References

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Toxicogenomics Evolution Of The Field

Toxicogenomics evolved from early gene expression studies on the response of a biological system to a particular toxicant or panel of reference agents, toward more mature investigations that integrate several -omics domains with toxicology and pathology data (see Table 5.1). Exposure-specific and outcome-specific patterns of gene, protein, and metabolite profiles have been used to identify molecular changes that serve as biomarkers of toxicity 23,38-44 and provide insights into mechanisms of...

Info

Portier CJ, Kopp-Schneider A, Sherman CD. Calculating tumor incidence rates in stochastic models of carcinogenesis. Math Biosci 1996 135 129-46. 48. Thomas RS, Lytle WE, Keefe TJ, Constan AA, Yang RSH. Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using advanced continuous simulation language (ACSL) A computational method. Fundam Appl Toxicol 1996 31 19-28. 49. Bernillon P, Bois FY. Statistical issues in toxicokinetic modeling A Bayesian perspective....

Fields Of Expertise Within Toxicology

Toxicology can be classified according to the effects on the organ systems damaged. Alternatively, it can be classified according to the mechanisms of toxicity. Almost anything that can go wrong with almost any tissue in the body will occur. Each of these areas comprises its own realm of toxicological expertise. We will first examine several examples of organ-based toxicity. In some cases there will be extensive overlap between categories. One of the important questions is why there frequently...

Pharmaceutical Industry and FDA Perspective

According to the FDA, severe hepatotoxicity is one of the most common causes for pharmaceutical product recalls and labeling changes, and this raises the question of how effective nonclinical and clinical testing are in recognizing such toxicity. Although much attention has been focused on the predictivity of animal models for clinical findings in humans, clinical trials of pharmaceuticals are in fact a relatively poor source of information for ascertaining the probability that an event...

Computation In Toxicology

The primary advantage of the computer is to deal with work that is so large and so complex that it cannot otherwise readily be possible. One example of such a need is the highly complicated chemical toxicological biomedical literature that exists. A computer can search and mine the literature, and it can organize it into mutually relevant collections of articles. Data clustering is one example of such an intelligent organization of the literature 36 . Other examples include directory searches,...

Mechanisms Of Toxic Injury

Although many different cells and tissues can be injured by toxicants, there are not many different fundamental mechanisms by which injury can occur. Each of these categories can be very broad, however. Mechanisms of injury include ligand binding by heavy metals, covalent binding, oxidative stress by active oxygen species, antimetabolites, the extension of pharmacologic action, dysregulation of cellular signaling, and a miscellaneous category, all of which are now described in a little more...