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- Golsteijn, Laura, et al.
(författare)
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Assessing predictive uncertainty in comparative toxicity potentials of triazoles
- 2014
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 33:2, s. 293-301
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Tidskriftsartikel (refereegranskat)abstract
- Comparative toxicity potentials (CTPs) quantify the potential ecotoxicological impacts of chemicals per unit of emission. They are the product of a substance's environmental fate, exposure, and hazardous concentration. When empirical data are lacking, substance properties can be predicted. The goal of the present study was to assess the influence of predictive uncertainty in substance property predictions on the CTPs of triazoles. Physicochemical and toxic properties were predicted with quantitative structure-activity relationships (QSARs), and uncertainty in the predictions was quantified with use of the data underlying the QSARs. Degradation half-lives were based on a probability distribution representing experimental half-lives of triazoles. Uncertainty related to the species' sample size that was present in the prediction of the hazardous aquatic concentration was also included. All parameter uncertainties were treated as probability distributions, and propagated by Monte Carlo simulations. The 90% confidence interval of the CTPs typically spanned nearly 4 orders of magnitude. The CTP uncertainty was mainly determined by uncertainty in soil sorption and soil degradation rates, together with the small number of species sampled. In contrast, uncertainty in species-specific toxicity predictions contributed relatively little. The findings imply that the reliability of CTP predictions for the chemicals studied can be improved particularly by including experimental data for soil sorption and soil degradation, and by developing toxicity QSARs for more species. (c) 2013 SETAC
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| 2. |
- Tebby, Cleo, et al.
(författare)
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A generic PBTK model implemented in the MCRA platform : Predictive performance and uses in risk assessment of chemicals
- 2020
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.
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