A Probabilistic Transmission Dynamic Model to Assess Indoor Airborne Infection Risks

The purpose of this article is to quantify the public health risk associated with inhalation of indoor airborne infection based on a probabilistic transmission dynamic modeling approach. We used the Wells-Riley mathematical model to estimate (1) the CO2 exposure concentrations in indoor environments where cases of inhalation airborne infection occurred based on reported epidemiological data and epidemic curves for influenza and severe acute respiratory syndrome (SARS), (2) the basic reproductive number, R0 (i.e., expected number of secondary cases on the introduction of a single infected individual in a completely susceptible population) and its variability in a shared indoor airspace, and (3) the risk for infection in various scenarios of exposure in a susceptible population for a range of R0. We also employ a standard susceptible-infectious-recovered (SIR) structure to relate Wells-Riley model derived R0 to a transmission parameter to implicate the relationships between indoor carbon dioxide concentration and contact rate. We estimate that a single case of SARS will infect 2.6 secondary cases on average in a population from nosocomial transmission, whereas less than 1 secondary infection was generated per case among school children. We also obtained an estimate of the basic reproductive number for influenza in a commercial airliner: the median value is 10.4. We suggest that improving the building air cleaning rate to lower the critical rebreathed fraction of indoor air can decrease transmission rate. Here, we show that virulence of the organism factors, infectious quantum generation rates (quanta/s by an infected person), and host factors determine the risk for inhalation of indoor airborne infection.     

Modeled Estimates of Soil and Dust Ingestion Rates for Children

Daily soil/dust ingestion rates typically used in exposure and risk assessments are based on tracer element studies, which have a number of limitations and do not separate contributions from soil and dust. This article presents an alternate approach of modeling soil and dust ingestion via hand and object mouthing of children, using EPA's SHEDS model. Results for children 3 to <6 years old show that mean and 95th percentile total ingestion of soil and dust values are 68 and 224 mg/day, respectively; mean from soil ingestion, hand‐to‐mouth dust ingestion, and object‐to‐mouth dust ingestion are 41 mg/day, 20 mg/day, and 7 mg/day, respectively. In general, hand‐to‐mouth soil ingestion was the most important pathway, followed by hand‐to‐mouth dust ingestion, then object‐to‐mouth dust ingestion. The variability results are most sensitive to inputs on surface loadings, soil‐skin adherence, hand mouthing frequency, and hand washing frequency. The predicted total soil and dust ingestion fits a lognormal distribution with geometric mean = 35.7 and geometric standard deviation = 3.3. There are two uncertainty distributions, one below the 20th percentile and the other above. Modeled uncertainties ranged within a factor of 3–30. Mean modeled estimates for soil and dust ingestion are consistent with past information but lower than the central values recommended in the 2008 EPA Child‐Specific Exposure Factors Handbook. This new modeling approach, which predicts soil and dust ingestion by pathway, source type, population group, geographic location, and other factors, offers a better characterization of exposures relevant to health risk assessments as compared to using a single value.     

Combining Food Frequency and Survey Data to Quantify Long-Term Dietary Exposure: A Methyl Mercury Case Study

Twenty-four-hour recall data from the Continuing Survey of Food Intake by Individuals (CSFII) are frequently used to estimate dietary exposure for risk assessment. Food frequency questionnaires are traditional instruments of epidemiological research; however, their application in dietary exposure and risk assessment has been limited. This article presents a probabilistic method of bridging the National Health and Nutrition Examination Survey (NHANES) food frequency and the CSFII data to estimate longitudinal (usual) intake, using a case study of seafood mercury exposures for two population subgroups (females 16 to 49 years and children 1 to 5 years). Two hundred forty-nine CSFII food codes were mapped into 28 NHANES fish/shellfish categories. FDA and state/local seafood mercury data were used. A uniform distribution with minimum and maximum blood-diet ratios of 0.66 to 1.07 was assumed. A probabilistic assessment was conducted to estimate distributions of individual 30-day average daily fish/shellfish intakes, methyl mercury exposure, and blood levels. The upper percentile estimates of fish and shellfish intakes based on the 30-day daily averages were lower than those based on two- and three-day daily averages. These results support previous findings that distributions of "usual" intakes based on a small number of consumption days provide overestimates in the upper percentiles. About 10% of the females (16 to 49 years) and children (1 to 5 years) may be exposed to mercury levels above the EPA's RfD. The predicted 75th and 90th percentile blood mercury levels for the females in the 16-to-49-year group were similar to those reported by NHANES. The predicted 90th percentile blood mercury levels for children in the 1-to-5-year subgroup was similar to NHANES and the 75th percentile estimates were slightly above the NHANES.     

Bias in Population Estimates of Long-Term Exposure from Short-Term Measurements of Individual Exposure

A population's long-term exposure distribution for a specified compound is typically estimated from short-term measurements of a sample of individuals from the population of interest. In this situation, estimates of a population's long-term exposure parameters contain two sources of sampling error: the typical sampling error associated with taking a sample from the population and the sampling error from estimating individual long-term exposure. These components are not separable in the data collected, i.e. , the value observed is due partly to the individual sampled and partly to the time at which the individual was sampled. Hence, the distribution of the data collected is not the same as the population exposure distribution. Monte Carlo simulations are used to compare the distribution of the observed data with the population exposure distribution for a simple additive model. A simple adjustment to standard estimates of percentiles and quantils is shown to be effective in reducing bias particularly for the upper percentiles and quantils of the population distribution.     

Estimates of per Capita Fish Consumption in the U.S. Based on the Continuing Survey of Food Intake by Individuals (CSFII)

This paper presents estimates of daily average per capita fish consumption by age and gender for the 48 conterminous states. The estimated consumption rates are reported for three fish habitats: freshwater/estuarine fish, marine fish, and all fish. The estimates were generated from the combined 1989, 1990, and 1991 Continuing Survey of Food Intake by Individuals (CSFII), a national food consumption survey conducted by the United States Department of Agriculture (USDA). Point and interval estimates of per capita fish consumption were generated from the empirical distribution of daily average per capita consumption. The point estimates include the mean, 50th, 75th, 90th, 95th, and 99th percentiles. Ninety percent confidence intervals are provided for the estimated mean and 90% bootstrap intervals are provided for percentile estimates. Information in a recipe file provided by USDA was used to calculate the amount of fish in recipes which contain fish. The estimated consumption rates are based on the weight of fish in its prepared or "as consumed" condition. The estimated mean consumption rate for all fish for the U.S. population of the 48 conterminous states was 15.65 grams/person/day (C.I.:14.67–16.63) of which 4.71 grams/person/day (C.I.:4.17–5.25) was freshwater/estuarine fish and 10.94 grams/person/day (C.I.: 10.14–11.73) was marine fish.     

Effects of Uncertainties on Exposure Estimates to Methylmercury: A Monte Carlo Analysis of Exposure Biomarkers versus Dietary Recall Estimation

This article presents a general model for estimating population heterogeneity and "lack of knowledge" uncertainty in methylmercury (MeHg) exposure assessments using two-dimensional Monte Carlo analysis. Using data from fish-consuming populations in Bangladesh, Brazil, Sweden, and the United Kingdom, predictive model estimates of dietary MeHg exposures were compared against those derived from biomarkers (i.e., [Hg]hair and [Hg]blood). By disaggregating parameter uncertainty into components (i.e., population heterogeneity, measurement error, recall error, and sampling error) estimates were obtained of the contribution of each component to the overall uncertainty. Steady-state diet:hair and diet:blood MeHg exposure ratios were estimated for each population and were used to develop distributions useful for conducting biomarker-based probabilistic assessments of MeHg exposure. The 5th and 95th percentile modeled MeHg exposure estimates around mean population exposure from each of the four study populations are presented to demonstrate lack of knowledge uncertainty about a best estimate for a true mean. Results from a U.K. study population showed that a predictive dietary model resulted in a 74% lower lack of knowledge uncertainty around a central mean estimate relative to a hair biomarker model, and also in a 31% lower lack of knowledge uncertainty around central mean estimate relative to a blood biomarker model. Similar results were obtained for the Brazil and Bangladesh populations. Such analyses, used here to evaluate alternative models of dietary MeHg exposure, can be used to refine exposure instruments, improve information used in site management and remediation decision making, and identify sources of uncertainty in risk estimates.     

Quantifying the Distribution of Inhalation Exposure in Human Populations: 2. Distributions of Time Spent by Adults, Adolescents, and Children at Home, at Work, and at School

Using distributions of time spent at various ventilation levels, ranges of inhalation exposure in the population can be established. Distributions of exposure time were determined using results of a study by the California Air Resources Board (CARB) which focused on time spent by humans participating in various activities and the locations where the activities occurred. The daily at-home activities from the CARB study were assigned to one of three ventilation levels, generating aggregate time periods. Distinct age and gender populations were identified, and distributions for aggregate time were established for these populations at each of the ventilation levels. In addition to aggregate time spent at home, distributions for various ages and genders were established for aggregate time spent at school and work. By combining distributions of aggregate time with corresponding ventilation rates, the distribution of inhalation rates can be established for at home, at work, and at school exposures.     

Determination of Less-Than-Lifetime Exposures to Point Source Emissions

This paper presents a method of estimating long-term exposures to point source emissions. The method consists of a Monte Carlo exposure model (PSEM or Point Source Exposure Model) that combines data on population mobility and mortality with information on daily activity patterns. The approach behind the model can be applied to a wide variety of exposure scenarios. In this paper, PSEM is used to characterize the range and distribution of lifetime equivalent doses received by inhalation of air contaminated by the emissions of a point source. The output of the model provides quantitative information on the dose, age, and gender of highly exposed individuals. The model is then used in an example risk assessment. Finally, future uses of the model's approach are discussed.     

Daily Inhalation Rate and Time‐Activity/Location Pattern in Japanese Preschool Children

Lack of data on daily inhalation rate and activity of children has been an issue in health risk assessment of air pollutants. This study aimed to obtain the daily inhalation rate and intensity and frequency of physical activity in relation to the environment in Japanese preschool children. Children aged four–six years (n= 138) in the suburbs of Tokyo participated in this study, which involved three days' continuous monitoring of physical activity using a tri‐axial accelerometer and parent's completion of a time/location diary during daily life. The estimated three‐day mean daily inhalation rate (body temperature, pressure, saturated with water vapor) was 9.9 ± 1.6 m³/day (0.52 ± 0.09 m³/kg/day). The current daily inhalation rate value of 0.580 m³/kg/day proposed for use in health risk assessment in Japan is confirmed to be valid to calculate central value of inhaled dose of air pollutants in five‐ to six‐year‐old children. However, the 95th percentile daily inhalation rate of 0.83 m³/kg/day based on measurement for five‐year‐old children is recommended to be used to provide an upper bound estimate of exposure that ensure the protection of all five‐ to six‐year‐old children from the health risk of air pollutants. Children spent the majority of their time in sedentary and light level of physical activity (LPA) when indoors, while 85% of their time when outdoors was spent in LPA and moderate‐to‐vigorous physical activity. The results suggest the need to consider variability of minute respiratory ventilation rate according to the environment for more refined short‐term health risk assessment.     

A Probabilistic Arsenic Exposure Assessment for Children Who Contact CCA-Treated Playsets and Decks, Part 1: Model Methodology, Variability Results, and Model Evaluation

Concerns have been raised regarding the safety of young children who may contact arsenic residues while playing on and around chromated copper arsenate (CCA)-treated wood playsets and decks. Although CCA registrants voluntarily canceled the production of treated wood for residential use in 2003, the potential for exposure from existing structures and surrounding soil still poses concerns. The EPA's Office of Research and Development developed and applied the probabilistic Stochastic Human Exposure and Dose Simulation model for wood preservatives (SHEDS-Wood) to estimate children's absorbed dose of arsenic from CCA. Skin contact with, and nondietary ingestion of, arsenic in soil and wood residues were considered for the population of children in the United States who frequently contact CCA-treated wood playsets and decks. Model analyses were conducted to assess the range in population estimates and the impact of potential mitigation strategies such as the use of sealants and hand washing after play events. The results show predicted central values for lifetime annual average daily dose values for arsenic ranging from 10(-6) to 10(-5) mg/kg/day, with predicted 95th percentiles on the order of 10(-5) mg/kg/day. There were several orders of magnitude between lower and upper percentiles. Residue ingestion via hand-to-mouth contact was determined to be the most significant exposure route for most scenarios. Results of several alternative scenarios were similar to baseline results, except for the scenario with greatly reduced residue concentrations through hypothetical wood sealant applications; in this scenario, exposures were lower, and the soil ingestion route dominated. SHEDS-Wood estimates are typically consistent with, or within the range of, other CCA exposure models.     

Carcinogenic Polycyclic Aromatic Hydrocarbons: An Analysis of Screening Values,Guidelines, and Standards in the Northeast

Risk‐based, background, and laboratory quantitation limit‐derived standards for carcinogenic polycyclic aromatic hydrocarbons (cPAHs) in residential and nonresidential soils vary across the northeast region of the United States. The magnitude and extent of this variation, however, have not been systematically studied. This article examines the technical basis and methodology used by eight northeastern states in the development of risk‐based screening values, guidelines, and standards for cPAHs in soils. Exposure pathways, human receptors, algorithms, and input variables used by each state in the calculation of acceptable human health risks are identified and reviewed within the context of environmental policy and regulatory impacts. Emphasis is placed on a comparative analysis of multipathway exposures (incidental ingestion, dermal contact, and particulate inhalation) and key science‐policy decisions that have led to the promulgation and adoption of different exposure criteria for cPAHs in the Northeast. More than 425 data points and 20 distinct exposure factors across eight state programs, 18 age subgroups, six activity scenarios, and three exposure pathways were systematically evaluated. Risk‐based values for one state varied either above or below risk‐based, background or laboratory quantitation limit‐derived standards of another state for the same cPAH and receptor. Standards for cPAHs in soils were found to differ significantly across the northeast region—in some cases, by one or two orders of magnitude. While interstate differences can be expected to persist, future changes in federal guidance could mean a shift in risk drivers, compliance status, or calculated cumulative risks for individual properties impacted by PAH releases.     

Route-to-Route Extrapolation of the Toxic Potency of MTBE

MTBE is a volatile organic compound used as an oxygenating agent in gasoline. Inhalation from fumes while refueling automobiles is the principle route of exposure for humans, and toxicity by this route has been well studied. Oral exposures to MTBE exist as well, primarily due to ground-water contamination from leaking stationary sources, such as underground storage tanks. Assessing the potential public health impacts of oral exposures to MTBE is problematic because drinking water studies do not exist for MTBE, and the few oil-gavage studies from which a risk assessment could be derived are limited. This paper evaluates the suitability of the MTBE database for conducting an inhalation route-to-oral route extrapolation of toxicity. This includes evaluating the similarity of critical effect between these two routes, quantifiable differences in absorption, distribution, metabolism, and excretion, and sufficiency of toxicity data by the inhalation route. We conclude that such an extrapolation is appropriate and have validated the extrapolation by finding comparable toxicity between a subchronic gavage oral bioassay and oral doses we extrapolate from a subchronic inhalation bioassay. Our results are extended to the 2-year inhalation toxicity study by Chun et al. (1992) in which rats were exposed to 0, 400, 3000, or 8000 ppm MTBE for 6 hr/d, 5 d/wk. We have estimated the equivalent oral doses to be 0, 130, 940, or 2700 mg/kg/d. These equivalent doses may be useful in conducting noncancer and cancer risk assessments.     

Use of Quality-Adjusted Life Year Weights with Dose-Response Models for Public Health Decisions: A Case Study of the Risks and Benefits of Fish Consumption

Risks associated with toxicants in food are often controlled by exposure reduction. When exposure recommendations are developed for foods with both harmful and beneficial qualities, however, they must balance the associated risks and benefits to maximize public health. Although quantitative methods are commonly used to evaluate health risks, such methods have not been generally applied to evaluating the health benefits associated with environmental exposures. A quantitative method for risk-benefit analysis is presented that allows for consideration of diverse health endpoints that differ in their impact (i.e., duration and severity) using dose-response modeling weighted by quality-adjusted life years saved. To demonstrate the usefulness of this method, the risks and benefits of fish consumption are evaluated using a single health risk and health benefit endpoint. Benefits are defined as the decrease in myocardial infarction mortality resulting from fish consumption, and risks are defined as the increase in neurodevelopmental delay (i.e., talking) resulting from prenatal methylmercury exposure. Fish consumption rates are based on information from Washington State. Using the proposed framework, the net health impact of eating fish is estimated in either a whole population or a population consisting of women of childbearing age and their children. It is demonstrated that across a range of fish methylmercury concentrations (0-1 ppm) and intake levels (0-25 g/day), individuals would have to weight the neurodevelopmental effects 6 times more (in the whole population) or 250 times less (among women of child-bearing age and their children) than the myocardial infarction benefits in order to be ambivalent about whether or not to consume fish. These methods can be generalized to evaluate the merits of other public health and risk management programs that involve trade-offs between risks and benefits.     

A Trichloroethylene Risk Assessment Using a Monte Carlo Analysis of Parameter Uncertainty in Conjunction with Physiologically-Based Pharmacokinetic Modeling

A Monte Carlo simulation is incorporated into a risk assessment for trichloroethylene (TCE) using physiologically-based pharmacokinetic (PBPK) modeling coupled with the linearized multistage model to derive human carcinogenic risk extrapolations. The Monte Carlo technique incorporates physiological parameter variability to produce a statistically derived range of risk estimates which quantifies specific uncertainties associated with PBPK risk assessment approaches. Both inhalation and ingestion exposure routes are addressed. Simulated exposure scenarios were consistent with those used by the Environmental Protection Agency (EPA) in their TCE risk assessment. Mean values of physiological parameters were gathered from the literature for both mice (carcinogenic bioassay subjects) and for humans. Realistic physiological value distributions were assumed using existing data on variability. Mouse cancer bioassay data were correlated to total TCE metabolized and area-under-the-curve (blood concentration) trichloroacetic acid (TCA) as determined by a mouse PBPK model. These internal dose metrics were used in a linearized multistage model analysis to determine dose metric values corresponding to 10^-6 lifetime excess cancer risk. Using a human PBPK model, these metabolized doses were then extrapolated to equivalent human exposures (inhalation and ingestion). The Monte Carlo iterations with varying mouse and human physiological parameters produced a range of human exposure concentrations producing a 10^-6 risk.     

The Impact of Cytochrome P450 2E1-Dependent Metabolic Variance on a Risk-Relevant Pharmacokinetic Outcome in Humans

Risk assessments include assumptions about sensitive subpopulations, such as the fraction of the general population that is sensitive and the extent that biochemical or physiological attributes influence sensitivity. Uncertainty factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD) components, allowing the inclusion of risk-relevant information to replace default assumptions about PK and PD variance (uncertainty). Large numbers of human organ donor samples and recent advances in methods to extrapolate in vitro enzyme expression and activity data to the intact human enable the investigation of the impact of PK variability on human susceptibility. The hepatotoxicity of trichloroethylene (TCE) is mediated by acid metabolites formed by cytochrome P450 2E1 (CYP2E1) oxidation, and differences in the CYP2E1 expression are hypothesized to affect susceptibility to TCE's liver injury. This study was designed specifically to examine the contribution of statistically quantified variance in enzyme content and activity on the risk of hepatotoxic injury among adult humans. We combined data sets describing (1) the microsomal protein content of human liver, (2) the CYP2E1 content of human liver microsomal protein, and (3) the in vitro Vmax for TCE oxidation by humans. The 5th and 95th percentiles of the resulting distribution (TCE oxidized per minute per gram liver) differed by approximately sixfold. These values were converted to mg TCE oxidized/h/kg body mass and incorporated in a human PBPK model. Simulations of 8-hour inhalation exposure to 50 ppm and oral exposure to 5 micro g TCE/L in 2 L drinking water showed that the amount of TCE oxidized in the liver differs by 2% or less under extreme values of CYP2E1 expression and activity (here, selected as the 5th and 95th percentiles of the resulting distribution). This indicates that differences in enzyme expression and TCE oxidation among the central 90% of the adult human population account for approximately 2% of the difference in production of the risk-relevant PK outcome for TCE-mediated liver injury. Integration of in vitro metabolism information into physiological models may reduce the uncertainties associated with risk contributions of differences in enzyme expression and the UF that represent PK variability.     

Ecological Risks to Fossorial Vertebrates from Volatile Organic Compounds in Soil

The past several years has seen an increased awareness of the need to conduct ecological risk assessments (ERAs) for hazardous waste sites. One technique used in ERAs involves estimating contaminant exposure to individual animals of selected species, which is then compared to a reference dose derived from the literature. Exposure estimates are conducted on those species which are representative of the different trophic levels found at the site. In many terrestrial systems, fossorial (burrowing) vertebrates are found in both lower and upper trophic levels. As part of the ERA conducted for Site 300, Lawrence Livermore National Laboratory's high-explosive test facility, contaminant exposures were estimated for fossorial and nonfossorial vertebrates spanning two trophic levels. The results of the evaluation revealed that a significant pathway by which fossorial vertebrates could be exposed to trichloroethylene in soil was through the inhalation of contaminated subsurface burrow air. This was the first time that the importance of this ecological exposure pathway has been recognized. The results of this analysis suggest that further research into the ecological significance of subsurface burrow air contaminated with volatile organic compounds is warranted.     

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.     

Potential Exposure and Cancer Risk from Formaldehyde Emissions from Installed Chinese Manufactured Laminate Flooring

Lumber Liquidators (LL) Chinese‐manufactured laminate flooring (CLF) has been installed in >400,000 U.S. homes over the last decade. To characterize potential associated formaldehyde exposures and cancer risks, chamber emissions data were collected from 399 new LL CLF, and from LL CLF installed in 899 homes in which measured aggregate indoor formaldehyde concentrations exceeded 100 μg/m³ from a total of 17,867 homes screened. Data from both sources were combined to characterize LL CLF flooring‐associated formaldehyde emissions from new boards and installed boards. New flooring had an average (±SD ) emission rate of 61.3 ± 52.1 μg/m²‐hour; >one‐year installed boards had ∼threefold lower emission rates. Estimated emission rates for the 899 homes and corresponding data from questionnaires were used as inputs to a single‐compartment, steady‐state mass‐balance model to estimate corresponding residence‐specific TWA formaldehyde concentrations and potential resident exposures. Only ∼0.7% of those homes had estimated acute formaldehyde concentrations >100 μg/m³ immediately after LL CLF installation. The TWA daily formaldehyde inhalation exposure within the 899 homes was estimated to be 17 μg/day using California Proposition 65 default methods to extrapolate cancer risk (below the regulation “no significant risk level” of 40 μg/day). Using a U.S. Environmental Protection Agency linear cancer risk model, 50th and 95th percentile values of expected lifetime cancer risk for residents of these homes were estimated to be 0.33 and 1.2 per 100,000 exposed, respectively. Based on more recent data and verified nonlinear cancer risk assessment models, LL CLF formaldehyde emissions pose virtually no cancer risk to affected consumers.     

An Analysis of the Uncertainties in Estimates of Radon-Induced Lung Cancer

A recent report by the National Academy of Sciences estimates that the radiation dose to the bronchial epithelium, per working level month (WLM) of radon daughter exposure, is about 30% lower for residential exposures than for exposures received in underground mines. Adjusting the previously published BEIR IV radon risk model accordingly, the unit risk for indoor exposures of the general population is about 2.2 x 10(-4) lung cancer deaths (lcd)/WLM. Using results from EPA's National Residential Radon Survey, the average radon level is estimated to be about 1.25 pCi/L, and the annual average exposure about 0.242 WLM. Based on these estimates, 13,600 radon-induced lcd/yr are projected for the United States. A quantitative uncertainty analysis was performed, which considers: statistical uncertainties in the epidemiological studies of radon-exposed miners; the dependence of risk on age at, and time since, exposure; the extrapolation of risk estimates from mines to homes based on comparative dosimetry; and uncertainties in the radon daughter levels in homes and in the average residential occupancy. Based on this assessment of the uncertainties in the unit risk and exposure estimates, an uncertainty range of 7000-30000 lcd/yr is derived.     

Human Interindividual Variability in Susceptibility to Airborne Particles

Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are much more susceptible to particle-induced responses than others. This study assembled a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied included data drawn from epidemiologic studies of doses of methacholine, flour dust, and other agents that induce acute changes in lung function. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters was greater than the variability in pharmacokinetic (breathing rate, deposition, and clearance) parameters. Quantitatively the results indicated that human interindividual variability of breathing rates and major pharmacokinetic parameters-total deposition and tracheobronchial clearance-were in the region of Log(GSD) = 0.1 to 0.2 (corresponding to geometric standard deviations of 10(.1)-10(.2) or 1.26-1.58). Deposition to the deep lung (alveolar region) appeared to be somewhat more variable: Log(GSD) of about 0.3 (GSD of about 2). Among pharmacodynamic parameters, changes in FEV1 in response to ozone and metabisulfite (an agent that is said to act primarily on neural receptors in the lung) were in the region of Log(GSD) of 0.2 to 0.4. However, similar responses to methacholine, an agent that acts on smooth muscle, seemed to have still more variability (0.4 to somewhat over 1.0, depending on the type of population studied). Similarly high values were suggested for particulate allergens. Central estimates of this kind of variability, and the close correspondence of the data to lognormal distributions, indicate that 99.9th percentile individuals are likely to respond at doses that are 150 to 450-fold less than would be needed in median individuals. It seems plausible that acute responses with this amount of variability could form part of the mechanistic basis for epidemiological observations of enhanced mortality in relation to ambient exposures to fine particles.