Whole-Body Nanoparticle Aerosol Inhalation Exposures

Abstract

Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σ g < 2.5 5 . The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size 6 , which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria 5 .A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO 2 inhalation toxicology studies. Critical components: 1) novel nano-TiO 2 aerosol generator; 2) 0.5 m 3 whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO 2 aerosols generated from bulk dry nano-TiO 2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm 3 ) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m /min), and t is the sampling time (minute). The chamber pressure, temperature, relative humidity (RH), O 2 and CO 2 concentrations were monitored and controlled continuously. Nano-TiO 2 aerosols collected on Nuclepore filters were analyzed with a scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analysis.In summary, we report that the nano-particle aerosols generated and delivered to our exposure chamber have: 1) steady mass concentration; 2) homogenous composition free of contaminants; 3) stable particle size distributions with a count-median aerodynamic diameter of 157 nm during aerosol generation. This system reliably and repeatedly creates test atmospheres that simulate occupational, environmental or domestic ENM aerosol exposures. Video LinkThe video component of this article can be found at http://www.jove.com/video/50263/ ProtocolThe whole-body nanoparticle inhalation exposure step-by-step operating procedures are described as follows.Note: 1) steps 1 and 3 should be performed in a fume hood; 2) operators must wear appropriate personal protective equipment (respirators, goggles and rubber gloves).

Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunction

“…Emissions from the chamber were pumped into the nose-only exposure tower. Real-time and time-integrated aerosol sampling and monitoring instrumentation analyzed the emissions in the generation chamber and nose-only exposure tower as previously described (Yi et al , 2013). Briefly, 3DPE particle size distribution and mass concentration were measured continuously with a scanning mobility particle sizer (SMPS, TSI Inc, Shoreview, MN), and an electric low-pressure impactor (ELPI, Dekati, Ltd., Kangasala, Finland).…”

Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

“…Our nanoparticle aerosol generator was developed, designed and tested specifically for rodent nanoparticle inhalation exposures (US patent #8,881,997, Yi and Nurkiewicz, 2011; Yi et al, 2013). Briefly, it consists of a vibrating fluidized bed cylinder with a baffle, a vibrating Venturi disperser, and a cyclone separator.…”

“…Once a steady-state aerosol concentration was achieved (final mass concentration of 10.1 ± 0.39 mg/m 3 for nano-TiO 2 ), exposure duration was adjusted to achieve a single calculated deposition of 41.6 ± 2 μg nano-TiO 2 (exposed) or 0 μg (control). Tremendous care was taken to achieve the same final mass concentration for each exposure; our ability to reliably and repeatedly characterize the aerosols in real time using the ELPI and SMPS enables us to achieve this day-to-day or exposure-to-exposure consistency (Yi et al, 2013). …”

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

“…These chambers have the advantage of housing several animals at once and the chambers can include food and water access. Commercially available devices include the Glas-Col ® inhalation exposure systems and other units from TSE-systems and Shibata Biotechnology (Yi et al, 2013;Chung et al, 2015). Other advantages of whole-body exposure chambers include the ability to house animals for long periods if the experimental design requires long-term exposure, and repeated dosing is also possible.…”