Utilizing literature-based rodent toxicology data to derive potency estimates for quantitative risk assessment

Abstract

Evaluating the potential occupational health risk of engineered nanomaterials is an ongoing need. The objective of this meta-analysis, which consisted of 36 studies containing 86 materials, was to assess the availability of published in vivo rodent pulmonary toxicity data for a variety of nanoscale and microscale materials and to derive potency estimates via benchmark dose modeling. Additionally, the potency estimates based on particle mass lung dose associated with acute pulmonary inflammation were used to group materials based on toxicity. The commonalities among the physicochemical properties of the materials in each group were also explored. This exploration found that a material’s potency tended to be associated primarily with the material class based on chemical composition and form (e.g. carbon nanotubes, TiO₂, ZnO) rather than with particular physicochemical properties. Limitations in the data available precluded a more extensive analysis of these associations. Issues such as data reporting and appropriate experimental design for use in quantitative risk assessment are the main reasons publications were excluded from these analyses and are discussed.

Keywords:

• Meta-analysis
• quantitative risk assessment
• toxicology
• potency estimation
• benchmark dose modeling

Acknowledgements

The authors acknowledge Dr. Harald F. Krug, formerly with Empa–Swiss Federal Laboratories for Science and Materials Technology, St. Gallen, Switzerland and currently with NanoCASE GmbH, Engelburg, Switzerland, for providing the initial Nano-AOP database and additional information about the database. We acknowledge Dr. Indrani Mahapatra, School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham, UK, for providing the updated Nano-AOP database and for performing an additional search of the Nano-AOP database for studies used in this analysis. We acknowledge Dr. Jayne-Anne Bond, formerly with ATL International Inc., for her contributions in developing the initial ATL database for NIOSH. We thank Ms Sarah Davidson, formally an Oak Ridge Associated Universities, ORAU, fellow at NIOSH, for her contributions in checking the initial ATL database and constructing a revised dataset used in this analysis. Additionally, we would like to thank Mr. Bill Bennett, formally at NIOSH, and Ms Sherry Fendinger, NIOSH, for their input on the literature searches we performed during construction of the NIOSHTIC-2 derived database used in this analysis.

Disclosure statement

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. No potential conflict of interest was reported by the author(s).

Data availability statement

The full set of potency estimates (BMDs, BMDLs, NOAELs, and LOAELs) used within this manuscript can be found in Table S-1 in Supplemental Material. Data used to calculate these potency estimates can be found in the corresponding publications.

Additional information

Funding

Dr. Mahapatra acknowledges funding from the EU H2020 research infrastructure for nanosafety, NanoCommons, [Grant Agreement No. 731032].