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Whole animal studies

2 CELLULAR STUDIES IN INTACT TISSUE 8.2.1 Whole-Animal Studies [Pg.130]

Although the emphasis of this chapter is on isolated cells in culture, responses at the cellular level can be assessed in intact tissue after exposure of the whole animal. Observations of cellular responses are most often made with in situ detection techniques and microscopic observation, such as immunohistochemisty (Chapter 7) and nucleic acid hybridization (Chapter 2). Preparations used for these in situ techniques are generally tissue that has been fixed after toxicant treatment, then embedded and sliced thinly enough (-5 pm) to enable observation by microscopy, usually [Pg.130]


A general prescreen to select likely developmental toxins for subsequent whole-animal studies. [Pg.287]

To provide supplementary information about developmental toxicity in addition to that provided by whole-animal studies. [Pg.288]

In vitro developmental toxicity systems have clearly been usefid for studies of mechanisms of developmental effects (e.g., Datson et al., 1989) — use (3) in the list above. It is unclear, though, whether in vitro developmental toxicity tests will provide useful information about developmental toxicity that is not derived from whole animal studies [use (4) from the list]. As is true for a possible use as a prescreen, the interpretation of a positive finding in an in vitro test will depend on knowing the exposure level in vivo. When this is known, the in vitro information could be helpful. The results of in vivo studies, though, would still likely be considered definitive for that species. [Pg.290]

Whole animal studies are generally necessary to determine the effect of the drug on organ systems and disease models. Cardiovascular and renal function studies of all new drugs are generally first performed in normal animals. Where appropriate, studies on disease models are performed. For a candidate antihypertensive drug, animals with hypertension would be treated to see whether blood pressure was lowered in a dose-related manner and to characterize other effects of the compound. Evidence would be collected on duration of action and efficacy after oral and parenteral administration. [Pg.98]

Whole-animal studies assess the percent of the applied dose absorbed into the body using classic techniques of bioavailability, where absorbed chemical is measured in the blood, urine, feces, and tissues with mass balance techniques. Recently, methods have been developed to assess absorption by measuring the amount of chemical in the stratum comeum because it is the driving force for diffusion. Cellophane tape strips are collected 30 minutes after chemical exposure and the amount of drug assayed in these tape strips correlates to the amount systemically absorbed. If the focus of the research is to determine the amount of chemical that has penetrated into skin, core biopsies may be collected and serially sectioned, and a profile of the chemical as a function of skin depth may be obtained. [Pg.869]

Biological data should pertain to an aspect of biological/biochemical function that can be measured. The events could be occurring in enzymes, isolated or bound receptors, in cellular systems, or whole animals. Because there is considerable variation in biological responses, test samples should be run in duplicate or preferably triplicate, except in whole animal studies where assay conditions (e.g., plasma concentrations of a drug) preclude such measurements. [Pg.7]

Effects on physiological parameters whole animal studies 330... [Pg.323]

Often it is possible to replace a toxicity test with an alternative methodology, especially when cellular or mechanistic studies are undertaken. Tissue in laboratory culture, microorganisms, or lower invertebrates can also be used in place of whole animal studies. In the case of screening tests, there now exists a broad variety of quantitative structure-activity models that can predict and... [Pg.91]

Why are in vivo (whole animal) studies still important to drug discovery All the new technology, as well as mathematical modeling using computers, has reduced but not eliminated the need for animal experimentation. Computer models still cannot accurately predict the effects of chemical compounds on the cell, let alone in systems with higher orders of complexity, that is whole tissues,... [Pg.48]

Extensive evidence conclusively demonstrates that another important mechanism of action of adrenotoxicants is the generation of ROS and the imbalance between prooxidants and antioxidants in the cell. The resulting oxidative stress is a mechanism mediating the toxic effects of numerous chemicals in a wide array of cells and organs, in many if not all, animal and plant species. Numerous studies with mammalian models using either in vitro exposures of tissues and cells or whole animal studies,... [Pg.346]

A further consideration that is very important in whole animal studies is the inter-individual variation in response to treatment. This variation can be quite high between animals and it has been recommended that at least 10 animals per treatment be used if one wishes to quantify apoptosis in a tissue (4). A final item that can become a concern is those situations where the basal apoptotic index is very low (<0.1 %), in which case counting sufficient apoptotic bodies to obtain an index of sufficient confidence may warrant the counting of far more cells than originally intended, perhaps as many as 6000 (3,44). [Pg.70]


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See also in sourсe #XX -- [ Pg.130 ]




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