Structure-Teratogenicity Relationships Among Antifungal Triazoles

Flint, Oliver; Boyle, F. Thomas

doi:10.1007/978-3-642-75458-6_11

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…Indeed, we found only two chemicals, 5-bromo-2´-deoxyuridine and all-trans-retinoic acid, for which the two endpoints provided consis-tent differences in the two endpoint values. Previous studies have found differences in ID50 and IC50 values for a larger number of chemicals, which may have been because the culture conditions used to assess effects on differentiation and cytotoxicity were not identical (18,19). In contrast, in the current study, differentiation and cytotoxicity were examined sequentially in the same cultures.…”

Section: Development Of the Prediction Modelmentioning

confidence: 72%

“…The low performance of the MM test is not surprising when taking into account the results obtained in earlier investigations. Several structure-activity studies have shown that the MM test can distinguish between embryotoxic and nonembryotoxic substances within specific chemical classes, for example, retinoids (18) and triazole anti-fungicides (19). Moreover, studies in several laboratories --including validation trials on smaller numbers of test chemicals --indicate that the predictivity for strongly embryotoxic chemicals in MM cultures may vary from 60% to 90% (20,21).…”

Section: Predictive Powermentioning

confidence: 99%

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Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests

Spielmann¹,

Genschow

Brown

et al. 2004

Altern Lab Anim

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A detailed report is presented on the performance of the rat limb bud micromass (MM) test in a European Centre for the Evaluation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects on animals and/or humans, were tested in four laboratories. The outcome showed that the MM test is an experimentally validated test, which holds promise for use for identifying strongly embryotoxic chemicals, but which needs to be improved before it can be recommended for use for regulatory purposes.

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Section: Development Of the Prediction Modelmentioning

confidence: 72%

Section: Predictive Powermentioning

confidence: 99%

Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests

Spielmann¹,

Genschow

Brown

et al. 2004

Altern Lab Anim

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show abstract

“…Several structure-activity studies have shown that the micromass test can distinguish between teratogens and nonteratogens within a particular chemical class, e.g., retinoids (28) and triazole antifungal drugs (29). In some cases, organ-, species-, and strain-specific toxicity have been modeled in micromass cultures.…”

Section: Aggregate and Micromass Culturesmentioning

confidence: 99%

Reproduction and development.

Spielmann

1998

Environ Health Perspect

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The currently developed and validated in vitro tests for female and male fertility and also for developmental toxicity are described and evaluated according to their potential use as screening or replacement alternatives to the established in vivo tests in reproductive and developmental toxicology. Alternative methods today can only be used to evaluate a few specific components of the integrated reproductive functions in both females and males. However, in the field of developmental toxicity testing there is a strong theoretical and empirical basis for the predictive power of in vitro screens using mammalian embryos as well as embryonic cells and tissues. Several of these assays have been validated or are currently undergoing validation in several laboratories and are > 80% concordant with in vivo results. Failure to achieve 100% accuracy reflects the inherent limitations of these systems, which are manageable, as the concordance rates are still good. The level of concordance suggests that these assays are adequate for screening purposes to complement traditional in vivo testing. The use of these assays as screens will save valuable in vivo testing resources for those compounds most likely to enter the market and to which people will be exposed.

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A Timetable for Replacing, Reducing and Refining Animal use with the Help of in Vitro Tests: The Limulus Amebocyte Lysate Test (LAL) as an Example

Flint¹

1994

Alternatives to Animal Testing

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Structure-Teratogenicity Relationships Among Antifungal Triazoles

Cited by 9 publications

References 16 publications

Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests

Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests

Reproduction and development.

A Timetable for Replacing, Reducing and Refining Animal use with the Help of in Vitro Tests: The Limulus Amebocyte Lysate Test (LAL) as an Example

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