• CADASTER:  Case studies on the Development and Application of in-Silico Techniques for Environmental hazard and Risk assessment

Contract n. FP7-ENV-2007-1, Grant n. 212668 http//www.cadaster.eu

The Insubria QSAR group was involved in the CADASTER project (2009-2012),  where Paola Gramatica was leader of WorkPackage 3 (Development and validation of QSARs). CADASTER was focused on four classes of emerging pollutants: Polybrominated diphenylethers (PBDE) and flame retardants; Perfluoroalkylated substances and their transformation products; Fragrances; Triazoles/benzotriazoles. Under the funding of this project, 27 papers have been published by the Insubria group on peer-reviewed ISI journals (see Publications section). Results from CADASTER project have been also presented in several international meetings (see Meetings section).

QSAR Comb. Sci, 2009, 28,  790. SAR QSAR Environ Res., 2009, 20, 767. Chem. Res. Toxicol., 2010, 23,  528.Chem Res. Toxicol., 2010, 23, 946. Mol.Inf. ,2011, 30, 189 and 240. Water Res., 2011, 45, 1463. Mol. Div., 2011,  15, 467. J. Comput. Chem., 2011,  32, 2386. J.Haz. Mat., 2011,190, 106. J. Chem. Inf. Mod., 2011, 51, 2320. Environ. Sci. Technol., 2011, 45, 8120 SAR QSAR Environ Res., 2012,23, 207. Mol. Inf., 2012, 31, 817. J. Chem. inf. Mod., 2012, 52, 2044. SAR QSAR Environ Res., 2013, 24, 599. ATLA, 2013, 41, 65. ATLA, 2013, 41, 49. Environ. Toxicol. Chem. 2013, 32, 1069. J. Haz. Mat., 2013, 258-259, 50.  ATLA , 2014, 42, 13. Environ. Toxicol. Chem. 2014, 33, 293. Environ Intern. 2015, 77C, 25. Environ. Tox. Chem. 2015, 34,  1224. Sus. Chem. Pharm., 2015, 1, 19. J. Haz. Mat., 2016, 306, 237. Green Chem, 2016, 18, 4315.

 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.

  •  BEAM: Bridging Effect Assessment of Mixtures to ecosystem situations and regulation contract n. FP5-EVK1-CT1999-00012
  •  PREDICT: Pediction and assessment of the aquatic toxicity of mixtures of chemicals Contract n. FP4-ENV4-CT96-0319

P. Gramatica had participated to both these following EU-Projects on mixture toxicity, as scientific responsible of Insubria Unit. QSAR models and chemometric tools have been developed and applied.

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.


  • UNARO: Uptake and Nitration of AROmatics in the tropospheric aqueous phase

Contract n. FP4-ENV4-CT97-0411

Gramatica collaborated with Milano-Bicocca University in the UNARO project on atmospheric pollution.

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.