Systematic Evidence Mapping of Potential Exposure Pathways for Per- and Polyfluoroalkyl Substances Based on Measured Occurrence in Multiple Media.

Given that human biomonitoring surveys show per- and polyfluoroalkyl substances (PFAS) to be ubiquitous, humans can be exposed to PFAS through various sources, including drinking water, food, and indoor environmental media. Data on the nature and level of PFAS in residential environments are required to identify important pathways for human exposure. This work investigated important pathways of exposure to PFAS by reviewing, curating, and mapping evidence for the measured occurrence of PFAS in exposure media. Real-world occurrence for 20 PFAS was targeted primarily in media commonly related to human exposure (outdoor and indoor air, indoor dust, drinking water, food, food packaging, articles, and products, and soil). A systematic-mapping process was implemented to conduct title-abstract and full-text screening and to extract PECO-relevant primary data into comprehensive evidence databases. Parameters of interest included the following: sampling dates and locations, numbers of collection sites and participants, detection frequencies, and occurrence statistics. Detailed data were extracted on PFAS occurrence in indoor and environmental media from 229 references and on PFAS occurrence in human matrices where available from those references. Studies of PFAS occurrence became numerous after 2005. Studies were most abundant for PFOA (80% of the references) and PFOS (77%). Many studies analyzed additional PFAS, particularly, PFNA and PFHxS (60% of references each). Food (38%) and drinking water (23%) were the commonly studied media. Most studies found detectable levels of PFAS, and detectable levels were reported in a majority of states in the United States. Half or more of the limited studies for indoor air and products detected PFAS in 50% or more of the collected samples. The resulting databases can inform problem formulation for systematic reviews to address specific PFAS exposure queries and questions, support prioritization of PFAS sampling, and inform PFAS exposure measurement studies. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Cloth-Air Partitioning of Neutral Per- and Polyfluoroalkyl Substances (PFAS) in North Carolina Homes during the Indoor PFAS Assessment (IPA) Campaign.

Partitioning of per- and polyfluoroalkyl substances (PFAS) to indoor materials, including clothing, may prolong the residence time of PFAS indoors and contribute to exposure. During the Indoor PFAS Assessment (IPA) Campaign, we measured concentrations of nine neutral PFAS in air and cotton cloth in 11 homes in North Carolina, for up to 9 months. Fluorotelomer alcohols (i.e., 6:2 FTOH, 8:2 FTOH, and 10:2 FTOH) are the dominant target species in indoor air, with concentrations ranging from 1.8 to 49 ng m-3, 1.2 to 53 ng m-3, and 0.21 to 5.7 ng m-3, respectively. In cloth, perfluorooctane sulfonamidoethanols (i.e., MeFOSE and EtFOSE) accumulated most significantly over time, reaching concentrations of up to 0.26 ng cm-2 and 0.24 ng cm-2, respectively. From paired measurements of neutral PFAS in air and suspended cloth, we derived cloth-air partition coefficients (Kca) for 6:2, 8:2, and 10:2 FTOH; ethylperfluorooctane sulfonamide (EtFOSA); MeFOSE; and EtFOSE. Mean log(Kca) values range from 4.7 to 6.6 and are positively correlated with the octanol-air partition coefficient. We investigated the effect of the cloth storage method on PFAS accumulation and the influence of home characteristics on air concentrations. Temperature had the overall greatest effect. This study provides valuable insights into PFAS distribution, fate, and exposure indoors.

Modeling Clothing as a Vector for Transporting Airborne Particles and Pathogens across Indoor Microenvironments.

Evidence suggests that human exposure to airborne particles and associated contaminants, including respiratory pathogens, can persist beyond a single microenvironment. By accumulating such contaminants from air, clothing may function as a transport vector and source of "secondary exposure". To investigate this function, a novel microenvironmental exposure modeling framework (ABICAM) was developed. This framework was applied to a para-occupational exposure scenario involving the deposition of viable SARS-CoV-2 in respiratory particles (0.5-20 µm) from a primary source onto clothing in a nonhealthcare setting and subsequent resuspension and secondary exposure in a car and home. Variability was assessed through Monte Carlo simulations. The total volume of infectious particles on the occupant's clothing immediately after work was 4800 µm3 (5th-95th percentiles: 870-32 000 µm3). This value was 61% (5-95%: 17-300%) of the occupant's primary inhalation exposure in the workplace while unmasked. By arrival at the occupant's home after a car commute, relatively rapid viral inactivation on cotton clothing had reduced the infectious volume on clothing by 80% (5-95%: 26-99%). Secondary inhalation exposure (after work) was low in the absence of close proximity and physical contact with contaminated clothing. In comparison, the average primary inhalation exposure in the workplace was higher by about 2-3 orders of magnitude. It remains theoretically possible that resuspension and physical contact with contaminated clothing can occasionally transmit SARS-CoV-2 between humans.

Assessment of Non-Occupational 1,4-Dioxane Exposure Pathways from Drinking Water and Product Use.

1,4-Dioxane is a persistent and mobile organic chemical that has been found by the United States Environmental Protection Agency (USEPA) to be an unreasonable risk to human health in some occupational contexts. 1,4-Dioxane is released into the environment as industrial waste and occurs in some personal-care products as an unintended byproduct. However, limited exposure assessments have been conducted outside of an occupational context. In this study, the USEPA simulation modeling tool, Stochastic Human Exposure and Dose Simulator-High Throughput (SHEDS-HT), was adapted to estimate the exposure and chemical mass released down the drain (DTD) from drinking water consumption and product use. 1,4-Dioxane concentrations measured in drinking water and consumer products were used by SHEDS-HT to evaluate and compare the contributions of these sources to exposure and mass released DTD. Modeling results showed that compared to people whose daily per capita exposure came from only products (2.29 × 10-7 to 2.92 × 10-7 mg/kg/day), people exposed to both contaminated water and product use had higher per capita median exposures (1.90 × 10-6 to 4.27 × 10-6 mg/kg/day), with exposure mass primarily attributable to water consumption (75-91%). Last, we demonstrate through simulation that while a potential regulatory action could broadly reduce DTD release, the proportional reduction in exposure would be most significant for people with no or low water contamination.

Textile Washing Conveys SVOCs from Indoors to Outdoors: Application and Evaluation of a Residential Multimedia Model.

Indoor environments have elevated concentrations of numerous semivolatile organic compounds (SVOCs). Textiles provide a large surface area for accumulating SVOCs, which can be transported to outdoors through washing. A multimedia model was developed to estimate advective transport rates (fluxes) of 14 SVOCs from indoors to outdoors by textile washing, ventilation, and dust removal/disposal. Most predicted concentrations were within 1 order of magnitude of measurements from a study of 26 Canadian homes. Median fluxes to outdoors [µg·(year·home)-1] spanned approximately 4 orders of magnitude across compounds, according to the variability in estimated aggregate emissions to indoor air. These fluxes ranged from 2 (2,4,4'-tribromodiphenyl ether, BDE-28) to 30 200 (diethyl phthalate, DEP) for textile washing, 12 (BDE-28) to 123 200 (DEP) for ventilation, and 0.1 (BDE-28) to 4200 (bis(2-ethylhexyl) phthalate, DEHP) for dust removal. Relative contributions of these pathways to the total flux to outdoors strongly depended on physical-chemical properties. Textile washing contributed 20% tris-(2-chloroisopropyl)phosphate (TCPP) to 62% tris(2-butoxyethyl)phosphate (TBOEP) on average. These results suggest that residential textile washing can be an important transport pathway to outdoors for SVOCs emitted to indoor air, with implications for human and ecological exposure. Interventions should try to balance the complex tradeoff of textile washing by minimizing exposures for both human occupants and aquatic ecosystems.

Assessing Human Exposure to Chemicals in Materials, Products and Articles: The International Risk Management Landscape for Phthalates.

Risk-based chemical safety assessments are increasingly being conducted to support chemical management decisions and informed substitution to protect public health. Rapid evaluation and prioritization of large numbers of chemicals used in materials, products, and other indoor articles has become a major focus of chemical risk management strategies. Internationally, although a shared understanding of the value of rapid risk-based evaluations appears to be emerging, implementation strategies and associated management decisions vary from one agency and jurisdiction to another. This paper highlights the international chemical risk management landscape focusing on phthalates as an example, and reviews how phthalate exposure assessments have been performed, resulting at times in different decisions based on the application of scientific information within different policy contexts. In general, the need for efficient and effective risk-based assessment approaches is driving increased needs for high-quality exposure data and validated, mechanistic exposure models. Further development of mechanistic models and related parameters will reduce uncertainties in exposure estimates and support scientific risk-based evaluations of chemical/product combinations for a variety of decisions.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials.

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.

Identifying important life stages for monitoring and assessing risks from exposures to environmental contaminants: results of a World Health Organization review.

In this paper, we summarize exposure-related issues to consider in determining the most appropriate age ranges and life stages for risk assessment. We then propose a harmonized set of age bins for monitoring and assessing risks from exposures to chemicals for global use. The focus is on preconception through adolescence, though the approach should be applicable to additional life stages. A two-tiered set of early life age groups is recommended. The first tier involves the adoption of guidance similar to the childhood age groups recommended by the U.S. Environmental Protection Agency, whereas the second tier consolidates some of those age groups to reduce the burden of developing age-specific exposure factors for different regions. While there is no single "correct" means of choosing a common set of age groups to use internationally in assessing early life exposure and risk, use of a set of defined age groups is recommended to facilitate comparisons of potential exposures and risks around the globe, the collection of data and analyses of aggregate exposure and cumulative risk. Application of these age groups for robust assessment of exposure and risk for specific populations will require region-specific exposure factors as well as local environmental monitoring data.

Modeling clothing as a secondary source of exposure to SVOCs across indoor microenvironments.

BACKGROUND: Evidence suggests that clothing can influence human exposure to semi-volatile organic compounds (SVOCs) through transdermal uptake and inhalation. OBJECTIVES: The objectives of this study were [1] to investigate the potential for clothing to function as a transport vector and secondary source of gas-phase SVOCs across indoor microenvironments, [2] to elucidate how clothing storage, wear, and laundering can influence the dynamics of transdermal uptake, and [3] to assess the potential for multiple human occupants to influence the multimedia dynamics of SVOCs indoors. METHODS: A computational modeling framework (ABICAM) was expanded, applied, and evaluated by simulating and augmenting two "real-world" chamber experiments. A primary strength of this framework was its representation of occupants and their clothing as unique entities with the potential for location changes. RESULTS: Estimates of transdermal uptake of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) were generally consistent with those extrapolated from measured concentrations of urinary metabolites, and those predicted by two other mechanistic models. ABICAM predicted that clean clothing (long sleeves, long pants, and socks, 100% cotton, 1 mm thick) readily accumulated DEP (6900-9700 µg) and DnBP (4500-4800 µg) from the surrounding chamber air over 6 h of exposure to average concentrations of 233 (DEP) and 114 (DnBP) µg·m-3. Because of their high capacity, clean clothing also effectively minimized transdermal uptake. In addition, ABICAM predicted that contaminated clothing functioned as a vector for transporting DEP and DnBP across indoor microenvironments and reemitted 13-80% (DEP) and 3-27% (DnBP) of the accumulated masses over 48 h. SIGNIFICANCE: Though the estimated secondary inhalation exposures from contaminated clothing were low compared to the corresponding primary exposures, these secondary exposures could be accentuated in other contexts, for example, involving longer timeframes of clothing storage, multiple occupants wearing contaminated clothing, and/or repeated instances of clothing-mediated transport of contaminants (e.g., from an occupational setting). IMPACT: This modeling study reaffirms the effectiveness of clean clothing in reducing transdermal uptake of airborne SVOCs and conversely, that contaminated clothing could be a source of SVOC exposure via transdermal uptake and by acting as a vector for transporting those contaminants to other locations.

Systematic evidence mapping of potential correlates of exposure for per- and poly-fluoroalkyl substances (PFAS) based on measured occurrence in biomatrices and surveys of dietary consumption and product use.

Per- and poly-fluoroalkyl substances (PFAS) are widely observed in environmental media and often are found in indoor environments as well as personal-care and consumer products. Humans may be exposed through water, food, indoor dust, air, and the use of PFAS-containing products. Information about relationships between PFAS exposure sources and pathways and the amounts found in human biomatrices can inform source-contribution assessments and provide targets for exposure reduction. This work collected and collated evidence for correlates of PFAS human exposure as measured through sampling of biomatrices and surveys of dietary consumption and use of consumer products and articles. A systematic evidence mapping approach was applied to perform a literature search, conduct title-abstract and full-text screening, and to extract primary data into a comprehensive database for 16 PFAS. Parameters of interest included: sampling dates and locations, cohort descriptors, PFAS measured in a human biomatrix, information about food consumption in 11 categories, use of products/articles in 11 categories, and reported correlation values (and their statistical strength). The literature search and screening process yielded 103 studies with information for correlates of PFAS exposures. Detailed data were extracted and compiled on measures of PFAS correlations between biomatrix concentrations and dietary consumption and other product/article use. A majority of studies (61/103; 59%) were published after 2015 with few (8/103; 8%) prior to 2010. Studies were most abundant for dietary correlates (n = 94) with fewer publications reporting correlate assessments for product use (n = 56), while some examined both. PFOA and PFOS were assessed in almost all studies, followed by PFHxS, PFNA, and PFDA which were included in >50% of the studies. No relevant studies included PFNS or PFPeS. Among the 94 studies of dietary correlates, significant correlations were reported in 83% of the studies for one or more PFAS. The significant dietary correlations most commonly were for seafood, meats/eggs, and cereals/grains/pulses. Among the 56 studies of product/article correlates, significant correlations were reported in 70% of the studies. The significant product/article correlations most commonly were for smoking/tobacco, cosmetics/toiletries, non-stick cookware, and carpet/flooring/furniture and housing. Six of 11 product/article categories included five or fewer studies, including food containers and stain- and water-resistant products. Significant dietary and product/article correlations most commonly were positive. Some studies found a mix of positive and negative correlations depending on the PFAS, specific correlate, and specific response level, particularly for fats/oils, dairy consumption, food containers, and cosmetics/toiletries. Most of the significant findings for cereals/grains/pulses were negative correlations. Substantial evidence was found for correlations between dietary intake and biomatrix levels for several PFAS in multiple food groups. Studies examining product/article use relationships were relatively sparse, except for smoking/tobacco, and would benefit from additional research. The resulting database can inform further assessments of dietary and product use exposure relationships and can inform new research to better understand PFAS source-to-exposure relationships. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Linking exposure to per- and polyfluoroalkyl substances (PFAS) in house dust and biomonitoring data in eight impacted communities.

Per- and polyfluoroalkyl substances (PFAS) are widely used in industry and have been linked to various adverse health effects. Communities adjacent to sites where PFAS are manufactured, stored, or used may be at elevated risk. In these impacted communities, significant exposure often occurs through contaminated drinking water, yet less is known about the role of other pathways such as residential exposure through house dust. We analyzed a paired serum and house dust dataset from the Agency for Toxic Substances and Disease Registry's PFAS Exposure Assessments, which sampled eight United States communities with a history of drinking water contamination due to aqueous film forming foam (AFFF) use at nearby military bases. We found that serum PFAS levels of residents were significantly positively associated with the dust PFAS levels in their homes, for three of seven PFAS analyzed, when accounting for site and participant age. We also found that increased dust PFAS levels were associated with a shift in the relative abundance of PFAS in serum towards those chemicals not strongly linked to AFFF contamination, which may suggest household sources. Additionally, we analyzed participant responses to exposure questionnaires to identify factors associated with dust PFAS levels. Dust PFAS levels for some analytes were significantly elevated in households where participants were older and had lived at the home longer, cleaned less frequently, used stain resistant products, and had carpeted living rooms. Our results suggest that residential exposure to PFAS via dust or other indoor pathways may contribute to overall exposure and body burden, even in communities impacted by AFFF contamination of drinking water, and the magnitude of this exposure may also be influenced by demographic, behavioral, and housing factors.

High-throughput models for exposure-based chemical prioritization in the ExpoCast project.

The United States Environmental Protection Agency (U.S. EPA) must characterize potential risks to human health and the environment associated with manufacture and use of thousands of chemicals. High-throughput screening (HTS) for biological activity allows the ToxCast research program to prioritize chemical inventories for potential hazard. Similar capabilities for estimating exposure potential would support rapid risk-based prioritization for chemicals with limited information; here, we propose a framework for high-throughput exposure assessment. To demonstrate application, an analysis was conducted that predicts human exposure potential for chemicals and estimates uncertainty in these predictions by comparison to biomonitoring data. We evaluated 1936 chemicals using far-field mass balance human exposure models (USEtox and RAIDAR) and an indicator for indoor and/or consumer use. These predictions were compared to exposures inferred by Bayesian analysis from urine concentrations for 82 chemicals reported in the National Health and Nutrition Examination Survey (NHANES). Joint regression on all factors provided a calibrated consensus prediction, the variance of which serves as an empirical determination of uncertainty for prioritization on absolute exposure potential. Information on use was found to be most predictive; generally, chemicals above the limit of detection in NHANES had consumer/indoor use. Coupled with hazard HTS, exposure HTS can place risk earlier in decision processes. High-priority chemicals become targets for further data collection.

Simulating patterns of life: More representative time-activity patterns that account for context.

BACKGROUND: Complex contributions of environment to health are intimately connected to human behavior. Modeling of human behaviors and their influences helps inform important policy decisions related to critical environmental and public health challenges. A typical approach to human behavior modeling involves generating daily schedules based on time-activity patterns of individual humans, simulating 'agents' with these schedules, and interpreting patterns of life that emerge from the simulation to inform a research question. Current behavior modeling, however, rarely incorporates the context that surrounds individuals' truly broad scope of activities and influences on those activities. OBJECTIVES: We describe in detail a range of elements involved in generating time-activity patterns and connect work in the social science field of behavior modeling with applications in exposure science and environmental health. We propose a framework for behavior modeling that takes a systems approach and considers the broad scope of activities and influences required to simulate more representative patterns of life and thus improve modeling that underlies understanding of environmental contributions to health and associated decisions to promote and protect public health. METHODS: We describe an agent-based modeling approach reliant on generating a population's schedules, filtering the schedules, simulating behavior using the schedules, analyzing the emergent patterns, and interrogating results that leverages general empirical information in a systems context to inform fit-for-purpose action. DISCUSSION: We propose a centralized and standardized program to codify behavior information and generate population schedules that researchers can select from to simulate human behavior and holistically characterize human-environment interactions for a variety of public health applications.

Geographic and demographic variability in serum PFAS concentrations for pregnant women in the United States.

BACKGROUND: While major pathways of human PFAS exposure are thought to be drinking water and diet, other pathways and sources have also been shown to contribute to a person's cumulative exposure. However, the degree of contribution of these other sources to PFAS body burdens is still not well understood and occurrence data for PFAS in conssumer products and household materials are sparse. Questionnaire data concordant with biomonitoring may improve understanding of associations between other PFAS exposure pathways and exposure in human populations. OBJECTIVE: This study aims to better understand maternal and early-life exposures to PFAS from various potential sources and pathways in the context of household and community level characteristics. METHODS: PFAS data from the National Children's Study (NCS) Vanguard Data and Sample Archive Access System were analyzed from serum of 427 pregnant women residing in 7 counties throughout the United States. Location and self-reported questionnaire responses were used to analyze variability in serum concentrations based on demographics, housing characteristics, behaviors, and geography. Spatial mapping analyses incorporated publicly available data to further hypothesize potential sources of exposure in two NCS counties. RESULTS: Location was associated with serum concentrations for all PFAS chemicals measured. Questionnaire responses for race/ethnicity, income, education level, number of household members, drinking water source, home age, and fast-food consumption were associated with PFAS levels. Statistical differences were observed between participants with the same questionnaire responses but in different locations. Spatial mapping analyses suggested that participants' proximity to local point sources can overshadow expected trends with demographic information. SIGNIFICANCE: By increasing understanding of maternal and early-life PFAS exposures from various potential sources and pathways, as well as highlighting the importance of proximity to potential sources in identifying vulnerable populations and locations, this work reveals environmental justice considerations and contributes to risk management strategies that maximize public health protection. IMPACT: This work increases understanding of maternal and early-life PFAS exposures, reveals environmental justice considerations, and contributes to study design and risk management strategies.

Rapid methods to estimate potential exposure to semivolatile organic compounds in the indoor environment.

A systematic and efficient strategy is needed to assess and manage potential risks to human health that arise from the manufacture and use of thousands of chemicals. Among available tools for rapid assessment of large numbers of chemicals, significant gaps are associated with the capability to evaluate exposures that occur indoors. For semivolatile organic compounds (SVOCs), exposure is strongly influenced by the types of products in which these SVOCs occur. We propose methods for obtaining screening-level estimates for two primary SVOC source classes: additives in products used indoors and ingredients in products sprayed or applied to interior surfaces. Accounting for product use, emission characteristics, and the properties of the SVOCs, we estimate exposure via inhalation of SVOCs in the gas-phase, inhalation of SVOCs sorbed to airborne particles, ingestion of SVOCs sorbed to dust, and dermal sorption of SVOCs from the air into the blood. We also evaluate how exposure to the general public will change if chemical substitutions are made. Further development of a comprehensive set of models including the other SVOC-containing products and the other SVOC exposure pathways, together with appropriate methods for estimating or measuring the key parameters (in particular, the gas-phase concentration in equilibrium with the material-phase concentration of the SVOC in the product, or y(0)), is needed. When combined with rapid toxicity estimates, screening-level exposure estimates can contribute to health-risk-based prioritization of a wide range of chemicals of concern.

Biogeographical analysis of chemical co-occurrence data to identify priorities for mixtures research.

A challenge with multiple chemical risk assessment is the need to consider the joint behavior of chemicals in mixtures. To address this need, pharmacologists and toxicologists have developed methods over the years to evaluate and test chemical interaction. In practice, however, testing of chemical interaction more often comprises ad hoc binary combinations and rarely examines higher order combinations. One explanation for this practice is the belief that there are simply too many possible combinations of chemicals to consider. Indeed, under stochastic conditions the possible number of chemical combinations scales geometrically as the pool of chemicals increases. However, the occurrence of chemicals in the environment is determined by factors, economic in part, which favor some chemicals over others. We investigate methods from the field of biogeography, originally developed to study avian species co-occurrence patterns, and adapt these approaches to examine chemical co-occurrence. These methods were applied to a national survey of pesticide residues in 168 child care centers from across the country. Our findings show that pesticide co-occurrence in the child care center was not random but highly structured, leading to the co-occurrence of specific pesticide combinations. Thus, ecological studies of species co-occurrence parallel the issue of chemical co-occurrence at specific locations. Both are driven by processes that introduce structure in the pattern of co-occurrence. We conclude that the biogeographical tools used to determine when this structure occurs in ecological studies are relevant to evaluations of pesticide mixtures for exposure and risk assessment.

Human exposure pathways to poly- and perfluoroalkyl substances (PFAS) from indoor media: A systematic review.

BACKGROUND: Human exposure to per- and polyfluoroalkyl substances (PFAS) has been primarily attributed to contaminated food and drinking water. There is information indicating other sources and pathways of exposure in residential environments, but few studies report relationships between these indoor media and human biomonitoring measurements. METHODS: This study adapts existing systematic review tools and methodologies to synthesize evidence for PFAS exposure pathways from indoor environment media including consumer products, household articles, cleaning products, personal care products, and indoor air and dust. Studies were identified using innovative machine learning approaches and pathway-specific search strings to reduce time needed for literature search and screening. The included studies and systematic review were evaluated using tools modified specifically for exposure studies. The systematic review was conducted following a previously published protocol (DeLuca et al., 2021) that describes the systematic review methodology used in detail. RESULTS: Only 7 studies were identified that measured the targeted subset of 8 PFAS chemicals in concordant household media (primarily house dust) and participant serum. Data extracted from the included studies were used to calculate exposure intake rates and estimate a percentage of occupant serum concentrations that could be attributed to the indoor exposure pathways. These calculations showed that exposure to PFOA, PFOS, PFNA, and PFHxS from contaminated house dust could account for 13%, 3%, 7%, and 25% of serum concentrations, respectively. Inhalation of PFAS in indoor air could account for less than 4% of serum PFOA concentrations and less than 2% of serum PFOS and PFNA concentrations. A risk of bias was identified due to participant profiles in most of the studies being skewed towards white, female, and higher socioeconomic status. CONCLUSIONS: Along with synthesizing evidence for estimated contributions to serum PFAS levels from indoor exposure media, this systematic review also identifies a consistent risk of bias across exposure study populations that should be considered in future studies. It highlights a major research gap and need for studies that measure concordant data from both indoor exposure media and participant serum and the need for continued research on exposure modeling parameters for many PFAS chemicals.

Human exposure pathways to poly- and perfluoroalkyl substances (PFAS) from indoor media: A systematic review protocol.

BACKGROUND: Human exposure to per- and polyfluoroalkyl substances (PFAS) has been primarily attributed to contaminated food and drinking water. However, additional PFAS exposure pathways have been raised by a limited number of studies reporting correlations between commercial and industrial products and PFAS levels in human media and biomonitoring. Systematic review (SR) methodologies have been widely used to evaluate similar questions using an unbiased approach in the fields of clinical medicine, epidemiology, and toxicology, but the deployment in exposure science is ongoing. Here we present a systematic review protocol that adapts existing systematic review methodologies and study evaluation tools to exposure science studies in order to investigate evidence for important PFAS exposure pathways from indoor media including consumer products, household articles, cleaning products, personal care products, plus indoor air and dust. OBJECTIVES: We will systematically review exposure science studies that present both PFAS concentrations from indoor exposure media and PFAS concentrations in blood serum or plasma. Exposure estimates will be synthesized from the evidence to answer the question, "For the general population, what effect does exposure from PFAS chemicals via indoor media have on blood, serum or plasma concentrations of PFAS?" We adapt existing systematic review methodologies and study evaluation tools from the U.S. EPA's Systematic Review Protocol for the PFBA, PFHxA, PFHxS, PFNA, and PFDA IRIS Assessments and the Navigation Guide for exposure science studies, as well as present innovative developments of exposure pathway-specific search strings for use in artificial intelligence screening software. DATA SOURCES: We will search electronic databases for potentially relevant literature, including Web of Science, PubMed, and ProQuest. Literature search results will be stored in EPA's Health and Environmental Research Online (HERO) database. STUDY ELIGIBILITY AND CRITERIA: Included studies will present exposure measures from indoor media including consumer products, household articles, cleaning products, personal care products, plus indoor air and dust, paired with PFAS concentrations in blood, serum or plasma from adults and/or children in the general population. We focus on a subset of PFAS chemicals including perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), perfluorobutanoic acid (PFBA), perfluorobutane sulfonate (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), and perfluorononanoic acid (PFNA). STUDY APPRAISAL AND SYNTHESIS METHODS: Studies will be prefiltered at the title and abstract level using computationally intelligent search strings to expedite the screening process for reviewers. Two independent reviewers will screen the prefiltered studies against inclusion criteria at the title/abstract level and then full-text level, after which the reviewers will assess the studies' risk of bias using an approach modified from established systematic review tools for exposure studies. Exposure estimates will be calculated to investigate the proportion of blood, serum or plasma) PFAS concentrations that can be explained by exposure to PFAS in indoor media.

A state-of-the-science review of polychlorinated biphenyl exposures at background levels: relative contributions of exposure routes.

Exposure to polychlorinated biphenyls (PCBs) can occur through multiple routes and sources, including dietary intake, inhalation, dermal contact, and ingestion of dust and soils. Dietary exposure to PCBs is often considered the primary exposure route for the general population; however, recent studies suggest an increasing contribution from indoor inhalation exposure. Here, we aim to estimate the relative contribution of different PCB exposure pathways for the general population, as well as for select age groups. We conducted a targeted literature review of PCB concentrations in environmental media, including indoor and outdoor air, indoor dust, and soils, as well as of total dietary intake. Using the average concentrations from the studies identified, we estimated PCB exposure through different routes for the general population. In addition, we assessed exposure via environmental media for select age groups. We identified a total of 70 studies, 64 that provided background PCB concentrations for one or more of the environmental media of interest and 6 studies that provided estimates of dietary intake. Using estimates from studies conducted worldwide, for the general population, dietary intake of PCBs was the major exposure pathway. In general, our review identifies important limitations in the data available to assess population exposures, highlighting the need for more current and population-based estimates of PCB exposure, particularly for indoor air and dietary intake.

Improving the quality of toxicology and environmental health systematic reviews: What journal editors can do.

Systematic reviews are fast increasing in prevalence in the toxicology and environmental health literature. However, how well these complex research projects are being conducted and reported is unclear. Since editors have an essential role in ensuring the scientific quality of manuscripts being published in their journals, a workshop was convened where editors, systematic review practitioners, and research quality control experts could discuss what editors can do to ensure the systematic reviews they publish are of sufficient scientific quality. Interventions were explored along four themes: setting standards; reviewing protocols; optimizing editorial workflows; and measuring the effectiveness of editorial interventions. In total, 58 editorial interventions were proposed. Of these, 26 were shortlisted for being potentially effective, and 5 were prioritized as short-term actions that editors could relatively easily take to improve the quality of published systematic reviews. Recent progress in improving systematic reviews is summarized, and outstanding challenges to further progress are highlighted.