A short-term inhalation study protocol: designed for testing of toxicity and fate of nanomaterials.

Abstract

The Short-Term Inhalation Toxicity Study Design described here was specifically developed for the testing of nanoparticles. It consists of a 5-day inhalation exposure with a subsequent 3-week exposure-free period. The protocol has been optimized for the detection of toxic effects in the respiratory tract by incorporation of additional endpoints like collection of bronchoalveolar lavage and measurement of biomarkers indicative for pro-inflammatory and inflammatory changes. Analytical determination of the test compound concentrations in the lung and other organs can be included in the study design for the determination of organ burden and fate of the tested nanomaterial. Over 20 nanomaterials have been tested with this method. In case of those compounds, where data of 90-day inhalation studies were available, the qualitative effects were comparable in both study types. Likewise, the No Observed Adverse Effect Levels were similar between the two study types, showing that the short-term design is suitable for a first risk assessment.