Application of physiologically based kinetic (PBK) modelling in the next generation risk assessment of dermally applied consumer products
| Autor: | Przemyslaw Piechota, Beate Nicol, Ruth Pendlington, Maria Teresa Baltazar, Hequn Li, Ian Sorrell, Thomas E. Moxon, Juliette Pickles, Mi-Young Lee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Toxicodynamics Computer science Skin Absorption Detergents Cosmetics Toxicology Administration Cutaneous Models Biological Risk Assessment 03 medical and health sciences 0302 clinical medicine Coumarins Isothiocyanates Caffeine Humans Computer Simulation ADME General Medicine Product type 030104 developmental biology Human exposure Consumer Product Safety 030220 oncology & carcinogenesis Sulfoxides Margin of safety Biochemical engineering Risk assessment |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 63 |
| ISSN: | 1879-3177 |
| Popis: | Next Generation Risk Assessment (NGRA) is a procedure that integrates new approach methodologies (NAMs) to assure safety of a product without generating data from animal testing. One of the major challenges in the application of NGRA to consumer products is how to extrapolate from the in vitro points of departure (PoDs) to the human exposure level associated with product use. To bridge the gap, physiologically based kinetic (PBK) modelling is routinely used to predict systemic exposure (Cmax or AUC) from external exposures. A novel framework was developed for assessing the exposure of new ingredients in dermally applied products based on the construction of PBK models describing consumer habits and practices, formulation type, and ADME (absorption, distribution, metabolism and excretion) properties exclusively obtained from NAMs. This framework aims to quantify and reduce the uncertainty in predictions and is closely related to the risk assessment process (i.e., is the margin of safety sufficient to cover the uncertainties in the extrapolation between the in vitro and in vivo toxicodynamics and toxicokinetics?). Coumarin, caffeine, and sulforaphane in four product types (kitchen cleaner liquid, face cream, shampoo, and body lotion) were selected to exemplify how this framework could be used in practise. Our work shows initial levels of the framework provide a conservative estimate of Cmax in most cases which can be refined using sensitivity analysis to inform the choice of follow-up in vitro experiments. These case studies show the framework can increase confidence in use of PBK predictions for safety assessment. |
| Databáze: | OpenAIRE |
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