Prediction of physico-chemical properties in the
context of the French PREDIMOL project
P. Rotureaua, G. Fayeta, V. Pranaa,c, C. Nieto-Draghib, C. Adamoc, B. Rousseaud, B. Leblance, X. Rozanskae, P. Ungerere, D. Andréf
aINERIS,
Parc Technologique Alata, BP2, 60550 Verneuil-en-Halatte, France
Nouvelles, 1 et 4 avenue de Bois-Préau, 92852 Rueil-Malmaison, France
d’Electrochimie, Chimie des Interfaces et Modélisation pour l’Energie, CNRS UMR-7575, Chimie ParisTech, 11 rue P. et M. Curie, 75231 Paris, France
dLaboratoire de Chimie-Physique, Bât 349, Université Paris-Sud, 91405 Orsay, France
eMaterials Design, 18 rue de Saisset, 92120 Montrouge, France
fArkema, rue Henri Moissan, BP63, 69493 Pierre Benite, France
bIFP Energies
cLaboratoire
French PREDIMOL Project (2010-2013)
Context and objectives
REACH
1 June 2007: Entry into force
PREDIction of physico-chemical properties of products by
MOLecular modeling
1 June 2008: Entry into operation
Until 1 December 2008 : Pre-registration
Until 31 May 2018 : Registration of existing substances*
* Upon quantities and potential hazards
• More than 140 000 pre-registered substances by 65 000 companies by
the end of 2008; More than 17 400 registration files completed by the
end of 2010
7. PHYSICO-CHEMICAL PROPERTIES
REACH
required
properties
7.1 State of the substance at 20 C and 101.3 kPa
7.2 Melting/freezing point
7.3 Boiling point
7.4 Relative density
7.5 Vapour pressure
7.6 Surface tension
7.7 Water solubility
7.8 Partition coefficient n-octanol/water
7.9 Flash point
7.10 Flammability
7.11 Explosive properties
7.12 Self-ignition temperature
7.13 Oxidising properties
7.14 Granulometry
7.15 Stability on organic solvents and identity of
degradation products
7.16 Dissociation constant
7.17 Viscosity
• Financial support: National Research Agency (ANR)
• Coordinator: INERIS
• Partners: IFP Energies Nouvelles, Chimie ParisTech, LCP
(Université Paris-Sud), Materials Design, Arkema
Cost
• Objectives: calculation of all physico-chemical properties
required by REACH (annexes VII and IX)
substances
Availability
Development of QSPR models for hazardous properties
of tests
(explosibility, flammability, oxidizing properties)
Ethic (tests on
Development of molecular simulation methods (Molecular
animals)
Dynamics, Monte Carlo) for thermo-physical properties
Regulatory validation of models
Demonstration of the feasibility of ‘fast speed screening’
Alternative methods
by molecular modeling
Time
http://www.ineris.fr/predimol/
Methods
QSPR: Quantitative Structure-Property Relationship
Cramer, Essentials of
Computational Chemistry, 2004
Klamt, JPC, 1995, 2224
Klamt et al., JPCA, 1998, 5074
Results and future works
Inventory of existing experimental data from
literature
• For organic peroxides (OPs)
Data from Arkema, INERIS
• Examination of Existing ‘Datatop 2005’ (TNO) on OPs
116 different OPs/structures, some at various
concentrations, with different diluents
40 explosive properties according to Transport of
Dangerous Goods regulation (UN Manual)
• For amines
In DIPPR, NIST, CarAtex, CRC Handbook of Chemistry
and Physics…
Development of QSPR models
• Development of a consolidated database for 30 organic
peroxides (heat and temperature of decomposition
from Differential Scanning Calorimetry, flash point,
density, impact sensitivity)
The most accurate database after Datatop with
homogeneous experimental data
• Performant preliminary MLR models for OPs using
cross validation method:
Properties
Nmol
R2
Q2
Ndesc
Temperature of
decomposition
29
0.77
0.73
2
Heat of
decomposition
29
0.84
0.68
4
Density
28
0.96
0.94
4
Flash point
22
0.89
0.83
4
Stressing onto performances and limits of each
approach
• Another critical objective of this project is the regulatory
validation of models by European chemical instances in
order that predictive data could be used for registration of
chemicals in REACH.
Models will be submitted to the Joint Research
Center comity for acceptance or to existing tools (like
OECD ECHA QSAR toolbox) for integration
Redaction and submission of QMRF (QSAR Model
Reporting Format) files
External validation with
extended database
Study of decomposition
mechanisms of OPs
Identification of missing experimental data for
development and validation of models
• Identification of existing models and methods: group
contribution methods, QSPR models notably associated
with quantum chemical description of molecular
structures, SAFT equations, COSMO-RS approach and
force fields that could be used for the prediction of
physico-chemical properties of OPs and amines
Availability of models for industrial and
EU regulatory authorities
Application of force fields for OPs and
amines
• AUA force field selected
Study of applicability of this force field to more
complex molecules (like multifunctional OPs)
Towards the development of validated models relevant
for regulatory purpose
Towards the development of high throughout
predictions
Acknowledgments
This project (ANR- 10-CDII-007) was financed by ANR
and the french Ministry in charge of environment