Inhalation studies for the safety assessment of nanomaterials: status quo and the way forward

Abstract

While technical and medical potential offered by nanotechnologies increase, the safety assessment of engineered nanomaterials (NMs) needs to follow this pace. Inhalation is a major route of occupational and environmental exposure, and is most relevant for most of the respective safety assessment studies. Control and generation of aerosol from the test materials for this route of administration are technically demanding, and not surprisingly, there are relatively few NMs tested in toxicokinetic, short-term, and subchronic inhalation studies. These studies were in part adapted to the peculiarities of inhaled NMs, but few were also conducted according to organization for economic co-operation and development (OECD) test guidelines. Inhalation studies on the potential to develop chronic diseases, or studies to check the potential analogy to cardiovascular diseases associated with adverse health effects from ambient air pollution, are largely missing. On the way forward, appropriate inhalation studies need to be performed on a number of NMs to assess their hazards and to provide a sound database for correlation and validation of alternative in vitro methods. Moreover, these studies can potentially aid in the grouping of different NMs based on their biokinetics or biological effects. For carcinogenic and cardiovascular effects, research studies are needed to verify-or disprove-the relevance and the mechanisms by which NMs contribute to these effects.

Influence of dispersive agent on nanomaterial agglomeration and implications for biological effects in vivo or in vitro

“…Reaching the alveoli, inhaled, uncoated nanoparticles come into contact with pulmonary surfactants forming a 'corona' on the particle surface, which affects particokinetics (Landsiedel et al, 2012). Dispersing agents rendering NM preparations more stable and NMs less likely to sediment are applied in in vitro assays to reflect NM deposition in the lower respiratory tract.…”

Allergenicity and toxicology of inhaled silver nanoparticles in allergen-provocation mice models

“…Landsiedel et al suggested the urgency of performing toxicokinetic and inhalation studies to investigate the hazards associated with NP exposure. 31 The evaporation-condensation method was used to produce AgNP for the investigation of allergic responses after successive inhalation of AgNP in mice, and the principle of the method has been described by Singh et al 20 The advantage of this system is that AgNP can be generated continuously and stably for long-term inhalation within a range of levels, reflecting the natural exposure route for respirable NPs rather than exposure via intratracheal instillation or pulmonary aspiration. Moreover, the SEM-EDX showed that the spherical AgNPs generated by this system were uncontaminated, suggesting that the allergenicity and toxicity observed in this study were attributable to the AgNP.…”

Safety assessment of nanomaterials using an advanced decision-making framework, the DF4nanoGrouping

“…In Tier 3, the Tier 1 and Tier 2 MG assignment that is based upon non-animal testing alone is confirmed or corrected using data from in vivo short-term studies. For the inhalation route of exposure, i.e., the predominant route of uptake for most nanomaterials (Landsiedel et al 2012a), the rat short-term inhalation study (STIS; Ma-Hock et al 2009a; Landsiedel et al 2014a) is recommended.…”