20 An Approach Towards in Vitro-Based Human Toxicity Effect Factors for the Life Cycle Impact Assessment of Inhaled Low-Solubility Particles.

Abstract

Abstract Life Cycle Assessment (LCA) calculations of products containing nanomaterials are limited in their comprehensiveness by the lack of characterization factors linking nanomaterial emissions to their impacts on human health. This is mainly due to the scarcity of animal toxicological data compared to the number of existing nanomaterials, a constraint that could be lifted if in vivo data could be substituted by in vitro data to calculate nanomaterials' effect factors (EF). To support a future animal-independent LCA methodology, we present a step-by-step procedure to calculate in vitro-to-in vivo extrapolation factors to estimate human Benchmark Doses and subsequently in vitro-based EFs for inhaled non-soluble nanomaterials. Titanium dioxide, amorphous silica, cerium oxide and crystalline silica are presented as case studies. Based on mouse data, the in vitro-based EF of TiO2 is between 2.76*10-4 and 1.10*10-3 cases/(m2/g *kg intake), depending on the aerodynamic size of the particle, which is in good agreement with in vivo-based EFs (1.51*10-4 - 5.6*10-2 cases/(m2/g *kg intake)). The EF for amorphous silica is in a similar range as for TiO2, but the result is less robust due to only few in vivo data available. The discrepancy between in vivo and animal in vitro data in terms of availability and quality limits the coverage of further nanomaterials. While the work focused on LCA, the procedure can be easily adapted for risk assessment as well, thus increasing the relevance of our findings.