a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.
Exposure to methyl mercury, a risk factor for neurodevelopmental toxicity, was assessed in U.S. Hair mercury levels were associated with age and fish consumption frequency.
The US Food and Drug Administration (FDA) has conducted the Total Diet Study (TDS) since 1961, which designed to monitor the US food supply for chemical contaminants, nutritional elements, and toxic elements. Recently, perchlorate was analyzed in TDS samples. Perchlorate is used as an oxidizing agent in rocket propellant, is found in other items (e.g., explosives, road flares, fireworks, and car airbags), occurs naturally in some fertilizers, and may be generated under certain climatic conditions. It has been detected in surface and groundwater and in food. Perchlorate at high (e.g., pharmacological) doses can interfere with iodide uptake into the thyroid gland, disrupting its function. The National Academy of Sciences (NAS) has identified that ''the fetuses of pregnant women who might have hypothyroidism or iodide deficiency as the most sensitive population.'' This study reports on intake estimates of perchlorate and iodine, a precursor to iodide, using the analytical results from the TDS. Estimated average perchlorate and iodine daily intakes as well as the contribution of specific food groups to total intakes were estimated for 14 age/sex subgroups of the US population. The estimated smallest lower bound to the largest upper bound average perchlorate intakes by the 14 age/sex groups range from 0.08 to 0.39 micrograms per kilogram body weight per day (mg/kg bw/day), compared with the US Environmental Protection Agency (EPA) reference dose (RfD) of 0.7 mg/kg bw/day. Infants and children demonstrated the highest estimated intakes of perchlorate on a body weight basis. The estimated average iodine intakes by the 14 age/sex groups reveal a lower bound (ND ¼ 0) and upper bound (ND ¼ LOD) range of average intakes from 138 to 353 mg/person/day. Estimated iodine intakes by infants 6-11 months exceed their adequate intake (AI), and intakes by children and adult age/sex groups exceed their relevant estimated average requirement (EAR).
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