Inhalation Bioaccessibility And Cytotoxicity Of Toxic Components In Simulants Of Fine Ambient Particulate Matter

Fine/ultra fine ambient particulate matter(APM)were defined and clarified by their aerodynamic diameter(Dae),which APM with Dae<2.5 ?m was fine fraction and Dae<0.1 ?m was ultrafine fraction.The much complicated physicochemical properties of APM may be huge difference for them sources from different areas or the same area at different time.These characters of APM limits to a large extent the development of researching the toxicities and assessment of health risks related to the inhalation exposure of them which should have supplied the scientific data to support the career of preventing and controlling the certain diseases.Inhalation bioaccessibility testing was suggested to serve as a potential alternative and supplements data for exposure assessment.Inhalation bioaccessibility may be defined as the fraction of toxicants dissolved in simulated lung fluids lining the respiratory system that is potentially available to cross the air-blood barrier of the respiratory system to reach blood circulation.In addition,parts of ultra fine fraction reached into deep airway could pass through the cell membrane of lung epithelial cell and internalize into cytoplasm,which could impair the lung cells and cause respiratory diseases.This paper choose the nanoparticles and fine soils as simplified model of APM and carried out a series of studies for making the exposure process more clear.Nanoparticles as ultra fine faction of APM were introduced into simulated biological fluids and the bioaccessibility of toxicants in a certain fluid were obtained.The process of aggregation/sedimentation and dissolution in suspensions about the nanoparticles were disclosed with the possible influences of natural organic matters(NOMs).The internalizing processes into A549 cell were also studied under the influences of natural organic matters.The designed lead contaminated fine soils were used to study the regularity of Pb inhalation bioavailability and optimize the existing in vitro inhalation bioaccessibility testing.The major contents of this thesis are described as follow:(1)The bioaccessibility about the inhalation exposure and oral exposure of toxic elements in two types of particles(metal oxide nanoparticles:nZnO,nCuO,nTiO2,nCeO2 and nFe3O4,17?42 nm,and the related bulk compounds:ZnO,ZnSiO3,ZnS and CuO)were studied by two simulated gastric-intestinal fluids(Solubility bioavailability research consortium,SBRC and In vitro gastrointestinal,IVG)and two simulated lung fluids(Artificial lysosomal fluids,ALF and Gamble Solution),respectively.The suspension related properties of these particles suspending in the fluid such as zeta potential and aggregation/sedimentation were researched to bridge them with their bioaccessibility.The outcomes in this study were significant to assessment the health risk of these particles exposure by oral tract or inhalation tract.(2)NOMs such as citric acid,tartaric acid and fulvic acid which are ubiquitous in the environment and widely accepted to play a predominant role in the transport,fate,and bioavailability of toxic chemicals in the environment were studied for their effects in nAg and nZnO of the dissolution and aggregation in two simulated lung fluids(ALF and Gamble Solution),which disclosed the influences of environment factors in exposure of nanoparticles by inhalation tract.(3)Nano silver(nAg,27.9±7.9 nm)was synthesized and then treated by NOMs.The influences of NOMs to nAg internalizing to A549 cells such as internalizing pathway,capacity and velocity,and increasing ROS level to A549 cells were studied.The cellular uptake process of nAg as a supplement of bioaccessibility of nanoparticles were proved to be sensitive to NOMs.(4)The inhalation method were built up for the bioavailability of Pb in fine APM by grinded soils in laboratory conditions with the addition of controlled mass of Pb with different Pb compounds and their intra-nasal instilling to Balb/c mouse(8?10 weeks).The data of inhalation bioavailability of Pb based on the good linear response kidney model were used to test four in vitro methods which were usually applied to research the inhalation bioaccessibility of Pb in APM and optimize the parameters of in vitro methods.A robust linear relationship were built up to bridge the inhalation bioaccessibility with the inhalation bioavailability of Pb in APM.