Master internship - Improvement of CLASS: a prediction model for skin sensitisation
Type de contrat: Internship
Location: L'Isle d'Abeau (38)
Date of beginning: ~14/10/2024
Internship : HA-QSAR in toxicology
Start date : February 2025
Length : 6 months
Locality : KREATiS office (L'Isle d'Abeau, 38)
Level of diploma : Master 2 / Bac+5
Context : Under the REACH regulation of chemical substances (1) chemical substances are generally evaluated
using in vivo or in vitro experimental methods following OECD guidelines. These tests can be long and
expensive to perform and they are not acceptable anymore on an ethical point of view such as the
acute/dermal oral toxicity for example. To help the chemical industry to limit experimentation, KREATiS
offers in silico alternatives to experimentation according to the 3Rs principles (Replace – Reduce –
Refine). The aim of KREATiS is to provide in silico models which are as accurate and reliable as good
laboratory studies.
Purpose : It is propose to participate in the Research & Development of iSafeRat® (2) CLASS model, a HighAccuracy Quantitative Structure-Activity Relationship model (HA-QSAR models) use to predict skin
sensitisation in human.
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
sensitisation potential and potency of a chemical.
Several existing in vivo studies were used to assess the skin sensitisation before their replacement by in
vitro studies from 2015 (OECD guideline 406, 429). These studies allow to determine the classification of
the substance according to the CLP.
Currently, KREATiS wants to build a new database based on OECD
406 guidelines data.
Thus, the intern will collect in vivo data (based on OECD 406 guidelines) from well documented
databases (ECHA website), validate it and assess the reliability of each studies based on a Klimisch
score.
From these collected data, a dataset will be build and only the best quality data will be used for QSAR
model development to assess skin sensitisation.
If time allows, the first steps of model development according to the five OECD principles (4) of
development of a model will also be considered during the internship.
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 toxicology including CLP classification, organic chemistry, 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 QSARs of good quality
and will have a general comprehension of alternative methods, such as in silico techniques.
(1) Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals
Agency
(2) iSafeRat® – in Silico Algorithms For Environmental Risk And Toxicity (2014) https://isaferat.kreatis.eu/
(3) OECD Guideline for testing of chemicals No. 406, 429 for the skin sensitisation
(4) OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship
Models
If you are interested, please send us your CV and cover letter to carole.charmeau@kreatis.eu.