Type de contrat:
Location:
Date of beginning: ~17/10/2024
Internship : PBK model
Start date : February
2025
Length : 6 months
Locality : KREATiS office
Level of diploma : Master 2 / Bac+5
Context
Website : KREATiS : https://www.kreatis.eu/
Purpose
The skin is one of the main route of exposure for many chemicals, especially for cosmetics and topically applied medication. Thus, testing methods are needed in order to estimate the skin penetration or absorption of substances. Many experimental protocols can be designed, but they need to be thorough enough to satisfy the regulatory requirements. To ensure the quality of an laboratory experiment, the OECD (Organisation for Economic Co-operation and Development) produces guidelines to act as standards in safety testing. In silico test methods based on computer models can predict skin penetration or absorption parameters from various input variables. The models used are usually QSARs, or physiologically based pharmacokinetic modelling (PBPK), which is a kind of compartment model. These methods allows for a total replacement of animal testing once the model is fully validated, and can be tuned for human skin characteristics. Running simulations is also quicker and cheaper than experimental studies. Even if several in silico models for skin penetration are still available, no existing model is available to estimate the skin absorption of substance , i.e. diffusion of the substance from the dermis into the blood.
It is propose to participate in the Research & Development of skin absorption model from the current skin penetration model.
For the project needs, a training will be given to the intern in order for him/her to have a sufficiently high level of understanding of the subject and the test performed (OECD guidelines) to measure the skin absorption of substance in vivo.
An existing in vivo study is used to assess the skin absorption (OECD guideline 427). KREATiS wants to build a database based on OECD TG 427 data.
Thus, the intern will collect in vivo skin absorption data from documented databases (ECHA website), validate it and assess the reliability of each studies.
From these collected data, a dataset with only the best quality data will be used for PBK model development to estimate skin absorption.
Adaptation of the current skin penetration model to the skin absorption using physiological and mathematical parameters.
The building of the model will be supervised by a multidisciplinary team and different consideration will be taken to build the most reliable model.
Knowledge in mammal physiology, biochemistry and modelling using excel are required as well as good analytical skills and a B2 level of English.
At the end of the project the intern will have a good understanding of how to validate input data for in silico model development, will have learned how to set up a dataset to build a PBK of good quality and will have a general comprehension of alternative methods, such as in silico techniques.
(1) iSafeRat® – in Silico Algorithms For Environmental Risk And Toxicity (2014) https://isaferat.kreatis.eu/
(2) OECD Guideline for testing of chemicals No. 406, 429 for the skin sensitisation
If you are interested, please send us your CV and cover letter to carole.charmeau@kreatis.eu.