Biological systems animal models

This section discusses potential health effects from exposures during the period from conception to maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect effects on the fetus and neonate due to maternal exposure during gestation and lactation. Relevant animal and in vitro models are also discussed. 

The vast majority of research focused on selenium in biology (primarily in the fields of molecular biology, cell biology, and biochemistry) over the past 20 years has centered on identification and characterization of specific selenoproteins, or proteins that contain selenium in the form of selenocysteine. In addition, studies to determine the unique machinery necessary for incorporation of a nonstandard amino acid (L-selenocysteine) during translation also have been central to our understanding of how cells can utilize this metalloid. This process has been studied in bacterial models (primarily Escherichia colt) and more recently in mammals in vitro cell culture and animal models). In this work, we will review the biosynthesis of selenoproteins in bacterial systems, and only briefly review what is currently known about parallel pathways in mammals, since a comprehensive review in this area has been recently published. Moreover, we summarize the global picture of the nonspecific and specific use of selenium from a broader perspective, one that includes lesser known pathways for selenium utilization into modified nucleosides in tRNA and a labile selenium cofactor. We also review recent research on newly identified mammalian selenoproteins and discuss their role in mammalian cell biology. 

Biological chemistry takes place in the aqueous environment of the body of an animal or plant. Therefore, in spite of the fact that the molecules involved are largely organic in nature, the chemistry is essential acid-base chemistry and therefore a good candidate for the application of the bond valence model, as the example of adenosine triphosphate discussed in the previous section (Section 13.5.4) shows. This section illustrates a number of other ways in which the model has been used in biological systems. 

Search for and validate animal models to analyse toxicological aspects of reproductive biology to develop appropriate systems that are reproducible, low cost and easier to extrapolate to human disease. 

Physiological toxicokinetic (or pharmacokinetic) models represent descriptions of biological systems and can be used to describe the behaviour of chemicals in the intact animal. Such models have been used to predict the disposition of butadiene and metabolites in rats, mice, and humans. For the case of rats and mice, these predictions can be compared with experimental data. In some cases (see below), the models successfully describe (and accurately predict) the disposition of butadiene and metabolites. Human physiological toxicokinetic model predictions normally cannot be verified due to lack of experimental data. 

PB-PK models, sometimes referred to as biologically-based disposition models, allow for accurate extrapolation of rodent data to estimate human dose-response relationships (Paustenbach, 1995). PB-PK models, unlike compartmental models, have the capability of simulating a chemical s behavior in biological systems. The purpose of a PB-PK model is to predict the human dose-response relationship based on animal data by quantitatively estimating the delivered dose of the biologically relevant chemical species in a target tissue (Andersen etal., 1987 Clewell etal., 1994 Leung and Paustenbach, 1995 Ramsey and Andersen, 1984). 

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