Community Research and Development Information Service - CORDIS


InSilicoTox Project - Deliverable 4 (D4) - Report on Reaction Mechanisms in Toxicology

Project ID: 42328
Funded under: FP6-MOBILITY


The toxicity of a compound, related to different modes of action, is linked to the specific chemical reactivity of this compound. Therefore, a mechanistic understanding is needed for a sound assessment and prediction of toxicological and ecotoxicological behaviour. In the framework of the EU regulations Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), risk assessment of industrial chemicals is a very important issue in the upcoming decade.

Depending on the specific target site of a toxicological mode of action, the compound shows a variation in the underlying biochemical mechanism. This comes along with Pearson’s Hard and Soft Acid and Bases (HSAB) concept. Molecular interactions between electrophiles and nucleophiles are governed by their properties, which follow hardness and softness patterns in general. Biological nucleophiles, such as the DNA molecule, are predominantly hard chemicals, acting via rather hard oxygen or nitrogen containing moieties. Softness of a nucleophile can be associated with easy oxidisability and low electronegativity, for example thiol residues of peptides and proteins with its sulphur atom. As many environmental pollutants are soft agents, this is a first clue to understand their toxicity. Dissimilar hardness leads to a higher potential energy barrier of reactions between electrophiles and nucleophiles.

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