A lot of data are known regarding acute and subacute toxicity of nanomaterials, whereas the long term outcome of inhalative exposure to nanomaterials is still unclear. Long-term inhalation exposure data are only available for nano-TiO2 and Carbon black particles at high aerosol concentrations. These studies indicated a chronic inflammation and subsequent tumor formation in the lungs. It is under discussion which mode of action is causative for the tumor formation.
Within the European NANoREG project and under the umbrella of the BMU (The Federal Environment Ministry, Germany) a cooperation project between BASF SE, Germany and the BAuA (Federal Institute for Occupational Safety and Health), BfR (Federal Institute for Risk Assessment) and UBA (Federal Environment Agency) for conducting and evaluation of a chronic inhalation study with nanomaterials was set up. Goal of this study is to derive profound conclusions of the outcome of inhalative long term exposure with selected nanomaterials. The test compounds are Ceroxid (CeO2) at several dose levels, and Bariumsulfate (BaSO4) at one high dose. The two particles are expected to cover a wider range of different biokinetic behaviours and toxicological responses with Bariumsulfate being more rapidly cleared and less toxic.
CeO2 and BaSO4 are tested in the long-term inhalation study. While CeO2 exposed animals are evaluated within the EU project NanoREG, this Cefic-LRI call will only concern BaSO4 exposed animals. The objective of this project is the investigation of the (i) effects and (ii) biokinetics of nanoparticles inhaled for a life-time.
Investigations of effects:
This includes histopathological processing (from wet formalin-fixed tissue to stained HE slides) as well as light microscopic evaluation and assessment of the groups treated with BaSO4 after 24 and 30 months of treatment (50 animals/time-point). The spectrum of histopathology has to be performed according to the following guidelines OECD 453 (Combined Chronic Toxicity\ Carcinogenicity Studies; 2009) and OECD 413 (Subchronic Inhalation Toxicity: 90-Day Study; 2009). The organ trimming has to be performed according to the published RITA guidance documents (“Revised guides for organ sampling and trimming in rats and mice”; Ruehl-Fehlert C et al. 2003, Kittel B et al. 2004, Morawietz G et al. 2004). The diagnostic criteria have to be used according to INHAND (International Harmonization of Nomenclature and Diagnostic Criteria). The respiratory tract, esp. lungs, has to be evaluated in an extended way (serial sections of lung tissue). The study pathologist should be a certified veterinary toxicopathologist with extensive experience in lung toxicopathology. A histopathological peer-review by a second pathologist is highly recommended. It should be possible to present all results within a PWG (Pathology Working Group), if necessary.
This works have to be done strictly under GLP. A GLP-conform pathology phase report with all data (summary and single data) has to be written.
Because the original study is a GLP study, the provided finalized pathology phase report will be part of the overall study report.
Download here the full version of the RfP LRI-N5.