Community Research and Development Information Service - CORDIS

FP6

InSilicoTox Project - Deliverable 1 (D1) - Report on Reactivity Measurement and Estimation

Project ID: 42328
Funded under: FP6-MOBILITY

Abstract

In the framework of the new European Union (EU) regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), risk assessment of industrial chemicals is a very important issue in the upcoming decade.[1] REACH calls for persuasive data of produced and used chemicals to assure human health and to provide environmental risk assessment. Toxicological effects are, for example, the irritation potential, skin sensitisation, mutagenicity, acute and chronic toxicity, reproductive toxicity and carcinogenicity.[2] To reduce animal testing in the context of requested toxicological and ecotoxicological endpoints, there is an increasing demand to introduce alternative testing strategies. These alternative testing strategies include in vitro, in chemico and in silico methods.

It is a common perception, that there can be a link between the toxicity of a compound and the specific chemical reactivity of the compound.[3] An indication of chemical reactivity can be provided by different in chemico and in silico assays, which will be represented in this report.

Dealing with reactivity in connection with toxicity, one should consider different interaction types.[3] Weak reversible interactions, including hydrophobic van der Waals’ interactions, hydrogen bonding and ionic bonds (e.g. by charged amino acids), are of great biological relevance, as they govern the interaction between receptors and the substrate. Reversible, non-covalent interaction with membrane components is called narcosis. Secondly, the hydrophobicity of a compound is principally responsible for the bioavailability at a specific target site.

The formation of coordination bonds between metals or their salts and heteroatoms, such as nitrogen or oxygen, is a broad field in the disquisition of the allergenic potential of metals.

Covalent bonds between a substrate and a target molecule are formed by reactions between electron-rich nucleophiles and electron-poor electrophiles. Electron-ri

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