Evaluation of an alternative in vitro test battery for detecting reproductive toxicants

A. H. Piersma; S. Bosgra; M. B. M. van Duursen; S. A. B. Hermsen; L. R. A. Jonker; E. D. Kroese; S. C. van der Linden; H. Man; M. J. E. Roelofs; S. H. W. Schulpen; M. Schwarz; F. Uibel; B. M. A. van Vugt-Lussenburg; J. Westerhout; A. P. M. Wolterbeek; B. van der Burg

doi:10.1016/j.reprotox.2013.03.002

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants

A. H. Piersma^*, S. Bosgra, M. B. M. van Duursen, S. A. B. Hermsen, L. R. A. Jonker, E. D. Kroese, S. C. van der Linden, H. Man, M. J. E. Roelofs, S. H. W. Schulpen, M. Schwarz, F. Uibel, B. M. A. van Vugt-Lussenburg, J. Westerhout, A. P. M. Wolterbeek, B. van der Burg

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.

Original language	English
Pages (from-to)	53-64
Journal	Reproductive Toxicology
Volume	38
DOIs	https://doi.org/10.1016/j.reprotox.2013.03.002
Publication status	Published - Jul 2013

Keywords

Alternative assay
CALUX
Embryonic stem cell test
Zebrafish embryotoxicity assay
ReProGlo
Test battery
Aromatase
Toxicokinetics

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10.1016/j.reprotox.2013.03.002

Cite this

Piersma, A. H., Bosgra, S., van Duursen, M. B. M., Hermsen, S. A. B., Jonker, L. R. A., Kroese, E. D., van der Linden, S. C., Man, H., Roelofs, M. J. E., Schulpen, S. H. W., Schwarz, M., Uibel, F., van Vugt-Lussenburg, B. M. A., Westerhout, J., Wolterbeek, A. P. M., & van der Burg, B. (2013). Evaluation of an alternative in vitro test battery for detecting reproductive toxicants. Reproductive Toxicology, 38, 53-64. https://doi.org/10.1016/j.reprotox.2013.03.002

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abstract = "The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays. ",

keywords = "Alternative assay, CALUX, Embryonic stem cell test, Zebrafish embryotoxicity assay, ReProGlo, Test battery, Aromatase, Toxicokinetics",

author = "Piersma, {A. H.} and S. Bosgra and {van Duursen}, {M. B. M.} and Hermsen, {S. A. B.} and Jonker, {L. R. A.} and Kroese, {E. D.} and {van der Linden}, {S. C.} and H. Man and Roelofs, {M. J. E.} and Schulpen, {S. H. W.} and M. Schwarz and F. Uibel and {van Vugt-Lussenburg}, {B. M. A.} and J. Westerhout and Wolterbeek, {A. P. M.} and {van der Burg}, B.",

year = "2013",

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Piersma, AH, Bosgra, S, van Duursen, MBM, Hermsen, SAB, Jonker, LRA, Kroese, ED, van der Linden, SC, Man, H, Roelofs, MJE, Schulpen, SHW, Schwarz, M, Uibel, F, van Vugt-Lussenburg, BMA, Westerhout, J, Wolterbeek, APM & van der Burg, B 2013, 'Evaluation of an alternative in vitro test battery for detecting reproductive toxicants', Reproductive Toxicology, vol. 38, pp. 53-64. https://doi.org/10.1016/j.reprotox.2013.03.002

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AU - Piersma, A. H.

AU - Bosgra, S.

AU - van Duursen, M. B. M.

AU - Hermsen, S. A. B.

AU - Jonker, L. R. A.

AU - Kroese, E. D.

AU - van der Linden, S. C.

AU - Man, H.

AU - Roelofs, M. J. E.

AU - Schulpen, S. H. W.

AU - Schwarz, M.

AU - Uibel, F.

AU - van Vugt-Lussenburg, B. M. A.

AU - Westerhout, J.

AU - Wolterbeek, A. P. M.

AU - van der Burg, B.

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AB - The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.

KW - Alternative assay

KW - CALUX

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KW - Zebrafish embryotoxicity assay

KW - ReProGlo

KW - Test battery

KW - Aromatase

KW - Toxicokinetics

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DO - 10.1016/j.reprotox.2013.03.002

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