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- CASE STUDIES ON THE DEVELOPMENT AND APPLICATION OF
IN-SILICO TECHNIQUES FOR ENVIRONMENTAL HAZARD AND RISK
ASSESSMENT (Acronym: CADASTER) Contract n. FP7-ENV-2007-1,
Grant n. 212668 http//www.cadaster.eu
- BRIDGING EFFECT ASSESSMENT OF MIXTURES TO ECOSYSTEM
SITUATIONS AND REGULATION (Acronym: BEAM) Contract n.
FP5-EVK1-CT1999-00012
- PREDICTION AND ASSESSMENT OF THE AQUATIC TOXICITY
OF MIXTURES OF CHEMICALS (Acronym: PREDICT) Contract
n. FP4-ENV4-CT96-0319
- UPTAKE AND NITRATION OF AROMATICS IN THE TROPOSPHERIC
AQUEOUS PHASE (Acronym: UNARO) Contract n. FP4-ENV4-CT97-0411
Paola Gramatica is leader of WP3 (Development and validation
of QSARs) in the CADASTER project now in development (2009-2012),
which is focused on four classes of emerging pollutants:
Polybrominated diphenylethers (PBDE) and flame retardants;
Perfluoroalkylated substances and their transformation
products; Fragrances; Triazoles/benzotriazoles.
Abstract:
Implementation of REACH requires demonstration of the
safe manufacture and use of chemicals. REACH aims to achieve
a proper balance between societal, economic and environmental
objectives, and attempts to efficiently use the scarce
and scattered information available on the majority of
substances. Thereupon REACH aims to reduce animal testing
by optimized use of in silico and in vitro information
on related compounds.
The REACH regulation advocates the use of non-animal testing
methods, but guidance is needed on how these methods should
be used. The procedures include alternative methods such
as chemical and biological read-across, in vitro results,
in vivo information on analogues, (Q)SARs, and exposure-based
waiving. The concept of Intelligent Testing Strategies
for regulatory endpoints has been outlined to facilitate
the assessments. Intensive efforts are needed to translate
the concept into a workable, consensually acceptable,
and scientifically sound strategy.
CADASTER aims at providing the practical guidance
to integrated risk assessment by carrying out a full hazard
and risk assessment for chemicals belonging to four compound
classes. A Decision Support System (DSS) will be developed
that will be updated on a regular basis in order to accommodate
and integrate the alternative methods mentioned above.
Operational procedures will be developed, tested, and
disseminated that guide a transparent evaluation of four
classes of emerging chemicals, explicitly taking account
of variability and uncertainty in data and in models.
QSAR models will be developed and validated, also externally,
according to the OECD principles for the validation of
QSAR. The prediction of data for chemicals of the four
selected classes, belonging to the applicability domain
of the developed models, will be used for hazard and risk
assessment, when experimental data are lacking. The main
goal is to exemplify the integration of information, models
and strategies for carrying out safety-, hazard- and risk
assessments for large numbers of substances. Real risk
estimates will be delivered according to the basic philosophy
of REACH of minimizing animal testing, costs, and time.
CADASTER will show how to increase the use of non-testing
information for regulatory decision whilst meeting the
main challenge of quantifying and reducing uncertainty.
Under the funding of this project, many papers have been
published on peer-reviewed ISI journals, since 2009, or
are in publication. (see Publications section). Results
from CADASTER project has been also presented in several
international meetings (see Meetings section)
- P.Gramatica had participated to EU-Projects on mixture
toxicity (PREDICT and BEAM), as scientific responsible
of Insubria Unit, and collaborated with Milano-Bicocca
University in the UNARO project on atmospheric pollution.
- In the three projects, QSAR models and chemometric tools
have been developed and applied.
Mixture Toxicity: P. Gramatica et al. Chemosphere,
2001, 42, 873; M. Vighi, P. Gramatica, et al. Ecotox and
Environ Safety, 2001, 49, 206. M.Faust et al. Aquatic
Toxicology, 2001, 56, 13; Aquatic Toxicology 2003, 63,
43. H. Walter et al. Ecotoxicology, 2002, 11, 299; M.Vighi,
et al. Ecotox. Environ. Safety, 54, 2003, 139-150. Backhaus,
T. et al. Continental Shelf Research 2003, 23, 1757; Environ.
Toxicol. Chem. 2004, 23, 258.
Atmospheric Pollution: P. Gramatica et al. Fresenius
Environ. Bull. 2002,11, 757; Analysis in air, toxicology
and QSAR modeling with nitrophenols. In: Air Pollution
X, WIT Press, A. Brebbia, J. F. Martin-Duque eds, Southampton,
U.K., pp 731-740. 2002.
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