Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS. OBJECTIVES: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest. This work builds from the 2022 evidence map that collated evidence on a separate set of ∼150 PFAS. Like our previous work, this SEM does not include PFAS that are the subject of ongoing or completed assessments at the US EPA. METHODS: SEM methods were used to search, screen, and inventory mammalian bioassay and epidemiological literature from peer-reviewed and gray literature sources using manual review and machine-learning software. For each included study, study design details and health end points examined were summarized in interactive web-based literature inventories. Some included studies also underwent study evaluation and detailed extraction of health end point data. All underlying data is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 13,000 studies were identified from scientific databases. Screening processes identified 121 mammalian bioassay and 111 epidemiological studies that met screening criteria. Epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Mammalian bioassay evidence (available for 30 PFAS) commonly assessed effects in the reproductive, whole-body, nervous, and hepatic systems. Overall, 41 PFAS had evidence across mammalian bioassay and epidemiology data streams (roughly 11% of searched chemicals). DISCUSSION: No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search. Results from this SEM, our 2022 SEM on ∼150 PFAS, and other PFAS assessment products from the US EPA are compiled into a comprehensive PFAS dashboard that provides researchers and regulators an overview of the current PFAS human health landscape including data gaps and can serve as a scoping tool to facilitate prioritization of PFAS-related research and/or risk assessment activities. https://doi.org/10.1289/EHP13423.

Advancing Methodologies Used in Trace Element-Based Mass Balance Studies to Separately Estimate Soil and Dust Ingestion Rates for Children.

Historically, soil ingestion rate estimates were based on trace element-based mass balance (MB) study results. These were used in assessing exposures and health risks for children residing in Superfund or chemically contaminated communities. However, soil and dust can have considerable differences with respect to their sources, chemical, physical, and toxicological characteristics. Unfortunately, the MB approach is incapable of disentangling dust ingestion rates from soil ingestion rates. Alternative methods, such as activity pattern and biokinetic modeling techniques, have also been used to predict soil and dust ingestion rates. The results from these studies differed from those obtained from the MB studies. This research evaluated the MB methodology and formulated a physical model which characterized the environmental and behavioral determinants of soil and dust ingestion exposures by children. This new approach explicitly separates outdoor soil exposures from the indoor tracked-in soil portion of the dust and total dust exposures by utilizing information from five key MB studies along with new information derived from the SHEDS-Soil/Dust time-activity pattern-based modeling runs. Application of this new hybrid methodology showed that the predicted mean soil ingestion rates are 30%-70% less than the "total soil" ingestion rates obtained from the selected MB studies. In contrast, most of the predicted dust ingestion rate estimates were typically greater than the predicted soil ingestion rates. Moreover, the predicted total soil plus dust ingestion rates were found to be mostly higher (by ≤ 60%) than the MB-based "total soil" ingestion rates. Except for one study these results were higher than the results produced by the stand-alone SHEDS-Soil/Dust model runs. Across the MB studies analyzed, predicted outdoor soil ingestion rate contributions to "total soil" ingestion rates varied between 29% and 70% while the tracked-in soil portion of the indoor dust ingestion rates varied between 30% and 71%.

Exposure Prioritization (Ex Priori): A Screening-Level High-Throughput Chemical Prioritization Tool.

To estimate potential chemical risk, tools are needed to prioritize potential exposures for chemicals with minimal data. Consumer product exposures are a key pathway, and variability in consumer use patterns is an important factor. We designed Ex Priori, a flexible dashboard-type screening-level exposure model, to rapidly visualize exposure rankings from consumer product use. Ex Priori is Excel-based. Currently, it is parameterized for seven routes of exposure for 1108 chemicals present in 228 consumer product types. It includes toxicokinetics considerations to estimate body burden. It includes a simple framework for rapid modeling of broad changes in consumer use patterns by product category. Ex Priori rapidly models changes in consumer user patterns during the COVID-19 pandemic and instantly shows resulting changes in chemical exposure rankings by body burden. Sensitivity analysis indicates that the model is sensitive to the air emissions rate of chemicals from products. Ex Priori's simple dashboard facilitates dynamic exploration of the effects of varying consumer product use patterns on prioritization of chemicals based on potential exposures. Ex Priori can be a useful modeling and visualization tool to both novice and experienced exposure modelers and complement more computationally intensive population-based exposure models.

Model-based predictions of soil and dust ingestion rates for U.S. adults using the stochastic human exposure and dose simulation soil and dust model.

BACKGROUND: Adults can be exposed to chemicals through incidental ingestion of soil and dust, either through hobbies, occupations, or behaviors that increase contact with soil or dust (e.g., cleaning or renovating). However, few data describing these ingestion rates are available. OBJECTIVE: Our objective was to use the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-Soil/Dust) model to estimate distributions of soil and dust ingestion rates for adults (≥21 years old) with varying degrees of soil and dust contact. METHODS: We parameterized SHEDS-Soil/Dust to estimate soil and dust ingestion rates for several categories of adults: adults in the general population; adults with moderate (higher) soil exposure (represented by hobbyists, such as gardeners, with increased soil contact); adults with high soil exposure (represented by occupationally exposed individuals, such as landscapers); and individuals who have high dust exposure (e.g., are in contact with very dusty indoor environments). RESULTS: Total soil plus dust ingestion for adults in the general population was 7 mg/day. Hobbyists or adults with moderate soil exposure averaged 33 mg/day and occupationally exposed individuals averaged 123 mg/day. Total soil plus dust ingestion for adults in the high dust exposure scenario was 25 mg/day. Results were driven by time spent in contact with soil and, thus, warmer seasons (e.g., summer) were associated with higher ingestion rates than colder seasons (e.g., winter). SIGNIFICANCE: These results provide modeled estimates of soil and dust ingestion rates for adults for use in decision making using real-world exposure considerations. These modeled estimates suggest that soil and dust ingestion is a potential concern for adults who spend a higher amount of time interacting with either soil or dusty environments. IMPACT STATEMENT: The parameterization of real-world scenarios within the application of SHEDS-Soil/Dust model to predict soil and dust ingestion rates for adults provides estimates of soil and dust ingestion rates useful for refining population-based risk assessments. These data illuminate drivers of exposure useful for both risk management decisions and designing future studies to improve existing tracer methodologies.

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS. OBJECTIVE: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing. METHODS: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement-only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams. DISCUSSION: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343.

Model based prediction of age-specific soil and dust ingestion rates for children.

BACKGROUND: Soil and dust ingestion can be a primary route of environmental exposures. Studies have shown that young children are more vulnerable to incidental soil and dust ingestion. However, available data to develop soil and dust ingestion rates for some child-specific age groups are either lacking or uncertain. OBJECTIVE: Our objective was to use the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-Soil/Dust) model to estimate distributions of soil and dust ingestion rates for ten age ranges from infancy to late adolescents (birth to 21 years). METHODS: We developed approaches for modeling age groups previously not studied, including a new exposure scenario for infants to capture exposures to indoor dust via pacifier use and accounting for use of blankets that act as a barrier to soil and dust exposure. RESULTS: Overall mean soil and dust ingestion rates ranged from ~35 mg/day (infants, 0-<6 m) to ~60 mg/day (toddlers and young children, 6m-<11 yr) and were considerably lower (about 20 mg/day) for teenagers and late adolescents (16-<21 y). The pacifier use scenario contributed about 20 mg/day to the median dust ingestion rate for young infants. Except for the infant age groups, seasonal analysis showed that the modeled estimates of average summer mean daily total soil plus dust ingestion rates were about 50% higher than the values predicted for the winter months. Pacifier use factors and carpet dust loading values were drivers of exposure for infants and younger children. For older children, influential variables included carpet dust loading, soil adherence, and factors that capture the frequency and intensity of hand-to-mouth behaviors. SIGNIFICANCE: These results provide modeled estimates of children's soil and dust ingestion rates for use in decision making using real-world exposure considerations. IMPACT STATEMENT: The parameterization of scenarios to capture infant soil and dust ingestion and the application of SHEDS-Soil/Dust to a broader age range of children provides additional estimates of soil and dust ingestion rates that are useful in refining population-based risk assessments. These data illuminate drivers of exposure that are useful to both risk management applications and for designing future studies that improve upon existing tracer methodologies.

Predicting polycyclic aromatic hydrocarbons using a mass fraction approach in a geostatistical framework across North Carolina.

Currently in the United States there are no regulatory standards for ambient concentrations of polycyclic aromatic hydrocarbons (PAHs), a class of organic compounds with known carcinogenic species. As such, monitoring data are not routinely collected resulting in limited exposure mapping and epidemiologic studies. This work develops the log-mass fraction (LMF) Bayesian maximum entropy (BME) geostatistical prediction method used to predict the concentration of nine particle-bound PAHs across the US state of North Carolina. The LMF method develops a relationship between a relatively small number of collocated PAH and fine Particulate Matter (PM2.5) samples collected in 2005 and applies that relationship to a larger number of locations where PM2.5 is routinely monitored to more broadly estimate PAH concentrations across the state. Cross validation and mapping results indicate that by incorporating both PAH and PM2.5 data, the LMF BME method reduces mean squared error by 28.4% and produces more realistic spatial gradients compared to the traditional kriging approach based solely on observed PAH data. The LMF BME method efficiently creates PAH predictions in a PAH data sparse and PM2.5 data rich setting, opening the door for more expansive epidemiologic exposure assessments of ambient PAH.

Effect measure modification of blood lead-air lead slope factors.

There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead-air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead-air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1-5, 6-11, and 12-19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1-5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

The influence of declining air lead levels on blood lead-air lead slope factors in children.

BACKGROUND: It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB-PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards. OBJECTIVES: The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature. METHODS: We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA. RESULTS: Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0-11 years of age. CONCLUSION: These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.

Contribution of particle-size-fractionated airborne lead to blood lead during the National Health and Nutrition Examination Survey, 1999-2008.

The objective of this work is to examine associations between blood lead (PbB) and air lead (PbA) in particulate matter measured at different size cuts by use of PbB concentrations from the National Health and Nutrition Examination Survey and PbA concentrations from the U.S. Environmental Protection Agency for 1999-2008. Three size fractions of particle-bound PbA (TSP, PM10, and PM2.5) data with different averaging times (current and past 90-day average) were utilized. A multilevel linear mixed effect model was used to characterize the PbB-PbA relationship. At 0.15 µg/m(3), a unit decrease in PbA in PM10 was significantly associated with a decrease in PbB of 0.3-2.2 µg/dL across age groups and averaging times. For PbA in PM2.5 and TSP, slopes were generally positive but not significant. PbB levels were more sensitive to the change in PbA concentrations for children (1-5 and 6-11 years) and older adults (≥ 60 years) than teenagers (12-19 years) and adults (20-59 years). For the years following the phase-out of Pb in gasoline and a resulting upward shift in the PbA particle size distribution, PbA in PM10 was a statistically significant predictor of PbB. The results also suggest that age could affect the PbB-PbA association, with children having higher sensitivity than adults.

A multi-level model of blood lead as a function of air lead.

National and local declines in lead (Pb) in blood (PbB) over the past several years coincide with the decline in ambient air Pb (PbA) concentrations. The objective of this work is to evaluate how the relationship between PbB levels and PbA levels has changed following the phase out of leaded gasoline and tightened controls on industrial Pb emissions over the past 30 years among a national population sample. Participant-level data from the National Health and Nutrition Examination Survey (NHANES) were employed for two time periods (1988-1994 and 1999-2008), and the model was corrected for housing, demographic, socioeconomic, and other covariates present in NHANES. NHANES data for PbB and covariates were merged with PbA data from the U.S. Environmental Protection Agency. Linear mixed effects models (LMEs) were run to assess the relationship of PbB with PbA; sample weights were omitted, given biases encountered with the use of sample weights in LMEs. The 1988-1994 age-stratified results found that ln(PbB) was statistically significantly associated with ln(PbA) for all age groups. The consistent influence of PbA on PbB across age groups for the years 1988-1994 suggests a ubiquitous exposure unrelated to age of the sample population. The comparison of effect estimates for ln(PbA) shows a statistically significant effect estimate and ANOVA results for ln(PbB) for the 6- to 11-year and 12- to 19-year age groups during 1999-2008. The more recent finding suggests that PbA has less consistent influence on PbB compared with other factors.

Chlorine dioxide reactions with indoor materials during building disinfection: surface uptake.

Chlorine dioxide received attention as a building disinfectant in the wake of Bacillus anthracis contamination of several large buildings in the fall of 2001. It is increasingly used for the disinfection of homes and other indoor environments afflicted by mold. However, little is known regarding the interaction of chlorine dioxide and indoor materials, particularly as related to the removal of chlorine dioxide from air. Such removal may be undesirable with respect to the subsequent formation of localized zones of depleted disinfectant concentrations and potential reductions in disinfection effectiveness in a building. The focus of this paper is on chlorine dioxide removal from air to each of 24 different indoor materials. Experiments were completed with materials housed in flow-through 48-L stainless steel chambers under standard conditions of 700 ppm chlorine dioxide inlet concentration, 75% relative humidity, 24 degrees C, and 0.5 h(-1) air changes. Chlorine dioxide concentration profiles, deposition velocities, and reaction probabilities are described in this paper. Deposition velocities and reaction probabilities varied over approximately 2 orders of magnitude across all materials. For most materials, deposition velocity decreased significantly over a 16-h disinfection period; that is, materials became smaller sinks for chlorine dioxide with time. Four materials (office partition, ceiling tile, medium density fiberboard, and gypsum wallboard) accounted for the most short- and long-term consumption of chlorine dioxide. Deposition velocity was observed to be a strong function of chlorine dioxide inlet concentration, suggesting the potential importance of chemical reactions on or within test materials.

Identification of surrogate measures of diesel exhaust exposure in a controlled chamber study.

Exposure to diesel exhaust (DE) has been associated with acute cardiopulmonary and vascular responses, chronic noncancer health effects, and respiratory cancers in humans. To better understand DE exposures and eventually their related health effects, we established a controlled chamber experiment wherein human volunteer subjects were exposed to approximately 100 microg/m3 DE. In general, human exposure assessment for DE is based on ambient air measurements of surrogates such as elemental carbon (EC) or total organic carbon (OC) collected on filters. As specific health effect mechanisms and dose-response are obscured bythe complex composition of DE, the linkage from exposure to internal dose can presumably be improved by use of specific biomarkers and metabolites in blood, breath, or urine. Because EC and OC are not suitable as biomarkers, in this study, we focus on identifying compounds that are demonstrated indicators of DE and can also be found in biological fluids. We measured an assortment of volatile, semivolatile, and particle-bound aromatic compounds in the chamber air and report their airborne concentrations in DE and purified air, as well as the estimated values of the corresponding exposure ratios (mean DE air concentration:mean purified air concentration). These estimated exposure ratios were used to identify naphthalene (Nap) and phenanthrene (Phe) as potentially useful surrogates for DE exposure that could also serve as biomarkers. Estimated mean levels of Nap and Phe associated with the nominal 100 microg/m3 DE were 2600 and 765 ng/m3 with estimated exposure ratios of 252 and 92.4, respectively. Nap levels were significantly correlated with OC and total particle-bound polycyclic aromatic hydrocarbons (PAHs); Phe levels were significantly correlated with total volatile + semivolatile PAHs. These results suggest that Nap and Phe may be particularly useful surrogates for DE concentrations. While Nap and Phe are not validated here as internal biomarkers of DE exposure, we are currently assessing human biological specimens collected during this study and will discuss those results in ensuing papers.

Volatile polar metabolites in exhaled breath condensate (EBC): collection and analysis.

Environmental exposures, individual activities and disease states can perturb normal metabolic processes and be expressed as a change in the patterns of polar volatile organic compounds (PVOCs) present in biological fluids. We explore the measurement of volatile endogenous biomarkers to infer previous exposures to complex mixtures of environmental stressors. It is difficult to extract such compounds for ultra-trace level analysis due to their high solubility in water, especially when assaying complex liquid biological media such as exhaled breath condensate (EBC). Existing methods tend to be limited in sample volume processed and restricted in sample throughput. We have developed an alternative passive extraction method wherein a 2 ml sample is injected into a 75 ml glass bulb creating a small pool of liquid; a standard Tenax® sampling tube is inserted above the fluid and allowed to equilibrate with the headspace for ∼24 h. The biomarker compounds are preferentially transferred by diffusion from the aqueous sample onto the Tenax® adsorbent; blanks and calibration samples are similarly processed. Numerous samples can be simultaneously prepared and stored awaiting routine analysis for a suite of alcohols and aldehydes using thermal desorption gas chromatography-mass spectrometry (GC-MS). We have optimized the procedures and estimated the sensitivity, precision and extraction efficiency resulting from the preparation and analytical procedures using synthetic samples. We subsequently demonstrated the method using anonymous biological specimens of EBC from healthy adults. The ultimate goal is to develop normal ranges and patterns for PVOCs to infer population-based environmental health states with simple spot measurements based on outlier determinations.

Methyl bromide as a building disinfectant: interaction with indoor materials and resulting byproduct formation.

Several buildings were contaminated with Bacillus anthracis in the fall of 2001. These events required consideration of how to disinfect large indoor spaces for continued worker occupation. The interactions of gaseous disinfectants with indoor materials may inhibit the disinfection process, cause persistence of the disinfectant, and lead to possible byproduct formation and persistence. Methyl bromide (CH3Br) is a candidate for disinfection/deactivation of biological agents in buildings. In this study, 24 indoor materials were exposed to CH3Br for 16 hr at concentrations ranging from 100 to 2500 ppm in 48-L electropolished stainless steel chambers. CH3Br concentrations were measured during and after disinfection. Its interactions with materials were observed to be small, with nearly complete and rapid desorption. Between 3% and 8% of CH3Br adsorbed to four materials (office partition, ceiling tile, particle-board, and gypsum wallboard with satin paint), and the degree of adsorption decreased with increasing relative humidity. The percentage of adsorption to all other materials was <2%. This result suggests that when designing disinfection events with CH3Br, loss to indoor materials can be neglected in terms of disinfectant dose calculations. Possible reaction products were identified and/or quantified before and after exposure to CH3Br. Several monomethylated and dimethylated aliphatic compounds were observed in chamber air at low concentrations after the exposures of six materials to CH3Br. Concentration increases also occurred for chemicals that were observed to naturally off-gas from materials before exposure to CH3Br, suggesting that CH3Br may play a role in enhancing the natural off-gassing of chemicals, for example, by competitive displacement of compounds that already existed in the materials. The results described in this paper should facilitate the design of building disinfection systems involving CH3Br.

Workgroup report: Indoor chemistry and health.

Chemicals present in indoor air can react with one another, either in the gas phase or on surfaces, altering the concentrations of both reactants and products. Such chemistry is often the major source of free radicals and other short-lived reactive species in indoor environments. To what extent do the products of indoor chemistry affect human health? To address this question, the National Institute for Occupational Safety and Health sponsored a workshop titled "Indoor Chemistry and Health" on 12-15 July 2004 at the University of California-Santa Cruz. Approximately 70 experts from eight countries participated. Objectives included enhancing communications between researchers in indoor chemistry and health professionals, as well as defining a list of priority research needs related to the topic of the workshop. The ultimate challenges in this emerging field are defining exposures to the products of indoor chemistry and developing an understanding of the links between these exposures and various health outcomes. The workshop was a step toward meeting these challenges. This summary presents the issues discussed at the workshop and the priority research needs identified by the attendees.