Multiscale modelling approaches for assessing cosmetic ingredients safety.
The European Union's ban on animal testing for cosmetic ingredients and products has generated a strong momentum for the development of in silico and in vitro alternative methods. One of the focus of the COSMOS project was ab initio prediction of kinetics and toxic effects through multiscale pharmacokinetic modeling and in vitro data integration. In our experience, mathematical or computer modeling and in vitro experiments are complementary. We present here a summary of the main models and results obtained within the framework of the project on these topics. A first section presents our work at the organelle and cellular level. We then go toward modeling cell levels effects (monitored continuously), multiscale physiologically based pharmacokinetic and effect models, and route to route extrapolation. We follow with a short presentation of the automated KNIME workflows developed for dissemination and easy use of the models. We end with a discussion of two challenges to the field: our limited ability to deal with massive data and complex computations.
INERIS, DRC/VIVA/METO, Parc ALATA, BP2, 60550 Verneuil-en-Halatte, France. Electronic address: frederic.bois@ineris.fr.
Frédéric Y
FY
Bois
Insilico Biotechnology AG, Meitnerstrasse 8, 70563 Stuttgart, Germany.
Juan G Diaz
JGD
Ochoa
European Commission Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit, Via Enrico Fermi 2749, Ispra, VA, Italy.
Monika
M
Gajewska
S-IN Soluzioni Informatiche, via G. Ferrari 14, 36100 Vicenza, Italy.
Simona
S
Kovarich
Insilico Biotechnology AG, Meitnerstrasse 8, 70563 Stuttgart, Germany.
Klaus
K
Mauch
European Commission Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit, Via Enrico Fermi 2749, Ispra, VA, Italy.
Alicia
A
Paini
INERIS, DRC/VIVA/METO, Parc ALATA, BP2, 60550 Verneuil-en-Halatte, France.
Alexandre
A
Péry
European Commission Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit, Via Enrico Fermi 2749, Ispra, VA, Italy.
Jose Vicente Sala
JVS
Benito
INERIS, DRC/VIVA/METO, Parc ALATA, BP2, 60550 Verneuil-en-Halatte, France.
Sophie
S
Teng
European Commission Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit, Via Enrico Fermi 2749, Ispra, VA, Italy.
Andrew
A
Worth
D000826:Animal Testing Alternatives; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D003257:Consumer Product Safety; D003358:Cosmetics / Q000737:chemistry*; D005062:European Union; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D018675:Toxicity Tests
D003358:Cosmetics; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
In silico toxicity prediction; Multiscale model; PBPK model