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.

A Scoping Assessment of Implemented Toxicokinetic Models of Per- and Polyfluoro-Alkyl Substances, with a Focus on One-Compartment Models.

Toxicokinetic (TK) models have been used for decades to estimate concentrations of per-and polyfluoroalkyl substances (PFAS) in serum. However, model complexity has varied across studies depending on the application and the state of the science. This scoping effort seeks to systematically map the current landscape of PFAS TK models by categorizing different trends and similarities across model type, PFAS, and use scenario. A literature review using Web of Science and SWIFT-Review was used to identify TK models used for PFAS. The assessment covered publications from 2005-2020. PFOA, the PFAS for which most models were designed, was included in 69 of the 92 papers, followed by PFOS with 60, PFHxS with 22, and PFNA with 15. Only 4 of the 92 papers did not include analysis of PFOA, PFOS, PFNA, or PFHxS. Within the corpus, 50 papers contained a one-compartment model, 17 two-compartment models were found, and 33 used physiologically based pharmacokinetic (PBTK) models. The scoping assessment suggests that scientific interest has centered around two chemicals-PFOA and PFOS-and most analyses use one-compartment models in human exposure scenarios.

Computational estimates of daily aggregate exposure to PFOA/PFOS from 2011 to 2017 using a basic intake model.

BACKGROUND: Human exposure to per- and polyfluoroalkyl substances has been modeled to estimate serum concentrations. Given that the production and use of these compounds have decreased in recent years, especially PFOA and PFOS, and that additional concentration data have become available from the US and other industrialized countries over the past decade, aggregate median intakes of these two compounds were estimated using more recent data. METHODS: Summary statistics from secondary sources were collected, averaged, and mapped for indoor and outdoor air, water, dust, and soil for PFOA and PFOS to estimate exposures for adults and children. European dietary intake estimates were used to estimate daily intake from food. RESULTS: In accordance with decreased concentrations in media, daily intake estimates among adults, i.e., 40 ng/day PFOA and 40 ng/day PFOS, are substantially lower than those reported previously, as are children's estimates of 14 ng/day PFOA and 17 ng/day PFOS. Using a first-order pharmacokinetic model, these results compare favorably to the National Health and Nutrition Examination Survey serum concentration measurements. CONCLUSION: Concomitant blood concentrations support this enhanced estimation approach that captures the decline of PFOA/PFOS serum concentration over a decade.

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.

The Residential Population Generator (RPGen): Parameterization of Residential, Demographic, and Physiological Data to Model Intraindividual Exposure, Dose, and Risk.

Exposure to chemicals is influenced by associations between the individual's location and activities as well as demographic and physiological characteristics. Currently, many exposure models simulate individuals by drawing distributions from population-level data or use exposure factors for single individuals. The Residential Population Generator (RPGen) binds US surveys of individuals and households and combines the population with physiological characteristics to create a synthetic population. In general, the model must be supported by internal consistency; i.e., values that could have come from a single individual. In addition, intraindividual variation must be representative of the variation present in the modeled population. This is performed by linking individuals and similar households across income, location, family type, and house type. Physiological data are generated by linking census data to National Health and Nutrition Examination Survey data with a model of interindividual variation of parameters used in toxicokinetic modeling. The final modeled population data parameters include characteristics of the individual's community (region, state, urban or rural), residence (size of property, size of home, number of rooms), demographics (age, ethnicity, income, gender), and physiology (body weight, skin surface area, breathing rate, cardiac output, blood volume, and volumes for body compartments and organs). RPGen output is used to support user-developed chemical exposure models that estimate intraindividual exposure in a desired population. By creating profiles and characteristics that determine exposure, synthetic populations produced by RPGen increases the ability of modelers to identify subgroups potentially vulnerable to chemical exposures. To demonstrate application, RPGen is used to estimate exposure to Toluene in an exposure modeling case example.

Advances on a Decision Analytic Approach to Exposure-Based Chemical Prioritization.

The volume and variety of manufactured chemicals is increasing, although little is known about the risks associated with the frequency and extent of human exposure to most chemicals. The EPA and the recent signing of the Lautenberg Act have both signaled the need for high-throughput methods to characterize and screen chemicals based on exposure potential, such that more comprehensive toxicity research can be informed. Prior work of Mitchell et al. using multicriteria decision analysis tools to prioritize chemicals for further research is enhanced here, resulting in a high-level chemical prioritization tool for risk-based screening. Reliable exposure information is a key gap in currently available engineering analytics to support predictive environmental and health risk assessments. An elicitation with 32 experts informed relative prioritization of risks from chemical properties and human use factors, and the values for each chemical associated with each metric were approximated with data from EPA's CP_CAT database. Three different versions of the model were evaluated using distinct weight profiles, resulting in three different ranked chemical prioritizations with only a small degree of variation across weight profiles. Future work will aim to include greater input from human factors experts and better define qualitative metrics.

Integrating exposure to chemicals in building materials during use stage.

PURPOSE: There do not currently exist scientifically defensible ways to consistently characterize the human exposures (via various pathways) to near-field chemical emissions and associated health impacts during the use stage of building materials. The present paper thus intends to provide a roadmap which summarizes the current status and guides future development for integrating into LCA the chemical exposures and health impacts on various users of building materials, with a focus on building occupants. METHODS: We first review potential human health impacts associated with the substances in building materials and the methods used to mitigate these impacts, also identifying several of the most important online data resources. A brief overview of the necessary steps for characterizing use stage chemical exposures and health impacts for building materials is then provided. Finally, we propose a systematic approach to integrate the use stage exposures and health impacts into building material LCA and describe its components, and then present a case study illustrating the application of the proposed approach to two representative chemicals: formaldehyde and methylene diphenyl diisocyanate (MDI) in particleboard products. RESULTS AND DISCUSSION: Our proposed approach builds on the coupled near-field and far-field framework proposed by Fantke et al. (Environ Int 94:508-518, 2016), which is based on the product intake fraction (PiF) metric proposed by Jolliet et al. (Environ Sci Technol 49:8924-8931, 2015), The proposed approach consists of three major components: characterization of product usage and chemical content, human exposures, and toxicity, for which available methods and data sources are reviewed and research gaps are identified. The case study illustrates the difference in dominant exposure pathways between formaldehyde and MDI and also highlights the impact of timing and use duration (e.g., the initial 50 days of the use stage vs. the remaining 15 years) on the exposures and health impacts for the building occupants. CONCLUSIONS: The proposed approach thus provides the methodological basis for integrating into LCA the human health impacts associated with chemical exposures during the use stage of building materials. Data and modeling gaps which currently prohibit the application of the proposed systematic approach are discussed, including the need for chemical composition data, exposure models, and toxicity data. Research areas that are not currently focused on are also discussed, such as worker exposures and complex materials. Finally, future directions for integrating the use stage impacts of building materials into decision making in a tiered approach are discussed.

Episodic Impacts from California Wildfires Identified in Las Vegas Near-Road Air Quality Monitoring.

Air pollutant concentrations near major highways are usually attributed to a combination of nearby traffic emissions and regional background, and generally presumed to be additive in nature. During a near-road measurement study conducted in Las Vegas, NV, the effects of distant wildfires on regional air quality were indicated over a several day period in the summer of 2009. Area-wide elevated particulate levoglucosan (maximum of 0.83 µg/m(3)) and roadside measurements of ultraviolet light-absorbing particulate matter (UVPM) in comparison to black carbon (Delta-C) were apparent over the three-day period. Back-trajectory modeling and satellite images supported the measurement results and indicated the transport of air pollutants from wildfires burning in southern California. Separating roadside measurements under apparent biomass burning event (Delta-C > 1000 ng m(-3)) and nonevent (Delta-C < 1000 ng m(-3)) periods, and constraining to specific days of week, wind speed range, wind direction from the road and traffic volume range, roadside carbon monoxide, black carbon, total particle number count (20-200 nm), and accumulation mode particle number count (100-200 nm) increased by 65%, 146%, 58%, and 366%, respectively, when biomass smoke was indicated. Meanwhile, ultrafine particles (20-100 nm) decreased by 35%. This episode indicates that the presence of aged wildfire smoke may interact with freshly emitted ultrafine particles, resulting in a decrease of particles in the ultrafine mode.

A decision analytic approach to exposure-based chemical prioritization.

The manufacture of novel synthetic chemicals has increased in volume and variety, but often the environmental and health risks are not fully understood in terms of toxicity and, in particular, exposure. While efforts to assess risks have generally been effective when sufficient data are available, the hazard and exposure data necessary to assess risks adequately are unavailable for the vast majority of chemicals in commerce. The US Environmental Protection Agency has initiated the ExpoCast Program to develop tools for rapid chemical evaluation based on potential for exposure. In this context, a model is presented in which chemicals are evaluated based on inherent chemical properties and behaviorally-based usage characteristics over the chemical's life cycle. These criteria are assessed and integrated within a decision analytic framework, facilitating rapid assessment and prioritization for future targeted testing and systems modeling. A case study outlines the prioritization process using 51 chemicals. The results show a preliminary relative ranking of chemicals based on exposure potential. The strength of this approach is the ability to integrate relevant statistical and mechanistic data with expert judgment, allowing for an initial tier assessment that can further inform targeted testing and risk management strategies.

Comparison of modeling approaches to prioritize chemicals based on estimates of exposure and exposure potential.

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecological health outcomes. Recent improvements and advances such as high throughput data gathering, high performance computational capabilities, and predictive chemical inherency methodology make this an opportune time to develop an exposure-based prioritization approach that can systematically utilize and link the asymmetrical bodies of knowledge for hazard and exposure. In response to the US EPA's need to develop novel approaches and tools for rapidly prioritizing chemicals, a "Challenge" was issued to several exposure model developers to aid the understanding of current systems in a broader sense and to assist the US EPA's effort to develop an approach comparable to other international efforts. A common set of chemicals were prioritized under each current approach. The results are presented herein along with a comparative analysis of the rankings of the chemicals based on metrics of exposure potential or actual exposure estimates. The analysis illustrates the similarities and differences across the domains of information incorporated in each modeling approach. The overall findings indicate a need to reconcile exposures from diffuse, indirect sources (far-field) with exposures from directly, applied chemicals in consumer products or resulting from the presence of a chemical in a microenvironment like a home or vehicle. Additionally, the exposure scenario, including the mode of entry into the environment (i.e. through air, water or sediment) appears to be an important determinant of the level of agreement between modeling approaches.

Toward a blended ontology: applying knowledge systems to compare therapeutic and toxicological nanoscale domains.

Bionanomedicine and environmental research share need common terms and ontologies. This study applied knowledge systems, data mining, and bibliometrics used in nano-scale ADME research from 1991 to 2011. The prominence of nano-ADME in environmental research began to exceed the publication rate in medical research in 2006. That trend appears to continue as a result of the growing products in commerce using nanotechnology, that is, 5-fold growth in number of countries with nanomaterials research centers. Funding for this research virtually did not exist prior to 2002, whereas today both medical and environmental research is funded globally. Key nanoparticle research began with pharmacology and therapeutic drug-delivery and contrasting agents, but the advances have found utility in the environmental research community. As evidence ultrafine aerosols and aquatic colloids research increased 6-fold, indicating a new emphasis on environmental nanotoxicology. User-directed expert elicitation from the engineering and chemical/ADME domains can be combined with appropriate Boolean logic and queries to define the corpus of nanoparticle interest. The study combined pharmacological expertise and informatics to identify the corpus by building logical conclusions and observations. Publication records informatics can lead to an enhanced understanding the connectivity between fields, as well as overcoming the differences in ontology between the fields.

Geoengineering: An Idea Whose Time Has Come?

Some engineers and scientists recently have suggested that it would be prudent to consider engaging in geoengineering to mitigate global warming. Geoengineering differs from other methods for mitigating global warming because it involves a deliberate effort to affect the climate at a global scale. Although geoengineering is not a new idea, it has taken on added significance as a result of difficulties with implementing other proposals to mitigate climate change. While proponents of geoengineering admit that it can have significant risks for the environment and public health, many maintain that it is worth pursuing, given the failure of other means of mitigating global warming. Some environmental groups have voiced strong opposition to all forms of geoengineering. In this article, we examine arguments for and against geoengineering and discuss some policy options. We argue that specific geoengineering proposals should not be implemented until there is good evidence concerning their safety, efficacy, and feasibility, as well as a plan for oversight. International cooperation and public input should also be sought. Other methods for mitigating global warming should be aggressively pursued while geoengineering is under consideration. The promise of an engineering solution to global warming should not be used as an excuse to abandon or cut back current, climate mitigation efforts.

Reconstructing population exposures to environmental chemicals from biomarkers: challenges and opportunities.

A conceptual/computational framework for exposure reconstruction from biomarker data combined with auxiliary exposure-related data is presented, evaluated with example applications, and examined in the context of future needs and opportunities. This framework employs physiologically based toxicokinetic (PBTK) modeling in conjunction with numerical "inversion" techniques. To quantify the value of different types of exposure data "accompanying" biomarker data, a study was conducted focusing on reconstructing exposures to chlorpyrifos, from measurements of its metabolite levels in urine. The study employed biomarker data as well as supporting exposure-related information from the National Human Exposure Assessment Survey (NHEXAS), Maryland, while the MENTOR-3P system (Modeling ENvironment for TOtal Risk with Physiologically based Pharmacokinetic modeling for Populations) was used for PBTK modeling. Recently proposed, simple numerical reconstruction methods were applied in this study, in conjunction with PBTK models. Two types of reconstructions were studied using (a) just the available biomarker and supporting exposure data and (b) synthetic data developed via augmenting available observations. Reconstruction using only available data resulted in a wide range of variation in estimated exposures. Reconstruction using synthetic data facilitated evaluation of numerical inversion methods and characterization of the value of additional information, such as study-specific data that can be collected in conjunction with the biomarker data. Although the NHEXAS data set provides a significant amount of supporting exposure-related information, especially when compared to national studies such as the National Health and Nutrition Examination Survey (NHANES), this information is still not adequate for detailed reconstruction of exposures under several conditions, as demonstrated here. The analysis presented here provides a starting point for introducing improved designs for future biomonitoring studies, from the perspective of exposure reconstruction; identifies specific limitations in existing exposure reconstruction methods that can be applied to population biomarker data; and suggests potential approaches for addressing exposure reconstruction from such data.

Efficiency of sampling and analysis of asbestos fibers on filter media: implications for exposure assessment.

To measure airborne asbestos and other fibers, an air sample must represent the actual number and size of fibers. Typically, mixed cellulose ester (MCE, 0.45 or 0.8 microm pore size) and, to a much lesser extent, capillary-pore polycarbonate (PC, 0.4 microm pore size) membrane filters are used to collect airborne asbestos for count measurement and fiber size analysis. In this research study, chrysotile asbestos (fibers both shorter and longer than 5 microm) were generated in an aerosol chamber and sampled by 25 mm diameter MCE filter media to compare the fiber retention efficiency of 0.45 microm pore size filters vs. 0.8 microm pore size filter media. In addition, the effect of plasma etching times on fiber densities was evaluated. This study demonstrated a significant difference in fiber retention efficiency between 0.45 microm and 0.8 microm pore size MCE filters for asbestos aerosols (structures longer than or equal to 0.5 microm length). The fiber retention efficiency of a 0.45 microm pore size MCE filter is statistically significantly higher than that of the 0.8 microm pore size MCE filter. However, for asbestos structures longer than 5 microm, there is no statistically significant difference between the fiber retention efficiencies of the 0.45 microm and 0.8 microm pore size MCE filters. The mean density of asbestos fibers (longer than or equal to 0.5 microm) increased with etching time. Doubling the etching time increased the asbestos filter loading in this study by an average of 13%. The amount of plasma etching time had no effect on the filter loading for fibers longer than 5 microm. Many asbestos exposure risk models attribute health effects to fibers longer than 5 microm. In these models, both the 0.45 microm and 0.8 microm pore size MCE filter can produce suitable estimates of the airborne asbestos concentrations. However, some models suggest a more significant role for asbestos fibers shorter than 5 microm. Exposure monitoring for these models should consider only the 0.45 microm pore size MCE filters as recommended by the U.S. Environmental Protection Agency Asbestos Hazard Emergency Response Act (AHERA) protocol and other methods.

ISEA2007 panel: integration of better exposure characterizations into disaster preparedness for responders and the public.

An expert panel was convened in October 2007 at the International Society for Exposure Analysis Annual Meeting in Durham, NC, entitled "The Path Forward in Disaster Preparedness Since WTC-Exposure Characterization and Mitigation: Substantial Unfinished Business!" The panel prospectively discussed the critical exposure issues being overlooked during disaster responses and highlighted the needs for an optimal blending of exposure characterizations and hazard controls within disaster settings. The cases were made that effective and timely exposure characterizations must be applied during responses to any disaster, whether terrorist, manmade, or natural in origin. The consistent application of exposure sciences across acute and chronic disaster timelines will assure that the most effective strategies are applied to collect the needed information to guide risk characterization and management approaches. Exposure sciences must be effectively applied across all phases of a disaster (defined as rescue, reentry, recovery, and rehabitation-the four Rs) to appropriately characterize risks and guide risk-mitigation approaches. Failure to adequately characterize and control hazardous exposures increases the likelihood of excess morbidity and mortality. Advancing the infrastructure and the technologies to collect the right exposure information before, during, and immediately after disasters would advance our ability to define risks and protect responders and the public better. The panel provided conclusions, recommendations, and next steps toward effective and timely integration of better exposure science into disaster preparedness, including the need for a subsequent workshop to facilitate this integration. All panel presentations and a summary were uploaded to the ISES(1) website (http://www.iseaweb.org/Disaster_Preparedness/index.php).

Polycyclic aromatic hydrocarbons and other semivolatile organic compounds collected in New York City in response to the events of 9/11.

Concentrations of over 60 nonpolar semivolatile and nonvolatile organic compounds were measured in Lower Manhattan, NY, using a high-capacity integrated organic gas and particle sampler after the initial destruction of the World Trade Center (WTC). The results indicate that the remaining air plumes from the disaster site were comprised of many pollutants and classes and represent a complex mixture of biogenic (wood-smoke) and anthropogenic sources. This mixture includes compounds that are typically associated with fossil fuel emissions and their combustion products. The molecular markers for these emissions include the high molecular weight PAHs, the n-alkanes, a Carbon Preference Index approximately 1 (odd carbon:even carbon approximately 1), as well as pristane and phytane as specific markers for fuel oil degradation. These results are not unexpected considering the large number of diesel generators and outsized vehicles used in the removal phases. The resulting air plume would also include emissions of burning and remnant materials from the WTC site. Only a small number of molecular markers for these emissions have been identified such as retene and 1,4a-dimethyl-7-(methylethyl)-1,2,3,4,9,10,10a,4a-octahydrophenanthrene that are typically biogenic in origin. In addition, the compound 1,3-diphenylpropane[1',1'-(1,3-propanediyl)bis-benzene] was observed, and to our knowledge, this species has not previously been reported from ambient sampling. It has been associated with polystyrene and other plastics, which are in abundance at the WTC site. These emissions lasted for at least 3 weeks (September 26-October 21, 2001) after the initial destruction of the WTC.