Particulate Matter Exposure Concentrations Research Articles

Particulate matter induced cognitive impairments via endoplasmic reticulum stress-mediated damage to mitochondria-associated endoplasmic reticulum membranes in immature rats

Particulate matter (PM) exposure has been increasingly recognized as detrimental to cognitive function and is associated with neurodevelopmental disorders. Mitochondria-associated endoplasmic reticulum membranes (MAMs) form an integrated interface between mitochondria and the endoplasmic reticulum (ER), facilitating crucial cellular functions. Prolonged ER stress (ERS) is implicated in various pathological states in the nervous system. MAMs and ERS may play vital roles in adverse effects of early-life PM exposure on cognitive abilities. This study investigated whether ERS plays a role in PM-induced MAMs dysfunction, leading to neuronal damage and cognitive impairments in early postnatal rats. Using a rat model with PM exposure concentrations of 2 and 10 mg/kg from postnatal Day 3 (PND3) to PND28, we observed that PM exposure resulted in anxiety-like behavior and impaired spatial working memory. The protein levels of ERS markers, including GRP78 and CHOP, were significantly increased in response to PM exposure. Western blot, transmission electron microscopy (TEM), and immunofluorescence analyses revealed decreased MAMs-related proteins and disrupted MAM structure and function caused by PM exposure. Administration of the ERS inhibitor 4-phenylbutyric acid (4-PBA) ameliorated these effects, restoring MAMs integrity and improving cognitive deficits. These findings highlighted the key role of ERS-MAMs dysfunction in PM-induced neurotoxicity and cognitive impairments, providing a new perspective and strategy for the prevention of cognitive deficits in early age with PM exposure.

The Long Hazy Tail: Analysis of the Impacts and Trends of Severe Outdoor and Indoor Air Pollution in North China.

China, especially the densely populated North China region, experienced severe haze events in the past decade that concerned the public. Although the most extreme cases have been largely eliminated through recent mitigation measures, severe outdoor air pollution persists and its environmental impact needs to be understood. Severe indoor pollution draws less public attention due to the short visible distance indoors, but its public health impacts cannot be ignored. Herein, we assess the trends and impacts of severe outdoor and indoor air pollution in North China from 2014 to 2021. Our results demonstrate the uneven contribution of severe hazy days to ambient and exposure concentrations of particulate matter with an aerodynamic diameter <2.5 (PM2.5). Although severe indoor pollution contributes to indoor PM2.5 concentrations (23%) to a similar extent as severe haze contributes to ambient PM2.5 concentrations (21%), the former's contribution to premature deaths was significantly higher. Furthermore, residential emissions contributed more in the higher PM2.5 concentration range both indoors and outdoors. Notably, severe haze had greater health impacts on urban residents, while severe indoor pollution was more impactful in rural areas. Our findings suggest that, besides reducing severe haze, mitigating severe indoor pollution is an important aspect of combating air pollution, especially toward improving public health.

Long-term exposure to ambient particulate matter is associated with prognosis in people living with HIV/AIDS: Evidence from a longitudinal study

BackgroundEvidence on the association between particulate matter (PM) exposure and prognosis in people living with HIV/AIDS (PWHA) is scarce. We aim to investigate the associations of long-term exposure to PM with AIDS-related deaths and complications. MethodsWe collected follow-up information on 7444 PWHAs from 2000 to 2021 from the HIV/AIDS Comprehensive Response Information Management System of the Wuhan Center for Disease Control and Prevention. The AIDS-related deaths and complications were assessed by physicians every 3 to 6 months, and the monthly average PM concentrations for each PWHA were extracted from the China High Air Pollutants dataset. We employed time-varying Cox regression models to evaluate the associations of the average cumulative PM exposure concentrations with AIDS-related deaths and complications, as well as the mediating effects of AIDS-related complications in PM-induced AIDS-related deaths. ResultsFor each 1 μg/m3 increase in PM1, PM2.5, and PM10, the adjusted hazard ratios (HRs) for AIDS-related deaths were 1.021 (1.009, 1.033), 1.012 (1.005, 1.020), and 1.010 (1.005, 1.015), respectively; and the HRs for AIDS-related complications were 1.049 (1.034, 1.064), 1.029 (1.020, 1.038), and 1.031 (1.024, 1.037), respectively. AIDS-related complications mediated 18.38 % and 18.68 % of the association of exposure to PM1 and PM2.5 with AIDS-related deaths, respectively. The association of PM exposure with AIDS-related deaths was more significant in older PWHA. Meanwhile, the association between PM exposure and AIDS-related complications was stronger in PWHA with a BMI ≥ 24 kg/m2. ConclusionLong-term exposure to PM is positively associated with AIDS-related deaths and complications, and AIDS-related complications have mediating effects in PM-induced AIDS-related deaths. Our evidence emphasizes that enhanced protection against PM exposure for PWHAs is an additional mitigation strategy to reduce AIDS-related deaths and complications.

Autophagy alleviates hippocampal neuroinflammation by inhibiting the NLRP3 inflammasome in a juvenile rat model exposed particulate matter

Ambient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50–200 μg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1β and IL-18 in the rat hippocampus and BV-2 cells. Furthermore, inhibition of the NLRP3 inflammasome with MCC950 effectively reduced neuroinflammation and ameliorated hippocampal damage. In addition, autophagy activation was observed in the hippocampus of PM-exposed rats, and the promotion of autophagy by rapamycin (Rapa) effectively attenuated the NLRP3-mediated neuroinflammation induced by PM exposure. However, autophagic flow was blocked in BV-2 cells exposed to PM, and Rapa failed to ameliorate NLRP3 inflammasome activation. We found that autophagy was activated in HT-22 cells exposed to PM and that treatment with Rapa reduced the release of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as cell apoptosis. In a subsequent coculture model of BV-2 and HT-22 cells, we observed the activation of the NLRP3 inflammasome in BV-2 cells when the HT-22 cells were exposed to PM, and this activation was alleviated when PM-exposed HT-22 cells were pretreated with Rapa. Overall, our study revealed that PM exposure triggered hippocampal neuroinflammation by activating the NLRP3 inflammasome. Notably, autophagy mitigated NLRP3 inflammasome activation, potentially by reducing neuronal ROS and apoptosis. This research emphasized the importance of reducing PM exposure and provided valuable insight into its neurotoxicity.

Micro-scale particle simulation and traffic-related particle exposure assessment in an Asian residential community

Conducting studies on sharp particulate matter (PM) gradients in Asian residential communities is difficult due to their complex building arrangements and various emission sources, particularly road traffic. In this study, a synthetic methodology, combining numerical simulations and minor field observations, was set up to investigate the dispersion of traffic-related PM in a typical Asian residential community and its contribution to PM exposure. A Lagrangian particle model (GRAL) was applied to estimate the spatiotemporal variation of the traffic-related PM increments within the community. A detailed topography dataset with 5 m horizontal resolution was used to simulate a micro-scale flow field. The model performance was comprehensively validated using both in-situ and mobile observations. The coefficient of determination (R2) of the simulated vs. observed PM2.5 reached 0.81 by an artery road, and 0.85 in alleys without significant road traffic. The maximum increments of kerbside PM exposure concentration contributed by road traffic during rush hour were found to be 38% (PM10) and 40% (PM2.5). This synthetic method was used to assess the impact of synoptic wind and canyon orientation on residents’ PM2.5 exposure related to traffic exhaust. Perfect exponential decay curves of traffic-related PM2.5 were found within canyons. The decrease of road-traffic PM2.5 on five different floor levels, compared with that on kerbside levels, ranged between 42% and 100%. The results demonstrated that in complex Asian communities, Lagrangian particle models such as GRAL can simulate the spatial distribution of PM10 and PM2.5 and assess the residents’ outdoor exposure.

Commuter exposure to particulate matter in urban public transportation of Xi'an, China.

To investigate commuter exposures to particulate matter (PM) in urban public transportation buses and subways, PM concentrations were simultaneously monitored for these two modes, over the same routes, in Xi'an, China. The microenvironment variabilities in each stage of the total trip were analyzed. Exposure doses for the different commute processes were estimated based on the heart rates of volunteers. Experimental measurements were taken during peak traffic hours in July and October (summer and autumn) on two typical commute routes, for a total of 36 trips. One-way ANOVA was used to analyze the effects of different variables on commuter exposures. On the same route, the average PM exposure concentration of bus commuters was higher than those of subway commuters. For example, on Route 1 in the case study, the average PM10, PM2.5, and PM1 exposure concentrations of bus commuters were 71.6%, 19%, and 10.4% higher, respectively, than those of subway commuters. In the ground transportation mode, the exposure concentration of bus commuters was affected by the type of vehicle. Particle concentrations were significantly higher inside compressed natural gas (CNG) buses, than in pure electric (PE) buses, and in summer, the PM10 concentration in a CNG bus was 4.3 times higher than that in a PE bus. In a CNG bus, commuters in the back door area suffered the highest PM10 exposure concentration (179.6μg/m3), followed by those in the rear of the carriage (142.8μg/m3), and then those in the front door area (105.4μg/m3). Commuters' avoidance of ground traffic sources, effective ventilation systems in buses, and the use of screens in subway systems can all help to lower the PM exposure of commuters. For all the modes of transportation in our study, the hottest spots for PM exposure appeared in the period when commuters were waiting for transit vehicles to arrive.

Individual exposure to particulate matter in urban and rural Chinese households: estimation of exposure concentrations in indoor and outdoor environments

According to the World Health Report, an estimated 540,000 people in China died prematurely due to indoor air pollution in 2009. The major source of indoor air pollution is the burning of solid fuels, such as coal and biomass, for household heating and cooking. To understand the current state of indoor air pollution in China, we quantified the total domestic energy consumption and exposure concentrations of pollutants in indoor environments. We investigated domestic energy consumption by fuel type and energy use in both urban and rural areas in 31 provinces in China and modified a microenvironmental exposure model to estimate the exposure concentrations of particulate matter with a diameter of less than 2.5 μm (PM2.5). Our results revealed that in urban areas, the main source of indoor PM2.5 pollution was inflow from outdoor pollution sources. In contrast, the main source of indoor pollution in rural areas was the combustion of coal and biomass. Men who spent more time in heated indoor environments were exposed to higher PM2.5 concentrations than women. However, in rural areas, women were exposed to twice the PM2.5 concentrations than men, as they spent more time cooking and heating water.

Exposure to air pollution is associated with adverse cardiopulmonary health effects in international travellers.

With the number of annual global travellers reaching 1.2 billion, many individuals encounter greater levels of air pollution when they travel abroad to megacities around the world. This study's objective was to determine if visits to cities abroad with greater levels of air pollution adversely impact cardiopulmonary health. A total of 34 non-smoking healthy adult participants who travelled abroad to selected cities from the New York City (NYC) metropolitan area were pre-trained to measure lung function, blood pressure and heart rate (HR)/HR variability (HRV) and record symptoms before, during and after travelling abroad. Outdoor particulate matter (PM)2.5 concentrations were obtained from central monitors in each city. Associations between PM exposure concentrations and cardiopulmonary health endpoints were analysed using a mixed effects statistical design. East and South Asian cities had significantly higher PM2.5 concentrations compared with pre-travel NYC PM2.5 levels, with maximum concentrations reaching 503μg/m3. PM exposure-related associations for lung function were statistically significant and strongest between evening Forced Expiratory Volume in the first second (FEV1) and same-day morning PM2.5 concentrations; a 10-μg/m3 increase in outdoor PM2.5 was associated with a mean decrease of 7mL. Travel to a highly polluted city (PM2.5 > 100μg/m3) was associated with a 209-ml reduction in evening FEV1 compared with a low polluted city (PM2.5 < 35μg/m3). In general, participants who travelled to East and South Asian cities experienced increased respiratory symptoms/scores and changes in HR and HRV. Exposure to increased levels of PM2.5 in cities abroad caused small but statistically significant acute changes in cardiopulmonary function and respiratory symptoms in healthy young adults. These data suggest that travel-related exposure to increased PM2.5 adversely impacts cardiopulmonary health, which may be particularly important for travellers with pre-existing respiratory or cardiac disease.

In-vehicle airborne fine and ultra-fine particulate matter exposure: The impact of leading vehicle emissions

Airborne particulate matter (PM) concentrations inside vehicle cabins are often extremely high compared to background levels. The present study was motivated by the fact that in the last few decades, the implementation of new emission standards has led to the reduction of vehicle particle emissions. This study addresses for the first time the relationship between leading vehicle (LV) emissions and in-cabin PM exposure levels in the immediately following vehicle (henceforth called the study vehicle - SV), with particular emphasis on the role of the LV's emission reduction technologies (e.g., diesel particulate filter-DPF) as an effective risk management measure.The study was performed using an instrumented study vehicle (always to be considered as the following vehicle) on a 26-km fixed route where 10 repeated tests were conducted during 60-minute trips. On-line monitoring of the fine 0.3–1 μm and 1–2.5 μm (PM0.3–1 and PM1–2.5) and ultra-fine particle (UFP) concentrations was performed inside the SV's car cabin with fixed ventilation settings (i.e., windows closed, air conditioning off, and recirculation fan off). Simultaneously, the license plate numbers of the LVs along the route were recorded to retrieve information pertaining to their fuel type and Euro emission standard category.The results clearly showed that the in-cabin PM levels were significantly affected by the LV's Euro emission standard. Regarding petrol-fuelled LVs, the median in-cabin particle exposure levels were statistically lower (e.g., −34% for PM0.3–1) when following vehicles with stricter emission standards (in particular, Euro 6) than when following a low-emission standard vehicle (i.e., Euro 0–2). Concerning diesel-fuelled LVs, a strong and significant decrease in the in-cabin median exposure levels (up to −62%, −44%, and −48% for UFPs, PM0.3–1, and PM1–2.5, respectively) was observed for recent-emission standards LVs (i.e., Euro 5–6) with respect to older-emission standard LVs (i.e., Euro 0–4).A specific analysis revealed that the in-cabin median exposure concentrations of PM were highly and significantly reduced by DPF-equipped LVs. For UFPs, this resulted in a 47% reduction compared to diesel-fuelled (non-DPF) LVs. For PM0.3–1, an approximate 80% reduction was observed compared to both petrol-fuelled and diesel-fuelled (non-DPF) LVs. For PM1–2.5, an approximate 38% reduction was observed compared to petrol-fuelled LVs and a 46% reduction compared to non-DPF LVs.

An investigation of particulate matter and relevant cardiovascular risks in Abadan and Khorramshahr in 2014–2016

Over the last decades, air pollution has been regarded as one of the major environmental problems. Cardiovascular and respiratory diseases are among the most common illnesses arising from air pollution and dust storm. Nowadays, non-communicable diseases resulting from air pollution have affected many people around the world. In recent years, the cities of Abadan and Khorramshahr, located in the southwestern Iran have been adversely affected by air pollution and dust storm. To address the issue, this study set out to investigate the relationship between hospital admissions for cardiovascular diseases and dust storms in Abadan and Khorramshahr in 2014–2016. The data was collected by the Abadan Environmental Protection Agency (Abadan EPA) office. The monitoring station is fully automated and provides hourly particulate matter (PM10) concentrations using a β-ray absorption monitor (Met One Model BAM-1020-Continuous Beta, USA). The annual PM10 mean concentrations reached 169, 187 and 201 µg/m3 in 2014, 2015, and 2016, respectively. The number of people suffering from cardiovascular diseases attributed to PM10 during this period was 237, 259, and 274, respectively. The results showed that high levels of particulate matter (PM) in the air drastically increased the number of people with cardiovascular diseases. The results also revealed that there was a significant relationship between concentrations of PM10 in dusty days and the cases of cardiovascular diseases in Abadan and Khorramshahr. According to the results of the study, an increase in the exposure concentrations of particulate matter could potentially cause different health problems.

Electrostatic Dust Cloth: A Passive Screening Method to Assess Occupational Exposure to Organic Dust in Bakeries

Organic dust is widespread in the environment including occupational settings, such as bakeries. Recently, a new collection device—the electrostatic dust cloth (EDC)—has been described for the assessment of occupational exposures. The aim of this study was to investigate the suitability of EDC for identifying the distribution patterns and exposure concentrations of particulate matter and microbial contaminants such as fungi and bacteria in bakeries. Twelve bakeries were selected, and dust was allowed to settle for 13 to 16 days on EDCs (a total of 33 samples). Particle counts and size distribution (0.3 µm, 0.5 µm, 1 µm, 2.5 µm, 5 µm and 10 µm) were measured with direct-reading equipment. Higher EDC mass was significantly correlated (p values &lt; 0.05) with higher fungal load on dichloran glycerol (DG18) and with particle size distribution in the 0.3 µm, 0.5 µm, 1.0 µm and 10.0 µm range. Fungal levels on malt extract agar (MEA) ranged from 0 to 2886 CFU/m2 EDC in the warehouse setting, 0 to 500 CFU/m2 EDC in the production setting, and 0 to 3135 CFU/m2 EDC in the store. Penicillium sp. (42.56%) was the most frequent fungi. Total bacterial load ranged from 0 to 18,859 CFU/m2 EDC in the warehouse, 0 to 71,656 CFU/m2 EDC in production, and 0 to 21,746 CFU/m2 EDC in the store. EDC assessment provided a longer-term integrated sample of organic dust, useful for identifying critical worksites in which particulate matter and bio-burden exposures are elevated. These findings suggest that EDC can be applied as a screening method for particulate matter-exposure assessment and as a complementary method to quantify exposures in occupational environments.

Particulate Matter Exposure in a Police Station Located near a Highway.

People living or working near roadways have experienced an increase in cardiovascular or respiratory diseases due to vehicle emissions. Very few studies have focused on the PM exposure of highway police officers, particularly for the number concentration and size distribution of ultrafine particles (UFP). This study evaluated exposure concentrations of particulate matter (PM) in the Sinying police station near a highway located in Tainan, Taiwan, under different traffic volumes, traffic types, and shift times. We focused on periods when the wind blew from the highway toward the police station and when the wind speed was greater than or equal to 0.5 m/s. PM2.5, UFP, and PM-PAHs concentrations in the police station and an upwind reference station were measured. Results indicate that PM2.5, UFP, and PM-PAHs concentrations in the police station can be on average 1.13, 2.17, and 5.81 times more than the upwind reference station concentrations, respectively. The highest exposure level for PM2.5 and UFP was observed during the 12:00 PM–4:00 PM shift while the highest PAHs concentration was found in the 4:00 AM–8:00 AM shift. Thus, special attention needs to be given to protect police officers from exposure to high PM concentration.

Occupational exposure to particulate matter and endotoxin for California dairy workers

Occupational exposure of dairy workers to particulate matter (PM) and endotoxin has been considered by some to be of potential concern. This paper reports personal exposure concentrations of PM (μg/m3) and endotoxin (EU/m3) for 226 workers from 13 California dairies. Arithmetic mean personal concentrations for PM2.5, inhalable PM and endotoxin were 48 μg/m3 (N = 222), 987 μg/m3 (N = 225) and 453 EU/m3 (N = 225), respectively. Using mixed effects models, time spent re-bedding of freestall barns versus any other job conducted on a dairy led to the highest exposure for PM2.5, inhalable PM, and endotoxin. Personal exposure concentrations were found to be greater than those reported for ambient area based concentrations at the same dairies. A pseudo R-square approach revealed that one area based measure combined with time spent performing tasks explained a significant portion of variation in personal exposure concentrations.

Comparison of exposure estimation methods for air pollutants: Ambient monitoring data and regional air quality simulation

Air quality modeling could potentially improve exposure estimates for use in epidemiological studies. We investigated this application of air quality modeling by estimating location-specific (point) and spatially-aggregated (county level) exposure concentrations of particulate matter with an aerodynamic diameter less than or equal to 2.5μm (PM2.5) and ozone (O3) for the eastern U.S. in 2002 using the Community Multi-scale Air Quality (CMAQ) modeling system and a traditional approach using ambient monitors. The monitoring approach produced estimates for 370 and 454 counties for PM2.5 and O3, respectively. Modeled estimates included 1861 counties, covering 50% more population. The population uncovered by monitors differed from those near monitors (e.g., urbanicity, race, education, age, unemployment, income, modeled pollutant levels). CMAQ overestimated O3 (annual normalized mean bias=4.30%), while modeled PM2.5 had an annual normalized mean bias of −2.09%, although bias varied seasonally, from 32% in November to –27% in July. Epidemiology may benefit from air quality modeling, with improved spatial and temporal resolution and the ability to study populations far from monitors that may differ from those near monitors. However, model performance varied by measure of performance, season, and location. Thus, the appropriateness of using such modeled exposures in health studies depends on the pollutant and metric of concern, acceptable level of uncertainty, population of interest, study design, and other factors.

COMPARISON OF EXPOSURE ESTIMATION METHODS FOR AIR POLLUTANTS: AMBIENT MONITORING DATA AND REGIONAL AIR QUALITY SIMULATION

Air quality modeling could potentially improve exposure estimates for use in epidemiological studies. We investigated this application of air quality modeling by estimating location-specific (point) and spatially-aggregated (county level) exposure concentrations of particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM(2.5)) and ozone (O(3)) for the eastern U.S. in 2002 using the Community Multi-scale Air Quality (CMAQ) modeling system and a traditional approach using ambient monitors. The monitoring approach produced estimates for 370 and 454 counties for PM(2.5) and O(3), respectively. Modeled estimates included 1861 counties, covering 50% more population. The population uncovered by monitors differed from those near monitors (e.g., urbanicity, race, education, age, unemployment, income, modeled pollutant levels). CMAQ overestimated O(3) (annual normalized mean bias=4.30%), while modeled PM(2.5) had an annual normalized mean bias of -2.09%, although bias varied seasonally, from 32% in November to -27% in July. Epidemiology may benefit from air quality modeling, with improved spatial and temporal resolution and the ability to study populations far from monitors that may differ from those near monitors. However, model performance varied by measure of performance, season, and location. Thus, the appropriateness of using such modeled exposures in health studies depends on the pollutant and metric of concern, acceptable level of uncertainty, population of interest, study design, and other factors.

The Response of Children with Asthma to Ambient Particulate Is Modified by Tobacco Smoke Exposure

Ambient particulate matter concentrations have been positively associated with urinary leukotriene E(4) (LTE(4)) levels and albuterol usage in children with asthma but interactions with environmental tobacco smoke (ETS) exposure have not been demonstrated despite obvious exposure to both pollutants in an urban setting. To assess the health effects of concurrent ETS and ambient particulate matter exposure in children with asthma. Albuterol usage and LTE(4) levels were monitored in 82 urban schoolchildren with asthma over three consecutive fall to spring school periods. Concentrations of morning maximum ambient particulate matter <2.5 μm in aerodynamic diameter (mmPM(2.5)) and urine cotinine levels were also measured daily. Albuterol usage and LTE(4) were related to mmPM(2.5) concentrations on days when urine cotinine levels were low (<10 ng/ml/mg creatinine); on these days, mean albuterol usage and LTE(4) increased up to 5 or 6% per 10 μg/m(3) increase in mmPM(2.5). In contrast, no significant relationship was observed when cotinine was high, although mean albuterol usage and LTE(4) levels were greater in this case. Model fits for LTE(4) levels as a function of mmPM(2.5) concentrations were improved when mmPM(2.5) concentrations were logged, suggesting a nonlinear dose-response relationship between particulate matter exposure concentrations and airway mediators of asthma, for which the relationship tends to flatten at higher concentrations. This study suggests that ETS modifies the acute effects of low-level ambient PM(2.5) exposure on childhood asthma. This negative interaction, the smaller effect of particulate matter exposure in children exposed to higher ETS, may be related to a nonlinear dose-response relationship between asthma mediators and particulate exposures.

Dosimetric Comparisons of Particle Deposition and Retention in Rats and Humans

Much of the information on the toxicity of particulate matter (PM) comes from studies in which laboratory rats were exposed to PM by inhalation or instillation. Optimal use of these toxicologic data requires extrapolation to the human scenario. Assuming that comparable doses should cause comparable effects across species and that species respond similarly to a given dose at a target site, extrapolations only require that dose be defined and then characterized. Dose may be defined in terms of a PM indicator (e.g., particle number or mass), a respiratory region, and the time over which the dose is integrated (i.e., deposited versus retained dose and incremental versus accumulated dose). Dose must also be normalized: for example, unit of dose per body mass, respiratory region surface area, or number of alveolar macrophages. The parameters chosen to define a normalized dose can drastically affect the rat exposure concentration required to provide a normalized dose equivalent to that occurring in a human. The publicly available multiple path particle dosimetry model developed by CIIT Centers for Health Research was used to predict particle deposition and retention in rats and humans. Estimates of particle concentration and exposure duration required for a rat to receive the same dose as received by a human were obtained with consideration of daily activity levels and ambient PM size distributions. These techniques were also used to compare dose and response between rats and humans in several published studies. Results indicate that the relationship between PM dose and response may differ between rats and humans. For acute PM exposures, rats may be less susceptible to inflammatory responses than humans. For chronic exposures to high levels of PM, however, an overload of alveolar clearance in rats may cause them to become more susceptible than humans to adverse pulmonary effects. The dosimetric calculations indicate that to achieve nominally similar acute doses per surface area in rats, relative to humans undergoing moderate to high exertion, PM exposure concentrations for rats would need to be somewhat higher than for humans. Since the clearance of PM is faster from the lung of rats than humans, much higher exposure concentrations are required for the rat to simulate retained burdens. In other cases, rats will require lower exposures than humans to have comparable doses, illustrating the complexity of such analyses. To make accurate estimates of dose, it is essential to have accurate and complete information regarding exposure conditions—that is, not only concentration and duration of exposure, but also the aerosol size distribution. Establishing a firm linkage between exposure and dose requires that consideration be given to particle characteristics, definitions of dose metrics, and biological normalizing factors.