Examining Uncertainty in In Vitro–In Vivo Extrapolation Applied in Fish Bioconcentration Models
| Autor: | Lu Hostettler, Jon A. Arnot, Gordon Sanders, Andreas Natsch, Karen J. Jenner, Heike Laue, Remo P. Badertscher |
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| Rok vydání: | 2020 |
| Předmět: |
Chemistry
Uncertainty Extrapolation Bioconcentration General Chemistry 010501 environmental sciences Bioaccumulation Models Biological 01 natural sciences Liver Biotransformation In vivo Oncorhynchus mykiss Environmental chemistry Animals Environmental Chemistry Fish In vitro in vivo Uptake rate Whole body Water Pollutants Chemical 0105 earth and related environmental sciences |
| Zdroj: | Environmental Science & Technology. 54:9483-9494 |
| ISSN: | 1520-5851 0013-936X |
| DOI: | 10.1021/acs.est.0c01492 |
| Popis: | In vitro biotransformation rates were determined for 30 chemicals, mostly fragrance ingredients, using trout liver S9 fractions (RT-S9) and incorporated into in vitro-in vivo extrapolation (IVIVE) models to predict bioconcentration factors (BCFs). Predicted BCFs were compared against empirical BCFs to explore potential major uncertainties involved in the in vitro methods and IVIVE models: (i) in vitro chemical test concentrations; (ii) different gill uptake rate constant calculations (k1); (iii) protein binding (different calculations and measurement of the fraction of unbound chemical, fU); (iv) species differences; and (v) extrahepatic biotransformation. Predicted BCFs were within 0.5 log units for 44% of the chemicals compared to empirical BCFs, whereas 56% were overpredicted by >0.5 log units. This trend of overprediction was reduced by alternative k1 calculations to 32% of chemicals being overpredicted. Moreover, hepatic in vitro rates scaled to whole body biotransformation rates (kB) were compared against in vivo kB estimates. In vivo kB was underestimated for 79% of the chemicals. Neither lowering the test concentration, nor incorporation of new measured fU values, nor species matching avoided the tendency to overpredict BCFs indicating that further improvements to the IVIVE models are needed or extrahepatic biotransformation plays an underestimated role. |
| Databáze: | OpenAIRE |
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