Century Toxicology

As discussed in the introduction, there are an innumerable numbCT of environmental chemicals for which little or no toxicity information is available and for many others for which it is inadequate. HTS studies could be invaluable at three related areas. First, they could identify those chemicals with the greatest potential toxicity and hazard which would then be prioritized for further testing. Second, they may be able to identify pathways of toxicity. Third, they may be able to identify and quantify metabolic pathways. 

The array of tests performed can also include purely computational methods to identify, for example, potential for receptor interaction or metabolic pathway. Both structitee-activity-based studies and quantum-based computational techniques are among the methods employed (see Chapter 20). The advent of relational 

Systems Biology. This then brings us back to modeling and to the next generation of modeling. As discussed, modeling in risk assessment has been of 

As described, PBPK models are systems of mass balance equations describing the mass or concentration of chemicals at various loci within the tissues. Most often the loci have been at the level of the whole organ. However, the mass can be described at as fine a resolution as is necessary and as knowledge allows. For example, a PBPK model can describe the concentration at the cellular or subcellular level (Blancato and Bischoff 1993). Ultimately, the chemical input into pharmacodynamic and systems level models could easily be the output of PBPK models at whatever the necessary resolution. For example, if a perturbation in a specific cell is directly related to a concentration or mass of chemical at that cell, the PBPK model would be expanded to describe that mass or concentration. This though raises 

Andersen, M. E. (1981). Saturable metabolism and its relationship to toxicity. Crit Rev Toxicol 9, 105-150. 

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Keller DA, fuberg DR, Catlin N, Farland WH, Hess FG, Wolf DC, Doerrer NG (2012) Identification and characterization of adverse effects in 21st century toxicology. Toxicol Sci 126(2) 291-297... 

Natural and synthetic chemicals affect every phase of our daily Hves ia both good and noxious manners. The noxious effects of certain substances have been appreciated siace the time of the ancient Greeks. However, it was not until the sixteenth century that certain principles of toxicology became formulated as a result of the thoughts of Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus (1493—1541). Among a variety of other achievements, he embodied the basis for contemporary appreciation of dose—response relationships ia his often paraphrased dictum "Only the dose makes a poison."... 

The bactericidal effects of ionizing radiation have been known for a century, and for over 80 years it has been known that ionizing radiation kills the Ttichinella spiralis parasite, which infects raw pork. By the mid-1970s, international experts had concluded that irradiating foods preserves them without creating any toxicological hazards. Only in the last decade, however, has preservation by irradiation been applied commercially. 

Hartung, T. (2009) Toxicology for the twenty-first century. Nature, 460 (7252), 208-212. 

Walker, N.J. and Bucher, J.R. (2009) A 21st century paradigm for evaluating the health hazards of nanoscale materials Toxicological Sciences,... 

Morrison, J., Quinton, R. and Reinert, H. (1968). The purpose and value of LD50 determinations. In Modern Trends in Toxicology, Vol. I (Boyland, E. and Goulding, R., Eds.). Appleton-Century-Crofts, London, pp. 1-17. 

Since the last part of the 20th Century, the issue of pesticides in foods has generated considerable public concern and debate. Pesticides are chemicals designed specifically for their toxicological effects on target pests, such as insects, weeds, and plant diseases. Public awareness that such chemicals are commonly detected in the food supply as residues contributes greatly to the debate. 

Chapin RE, Stedman DB (2009) Endless possibilities stem cells and the vision for toxicology testing in the 21st century. Toxicol Sci 112 17-22... 

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