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Chapter 8: Target Organ and Target System Toxicity

Chapter 8: Target Organ and Target System Toxicity ATLA 30, Supplement 1, 71–82, 2002 71 (OECD TG 408), and the combined repeat-dose tox- Introduction icity and reproductive toxicity screening test. During long-term exposure, some compounds can The detection of specific target organ and target induce adaptive processes in their target cells. organ system toxicity is an important aspect of tox- Changes in gene expression at the transcriptional, icological testing, and the conventional test proce- translational or post-translational levels can result dures involve chronic, repeat-dose in vivo testing, from the induction or inhibition of enzyme systems, often in a non-rodent species as well as in a rodent or by up-regulation or down-regulation of recep- species. This kind of predictive testing represents tor–ligand interactions, thereby changing the func- an enormous challenge to those who, for a variety of tions of intracellular signal cascades. For instance, scientific and ethical reasons, would like to see ani- the increase of metallothionein expression follow- mal testing replaced by non-animal tests and test- ing exposure to low doses of metals permits a higher ing strategies. It will be worthwhile putting toxic dose to be tolerated (2). considerable skill and effort into attempts to meet Another important parameter to take into con- this challenge, not http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alternatives to Laboratory Animals SAGE

Chapter 8: Target Organ and Target System Toxicity

Alternatives to Laboratory Animals , Volume 30 (1_suppl): 12 – Jul 1, 2002

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References (45)

Publisher
SAGE
Copyright
© 2002 Fund for the Replacement of Animals in Medical Experiments
ISSN
0261-1929
eISSN
2632-3559
DOI
10.1177/026119290203001S08
Publisher site
See Article on Publisher Site

Abstract

ATLA 30, Supplement 1, 71–82, 2002 71 (OECD TG 408), and the combined repeat-dose tox- Introduction icity and reproductive toxicity screening test. During long-term exposure, some compounds can The detection of specific target organ and target induce adaptive processes in their target cells. organ system toxicity is an important aspect of tox- Changes in gene expression at the transcriptional, icological testing, and the conventional test proce- translational or post-translational levels can result dures involve chronic, repeat-dose in vivo testing, from the induction or inhibition of enzyme systems, often in a non-rodent species as well as in a rodent or by up-regulation or down-regulation of recep- species. This kind of predictive testing represents tor–ligand interactions, thereby changing the func- an enormous challenge to those who, for a variety of tions of intracellular signal cascades. For instance, scientific and ethical reasons, would like to see ani- the increase of metallothionein expression follow- mal testing replaced by non-animal tests and test- ing exposure to low doses of metals permits a higher ing strategies. It will be worthwhile putting toxic dose to be tolerated (2). considerable skill and effort into attempts to meet Another important parameter to take into con- this challenge, not

Journal

Alternatives to Laboratory AnimalsSAGE

Published: Jul 1, 2002

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