DEVELOPMENT AND VALIDATION OF AN INHALATION SYSTEM SUITABLE FOR RODENT EXPOSURE TO NANOAEROSOLS

Due to the growing use of nanoparticles in industrial processes, the number of workers potentially exposed is increasing while the toxicological effects of these compounds have not been fully characterized yet. Because inhalation represents the main route of occupational exposure to airborne nanoparticles, the first organs to be exposed are those from the respiratory system. In this respect, the experimental toxicology studies conducted by inhalation in animals appear to be the most relevant for the early evaluation of the hazard associated with exposure to nanoaerosols.
In this framework, INRS has built a dedicated laboratory (inside its new nanomaterials research unit) which meets the highest requirements for animal testing in terms of protection of operators against risks associated with nanoparticles and biohazard.
The key element of this laboratory is NanoTIREx: Nanomaterial Toxicology Inhalation system for Rodent Exposure. It has been designed according to OECD guidelines for the testing of chemicals and is mainly composed of an aerosol generation system and inhalation towers for nose-only exposure. Exposure capability is around 100 rats: 50 nanomaterials exposed rats (in 6 9 ports manifold) and 50 control rats (in 2 27 ports manifold).
The integrated control of the exposure conditions (flow rates, temperature, relative humidity, relative pressure, etc) is managed and recorded using dedicated software.
The monitoring and the characterization of the aerosol are ensured by both real-time devices (condensation particle counter, optical particle sizer) and samples taken for further off-line analyses (gravimetric analysis, mass size distribution from cascade impactor, TEM observations).
This installation is currently used for 28-day inhalation studies with TiO2 nanoparticles focusing on their respiratory and neurological toxicity as well as their toxicokinetics. As the planned test approach for these studies is risk-driven, a dry powder generation method to produce test aerosols of nanoparticles and aggregates and agglomerates (NOAA according to ISO/TS 12901-2 (2014)) has been chosen (rotating brush generator). The NanoTIREx was tested for operation performances with target exposure mass concentration of 10 mg/m3. As illustrated on the figures below, the validation results show that an aerosol of NOAA can be stably generated over several hours (left), the concentration being homogeneous between the different inhalation towers (right). Particle size distributions measurements demonstrated that mass- and number-median aerodynamic diameters are around 420 and 300 nm, respectively.