Abstract
Toxicodynamic testing is aimed at the elucidation of adverse effects of chemicals including understanding of their mode of action. In many cases, the “standard program” of toxicological testing on acute, subchronic, or chronic toxicity, genotoxicity, carcinogenicity, teratogenicity, and developmental and reproductive toxicity, which is needed for many regulatory purposes, already provides important information on the mode(s) of action of a compound. Targeted mechanistic investigations often follow, which use specifically designed models such as genetically modified cells or animals, studies using specific cell types, subcellular fractions, enzymes, etc. The understanding of the mechanisms underlying a certain mode of action and gained information on the dose- or concentration-response from in vivo or in vitro studies is crucial to derive point of departures for further human risk assessment and for regulatory toxicology of chemicals since it allows decisions on the options for extrapolation of experimental data to the human situation. This text follows the different levels of experimental models in toxicodynamic testing from isolated target molecules up to whole organisms like laboratory animals and humans.
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References
Anderson MW, Reynolds SH, You M, Maromnpot RM (1992) Role of proto-oncogene activation in carcinogenesis. Environ Health Perspect 98:13–24
EURL-ECVAM Status Report on the development, validation and regulatory acceptance of alternative methods and approaches (2018). https://ec.europa.eu/jrc/en/publication/eur-scientific-and-technical-research-reports/eurl-ecvam-status-report-development-validation-and-regulatory-acceptance-alternative-3
Gregus Z, Klaassen CD (2001) Mechanisms of toxicity. In: Klaassen CD (ed) Casarett and Doull’s toxicology. McGraw-Hill, New York
Hayes AW (2001) Principles and methods of toxiocology, 4th edn. Taylor and Francis, New York
Keller GA, Gago MLF, Diez RA, Di Girolamo G (2017) In vivo phenotyping methods: cytochrome P450 probes with emphasis on the cocktail approach. Curr Pharm Des 23:2035–2049
Krewski D, Andersen ME, Tyshenko MG, Krishnan K, Hartung T, Boekelheide K, Wambaugh JF, Jones D, Whelan M, Thomas R, Yauk C, Barton-Maclaren T, Cote I (2020) Toxicity testing in the 21st century: progress in the past decade and future perspectives. Arch Toxicol 94(1):1–58
Messina A, Luce E, Hussein M, Dubart-Kupperschmitt A (2020) Pluripotent-stem-cell-derived hepatic cells: hepatocytes and organoids for liver therapy and regeneration. Cells 9(2):420
OECD Test guidelines. https://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm
Pumford NR, Halmes NC (1997) Protein targets of xenobiotic reactive intermediates. Annu Rev Pharmacol Toxicol 37:91–117
Wyllie AH (1997) Apoptosis: an overview. Br Med Bull 53:451–465
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Cartus, A., Schrenk, D. (2021). Toxicodynamic Tests. In: Reichl, FX., Schwenk, M. (eds) Regulatory Toxicology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36206-4_39-2
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DOI: https://doi.org/10.1007/978-3-642-36206-4_39-2
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