Inclusion of Physicochemical Data in Quantitative Comparisons of In Vitro and In Vivo Toxic Potencies

1994 ◽  
Vol 22 (3) ◽  
pp. 185-192 ◽  
Author(s):  
Michael Gulden ◽  
Hasso Seibert ◽  
Jens-Uwe Voss

In order to evaluate the relevance of in vitro test systems for acute toxicity assessment, quantitative comparisons of in vitro and in vivo potency data have to be performed. The potency of chemicals to cells in vitro is usually characterised by nominal effective concentrations (e.g. EC50 values). Often, the only available in vivo data are acute lethal body doses (e.g. LD50 values). To enable a reasonable quantitative in vitro–in vivo comparison to be made, a formula has been developed to permit the conversion of EC50 values into “effective model body doses, ED50 values”. This formula takes into account the lipophilicity of the compounds and the very different relationships between the volumes of the lipid and water compartments in vitro and in vivo. The suitability of this approach is evaluated with results obtained for the first 30 MEIC chemicals.

2009 ◽  
Vol 33 (1) ◽  
pp. 176-181 ◽  
Author(s):  
Maressa Malini ◽  
Maria Aparecida Marin-Morales ◽  
Mário Sérgio Mantovani ◽  
Claudia Masrouah Jamal ◽  
Natália Nati ◽  
...  

Skin Models ◽  
1986 ◽  
pp. 327-332
Author(s):  
P. J. Dykes ◽  
D. L. Williams ◽  
L. A. Jenner ◽  
R. Marks

1990 ◽  
Vol 15 (3) ◽  
pp. 131-135 ◽  
Author(s):  
P. Perocco ◽  
G. Ancora ◽  
P. Rani ◽  
A. M. Valenti ◽  
M. Mazzullo ◽  
...  

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase

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.


1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.


Author(s):  
Kristina V. Kitaeva ◽  
Catrin S. Rutland ◽  
Albert A. Rizvanov ◽  
Valeriya V. Solovyeva

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