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Considerations for using reproduction data in toxicokinetic-toxicodynamic modelling

View ORCID ProfileTjalling Jager, Marie Trijau, View ORCID ProfileNeil Sherborne, View ORCID ProfileBenoit Goussen, View ORCID ProfileRoman Ashauer
doi: https://doi.org/10.1101/2021.05.03.442410
Tjalling Jager
1DEBtox Research, Stevensweert, The Netherlands
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  • For correspondence: tjalling@debtox.nl
Marie Trijau
2Ibacon GmbH, Roßdorf, Germany
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Neil Sherborne
3Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom
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Benoit Goussen
2Ibacon GmbH, Roßdorf, Germany
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Roman Ashauer
4Syngenta Crop Protection AG, 4058, Basel, Switzerland
5Department of Environment and Geography, University of York, Wentworth Way, Heslington, York, YO10 5NG, UK
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ABSTRACT

Toxicokinetic-toxicodynamic (TKTD) modelling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time-varying exposure. These advantages have been recognised in the regulatory arena, especially for environmental risk assessment (ERA) of pesticides, where time-varying exposure is the norm. We critically evaluate the link between the modelled variables in TKTD models and the observations from laboratory ecotoxicity tests. For the endpoint reproduction, this link is far from trivial. The relevant TKTD models for sub-lethal effects are based on Dynamic-Energy Budget (DEB) theory, which specifies a continuous investment flux into reproduction. In contrast, experimental tests score egg or offspring release by the mother. The link between model and data is particularly troublesome when a species reproduces in discrete clutches, and even more so when eggs are incubated in the mother’s brood pouch (and release of neonates is scored in the test). This situation is quite common among aquatic invertebrates (e.g., cladocerans, amphipods, mysids), including many popular test species. We discuss these and other issues with reproduction data, reflect on their potential impact on DEB-TKTD analysis, and provide preliminary recommendations to correct them. Both modellers and users of model results need to be aware of these complications, as ignoring them could easily lead to unnecessary failure of DEB-TKTD models during calibration, or when validating them against independent data for other exposure scenarios.

Competing Interest Statement

We acknowledge funding from Syngenta. All authors have an interest in the (regulatory) acceptance of DEB-TKTD models.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 04, 2021.
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Considerations for using reproduction data in toxicokinetic-toxicodynamic modelling
Tjalling Jager, Marie Trijau, Neil Sherborne, Benoit Goussen, Roman Ashauer
bioRxiv 2021.05.03.442410; doi: https://doi.org/10.1101/2021.05.03.442410
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Considerations for using reproduction data in toxicokinetic-toxicodynamic modelling
Tjalling Jager, Marie Trijau, Neil Sherborne, Benoit Goussen, Roman Ashauer
bioRxiv 2021.05.03.442410; doi: https://doi.org/10.1101/2021.05.03.442410

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