Zürich II Statement on Per- and Polyfluoroalkyl Substances (PFASs): Scientific and Regulatory Needs.

Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic organic chemicals of global concern. A group of 36 scientists and regulators from 18 countries held a hybrid workshop in 2022 in Zürich, Switzerland. The workshop, a sequel to a previous Zürich workshop held in 2017, deliberated on progress in the last five years and discussed further needs for cooperative scientific research and regulatory action on PFASs. This review reflects discussion and insights gained during and after this workshop and summarizes key signs of progress in science and policy, ongoing critical issues to be addressed, and possible ways forward. Some key take home messages include: 1) understanding of human health effects continues to develop dramatically, 2) regulatory guidelines continue to drop, 3) better understanding of emissions and contamination levels is needed in more parts of the world, 4) analytical methods, while improving, still only cover around 50 PFASs, and 5) discussions of how to group PFASs for regulation (including subgroupings) have gathered momentum with several jurisdictions proposing restricting a large proportion of PFAS uses. It was concluded that more multi-group exchanges are needed in the future and that there should be a greater diversity of participants at future workshops.

Translating community-based participatory research into broadscale sociopolitical change: insights from a coalition of women firefighters, scientists, and environmental health advocates.

BACKGROUND: We report on community-based participatory research (CBPR) initiated by women firefighters in order to share successful elements that can be instructive for other community-engaged research. This CBPR initiative, known as the Women Worker Biomonitoring Collaborative (WWBC) is the first we are aware of to investigate links between occupational exposures and health outcomes, including breast cancer, for a cohort of exclusively women firefighters. METHODS: In order to be reflective of the experiences and knowledge of those most intimately involved, this article is co-authored by leaders of the research initiative. We collected leaders' input via recorded meeting sessions, emails, and a shared online document. We also conducted interviews (N = 10) with key research participants and community leaders to include additional perspectives. RESULTS: Factors contributing to the initiative's success in enacting broadscale social change and advancing scientific knowledge include (1) forming a diverse coalition of impacted community leaders, labor unions, scientists, and advocacy organizations, (2) focusing on impacts at multiple scales of action and nurturing different, yet mutually supportive, goals among partners, (3) adopting innovative communication strategies for study participants, research partners, and the broader community, (4) cultivating a prevention-based ethos in the scientific research, including taking early action to reduce community exposures based on existing evidence of harm, and (5) emphasizing co-learning through all the study stages. Furthermore, we discuss external factors that contribute to success, including funding programs that elevate scientist-community-advocacy partnerships and allow flexibility to respond to emerging science-policy opportunities, as well as institutional structures responsive to worker concerns. CONCLUSIONS: While WWBC shares characteristics with other successful CBPR partnerships, it also advances approaches that increase the ability for CBPR to translate into change at multiple levels. This includes incorporating partners with particular skills and resources beyond the traditional researcher-community partnerships that are the focus of much CBPR practice and scholarly attention, and designing studies so they support community action in the initial stages of research. Moreover, we emphasize external structural factors that can be critical for CBPR success. This demonstrates the importance of critically examining and advocating for institutional factors that better support this research.

A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a "safe" or "no-risk" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment.

A key element of risk assessment is accounting for the full range of variability in response to environmental exposures. Default dose-response methods typically assume a 10-fold difference in response to chemical exposures between average (healthy) and susceptible humans, despite evidence of wider variability. Experts and authoritative bodies support using advanced techniques to better account for human variability due to factors such as in utero or early life exposure and exposure to multiple environmental, social, and economic stressors.This review describes: 1) sources of human variability and susceptibility in dose-response assessment, 2) existing US frameworks for addressing response variability in risk assessment; 3) key scientific inadequacies necessitating updated methods; 4) improved approaches and opportunities for better use of science; and 5) specific and quantitative recommendations to address evidence and policy needs.Current default adjustment factors do not sufficiently capture human variability in dose-response and thus are inadequate to protect the entire population. Susceptible groups are not appropriately protected under current regulatory guidelines. Emerging tools and data sources that better account for human variability and susceptibility include probabilistic methods, genetically diverse in vivo and in vitro models, and the use of human data to capture underlying risk and/or assess combined effects from chemical and non-chemical stressors.We recommend using updated methods and data to improve consideration of human variability and susceptibility in risk assessment, including the use of increased default human variability factors and separate adjustment factors for capturing age/life stage of development and exposure to multiple chemical and non-chemical stressors. Updated methods would result in greater transparency and protection for susceptible groups, including children, infants, people who are pregnant or nursing, people with disabilities, and those burdened by additional environmental exposures and/or social factors such as poverty and racism.

Presumptive Contamination: A New Approach to PFAS Contamination Based on Likely Sources.

While research and regulatory attention to per- and polyfluoroalkyl substances (PFAS) has increased exponentially in recent years, data are uneven and incomplete about the scale, scope, and severity of PFAS releases and resulting contamination in the United States. This paper argues that in the absence of high-quality testing data, PFAS contamination can be presumed around three types of facilities: (1) fluorinated aqueous film-forming foam (AFFF) discharge sites, (2) certain industrial facilities, and (3) sites related to PFAS-containing waste. While data are incomplete on all three types of presumptive PFAS contamination sites, we integrate available geocoded, nationwide data sets into a single map of presumptive contamination sites in the United States, identifying 57,412 sites of presumptive PFAS contamination: 49,145 industrial facilities, 4,255 wastewater treatment plants, 3,493 current or former military sites, and 519 major airports. This conceptual approach allows governments, industries, and communities to rapidly and systematically identify potential exposure sources.

Information Requirements under the Essential-Use Concept: PFAS Case Studies.

Per- and polyfluoroalkyl substances (PFAS) are a class of substances for which there are widespread concerns about their extreme persistence in combination with toxic effects. It has been argued that PFAS should only be employed in those uses that are necessary for health or safety or are critical for the functioning of society and where no alternatives are available ("essential-use concept"). Implementing the essential-use concept requires a sufficient understanding of the current uses of PFAS and of the availability, suitability, and hazardous properties of alternatives. To illustrate the information requirements under the essential-use concept, we investigate seven different PFAS uses, three in consumer products and four industrial applications. We investigate how much information is available on the types and functions of PFAS in these uses, how much information is available on alternatives, their performance and hazardous properties and, finally, whether this information is sufficient as a basis for deciding on the essentiality of a PFAS use. The results show (i) the uses of PFAS are highly diverse and information on alternatives is often limited or lacking; (ii) PFAS in consumer products often are relatively easy to replace; (iii) PFAS uses in industrial processes can be highly complex and a thorough evaluation of the technical function of each PFAS and of the suitability of alternatives is needed; (iv) more coordination among PFAS manufacturers, manufacturers of alternatives to PFAS, users of these materials, government authorities, and other stakeholders is needed to make the process of phasing out PFAS more transparent and coherent.

Addressing Urgent Questions for PFAS in the 21st Century.

Despite decades of research on per- and polyfluoroalkyl substances (PFAS), fundamental obstacles remain to addressing worldwide contamination by these chemicals and their associated impacts on environmental quality and health. Here, we propose six urgent questions relevant to science, technology, and policy that must be tackled to address the "PFAS problem": (1) What are the global production volumes of PFAS, and where are PFAS used? (2) Where are the unknown PFAS hotspots in the environment? (3) How can we make measuring PFAS globally accessible? (4) How can we safely manage PFAS-containing waste? (5) How do we understand and describe the health effects of PFAS exposure? (6) Who pays the costs of PFAS contamination? The importance of each question and barriers to progress are briefly described, and several potential paths forward are proposed. Given the diversity of PFAS and their uses, the extreme persistence of most PFAS, the striking ongoing lack of fundamental information, and the inequity of the health and environmental impacts from PFAS contamination, there is a need for scientific and regulatory communities to work together, with cooperation from PFAS-related industries, to fill in critical data gaps and protect human health and the environment.

Finding essentiality feasible: common questions and misinterpretations concerning the "essential-use" concept.

The essential-use concept is a tool that can guide the phase-out of per- and polyfluoroalkyl substances (PFAS) and potentially other substances of concern. This concept is a novel approach to chemicals management that determines whether using substances of concern, such as PFAS, is truly essential for a given functionality. To assess the essentiality of a particular use case, three considerations need to be addressed: (1) the function (chemical, end use and service) that the chemical provides in the use case, (2) whether the function is necessary for health and safety and critical for the functioning of society and (3) if the function is necessary, whether there are viable alternatives for the chemical for this particular use. A few illustrative examples of the three-step process are provided for use cases of PFAS. The essential-use concept takes chemicals management away from a substance-by-substance approach to a group approach. For PFAS and other substances of concern, it offers a more rapid pathway toward effective management or phase-out. Parts of the concept of essential use have already been widely applied in global treaties and international regulations and it has also been recently used by product manufacturers and retailers to phase out substances of concern from supply chains. Herein some of the common questions and misinterpretations regarding the practical application of the essential-use concept are reviewed, and answers and further clarifications are provided.