Approach toward In Vitro-Based Human Toxicity Effect Factors for the Life Cycle Impact Assessment of Inhaled Low-Solubility Particles.

Today's scarcity of animal toxicological data for nanomaterials could be lifted by substituting in vivo data with in vitro data to calculate nanomaterials' effect factors (EF) for Life Cycle Assessment (LCA). Here, 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 several inhaled nonsoluble nanomaterials. 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 results based on rat data are very different, confirming the importance of selecting animal species representative of human responses. The discrepancy between in vivo and in vitro animal data in terms of availability and quality limits the coverage of further nanomaterials. Systematic testing on human and animal cells is needed to reduce the variability in toxicological response determined by the differences in experimental conditions, thus helping improve the predictivity of in vitro-to-in vivo extrapolation factors.