Multiple-Path Particle Dosimetry Research Articles

ENanoMapper – A database and ontology framework for design and safety assessment of nanomaterials

In this paper, we discuss the derivation of respiratory health effect factors (HEFs) for use in Life Cycle Impact Assessment (LCIA) for five nanoparticles: nanosilver, nano TiO2, carbon black, high-aspect ratio, rigid MWCNT and flexible MWCNT. For this purpose, we applied the methodology of USEtox™, a consensus model to calculate human toxicity and ecotoxicity characterization factors. In view of the available data, the non-carcinogenic HEFs for carbon black and TiO2 can be attributed the recommended status. For MWCNT and nanosilver the non-carcinogenic HEFs should be awarded the indicative status due to the minimal effects observed in the animal studies. All carcinogenic HEFs are currently labelled as indicative since there is no consensus with respect to the human relevance of the overload mechanism of carcinogenicity observed in rats exposed to poorly soluble particles (carbon black, flexible MWCNT and TiO2), whereas for high-aspect ratio, rigid MWCNT, the extrapolation from asbestos carcinogenicity introduces uncertainty. For nanosilver no carcinogenic HEF could be derived.The present study clearly demonstrates the difficulties associated with the derivation of HEFs for the nanomaterials considered, in particular in the USEtox™ framework for comparative risk assessment, and makes recommendations to overcome them:•Nanoparticles for which a dose metric other than its mass is relevant for their toxicity require ‘normalisation’ to the mass metric. Adaptation of USEtox™ to accommodate other dose metrics than mass intake is therefore recommended.•Simplified estimates of deposited and retained dose are currently needed, ignoring particle size distribution dependency. Therefore, it is recommended to include kg deposited and kg retained as dose parameters for HEFs in USEtox™ and to link USEtox™ to the Multiple Path Particle Dosimetry model to convert kg intake to these dose parameters.•Establishment of the Point of Departure (PoD) for the derivation of the HEFs and the extrapolation factors to be used is recommended through consensus building. Although the ED50 is preferred as the PoD from the perspective of comparative risk assessment in LCA, for some nanoparticles, other PoDs could be considered when the dose-response data are limited.•Overall, the assessed nanoparticles are likely to be more toxic than most bulk chemicals regarding non-carcinogenic effects. However, the results of LCIA based on these HEFs must be interpreted with the necessary constraints and reservations due to the large uncertainty involved.

Benchmark study on fine-mode aerosol in a big urban area and relevant doses deposited in the human respiratory tract

It is well-known that the health effects of PM increase as particle size decreases: particularly, great concern has risen on the role of UltraFine Particles (UFPs). Starting from the knowledge that the main fraction of atmospheric aerosol in Rome is characterized by significant levels of PM2.5 (almost 75% of PM10 fraction is PM2.5), the paper is focused on submicron particles in such great urban area. The daytime/nighttime, work-/weekdays and cold/hot seasonal trends of submicron particles will be investigated and discussed along with NOx and total PAH drifts demonstrating the primary origin of UFPs from combustion processes. Furthermore, moving from these data, the total dose of submicron particles deposited in the respiratory system (i.e., head, tracheobronchial and alveolar regions in different lung lobes) has been estimated. Dosimeter estimates were performed with the Multiple-Path Particle Dosimetry model (MPPD v.2.1). The paper discusses the aerosol doses deposited in the respiratory system of individuals exposed in proximity of traffic. During traffic peak hours, about 6.6 × 1010 particles are deposited into the respiratory system. Such dose is almost entirely made of UFPs. According to the greater dose estimated, right lung lobes are expected to be more susceptible to respiratory pathologies than left lobes.

Polonium in size fractionated mainstream cigarette smoke, predicted deposition and associated internal radiation dose

In this study, size fractionated mass and 210Po activity concentrations in mainstream cigarette smoke (MCS) were monitored for three popular cigarette brands. Size segregated collection of MCS was carried out using a cascade type impactor, while mass and 210Po activity concentration were analyzed gravimetrically and alpha spectrometry (following the radiochemical separation) respectively. Multiple-Path Particle Dosimetry (MPPD V2.11) model is used for prediction of deposition fraction calculations for the MCS deposition in different compartment of human respiratory tract. The activity concentration of 210Po is founds 10.56 ± 2.46 mBq per cigarette for the tested cigarette brands. 210Po size distribution indicates most of this associates with fine fraction (Dp < 2.23 μm) of cigarette smoke. The committed annual effective dose to smokers (smoking on an average 20 cigarette a day), considering the 210Po and 210Pb concentrations (assuming it is in secular equilibrium with 210Po) in MCS, was estimated between 0.22 and 0.40 mSv, with mean value of 0.30 mSv for tested cigarette brands. Considering the risk factor of fatal cancer due to radiation exposure of lung (exposure time of 30 years); the average collective estimated fatal cancer risk is estimated as 1.5 × 10−4 due to 210Po and 210Pb exposure to smokers.

On the relationship between response to inhaled methacholine and airway dimensions

Site-specific dosimetry was used to address the hypothesis that, given the airway dimensions of one subject, the airway dimensions of a second subject can be obtained by comparing responses to a modified bronchoconstrictor inhalation-protocol. Fourteen healthy, nonsmoking subjects received a high-resolution computed tomography (HRCT) scan prior to performing a methacholine challenge and measurement of change in forced-expiratory-volume-in-one-second, (∆FEV1). Scale factors of average length (L) and diameter (d) of the first six tracheobronchial airway generations were used to construct typical path lungs. The Multiple Path Particle Dosimetry (MPPD) model calculated surface density of methacholine. Airway circumference change, ∆C/C0, was used to calculate ∆FEV1 in terms of airway smooth muscle sensitivity, K (cm/µg/cm2). Virtual protocols were modeled such that fractional changes in ∆FEV1,“∆Y”, were independent of K. Eight subjects responded to methacholine with ∆FEV1 >3% and Ks from 0.011 to 35.8. For one virtual protocol, the linear relations between ∆Y and length and diameter scale factors had R2s respectively of 0.49 and 0.57. Within the limits of these measurements, the hypothesis is demonstrated; — any continuously increasing function of ∆Y vs. scale factor being sufficient to allow (without HRCT scans) classification of subjects according to airway size.

Improvements and additions to the Multiple Path Particle Dosimetry model

A little over a decade ago, the first UC Irvine dosimetry conference was held entitled “Frontiers in Aerosol Dosimetry Research”. At that time, mechanistic dosimetry models, such as the multiple path particle dosimetry (MPPD) model, primarily focused on humans, with a model for the Long Evans rat also being available. In the intervening years, advances have occurred on a number of fronts that have led to improvements and additions to the user-friendly MPPD software program that is available free to the public. Here, we review a number of the expanded capabilities of the MPPD model. These include:•Calculating deposition and clearance simultaneously for up to 4 lognormal distributions having different mass median aerodynamic diameters and geometric standard deviations. This feature is useful whenever the exposure atmosphere is multimodal as is often the case with workplace exposure atmospheres and can occur in inhalation toxicology studies if the particulate aerosol is difficult to generate stably.•The ability to adjust the total aerosol deposition for the amount of particle “X” when “X” is a subset of the total aerosol. This is particularly important for workplace exposures where the particles of interest (e.g., copper containing particles) are part of the total dust aerosol that was measured.•The ability to specify clearance rates and mucous velocities for both animals and humans so any type of particle can be modeled as well as various lung disease states.•The addition of dose metrics for the upper respiratory tract and enhancements to dose metrics for the lower respiratory tract.•Addition of a lung geometry/morphometry model and physiologic input variables for mice (Balb/c and B6C3F1), Sprague-Dawley rats, male rhesus monkeys, sheep, and pigs. The deposition and clearance of particles in these species can now be examined.

Traffic aerosol lobar doses deposited in the human respiratory system.

Aerosol pollution in urban environments has been recognized to be responsible for important pathologies of the cardiovascular and respiratory systems. In this perspective, great attention has been addressed to Ultra Fine Particles (UFPs < 100nm), because they efficiently penetrate into the respiratory system and are capable of translocating from the airways into the blood circulation. This paper describes the aerosol regional doses deposited in the human respiratory system in a high-traffic urban area. The aerosol measurements were carried out on a curbside in downtown Rome, on a street characterized by a high density of autovehicular traffic. Aerosol number-size distributions were measured by means of a Fast Mobility Particle Sizer in the range from 5.6 to 560nm with a 1s time resolution. Dosimetry estimates were performed with the Multiple-Path Particle Dosimetry model by means of the stochastic lung model. The exposure scenario close to traffic is represented by a sequence of short-term peak exposures: about 6.6 × 1010 particles are deposited hourly into the respiratory system. After 1h of exposure in proximity of traffic, 1.29 × 1010, 1.88 × 1010, and 3.45 × 1010 particles are deposited in the head, tracheobronchial, and alveolar regions. More than 95% of such doses are represented by UFPs. Finally, according to the greater dose estimated, the right lung lobes are expected to be more susceptible to respiratory pathologies than the left lobes.

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

Consumer exposure to sprays containing nano-objects is a continuing concern as a potential health hazard. One potential hazard has been formulated in the overload hypothesis. It describes a volume fraction of the macrophages that is occupied by deposited nanoparticles that leads to reduced macrophage mobility. Subsequent chronic inflammation may then lead to severe health consequences including cancer. To calculate lung deposition of spherical particles, the Multiple-Path Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds of lung models and age settings. Using the MPPD v 2.11 software, we modeled several consumer-related exposure scenarios. Different body orientations and age groups were investigated. Moreover, a number of materials representing different densities were used, and the exposure calculated using MPPD is compared to the hazard derived from the overload hypothesis. Conditions leading to macrophage overload were found for exposures to high particle doses for prolonged times and repeated exposure. Such conditions are unlikely in the context of regular consumer exposure. The overload hypothesis assumes the particles to be inert and biopersistent, a condition that currently lacks a clear regulatory definition and is valid only for a few selected materials. Furthermore, because of material-specific effects and the possibility of surface adsorption of hazardous chemicals, nano-objects in propellant sprays remain of concern for consumer health.

Dry Lung as a Physical Model in Studies of Aerosol Deposition.

A new physical model was developed to evaluate the deposition of micro- and nanoaerosol particles (NAPs) into the lungs as a function of size and charges. The model was manufactured of a dry, inflated swine lung produced by Nasco company (Fort Atkinson, WI). The dry lung was cut into two lobes and a conductive tube was glued into the bronchial tube. The upper 1-2-mm-thick layer of the lung lobe was removed with a razor blade to expose the alveoli. The lobe was further enclosed into a plastic bag and placed within a metalized plastic box. The probability of aerosol deposition was calculated by comparing the size distribution of NAPs passed through the lung with that of control, where aerosol passed through a box bypassing the lung. Using this new lung model, it was demonstrated that charged NAPs are deposited inside the lung substantially more efficiently than neutral ones. It was also demonstrated that deposition of neutral NAPs well fits prediction of the Multiple-Path Particle Dosimetry (MPPD) model developed by the Applied Research Associates, Inc. (ARA).

Development of a chronic inhalation reference value for hexamethylenediamine using an exposure model based on the dihydrochloride salt

The Texas Commission on Environmental Quality has developed a chronic inhalation Reference Value (ReV) for hexamethylenediamine (HMDA, CAS 124-09-4) based on respiratory effects identified in an animal study. HMDA is used in the fiber and plastics industry as an intermediate in the production of nylon, high-strength resins and polyamide adhesives. As a toxicant, HMDA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract, although systemic effects have been noted at higher concentrations. ReVs are chemical-specific air concentrations derived to protect human health. Acute and chronic ReVs were developed for HDMA based on an inhalation study conducted by the National Toxicology Program (NTP), which used the salt of HMDA, hexamethylenediamine dihydrochloride (HDDC, CAS 6055-52-3). For the chronic evaluation, rats and mice were exposed to 0, 1.6, 5, 16, 50 and 160 mg HDDC/m3 for 13 weeks. The critical effect identified for the most sensitive species was hyaline degeneration in the olfactory epithelium in mice. The data provided in this study were suitable to benchmark concentration (BMC) modeling. Dosimetric adjustments using the rat and mouse Multiple-Path Particle Dosimetry Model (version 3.0) were made to the 95% lower limit of the BMC(10) to determine the human equivalent point of departure. Uncertainty factors were applied to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and use of a subchronic study. The ReV was initially calculated for HDDC and then adjusted for HMDA. The chronic ReV is 1.8 µg/m3 for respirable HMDA ≤ 10 µm in diameter.

Modeled deposition of fine particles in human airway in Beijing, China

Abstract This study aims to simulate depositions of size-segregated particles in human airway in Beijing, China during seasons when fine particulate matter concentrations are high (December 2011 and April 2012). Particle size distributions (5.6–560 nm, electrical mobility diameter) near a major road in Beijing were measured by the TSI Fast Mobility Particle Sizer (FMPS). The information of size distributions provided by FMPS was applied in the Multiple-Path Particle Dosimetry model (MPPD) to quantify number and mass depositions of particles in human airway including extrathoracic (ET), tracheobronchial (TB), and pulmonary (PUL) regions of exposed Chinese in Beijing. Our results show that under ambient conditions, particle number concentration (NC) deposition in PUL is the highest in the three major regions of human airway. The total particle NC deposition in human airway in winter is higher than that in spring, especially for ultrafine particles (1.8 times higher) while particle mass concentration (MC) deposition is higher in spring. Although particle MC in clean days are much lower than that in heavily polluted days, total particle NC deposition in human airway in clean days is comparable to that in heavily polluted days. NC deposition for nucleation mode particles (10–20 nm, aerodynamic diameter) in clean days is higher than that in heavily polluted days. MC deposition for accumulation mode particles (100–641 nm, aerodynamic diameter) in heavily polluted days is much higher than that in clean days, while that of nucleation mode is negligible. The temporal variation shows that the arithmetic mean and the median values of particle NC and MC depositions in the evening are both the highest, followed by morning and noon, and it is most likely due to increased contribution from traffic emissions.

Refining Assessment of PAH Exposure and Potential Carcinogenic Risk Assessment from Biomass Burning Incorporating Internal Dosimetry Metrics

Refining Assessment of PAH Exposure and Potential Carcinogenic Risk Assessment from Biomass Burning Incorporating Internal Dosimetry MetricsAbstract Number:2574 Dimosthenis Sarigiannis*, Dimitris Zikopoulos, Marianthi Kermenidou, Spyridoula Nikolaki, and Spyridon Karakitsios Dimosthenis Sarigiannis* Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Greece, E-mail Address: [email protected] Search for more papers by this author , Dimitris Zikopoulos Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Greece, E-mail Address: [email protected] Search for more papers by this author , Marianthi Kermenidou Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Greece, E-mail Address: [email protected] Search for more papers by this author , Spyridoula Nikolaki Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Greece, E-mail Address: [email protected] Search for more papers by this author , and Spyridon Karakitsios Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Greece, E-mail Address: [email protected] Search for more papers by this author AbstractThe current study deals with the assessment of the cancer risk attributable to exposure to PAHs due to increased use of biomass for space heating in Greece in the winter of 2012- 2013. The study incorporated ambient air PM sampling in several sites in the city of Thessaloniki, as well as chemical analysis of PAHs and levoglucosan, used here as the most specific tracer of biomass combustion. Internal exposure to PAHs was estimated taking into account the deposition of the respective PM fractions across the human respiratory tract (HRT) and the respective PAHs concentration of the respective PM fractions. Deposition at different regions of the HRT was estimated using the Multiple- Path Particle Dosimetry (MPPD) model. Potential cancer risk due to exposure to the mixture of urban ambient air PAHs was calculated using the toxicity equivalence factor (TEF) approach using as basis the benzo(a)pyrene (B[a]P) cancer potency. The BaP-TEQ (Toxicity Equivalent Quotient) (carcinogenic equivalent expressed in ng/m3) was calculated by multiplying the concentrations of each compound in the PAH mixture with the respective TEF for cancer potency relative to BaP. Cancer risk was estimated by multiplying the TEQ of the respective fraction of particulate matter deposited daily across HRT by a slope-factor equal to 0.25•10-6 ng/kg_bw/day) function, initially derived by the B[a]P Inhalation Unit Risk (equal to 0.88•10-6 (ng/m3)-1). Significant variation in internal exposure to PAHs (and respectively to the estimated risk) was observed among different age groups, much larger than variation due to geospatial attributes. Bodyweight normalized uptake (and the attributed risk) for children is four times higher than for adults. Only limited difference was found between traffic and urban background sites in the winter; the latter indicates that biomass emitted PM are not significantly different in terms of carcinogenic potency compared to traffic ones.

Characterization and estimation of human airway deposition of size-resolved particulate-bound trace elements during a recent haze episode in Southeast Asia.

Toxic elements present in airborne particulate matter (PM) are associated with human health effects; however, their toxic characteristics depend on the source of their origins and their concentrations in ambient air. Twenty four elements (Al, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, K, Li, Mg, Mn, Na, Ni, Pb, Se, Sr, Te, Tl, and Zn) in 12 different size fractions of PM ranging from 10nm to 10μm were characterized in Singapore during two different atmospheric conditions (smoke haze and non-haze periods) in 2012 for the first time. In addition, their possible sources were identified based on backward air trajectory analysis and principal component analysis (PCA). The health implications of inhalable particles were assessed using a human airway deposition model, the Multiple-Path Particle Dosimetry model (MPPD). The results concerning particle-bound trace elements are interpreted in terms of coarse (PM2.5-10), fine (PM2.5), ultrafine (PM0.01-0.1, 0.01μm < Dp < 0.10μm), and nano (PM0.01-0.056, 0.01μm < Dp < 0.056μm) particles. The ratios of elemental concentrations measured between the smoke haze episode and the non-haze period in coarse, fine, ultrafine, and nano particles varied from 1.2 (Bi) to 6.6 (Co). Both the PCA and backward trajectory analysis revealed that trans-boundary biomass-burning emissions from Indonesia were primarily responsible for enhanced concentrations of particulate-bound elements during the smoke haze episode. The particle depositions in the respiratory system were higher during the smoke haze episode compared to the non-haze period. The study finds that ultrafine and nano particles present in the atmosphere have higher tendencies to be deposited into the deeper parts of the respiratory system, compared to coarse and fine particles.

Characterization of different vitamin E carriers intended for pulmonary drug delivery

The targeted release of drugs intended for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano-emulsion, and solid lipid particles) were prepared using various methods based on membrane contactor. The dispersions were nebulized and aerodynamic characteristics of the generated aerosols were assessed using two different methods: laser light scattering and cascade impaction. When the laser diffraction technique was used, results showed that fine particle fractions (<5μm) were 19, 29, 38 and 71% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. When the impaction method was applied, using a next generation pharmaceutical impactor operated at 30l/min, results showed that fine particle fractions were 39, 78, 82 and 87% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. The differences observed between the results obtained from both methods confirm that the laser diffraction method is not always suitable for aerodynamic characterization of aerosols and should be validated against an impaction method. Nebulization of the drug-carrier systems led to an increase of their size most likely due to aggregation phenomena. The size was increased by a factor of 2–26 depending on the encapsulation system. The most important aggregation was obtained with nano-emulsion; the less one with solid lipid particles. The mass median aerodynamic diameter (MMAD) of the generated aerosols ranged from 1.76 to 6.10μm. The application of a mathematical model, the Multiple-Path Particle Dosimetry (MPPD), for the prediction of the pulmonary deposit gave encouraging results. The rate of vitamin E able to reach the lung ranged from 37.6 (for the liposomes) to 51.6% (for the micelles). The obtained results showed that the different systems developed for vitamin E encapsulation were suitable to target the lung after pulmonary administration by nebulization.

2013 Southeast Asian Smoke Haze: Fractionation of Particulate-Bound Elements and Associated Health Risk

Recurring biomass burning-induced smoke haze is a serious regional air pollution problem in Southeast Asia (SEA). The June 2013 haze episode was one of the worst air pollution events in SEA. Size segregated particulate samples (2.5-1.0 μm; 1.0-0.5 μm; 0.5- 0.2 μm; and <0.2 μm) were collected during the June 2013 haze episode. PM2.5 concentrations were elevated (up to 329 μg/m(3)) during the haze episode, compared to those during the nonhaze period (11-21 μg/m(3)). Chemical fractionation of particulate-bound trace elements (B, Ca, K, Fe, Al, Ni, Zn, Mg, Se, Cu, Cr, As, Mn, Pb, Co, and Cd) was done using sequential extraction procedures. There was a 10-fold increase in the concentration of K, an inorganic tracer of biomass burning. A major fraction (>60%) of the elements was present in oxidizable and residual fractions while the bioavailable (exchangeable) fraction accounted for up to 20% for most of the elements except K and Mn. Deposition of inhaled potentially toxic trace elements in various regions of the human respiratory system was estimated using a Multiple-Path Particle Dosimetry model. The particle depositions in the respiratory system tend to be more severe during hazy days than those during nonhazy days. A prolonged exposure to finer particles can thus cause adverse health outcomes during hazy days. Health risk estimates revealed that the excessive lifetime carcinogenic risk to individuals exposed to biomass burning-impacted aerosols (18 ± 1 × 10(-6)) increased significantly (P < 0.05) compared to those who exposed to urban air (12 ± 2 × 10(-6)).

Particle Deposition in Respiratory Tracts of School-Aged Children

Exposure to ultrafine particles poses a potential health risk to school children. While many studies have focused on measuring ultrafine particle (UFP) concentrations in environments where children are at risk of high exposure, few studies have examined the particle deposition in the respiratory tract of children. This study aims to examine the particle deposition in the respiratory tract of school children in different microenvironments. UFP size distribution data were collected in residential homes, school buses, school classrooms, and from school outdoor air in both rural and urban areas of South Texas. The size distribution data were input to the Multiple Path Particle Dosimetry model to calculate regional and total particle deposition fraction. A 24-hour-school-day exposure was simulated by adding the time children spend in each microenvironment. The maximum pulmonary deposition fraction occurs at a diameter ranging from 18 to 40 nm, depending on condition. Age mostly affected the pulmonary region and the total lung deposition with the highest deposition fraction observed for younger children. In addition, comparison of size-dependent regional deposition and particle concentration establishes an accurate depiction of children's exposure and dose profiles. While children only spend 4% of the day in the home source environment, that environment may account for up to 77% of total daily dose intake. Higher deposition fraction occurs at smaller particle size. Younger children show increased levels of particle deposition than older children. Exposure period does not correlate to daily percentage of dose intake. This research can be used to assess children's accumulative exposure to UFPs.

Estimating lung burdens based on individual particle density estimated from scanning electron microscopy and cascade impactor samples

Workplace air is monitored for overall dust levels and for specific components of the dust to determine compliance with occupational and workplace standards established by regulatory bodies for worker health protection. Exposure monitoring studies were conducted by the International Copper Association (ICA) at various industrial facilities around the world working with copper. Individual cascade impactor stages were weighed to determine the total amount of dust collected on the stage, and then the amounts of soluble and insoluble copper and other metals on each stage were determined; speciation was not determined. Filter samples were also collected for scanning electron microscope analysis. Retrospectively, there was an interest in obtaining estimates of alveolar lung burdens of copper in workers engaged in tasks requiring different levels of exertion as reflected by their minute ventilation. However, mechanistic lung dosimetry models estimate alveolar lung burdens based on particle Stoke’s diameter. In order to use these dosimetry models the mass-based, aerodynamic diameter distribution (which was measured) had to be transformed into a distribution of Stoke’s diameters, requiring an estimation be made of individual particle density. This density value was estimated by using cascade impactor data together with scanning electron microscopy data from filter samples. The developed method was applied to ICA monitoring data sets and then the multiple path particle dosimetry (MPPD) model was used to determine the copper alveolar lung burdens for workers with different functional residual capacities engaged in activities requiring a range of minute ventilation levels.

Particle Size Distribution of Mainstream and Exhaled Cigarette Smoke and Predictive Deposition in Human Respiratory Tract

The particle size distribution of cigarette smoke is an important factor in predicting the deposition fraction of the inhaled particles in various regions of the respiratory tract. Mainstream cigarette smoke is a direct concern for smokers, while the exhaled and side stream smoke contribute to passive (second hand) smoking. The particle size distribution of tobacco smoke for mainstream and exhaled smoke has been studied in this work. This study investigates how smoking behavior, including puff volume and number of puffs, affect the particle size distribution of mainstream cigarette smoke. Scanning Mobility Particle Sizer (SMPS) was used to measure the particle size distribution of mainstream and exhaled cigarette smoke. The values of count median diameter (CMD) mobility size for the first four consecutive puffs were found to be 193 nm, 198 nm, 194 nm and 186 nm. As the volume of a puff increases from 35 mL to 85 mL, the CMD shifted slightly towards the higher particle size ranges, because of increased probability of coagulation and other combination processes. For the exhaled cigarette smoke, the growth factor was found to be 1.5 ± 0.3 with respect to mainstream cigarette smoke. The experimental results of particle size distributions were used in a Multiple Path Particle Dosimetry (MPPD) model to predict deposition patterns in the human respiratory tract. The MPPD model results show the deposition fractions for mainstream cigarette smoke were 0.163, 0.152 and 0.298 for the head, trachea and bronchi (TB) and pulmonary region, and those for exhaled cigarette smoke were 0.273, 0.064 and 0.134 respectively. The total calculated deposition fraction for mainstream and exhaled cigarette smoke was found to be 0.613 and 0.471, respectively.

Tissue Distribution of Inhaled Micro- and Nano-sized Cerium Oxide Particles in Rats: Results From a 28-Day Exposure Study

In order to obtain more insight into the tissue distribution, accumulation, and elimination of cerium oxide nanoparticles after inhalation exposure, blood and tissue kinetics were investigated during and after a 28-day inhalation study in rats with micro- and nanocerium oxide particles (nominal primary particle size: < 5000, 40, and 5-10 nm). Powder aerosolization resulted in comparable mass median aerodynamic diameter (1.40, 1.17, and 1.02 μm). After single exposure, approximately 10% of the inhaled dose was measured in lung tissue, as was also estimated by a multiple path particle dosimetry model (MPPD). Though small differences in pulmonary deposition efficiencies of cerium oxide were observed, no consistent differences in pulmonary deposition between the micro- and nanoparticles were observed. Each cerium oxide sample was also distributed to tissues other than lung after a single 6-h exposure, such as liver, kidney, and spleen and also brain, testis, and epididymis. No clear particle size-dependent effect on extrapulmonary tissue distribution was observed. Repeated exposure to cerium oxide resulted in significant accumulation of the particles in the (extra)pulmonary tissues. In addition, tissue clearance was shown to be slow, and, overall, insignificant amounts of cerium oxide were eliminated from the body at 48- to 72-h post-exposure. In conclusion, no clear effect of the primary particle size or surface area on pulmonary deposition and extrapulmonary tissue distribution could be demonstrated. This is most likely explained by similar aerodynamic diameter of the cerium oxide particles in air because of the formation of aggregates and irrespective possible differences in surface characteristics. The implications of the accumulation of cerium oxide particles for systemic toxicological effects after repeated chronic exposure via ambient air are significant and require further exploration.

Nanotoxicology: in Vitro–in Vivo Dosimetry

Nanotoxicology: in Vitro–in Vivo Dosimetry

Informing Selection of Nanomaterial Concentrations for ToxCast in Vitro Testing Based on Occupational Exposure Potential

Background: Little justification is generally provided for selection of in vitro assay testing concentrations for engineered nanomaterials (ENMs). Selection of concentration levels for hazard evaluation based on real-world exposure scenarios is desirable.Objectives: Our goal was to use estimates of lung deposition after occupational exposure to nanomaterials to recommend in vitro testing concentrations for the U.S. Environmental Protection Agency’s ToxCast™ program. Here, we provide testing concentrations for carbon nanotubes (CNTs) and titanium dioxide (TiO2) and silver (Ag) nanoparticles (NPs).Methods: We reviewed published ENM concentrations measured in air in manufacturing and R&D (research and development) laboratories to identify input levels for estimating ENM mass retained in the human lung using the multiple-path particle dosimetry (MPPD) model. Model input parameters were individually varied to estimate alveolar mass retained for different particle sizes (5–1,000 nm), aerosol concentrations (0.1 and 1 mg/m3), aspect ratios (2, 4, 10, and 167), and exposure durations (24 hr and a working lifetime). The calculated lung surface concentrations were then converted to in vitro solution concentrations.Results: Modeled alveolar mass retained after 24 hr is most affected by activity level and aerosol concentration. Alveolar retention for Ag and TiO2 NPs and CNTs for a working-lifetime (45 years) exposure duration is similar to high-end concentrations (~ 30–400 μg/mL) typical of in vitro testing reported in the literature.Conclusions: Analyses performed are generally applicable for providing ENM testing concentrations for in vitro hazard screening studies, although further research is needed to improve the approach. Understanding the relationship between potential real-world exposures and in vitro test concentrations will facilitate interpretation of toxicological results.