2015
DOI: 10.1016/j.tox.2014.04.004
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The long and winding road of progress in the use of in vitro data for risk assessment purposes: From “carnation test” to integrated testing strategies

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Cited by 15 publications
(6 citation statements)
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References 36 publications
(39 reference statements)
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“…Although tremendous progress has been achieved in adapting and validating in vitro tools to environmental monitoring and risk assessment (e.g., in Australasia, Coleman et al 2008;Mispagel et al 2009;Chinathamby et al 2013;Bain et al 2014;Escher et al 2014;Leusch et al 2014;Scott et al 2014;Roberts et al 2015;Boehler et al 2017;Neale, Achard et al 2017;Neale, Altenburger et al 2017;Chen et al 2018;Leusch et al 2018), some fundamental questions still need to be systematically addressed before these techniques can become reliable predictors of whole animal level effects: 1) Refine quantitative in vitro to in vivo extrapolation (QI-VIVE): Although there is a clear correlation between in vitro response and in vivo effects for some endpoints such as acute toxicity (Kaiser 1998;Tanneberger et al 2013;Natsch et al 2018) and receptor-mediated endocrine effects (Sonneveld et al 2006(Sonneveld et al , 2011Henneberg et al 2014), toxicokinetic factors (absorption, distribution, metabolism, and excretion) still pose a difficult challenge for QIVIVE (Blaauboer 2015;Meek and Lipscomb 2015), although groundbreaking studies suggest that this may soon be within reach (Rotroff et al 2010;Wetmore 2015). 2) Fully map relevant AOPs: There is still much work to be done to map key events (KEs) to connect the dots between the molecular or cellular initiating event and the ultimate apical consequence to produce comprehensive AOPs, for both humans and ecosystems ).…”
Section: Tools For Improving Risk Assessmentmentioning
confidence: 99%
“…Although tremendous progress has been achieved in adapting and validating in vitro tools to environmental monitoring and risk assessment (e.g., in Australasia, Coleman et al 2008;Mispagel et al 2009;Chinathamby et al 2013;Bain et al 2014;Escher et al 2014;Leusch et al 2014;Scott et al 2014;Roberts et al 2015;Boehler et al 2017;Neale, Achard et al 2017;Neale, Altenburger et al 2017;Chen et al 2018;Leusch et al 2018), some fundamental questions still need to be systematically addressed before these techniques can become reliable predictors of whole animal level effects: 1) Refine quantitative in vitro to in vivo extrapolation (QI-VIVE): Although there is a clear correlation between in vitro response and in vivo effects for some endpoints such as acute toxicity (Kaiser 1998;Tanneberger et al 2013;Natsch et al 2018) and receptor-mediated endocrine effects (Sonneveld et al 2006(Sonneveld et al , 2011Henneberg et al 2014), toxicokinetic factors (absorption, distribution, metabolism, and excretion) still pose a difficult challenge for QIVIVE (Blaauboer 2015;Meek and Lipscomb 2015), although groundbreaking studies suggest that this may soon be within reach (Rotroff et al 2010;Wetmore 2015). 2) Fully map relevant AOPs: There is still much work to be done to map key events (KEs) to connect the dots between the molecular or cellular initiating event and the ultimate apical consequence to produce comprehensive AOPs, for both humans and ecosystems ).…”
Section: Tools For Improving Risk Assessmentmentioning
confidence: 99%
“…But their applications have been limited (Sobanska et al 2014 ). There have been many debates about the limitations of in vitro assay systems and the lack of proper accounting for in vitro toxicokinetic testing (Blaauboer 2015 ). This argument overlooks scientific progress rooting HTS assays in adverse outcome pathways (Burden et al 2015 ) and unravelling the biokinetics of in vitro assays (Fischer et al 2018 ; Proença et al 2021 ) that strengthen the scientific basis for the use of HTS assays in risk assessment.…”
Section: Introductionmentioning
confidence: 99%
“…20,21 Cell lines can be a powerful method to study mechanisms of toxicity and potential species differences. 22 Cell lines have been established and successfully applied in toxicity testing for several cetaceans, including a number of Mediterranean dolphin species and Arctic beluga whales. 23,24 Recently, we developed a humpback whale broblast cell line (HuWa), for the rst time opening up the possibility for in vitro effect assessment for this species.…”
Section: Introductionmentioning
confidence: 99%