Introduction to ENVIRONMENTAL TOXICOLOGY Impacts of Chemicals Upon Ecological Systems - CHAPTER 2

CHAPTER 2 A Framework for Environmental Toxicology Environmental toxicology can be simplified to the understanding of only three functions. These functions are presented in Figure 2.1. First, there is the interaction of the introduced chemical, xenobiotic, with the environment. This interaction con-trols the amount of toxicant or the dose available to the biota. Second, the xenobiotic interacts with its site of action. The site of action is the particular protein or other biological molecule that interacts with the toxicant. Third, the interaction of the xenobiotic with a site of action at the molecular level produces effects at higher levels of biological organization. If environmental toxicologists could write appro-priate functions that would describe the transfer of an effect from its interaction with a specific receptor molecule to the effects seen at the community level, it would be possible to predict accurately the effects of pollutants in the environment. We are far from a suitable understanding of these functions. The remainder of the chapter introduces the critical factors for each of these functions. Unfortunately, we do not clearly understand how the impacts seen at the population and community levels are propagated from molecular interactions. THE CLASSICAL VIEWPOINT FOR CLASSIFYING TOXICOLOGICAL EFFECTS Techniques have been derived to evaluate effects at each step from the introduc-tion of a xenobiotic to the biosphere to the final series of effects. These techniques are not uniform for each class of toxicant, and mixtures are even more difficult to evaluate. Given this background, however, it is possible to outline the levels of biological interaction with a xenobiotic: Chemical Physical-Chemical Characteristics Bioaccumulation/Biotransformation/Biodegradation Site of Action Biochemical Monitoring Physiological and Behavioral Population Parameters Community Parameters Ecosystem Effects Each level of organization can be observed and examined at various degrees of resolution. The factors falling under each level are illustrated in Figure 2.2. Examples of these factors at each level of biological organization are given below. Chemical Physical-Chemical Characteristics The interaction of the atoms and electrons within a specific molecule determines the impact of the compound at the molecular level. The contribution of the physical-chemical characteristics of a compound to the observed toxicity is called quantitative structure-activity relationships (QSAR). QSAR has the potential of enabling envi-ronmental toxicologists to predict the environmental consequences of toxicants using only structure as a guide. The response of a chemical to ultraviolet radiation and its reactivity with the abiotic constituents of the environment determines a fate of a compound. It must be remembered that in most cases the interaction at a molecular level with a xenobiotic is happenstance. Often this interaction is a byproduct of the usual physiological function of the particular biological site with some other low molecular weight compound that occurs in the normal metabolism of the organism. Xenobiotics often mimic these naturally occurring organisms, causing degradation and detoxifi-cation in some cases and toxicity in others. Figure 2.1 The three functions of environmental toxicology. Only three basic functions need to be described after the introduction of a xenobiotic into the environment. The first describes the fate and distribution of the material in the biosphere and the organism after the initial release to the environment (f(f)). The second function describes the interaction of the material with the site of action (f(s)). The last function describes the impact of this molecular interaction upon the function of an ecosystem (f(e)). Figure 2.2 Parameters and indications of the interaction of a xenobiotic with the ecosystem. The examples listed are only a selection of the parameters that need to be understood for the explanation of the effects of a xenobiotic upon an ecosystem. However, biological systems appear to be organized within a hierarchy and that is how environmental toxicology must frame its outlook upon environmental problems. Bioaccumulation/Biotransformation/Biodegradation A great deal can occur to a xenobiotic from its introduction to the environment to its interaction at the site of action. Many materials are altered in specific ways depending upon the particular chemical characteristics of the environment. Bioac-cumulation, the increase in concentration of a chemical in tissue compared to the environment, often occurs with materials that are more soluble in lipid and organics (lipophilic) than in water (hydrophilic). Compounds are often transformed into other materials by the various metabolic systems that reduce or alter the toxicity of materials introduced to the body. This process is biotransformation. Biodegradation is the process that breaks down a xenobiotic into a simpler form. Ultimately, the biodegradation of organics results in the release of CO2 and H2O to the environment. Receptor and the Mode of Action The site at which the xenobiotic interacts with the organism at the molecular level is particularly important. This receptor molecule or site of action may be the nucleic acids, specific proteins within nerve synapses or present within the cellular membrane, or it can be very nonspecific. Narcosis may affect the organism, not by interaction with a particular key molecule, but by changing the characteristics of the cell membrane. The particular kind of interaction determines whether the effect is broad or more specific within the organism and phylogenetically. Biochemical and Molecular Effects There are broad ranges of effects at this level. We will use as an example, at the most basic and fundamental of changes, alterations to DNA. DNA adducts and strand breakages are indicators of genotoxic materials, com-pounds that affect or alter the transmission of genetic material. One advantage to these methods is that the active site can be examined for a variety of organisms. The methodologies are proven and can be used virtually regardless of species. However, damage to the DNA only provides a broad classification as to the type of toxicant. The study of the normal variation and damage to DNA in unpolluted environments has just begun. Cytogenetic examination of meiotic and mitotic cells can reveal damage to genetic components of the organism. Chromosomal breakage, micronuclei, and various trisomys can be detected microscopically. Few organisms, however, have the requisite chromosomal maps to accurately score more subtle types of damage. Properly developed, cytogenetic examinations may prove to be powerful and sensi-tive indicators of environmental contamination for certain classes of material. A more complicated and ultimately complex system, directly affected by damage to certain regions of DNA and to cellular proteins, is the inhibition of the immuno-logical system of an organism — immunological suppression. Immunological sup-pression by xenobiotics could have subtle but important impacts on natural popula-tions. Invertebrates and other organisms have a variety of immunological responses that can be examined in the laboratory setting from field collections. The immuno-logical responses of bivalves in some ways are similar to vertebrate systems and can be suppressed or activated by various toxicants. Mammals and birds have well documented immunological responses although the impacts of pollutants are not well understood. Considering the importance to the organism, immunological responses could be very valuable in assessing the health of an ecosystem at the population level. Physiological and Behavioral Effects Physiological and behavioral indicators of impact within a population are the classical means by which the health of populations is assessed. The major drawback has been the extrapolation of these factors based upon the health of an individual organism, attributing the damage to a particular pollutant and extrapolating this to the population level. Lesions and necrosis in tissues have been the cornerstone of much environmental pathology. Gills are sensitive tissues and often reflect the presence of irritant mate-rials. In addition, damage to the gills has an obvious and direct impact upon the health of the organism. Related to the detection of lesions are those that are tumor-agenic. Tumors in fish, especially flatfish, have been extensively studied as indicators of oncogenic materials in marine sediments. Oncogenesis also has been extensively studied in Medaka and trout as means of determining the pathways responsible for tumor development. Development of tumors in fish more commonly found in natural communities should follow similar mechanisms. As with many indicators of toxicant impact, relating the effect of tumor development to the health and reproduction of a wild population has not been as closely examined as the endpoint. Reproductive success is certainly another measure of the health of an organism and is the principal indicator of the Darwinian fitness of an organism. In a laboratory situation it certainly is possible to measure fecundity and the success of offspring in their maturation. In nature these parameters may be very difficult to measure accurately. Many factors other than pollution can lead to poor reproductive success. Secondary effects, such as the impact of habitat loss on zooplankton populations essential for fry feeding will be seen in the depression or elimination of the young age classes. Mortality is certainly easy to assay on the individual organism. Macroinverte-brates, such as bivalves and cnideria, can be examined and since they are relatively sessile, the mortality can be attributed to a factor in the immediate environment. Fish, being mobile, can die due to exposure kilometers away or because of multiple intoxications during their migrations. By the time the fish are dying, the other levels of the ecosystem are in a sad state. The use of the cough response and ventilatory rate of fish has been a promising system for the determination and prevention of environmental contamination. Pio-neered at Virginia Polytechnic Institute and State University, the measurement of the ventilatory rate of fish using electrodes to pick up the muscular contraction of the operculum has been brought to a very high stage of refinement. It is now possible to monitor continually the water quality as perceived by the test organisms with a desktop computer analysis system at a relatively low cost. Population Parameters A variety of endpoints have been used, including number and structure of a population, to indicate stress. Population numbers or density have been widely used for plant, animal, and microbial populations in spite of the problems in mark recapture and other sampling strategies. Since younger life stages are considered to be more sensitive to a variety of pollutants, shifts in age structure to an older population may indicate stress. In addition, cycles in age structure and population size occur due to the inherent properties of the age structure of the population and predator–prey interactions. Crashes in populations, such as those of the stripped bass in the Chesapeake Bay, do occur and certainly are observed. A crash often does not lend itself to an easy cause–effect relationship, making mitigation strategies difficult to create. The determination of alterations in genetic structure, i.e., the frequency of certain marker alleles, has become increasingly popular. The technology of gel electrophore-sis has made this a seemingly easy procedure. Population geneticists have long used this method to observe alterations in gene frequencies in populations of bacteria, protozoans, plants, various vertebrates, and the famous Drosophilla. 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