Animal models illustrative studies

During the 1970 s and early 1980 s a large number of test methods were developed to measure the toxic potency of the smoke produced from burning materials. The ones most widely used are in refs. 29-32. These tests differ in several respects the conditions under which the material is burnt, the characteristics of the air flow (i.e. static or dynamic), the type of method used to evaluate smoke toxicity (i.e. analytical or bioassay), the animal model used for bioassay tests, and the end point determined. As a consequence of all these differences the tests result in a tremendous variation of ranking for the smoke of various materials. A case in point was made in a study of the toxic potency of 14 materials by two methods [33]. It showed (Table I) that the material ranked most toxic by one of the protocols used was ranked least toxic by the other protocol Although neither of these protocols is in common use in the late 1980 s, it illustrates some of the shortcomings associated with small scale toxic potency of smoke tests. 

Comprehensive studies based on rodent models of anxiety have not only underlined that anxiety in itself represents a complex behavioral system but also that it is determined by both genetic and environmental factors as well as by the interaction between both. The examples used in this section have been selected to illustrate both the potential and the caveats of current models and the emerging possibilities offered by gene technology. These examples are thought to be representative of the different concepts followed in generating animal models. 

GC-MS has found wide application in studies of monoamines in both animal models and in human neuropharmacology [452]. Interest has centred on the use of selected ion monitoring in the determination of trace amounts of the amines, their metabolites and related substances with a possible function as neurotransmitters. The SIM approach complements established assay methods such as gas chromatography with electron capture detection (ECD), fluorimetry or enzymic assay. A check on specificity is afforded and in many cases enhancement in sensitivity and precision of measurement can be obtained. Method development, principally relating to estimation of central amine turnover, is noted in this Section and an outline of work on human depression serves to illustrate the potential of GC-MS to the study of CNS dysfunction. 

Dermal absorption of agricultural chemicals and animal drugs in food-producing animals must be considered as a potential route from which tissue residues of drugs and chemicals may occur. This has been supported in studies of topical pesticide exposure in cows and sheep. Despite the many advances made in in vitro and in vivo techniques for assessing percutaneous absorption in laboratory animals and man, very little systematic attention has been focussed on food-producing animals. The only exception is the pig since it is an accepted model for human studies. The purpose of this manuscript is to overview the literature on dermal xenobiotic absorption in food-producing animals to illustrate the risk that is present, and to outline how in vitro and in vivo methods could be applied to this problem. 

Another important ncunrtoxic sequel of OP exposure is developmental neurotoxicity. Since OP developmental neurotoxicity in both humans (Garry, 2004) and animal models (fzrael et ai. 2004) has been reviewed, we discuss only selected case studies to illustrate the conclusion that this neurotoxic effect of OPs can also occur independent of AChE inhibition. Initial studies indicated that the developing nervous system is far more sensitive to the acute cholinergic toxicity of OPs (Bushnell ei al, 1991 Pope and Chakraborti, 1992), most likely due to age-related differences in the hepatic detoxification of the AChE-active metabolites of OPs (Atierberry et ai, 1997 Benke and Murphy, 1975 Moitensen et ai, 1996). However, subsequent studies... 

TABLE 12.15 Illustrative Multisystem Toxicological Mechanisms for Lead Effects Relevant to CNS of Humans and Animal Models of Lead Toxicity In Vitro and In Vivo Studies—(cont.)... 

Many different non- or minimally-invasive techniques have been investigated for measuring the response of tissues to PDT treatment in vivo, either qualitatively or quantitatively, as summarized in Table 2. To date these techniques have mainly been applied in preclinical animal model studies, but there are a number of examples in the literature where some of the methods have been used in patients. Two of the optical imaging techniques, namely Doppler optical coherence tomography (DOCT) and bioluminescence imaging (BLI) will be illustrated here. 

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