Structural Alerts of Particle Toxicity: Looking to the past to predict the future

Having the tools to understand the potential hazards of particulates and, in particular, the new wave of functional nanoparticles before wide spread exposure occurs is imperative. This is not an easy undertaking and in order to identify if an untested material is hazardous to human health and identify the basis for this hazard with the greatest degree of confidence, toxicological testing is most often required. However, performing primary toxicological analysis on all new materials/ products, such as those in development or subject to modification (e.g. coating) places a substantial and potentially impossible burden of testing on industry and, in particular, on SMEs, may stifle innovation. As a result, the use of secondary sources of information, such as the toxicological literature may be used in place of, or to inform, targeted toxicological testing to identify causes for concern. Yet this often requires expert interpretation and is not necessarily tailored to the particle in question. In this paper we present a structural alert scheme based on a collation of the known biologically effective doses apparent in particle toxicology identified over decades of research which we have linked with particle physico-chemical properties such as particle shape, charge, and solubility. The scheme is aimed at simplifying the wealth of information available from the study of particulates which is of great relevance and applicability to nanoparticles and to provide a tool for non-specialists to rapidly identify potential influencers of toxicity in new particulate materials.