Abstract

GENOTOXICITY: A REAL CONCERN OF THE PHARMACEUTICAL INDUSTRY

Deepraj Paul* and Karthika Paul

ABSTRACT

In silico structure activity relationship (SAR) evaluation is a very promising technique which further gives an insight regarding the structural alerts for genotoxic substances present in active pharmaceutical ingredient (API). But the lethalness of such structural alerts is determined by their quantification and application of the threshold of toxicological concern (TTC) and Staged TTC limits based approach which eventually determines the fate of all APIs possessing them. Thus chemical substances with their reporting threshold, identification threshold and qualification threshold within acceptable TTC limits may be permitted for consumption by human even though they are identified as a structural alert for genotoxicity. But the limitations which restrict the application of TTC approach are requirement of knowledge about the chemical structure of the genotoxic substance and the availability of human exposure data. Even though many concepts like TTC concept, compound-specific risk assessments approach, Less-Than-Lifetime (LTL) exposures and multiple mutagenic impurities based approaches are established to control genotoxicity yet a complete control on the genotoxic hazard has not been achieved as can be seen in case of the impact of carbon nanomaterial on the industrial labourers or antimicrobial silver nanoparticle induced genotoxicity of human lung fibroblast cell and human glioblastoma cells or issues regarding the genotoxicity of soil etc.

Keywords: Genotoxicity, Structural alerts, TTC concept, OECD Guidelines, ICH guidelines, EMEA guidelines.