Predicting rodent carcinogenicity using potency measures of the in vitro sister chromatid exchange and chromosome aberration assays

Schildcrout, Jonathan S.; Margolin, Barry H.; Zeiger, Errol

doi:10.1002/(sici)1098-2280(1999)33:1<59::aid-em7>3.0.co;2-9

Cited by 11 publications

References 15 publications

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Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay

Brookmire

Chen

Levy

2012

Environ and Mol Mutagen

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There is controversy over the highest concentration to which an article should be tested in in vitro mammalian cell assays of genetic toxicity. Until recently, most guidelines specified the use of concentrations of up to 10 mM or 5,000 μg/ml (whichever is lower) when not limited by the toxicity of the test article to the cells used for the test. Several recent publications have called for lowering those limits. We examined concentration/response curves for in vitro chromosome aberrations assays. Data was extracted from two published databases to evaluate the lowest dose at which a positive response was reported. Concentration/response curves were simulated using Monte Carlo procedures on log normal distributions of the data. These curves were then used to predict the loss in assay sensitivity that would be incurred by arbitrarily lowering the highest concentration to which the assay is conducted. The simulations suggest that lowering the current high concentration limit from 10 mM would dramatically impact the sensitivity of the assay. In contrast, lowering the high concentration limit using the μg/ml scale, the most commonly applied scale in regulatory submissions, would not have a similar impact on assay sensitivity until the limit concentration was lowered to more than half of the current 5,000 μg/ml limit. This analysis suggests that the current limits of 10 mM and 5,000 μg/ml are not equivalent to one another and challenges the assumption that lowering the 10 mM limit will not decrease assay sensitivity.

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Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay

Brookmire

Chen

Levy

2012

Environ and Mol Mutagen

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In Vitro Genotoxicity Testing: Significance and Use in Environmental Monitoring

Umbuzeiro

Heringa

Zeiger³

2016

In Vitro Environmental Toxicology - Concepts, Application and Assessment

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There is ongoing concern about the consequences of mutations in humans and biota arising from environmental exposures to industrial and other chemicals. Genetic toxicity tests have been used to analyze chemicals, foods, drugs, and environmental matrices such as air, water, soil, and wastewaters. This is because the mutagenicity of a substance is highly correlated with its carcinogenicity. However, no less important are the germ cell mutations, because the adverse outcome is related not only to an individual but also to population levels. For environmental analysis the most common choices are in vitro assays, and among them the most widely used is the Ames test (Salmonella/microsome assay). There are several protocols and methodological approaches to be applied when environmental samples are tested and these are discussed in this chapter, along with the meaning and relevance of the obtained responses. Two case studies illustrate the utility of in vitro mutagenicity tests such as the Ames test. It is clear that, although it is not possible to use the outcome of the test directly in risk assessment, the application of the assays provides a great opportunity to monitor the exposure of humans and biota to mutagenic substances for the purpose of reducing or quantifying that exposure.

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Genetic Toxicology Testing

Zeiger¹

2018

Comprehensive Toxicology

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Predicting rodent carcinogenicity using potency measures of the in vitro sister chromatid exchange and chromosome aberration assays

Cited by 11 publications

References 15 publications

Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay

Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay

In Vitro Genotoxicity Testing: Significance and Use in Environmental Monitoring

Genetic Toxicology Testing

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