In silico toxicokinetics
This project is a collaboration between INERIS (France), Folkehelseinstituttet (Norway) and European Chemical Agency (ECHA)
To better predict a compound’s bioaccumulation potential in “air breathing terrestrial mammals (humans, rodents, dogs, horses, monkeys, …)”, ECHA (EU) initiated and has led a project fall 2015 – spring 2017 in which elimination half-lives (t1/2) for numerous compounds in various available toxicokinetic studies were collected and entered into an Excel format database. The basis for the TK studies were often OECD 417, a guideline with quite some flexibility depending on the characteristics of the compound. Presently (March 2017), the Excel sheet consists of nearly 2,900 t1/2 mainly for plasma, but also for various organs, for roughly 1,300 compounds. The Excel sheet also contains information regarding various physical parameters (Mw, log Pow, log Poa, solubility, pKa, functional groups, etc.), smiles codes and CAS nrs. There is generally also study details regarding animal strain, ages of animals, single or repeated administration, doses, etc.
This project aims at exploiting the generated database somehow both for regulatory and research purposes. This can include writing a script/program that can extract useful information from the database, e.g. for PBTK modeling that can predict toxicokinetics (bioaccumulation) parameters for a compound with unknown distribution profile/half-lives. Allometric scaling between types of animals will likely be necessary. A successful project can minimize the number of future animal studies needed.
Included in the project is a 3-5 months stay at INERIS in France where you will work together with a team of well-established specialists in physiologically-based Pharmacokinetic (PBPK) modelling. PBPK modelling is already playing a major role in both toxicology and pharmacology and both chemical and pharmaceutical industry as well governmental organisations and research institutes are very interested in this competence.
If you are interest please contact Hubert Dirven, Hubert.dirven@fhi.no, 2107 64 02 to discuss this project further.
Published Mar. 22, 2018 10:31 AM
- Last modified Apr. 19, 2018 8:14 AM