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Partner 11 Instituto di Richerche Farmacologiche "Mario Negri"

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Institute and research group information

Mario Negri Institute for Pharmacological Research is a not-for-profit biomedical research organization, established in 1961 in Milan.

Research is mainly concentrated on the fight against cancer, nervous system and mental illnesses, cardiovascular and kidney diseases, rare diseases, and the presence and potential toxic effects of environmental contaminants.

Along with its research activities, the Institute also provides professional training to laboratory technicians and graduate researchers and communication of biomedical information.

The Institute is divided in departments specialised in different research areas; the Laboratory of Environmental Chemistry and Toxicology and the Unit of Environmental Pollutants’ Risk Assessment, working within CASCADE NoE, belong to the Department of Environmental Health Science.

The activities of the Department of Environmental Health Science are devoted to investigate environmental factors and their effects on human health. The main research lines focus on the survey of environmental contaminants, the assessment of human exposure with related health risks, and toxicity mechanisms of pollutants.

Research is focused on the assessment of human exposure to toxic compounds such as PCBs, dioxins and other endocrine disruptors through environment and diet, and in the development of analytical methods based on advanced mass spectrometric techniques. The Department is divided into five Laboratories and two Units.

The researchers of the Laboratory of Environmental Chemistry and Toxicology are involved on different topics: Computer-based models for chemistry and toxicology; molecular descriptors; QSAR; toxicity prediction; metabolism studies; characterization and assessment of wastes, industrial effluents, emissions from landfill and incinerator; integration of chemical analysis and ecotoxicological data; chemical analysis of organic compounds by mass spectrometry.

Research activities of the Unit of Environmental Pollutants’ Risk Assessment include both the quantitative measure of contaminants in environmental samples and  the exposure and toxicological evaluation for the risk assessment. The specific projects are: analysis of PCBs in fish, analysis of PCBs and DDT metabolites in human samples, dietary exposure assessment to dioxins and PCBs, dose-response modelling of toxicological data, exposure assessment methodology development.

Contribution to CASCADE

The group of the Laboratory of Environmental Chemistry and Toxicology is involved in the development and application of analytical methods based on chromatographic and mass spectrometric techniques for the identification and quantification of selected contaminants in food.

Within WP12, methods based on SPE extraction have been developed for the analysis of BPA in water, Genistein in water and milk and research is going on for the analysis of Lignans in milk samples.

Within WP13 work is concentrated on modelling endocrine disrupting activities using in silico models, to identify potentially active compounds, in a screening exercise. Furthermore the group contributes to the activities of promoting integration within WP2.

The group of the Unit of Environmental Pollutants’ Risk Assessment is involved in risk assessment workpackages and its work is focused on the specific study case of  the dioxin soil contamination in Seveso to develop the exposure assessment methodology by using probabilistic approaches and more refined statistical models.

Representative scientific articles as relevant to CASCADE

E. Lo Piparo, K. Koehler, A. Chana, E. Benfenati. Receptor-Binding Affinity of Diphenolic Azoles to Estrogen Receptors a and b by Three-Dimensional Quantitative Virtual Screening for Aryl Hydrocarbon Receptor Binding Prediction J. Med. Chem. 49, 5702-5709 (2006).

S. Tavazzi, E. Benfenati, D. Barceló. Accelerated Solvent Extraction then Liquid Chromatography Coupled with Mass Spectrometry for Determination of 4-t-Octylphenol, 4-Nonylphenols, and Bisphenol A in Fish Liver.  Chromatographia  56, 463-468 (2002)

A. Roncaglioni, M. Novic, M. Vracko, E. Benfenati. Classification of potential endocrine disrupters on the basis of molecular structure using nonlinear modelling method. J. Chem. Inf. Comp. Sci. 44, 300-309 (2004).

A. Mandich, E. Benfenati, M.T.D. Cronin, A. Goksøyr, B.E. Grøsvik, A. Van Cauwenberg, L. Viganò. Environmental agent susceptibility assessment using existing and novel biomarkers as rapid non-invasive testing methods. Trends in Comparative Endocrinology and Neurobiology, NY Acad. Sci, 381-386 (2005).

D. Kovatcheva,  M.T.D. Cronin, E. Benfenati, A. Roncaglioni, E. Lo Piparo. Identification of the Structural Requirements of the Receptor-Binding Affinity of Diphenolic Azoles to Estrogen Receptors α and β by Three-Dimensional Quantitative Structure-Activity Relationship and Structure-Activity Relationship Analysis. J. Med. Chem. 48 (24), 7628-7636, (2005).