ATLA::Alternatives to Laboratory Animals

Volume 24, Number 3

In vitro toxicology methods in risk assessment.

ATLA 24, 325-331, May/June 1996

Iain F.H. Purchase

ZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 ATE

SUMMARY

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined and risk can then be assessed.

In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames SaImonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification.

The future development of in vitro methods is liked to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed In vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, win be more difficult to replace.

Keywords: alternative methods, hazard assessment, risk assessment, toxicity testing, validation