Citation

Boekelheide K, Campion SN. Toxicol. Sci. 2010; 114(1): 20-24.

Affiliation

Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912.

Copyright

(Copyright © 2010, Oxford University Press)

DOI

10.1093/toxsci/kfp307

PMID

20026472

PMCID

PMC2902917

Abstract

Distinguishing adaptive from adverse responses is fundamental to understanding toxicity and to implementing regulatory guidelines that are protective of human health. However, what we consider to be an adverse effect may change over time, as the cultural acceptance of risk alters and new knowledge and insight accumulate. The fact that the identification of an adverse effect is subject to change is obvious, necessary, and uncomfortable. In this commentary, a framework for defining adverse effects is proposed for the emerging paradigm of toxicity testing in the 21(st) century - a paradigm that focuses on human cells, in vitro approaches, toxicity pathways, and high throughput techniques. The traditional meaning of an adverse effect as a change at the organismal level is not compatible with this new system of toxicity testing. Instead, based upon the experience of accident investigators, we propose that a Toxicological Factors Analysis and Classification System (TFACS) will use the database resulting from the high throughput toxicity testing of the future to develop a Taxonomy of Adverse Effects. Similar to an accident, predisposing "latent failures" identified within categories of the toxicant response database will be associated with the "active failure" of an adverse effect.

Language: en