Pulmonary Toxicity of Nanomaterials: A Critical Comparison of Published In Vitro Assays and In Vivo Inhalation or Instillation Studies

Abstract

To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

Keywords::

• cytotoxicity
• inflammation
• intratracheal instillation
• metal oxide nanomaterials
• multiwalled carbon nanotubes
• particle dissolution
• short-term inhalation study

Financial & competing interests disclosure

R Landsiedel and L Ma-Hock are employees of and UGS a consultant to BASF SE, a company producing and marketing nanomaterials. The authors alone are responsible for the content and writing of the paper. Part of this work was supported by the BMBF project NanoGEM (grant number: 03X0105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

R Landsiedel and L Ma-Hock are employees of and UGS a consultant to BASF SE, a company producing and marketing nanomaterials. The authors alone are responsible for the content and writing of the paper. Part of this work was supported by the BMBF project NanoGEM (grant number: 03X0105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.