Characterization of Toxicity of Airborne ENMs using Direct In Vitro Exposure (DIVE)

Project Summary In recent years the use of engineered nanomaterialsENMshas exponentially increasedThese materials have been incorporated in new or developing technologiesand industries worldwide are using these nanomaterials as integrated sensorssemiconductorsdrug delivery systemsstructural materialsand components of sunscreens and cosmeticsclothing and children s toysThe principal properties that differentiate ENM from other materials are increased relative surface areaand high quantum effects which can change or enhance several properties of the manufactured materialsincluding their reactivitystrength and electrical characteristicsHoweverthese characteristics may also confer other detrimental properties related to their biological toxicityhigh rate of pulmonary deposition and high inflammatory potency per unit massamong otherswhich may lead to adverse health effectsEven though the number of ENMs entering the market is increasing every yearthere is a lack of information regarding the degree and conditions in which workers and consumers are exposed to ENMs and their potential adverse health outcomesIn vitro studies conducted with carbon nanotubes and titanium dioxide nanoparticles have provided inconsistent results regarding toxicityDifferences in ENM aerosolization and sampling methodsexposure mechanism and dosecell line and conducted cytotoxicity assayscontribute to these discrepancies in the resultsHoweverthe greatest challenges are associated with particle deliveryexposure mechanismand dosimetryIn additioncommon in vitro models use submerged cell cultures which is a simplistic representation of human lungIn recent yearsmore realistic cell cultures in the air liquid interfaceALIhave been used for assessing biological outcomes of airborne particles in generalAs a resultaerosol exposure chamberswhich culture and expose multiple ALI cells to aerosolized nanoparticles have been developedAlthough these systems provide new tools to study the toxicity of airborne particles there are still many shortcomingslong exposure timesdosimetry characterizationreduced particle deposition in the nanometer size rangelarge size and heavy weightetcthat must be resolved before their wide scale acceptanceHere we proposed the adaptation of a newly developed airborne particle delivery technology for efficient and reliable exposure of ALI cells to ENMs in both working and indoor environments Project Narrative Human exposure to engineered nanomaterialsENMscan occur in different environmentsfrom occupational settings during fabrication and handlingto homes while using consumer products containing ENMsTo assess the risks associated with exposure to the staggering number of ENMs produced annuallywe need to better understand their hazardswith emphasis in their toxicological propertiesHere we present a new system that can increase accuracy in the assessment of toxicological properties of ENMs by directly exposing lung cells to airborne ENMs