals (EDCs), and will be discussed in Chapter 15. The considerable range of biomarker assays (including bioassays) already developed is reviewed by Janssen, Faber, and Bosveld (1998). A surprisingly diverse range of chemicals can act as agonists or antagonists for the estrogen receptor, producing “feminizing” or “mas- culinizing” effects. These include o,pb-DDE, certain PAHs, PCBs, PCDDS, PCDFs, alkylphenols, and naturally occurring phyto- and myco-estrogens. However, it should be borne in mind that some EDCs (e.g., o,pb-DDE, PCBs) probably act through their hydroxymetabolites, which bear a closer resem- blance to natural estrogens than the parent compounds and, second, that oth- ers (e.g., alkylphenols) are only very weak estrogens. A number of biomarker assays have been developed for sh. Apart from a variety of nonspecic endpoints such as organ weight and histochemical change, vitellogenin synthesis has provided a specic and sensitive endpoint, which has been very useful for detecting the presence of environmental estrogens at low concentrations. A number of different cell lines have been developed for use in bioassays for rapid screening of environmental sam- ples. These include sh and bird hepatocytes, mouse hepatocytes, human mammary tumor cells, and yeast cells (Janssen, Faber, and Bosveld 1998). The endpoints include vitellogenin production, competitive binding to ER, © 2009 by Taylor & Francis Group, LLC Dealing with Complex Pollution Problems 247 the activation of galactosidase, the generation of light through the interme- diacy of reporter genes, and the elevation of mRNA levels. The diversity of the available bioassays reects the high prole that endocrine disruptors have been given in recent years. Some of these assays are described in more detail in Section 13.5. 6. Uncouplers of oxidative phosphorylation. Oxidative phosphorylation of ADP to generate ATP is a function of the mitochondrial inner membrane of animals and plants. Compounds that uncouple the process are general biocides, showing toxicity to animals and plants alike. For oxidative phos- phorylation to proceed, a proton gradient must be built up across the inner mitochondrial membrane. The maintenance of a proton gradient depends on the inner mitochondrial membrane remaining impermeable to protons. Most uncouplers of oxidative phosphorylation are weak acids that are lipo- philic when in the undissociated state. Examples include the herbicides dinitro ortho cresol (DNOC) and dinitro secondary butyl phenol (dinoseb), and the fungicide pentachlorophenol (PCP). The proton gradients across inner mitochondrial membranes are built up by active transport, utilizing energy from the electron transport chain that operates within the membrane. The direction of the gradient falls from the outside of the membrane to the inside (Figure 13.1). The dissociated forms (conjugate bases) of the weak acids combine with protons on the outside of the membrane to form undis- sociated lipophilic acids, which then dissolve in the membrane and diffuse across to the inside. Here, where the H + concentration is lower than on the outside of the membrane, they dissociate to release protons, and so act as proton translocators. They run down proton gradients, and hence “uncouple” #!' * !#! ! * * !#!# #%#!" !#!"" #!## $#" $ !#!"#" !#&!( )$"!#!" # * !%# $#"(#!"! #! ## Inside Outside ' " FIGURE 13.1 Uncouplers of oxidative phosphorylation. © 2009 by Taylor & Francis Group, LLC 248 Organic Pollutants: An Ecotoxicological Perspective, Second Edition oxidative phosphorylation, dissipating the energy that would otherwise have driven ATP synthesis. The action of uncouplers can be measured in isolated mitochondria with an oxygen electrode that follows the rate of oxygen con- sumption in relation to the rate of NADH consumption (see Nicholls 1982). Thus, the combined toxic action of mixtures of “uncouplers” can be studied in isolated mitochondria. Such studies can be used to investigate the signi- cance of tissue levels of mixtures of, for example, substituted phenols, found in tissues of animals after exposure to them in vivo. 7. The participation of some OPs in redox cycling with consequent oxidative stress. It has become increasingly apparent that the toxicity of certain com- pounds is due to their ability to facilitate the generation in tissues of highly unstable oxyradicals, such as the superoxide anion O 2 . − and the hydroxyl radical OH, as well as hydrogen peroxide, H 2 O 2 . These reactive species can cause cellular damage including lipid peroxidation and DNA damage, and have been implicated in certain disease states such as atherosclerosis and some forms of cancer (Halliwell and Gutteridge 1986). Because they are so unstable, they are difcult or impossible to detect. Proof of their existence depends upon indirect evidence. The appearance of characteristic products of oxyradical attack (e.g., oxidized lipids, malonaldehyde from lipid per- oxidation, and oxidative adducts of DNA), and the induction of enzymes involved in their destruction (e.g., superoxide dismutase, catalase, and per- oxidase) can all provide evidence for the presence of oxyradicals and give some indication of their cellular concentrations. These highly reactive species can be generated as a consequence of the presence of certain organic pollutants, such as bipridyl herbicides and aromatic nitro compounds (Figure 13.2). Taking as examples the herbicide paraquat (Hathway 1984), and nitro- pyrene (Hetherington et al. 1996), both can receive single electrons from reductive sources in the cell to form unstable free radicals. These radicals can then pass the electrons on to molecular oxygen to form superoxide anion, with regeneration of the original molecule. Thus, a cyclic process is established, the net effect being to transfer electrons from a reductive source to oxygen with generation of an oxyradical. Once formed, superoxide can undergo further reactions to form hydrogen peroxide and the highly reactive hydroxy radical. The toxicity of paraquat to plants and animals is believed to be due, largely or entirely, to cellular damage caused by oxyradicals. In the case of plants, these radicals attack the photosynthetic system (see Hassall 1990). In animals, toxic action is mainly against Type 1 and Type II alveolar cells, which take up the herbicide by a selective active transport system (see Timbrell 1999). There is evidence that mechanisms other than the production of free radicals of nitrogen-containing aromatic compounds are important in the case of pollutants. Refractory substrates for cytochrome P450, such as higher chlorinated PCBs, may facilitate the release into the cell of active forms of oxygen (e.g., the superoxide ion) by, in effect, blocking binding sites for substrates to be oxidized and thereby deect- ing activated oxygen produced by the heme nucleus. The unused activated oxygen may then escape from the domain of the cytochrome P450 in the form of superoxide to cause oxidative damage elsewhere in the cell. © 2009 by Taylor & Francis Group, LLC Dealing with Complex Pollution Problems 249 At the time of writing, the toxicity of oxyradicals generated by the action of pol- lutants is highly topical because of the relevance to human diseases. It is not an easy subject to investigate because of the instability of the radicals and the different mechanisms by which they may be generated. Hopefully rapid progress will be made so that monitoring the effects of oxyradicals will make an important contribution to the growing armory of mechanistic biomarkers for the study of environmental effects of organic pollutants. Viewing the foregoing examples overall, the rst ve all involve interaction between organic pollutants and discrete sites on proteins, one of them the active site of an enzyme, the others being “receptors” to which chemicals bind to produce toxicological effects. Knowledge of the structures and properties of such receptors facilitates the development of QSAR models for pollutants, where toxicity can be predicted from chemical parameters (Box 17.1). Indeed, new pesticides are some- times designed on the basis of models of this kind. For example, some ergosterol synthesis inhibitor fungicides (EBIs) that can lock into the catalytic site of P450s have been discovered by following this approach. Interactions such as these are essentially similar to the interactions of agonists and/or antagonists with receptors in pharmacology. The last two examples do not belong in the same category, there being no discrete single binding site on a protein. Uncouplers of oxidative phosphorylation operate across the inner mitochondrial membranes, their critical properties being the ability to reversibly interact with protons and their existence in the uncharged lipophilic state after protons are bound. Oxyradicals can, in principle, be generated by a variety of redox systems in differing locations, which are able to transfer single electrons to oxygen under cellular conditions. The systems that carry out one electron reduction of nitroaromatic compounds and aromatic amines have yet to be properly elucidated. R = Paraquat CH 3 N 3-Nitropyrene NCH 3 NCH 3 Free radical O 2 O 2 e O 2 O 2 NO 2 NO 2 e + + CH 3 N + FIGURE 13.2 Superoxide generation by 3-nitropyrene and paraquat. © 2009 by Taylor & Francis Group, LLC 250 Organic Pollutants: An Ecotoxicological Perspective, Second Edition Neither of these mechanisms of toxic action is susceptible to the kind of QSAR analysis referred to earlier, the employment of which depends on knowledge of the structure of particular binding sites. 13.4 TOXIC RESPONSES THAT SHARE COMMON PATHWAYS OF EXPRESSION When chemicals have toxic effects, the initial molecular interaction between the chemical and its site of action (receptor, membrane, redox system, etc.), is followed by a sequence of changes at the cellular and whole-organism levels that eventually lead to the appearance of overt symptoms of intoxication. Until now, discussion has been focused upon mechanisms of toxicity, that is, on the primary interaction of toxic chemicals with their sites of action. As we have seen, biomarker assays such as the measurement of acetylcholinesterase inhibition can monitor this initial interac- tion in a causal chain that leads to the overt expression of toxicity. Such mechanistic biomarkers are specic for particular types of chemicals acting at particular sites. By contrast, other biomarkers that measure consequent changes at higher levels of orga- nization, for example, the release of stress proteins, damage to cellular organelles, and disturbances to the nervous system or endocrine system are less specic, and can, in principle, provide integrated measures of the effects of diverse chemicals in a mixture operating through contrasting mechanisms of action. It is possible, there- fore, to measure the combined effects of chemicals working through different modes of action if these effects are expressed through a common pathway (e.g., the nervous system or the endocrine system) that can be monitored by a higher-level biomarker assay. For example, two chemicals may act on different receptors in the nervous system, but they may both produce similar disturbances such as tremors, hyperexcit- ability, and even certain changes in the EEG pattern, all of which can be measured by higher-level biomarker assays. When moving from the primary toxic lesion to the knock-on effects at higher levels of organization, the higher one goes, the harder it becomes to relate mea- sured effects to particular mechanisms of toxic action. Thus, it is advantageous to use combinations of biomarkers operating at different organizational levels rather than single biomarker assays when investigating toxic effects of mixtures of dissimilar compounds; it becomes possible to relate initial responses to higher-level responses in the causal chain of toxicity. Although they often do not give clear evidence of the mechanism of action, higher-level biomarker assays (e.g., scope for growth in mol- lusks, or behavioral effects in vertebrates) have the advantage that they can give an integrated measure of the toxic effects caused by a mixture of chemicals. Taken together, combinations of biomarker assays working at different organiza- tional levels can give an “in-depth” picture of the sequence of adverse changes that follows exposure to toxic mixtures, when compounds in the mixture with different modes of action cause higher-level changes through a common pathway of expres- sion. Two prime examples are (1) chemicals that cause endocrine disruption, and (2) neurotoxic compounds. To illustrate these issues further in more depth and detail, © 2009 by Taylor & Francis Group, LLC [...]... checking the quality of surface waters and effluents, and giving early warning of pollution problems In these respects they have considerable advantages over chemical analysis They can be very much cheaper and, because chemical analysis is not © 2009 by Taylor & Francis Group, LLC 252 Organic Pollutants: An Ecotoxicological Perspective, Second Edition comprehensive, they can measure the toxicity of compounds... Francis Group, LLC 254 Organic Pollutants: An Ecotoxicological Perspective, Second Edition of mixtures of industrial chemicals that may be released into the environment Even if such resources did exist, such an exercise would be very largely a waste of time because substantial potentiation of toxicity in mixtures is a rare event As understanding grows of biochemical mechanisms that lead to strong potentiation... detergents had an estrogenic effect in a highly polluted stretch of river The estrogen receptor is responsive to a number of environmental compounds, including organochlorine compounds such as dicofol and o,p -DDT, nonyl phenols (rather weak), and naturally occurring phytoestrogens (IEH Assessment 1995 and Chapter 15) Once again, an assay system that is mechanistically based can give an integrated measure... biomarkers operating at different organizational levels when investigating complex pollution problems Such an approach can give an in-depth picture of toxic effects Bioassays can be used for cost-effective biomonitoring and rapid screening of environmental samples to detect the presence of mixtures of toxic chemicals and to identify hot spots FURTHER READING Fossi, M.C and Leonzio, C (1994) Nondestructive... evidence to the contrary, an approach that has worked out reasonably well in practice However, there are important exceptions (Chapter 2, Section 2.5, and Chapters 10 and 12) Full consideration should be given to known mechanisms of potentiation when questions are raised about the possible toxicity of mixtures Where, on sound mechanistic grounds, there appears to be a clear risk of potentiation, appropriate... environmental risk assessment 13. 5 BIOASSAYS FOR TOXICITY OF MIXTURES Both cellular systems and genetically manipulated microorganisms have been used to measure the toxicity of individual compounds and mixtures present in environmental samples such as water, soil, and sediment Such bioassays can have the advantages of being simple, rapid, and inexpensive to use They can provide evidence for the existence... with resistant strains from the field These things said, bioassay systems have considerable potential for biomonitoring and environmental risk assessment By giving a rapid indication of where toxicity exists, they can identify “hot spots” and pave the way for the use of more sophisticated methods of establishing cause and effect, including chemical analysis and biomarker assays on living organisms In... testing (see Chapter 15, Section 15.6, and Walker 1998b) 13. 6 POTENTIATION OF TOXICITY IN MIXTURES The problem of potentiation was discussed earlier (Chapter 2, Section 2.5) Potentiation is often the consequence of interactions at the toxicokinetic level, especially inhibition of detoxication or increased activation The consequences of such potentiation may be evident not only at the whole animal level... mammalian hepatic microsomes with high monooxygenase activity Thus, a distinction can be made between pollutants that are themselves mutagenic and others that require metabolic activation by the P450 system A number of mammalian and fish cell lines have been used to test for toxicity, some of them measuring particular mechanisms Bioassay systems have been developed that test for Ah-receptor-mediated... of occupancy of the Ah receptor by these compounds determines the quantity of light that is emitted Thus, the CALUX system can give an integrated measure of the effects of mixtures of polyhalogenated compounds on the Ah receptor, and an indication, therefore, of the potential of such mixtures to cause Ah-receptor-mediated toxicity In another example, fish hepatocyte lines have been used to detect the . organochlorine insecticides, or on dog whelks and other aquatic mollusks following restrictions on © 2009 by Taylor & Francis Group, LLC 242 Organic Pollutants: An Ecotoxicological Perspective, . poly- chlorinated aromatic compounds and other pollutants (this book, Chapters 5, 6, and 7). A major difculty is that many factors other than the pollutants actually deter- mined by chemical analysis. and, because chemical analysis is not © 2009 by Taylor & Francis Group, LLC 252 Organic Pollutants: An Ecotoxicological Perspective, Second Edition comprehensive, they can measure the toxicity
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