An integrated new approach methodology for inhalation risk assessment of safe and sustainable by design nanomaterials.

The production and use of nanomaterials (NMs) has increased over the last decades posing relevant questions on their risk after release and exposure of the population or sub-populations. In this context, the safe and sustainable by design (SSbD) approach framework requires to assess the potential hazard connected with intrinsic properties of the material along the whole life cycle of the NM and/or of the nano enabled products. Moreover, in the last years, the use of new advanced methodologies (NAMs) has increasingly gained attention for the use of alternative methods in obtaining relevant information on NMs hazard and risk. Considering the SSbD and the NAMs frameworks, within the ASINA H2020 project, we developed new NAMs devoted at improving the hazard and risk definition of different Ag and TiO2 NPs. The NAMs are developed considering two air liquid interface exposure systems, the Vitrocell Cloud-α and the Cultex Compact module and the relevant steps to obtain reproducible exposures are described. The new NAMs build on the integration of environmental monitoring campaigns at nano-coating production sites, allowing the quantification by the multiple-path particle dosimetry (MPPD) model of the expected lung deposited dose in occupational settings. Starting from this information, laboratory exposures to the aerosolized NPs are performed by using air liquid interface exposure equipment and human alveolar cells (epithelial cells and macrophages), replicating the doses of exposure estimated in workers by MPPD. Preliminary results on cell viability and inflammatory responses are reported. The proposed NAMs may represent possible future reference procedures for assessing the NPs inhalation toxicology, supporting risk assessment at real exposure doses.

Critical aspects in occupational exposure assessment with different aerosol metrics in an industrial spray coating process.

Engineered Nanomaterials (ENMs) have several uses in various industrial fields and are embedded in a myriad of consumer products. However, there is continued concern over the potential adverse health effects and environmental impacts of ENMs due to their unique physico-chemical characteristics. Currently, there are no specific international regulations for various ENMs. There are also no Occupational Exposure Limits (OEL) regulated by the European Union (EU) for nanomaterials in the form of nano-objects, their aggregates or agglomerates (NOAA). For ENMs the question of which metric to be used (i.e., mass, surface area, number concentrations) to determine the exposure is still not resolved. The aim of this work is to assess the worker exposure by inhalation in an industrial spray coating process by using all three metrics mentioned above. Two target ENMs (N-doped TiO2, TiO2N and AgNPs capped with a quaternized hydroxyethyl-cellulose, AgHEC) generated for industrial-scale spraying processes were considered. Results showed that the averaged particle number concentration (10-100 nm) was below 2.7 104 cm-3 for both materials. The Lung Deposited Surface Area (LDSA) was in the range between 73 and 98 µm2cm-3 and the particle mass concentration (obtained by means of ICP-EOS off-line analysis) resulted below 70 µg m-3 and 0.4 µg m-3 for TiO2 and Ag, respectively. Although, the airborne particles concentration compared well with the NIOSH Recommended Exposure Level (REL) limits the contribution to the background, according to EN 17058 (Annex E) was significant (particularly in the particle number and PM1 mass concentrations). We successfully evaluated the worker exposure by means of the different airborne particles' metrics (number, surface and mass concentrations). We concluded that worker exposure assessment involving ENMs is a complex procedure with requires both real time and off-line measurements and a deep investigation of the background.

Burden of Disease (BoD) Assessment to Estimate Risk Factors Impact in a Real Nanomanufacturing Scenario.

An industrial nanocoating process air emissions impact on public health was quantified by using the burden of disease (BoD) concept. The health loss was calculated in Disability Adjusted Life Years (DALYs), which is an absolute metric that enables comparisons of the health impacts of different causes. Here, the health loss was compared with generally accepted risk levels for air pollution. Exposure response functions were not available for Ag nanoform. The health loss for TiO2 nanoform emissions were 0.0006 DALYs per 100,000 persons per year. Moreover, the exposure risk characterization was performed by comparing the ground level air concentrations with framework values. The exposure levels were ca. 3 and 18 times lower than the derived limit values of 0.1 µg-TiO2/m3 and 0.01 µg-Ag/m3 for the general population. The accumulations of TiO2 and Ag nanoforms on the soil top layer were estimated to be up to 85 µg-TiO2/kg and 1.4 µg-Ag/kg which was considered low as compared to measured elemental TiO2 and Ag concentrations. This assessment reveals that the spray coating process air emissions are adequately controlled. This study demonstrated how the BoD concept can be applied to quantify health impacts of nanoform outdoor air emissions from an industrial site.