The Use of Basal Cytotoxicity and Target Organ Toxicity Tests in Hazard Identification and Risk Assessment

Non-animal procedures, including in vitro test systems and test strategies, can already make a significant contribution to the background to risk assessment — in predicting both the toxic potential and toxic potency of chemicals, as well as, in some circumstances, the toxic hazard they may represent under specified conditions of exposure. They can be particularly useful for investigating molecular and cellular mechanisms of chemical-induced toxicity, and for identifying species-specific effects, which greatly limit the value of data from laboratory animal studies in the human risk assessment process. Attention is focused on the need for greater effort to be invested in the development of non-animal procedures for evaluating the biokinetic factors which will determine the ultimate form and concentration of a particular chemical at possible sites of toxic action. The relative merits of correlative and mechanistic approaches to test development and test validation are discussed. The need for realism is emphasised, not only in relation to our expectations of the validation process, but also in terms of the current and future status of regulatory toxicology, in vitro or in vivo, as a scientific discipline. Finally, it is concluded that the intelligent and strategic use of in vitro test systems, in conjunction with predictive computer modelling, could markedly improve the scientific basis of human risk assessment.

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In Vitro Toxicology Methods in Risk Assessment

Alternatives to Laboratory Animals ◽

10.1177/026119299602400305 ◽

1996 ◽

Vol 24 (3) ◽

pp. 325-331

Author(s):

Iain F. H. Purchase

Keyword(s):

Risk Assessment ◽

Hazard Assessment ◽

Human Health Risk ◽

In Vitro Test ◽

In Vitro Methods ◽

New Concepts ◽

Vitro Test

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 Salmonella 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 likely 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, will be more difficult to replace.

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