| Autor: |
Wang J; Department of Environmental Science, Radboud Institute for Biological and Environmental Sciences, Radboud University, Nijmegen 6500 GL, The Netherlands., Nolte TM; Department of Environmental Science, Radboud Institute for Biological and Environmental Sciences, Radboud University, Nijmegen 6500 GL, The Netherlands., Owen SF; AstraZeneca, Global Sustainability, Macclesfield, Cheshire SK10 2NA, United Kingdom., Beaudouin R; Institut national de l'environnement industriel et des risques (INERIS), Verneuil-en-Halatte 60550, France., Hendriks AJ; Department of Environmental Science, Radboud Institute for Biological and Environmental Sciences, Radboud University, Nijmegen 6500 GL, The Netherlands., Ragas AMJ; Department of Environmental Science, Radboud Institute for Biological and Environmental Sciences, Radboud University, Nijmegen 6500 GL, The Netherlands.; Department of Environmental Sciences, Faculty of Science, Open University, Heerlen 6419 AT, The Netherlands. |
| Abstrakt: |
An increasing number of pharmaceuticals found in the environment potentially impose adverse effects on organisms such as fish. Physiologically based kinetic (PBK) models are essential risk assessment tools, allowing a mechanistic approach to understanding chemical effects within organisms. However, fish PBK models have been restricted to a few species, limiting the overall applicability given the countless species. Moreover, many pharmaceuticals are ionizable, and fish PBK models accounting for ionization are rare. Here, we developed a generalized PBK model, estimating required parameters as functions of fish and chemical properties. We assessed the model performance for five pharmaceuticals (covering neutral and ionic structures). With biotransformation half-lives (HLs) from EPI Suite, 73 and 41% of the time-course estimations were within a 10-fold and a 3-fold difference from measurements, respectively. The performance improved using experimental biotransformation HLs (87 and 59%, respectively). Estimations for ionizable substances were more accurate than any of the existing species-specific PBK models. The present study is the first to develop a generalized fish PBK model focusing on mechanism-based parameterization and explicitly accounting for ionization. Our generalized model facilitates its application across chemicals and species, improving efficiency for environmental risk assessment and supporting an animal-free toxicity testing paradigm. |
