Towards next generation risk assessment of chemicals : bayesian meta-analysis of human variability in metabolism and transporters and application for the derivation of pathway-related uncertainty factors
Darney, K
| HERO ID | 12033083 |
|---|---|
| Year | 2020 |
| Title | Towards next generation risk assessment of chemicals : bayesian meta-analysis of human variability in metabolism and transporters and application for the derivation of pathway-related uncertainty factors |
| Authors | Darney, K |
| Abstract | In the modern world, humans are exposed to a wide range of chemicals throughout their life. Human risk assessment of chemicals is of considerable public health importance and provides means to derive safe levels of acute and chronic exposure for subgroups of the human population including neonates, children, elderly and populations of different geographical ancestry and genetic polymorphisms. The application of pathway-related kinetic data to address human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default uncertainty factors. This thesis aims to 1) quantify human variability by means of Bayesian meta-analysis for a range of phase I, phase II metabolic pathways and transporters using pharmacokinetic markers of acute and chronic exposure or enzyme activity data from available probe substrate, 2) derive pathway-related variability distributions and pathway-related uncertainty factors for their future integration in physiologically based kinetic models for human risk assessment of chemicals. |
| Is Certified Translation | No |
| Dupe Override | No |
| University Name | Laboratoire sur les interactions Epithéliums Neurones |
| Comments | Journal: ISSN: |
| Is Public | Yes |