A Hazard-Based Framework for Identifying Safer Alternatives to Classes of Chemicals: A Case Study on Phthalates in Consumer Products.

BACKGROUND: Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations. OBJECTIVES: To implement the law, the Department of Ecology developed a hazard-based framework for identifying safer alternatives to classes of chemicals. METHODS: We developed a hazard-based framework, termed the "Criteria for Safer," to set a transparent bar for determining whether new chemical alternatives are safer than existing classes of chemicals. Our "Criteria for Safer" is a framework that builds on existing hazard assessment methodologies and published approaches for assessing chemicals and chemical classes. DISCUSSION: We describe implementation of our criteria using a case study on the phthalates chemical class in two categories of consumer products: vinyl flooring and fragrances used in personal care and beauty products. Additional context and considerations that guided our decision-making process are also discussed, as well as benefits and limitations of our approach. This paper gives insight into our development and implementation of a hazard-based framework to address classes of chemicals in consumer products and will aid others working to build and employ similar approaches. https://doi.org/10.1289/EHP13549.

Implementation of the polluter pay's principle in tobacco control in the UK: a stakeholder analysis.

BACKGROUND: The polluter's pay principle (PPP) aims to internalise external costs and assign liability to the polluter for the harmful cost of their products to society. Tobacco companies continue to manufacture and sell harmful cigarettes, earning billions in profits each year from these products. Meanwhile, governments and their people are left to 'clean up' and deal with the detrimental health consequences. This paper explores with expert stakeholders how the PPP could be implemented within the context of tobacco control in the United Kingdom (UK). METHODS: Twenty-four semi-structured interviews and two follow-up discussion groups were conducted with UK and international experts on tobacco control, public health, economics, or law from the academic, public, private and third sector. Participants considered the facilitators and barriers to implementing the PPP to tobacco control in the UK. Thematic analysis was employed, aided by NVivo 12, and data were compared to examine the views expressed by the different types of experts. RESULTS: Stakeholders favoured the implementation of the PPP in the context of tobacco control and indicated that it could be acceptable and feasible to implement and that it would likely have support from policymakers and the public alike. Stakeholders unanimously agreed that any legislation and administration should be free from tobacco industry influence; however, differences arose concerning who should oversee the implementation. CONCLUSION: The PPP from environmental law was predominantly seen as an approach that could be usefully applied to the tobacco industry. However, there is no one size fits all template, therefore its implementation would need to be adapted to fit the UK context.

Expert views on high fat, salt and sugar food marketing policies to tackle obesity and improve dietary behaviours in the UK: a qualitative study.

BACKGROUND: There has been a lack of progress in reducing obesity in the United Kingdom (UK) despite Government strategies released over the last 30 years. These strategies, including the most recent publication from July 2020, have focused on childhood obesity and high fat, sugar and/or salt (HFSS) marketing restrictions, particularly broadcast advertising. In this study, we aimed to examine a range of expert views on the potential impact and the relative importance of such policies. METHODS: Semi-structured interviews were conducted with 42 experts in policy (n = 19), industry (n = 10), and advocacy (n = 13) with an interest in obesity. The UK Government's 2020 obesity strategy was used as a prompt to guide discussion on policy options. Qualitative thematic analysis was employed to answer the three research questions and themes were inductively coded within each research question. Data were also cross compared using matrix coding and a form of framework analysis to examine the views expressed by the different types of stakeholders. RESULTS: Reactions to the July 2020 proposal were mixed among policy and advocacy stakeholders, while commercial stakeholders expressed disappointment. A main theme emerging in all groups was frustration with the policy process and wishing to see more clarity regarding restrictions and their implementation. There was an overall lack of trust that the government would carry out their proposed plan and agreement that a more comprehensive, multi-sector approach aimed at the underlying drivers of obesity would be most effective, with some stakeholders indicating that some of the proposed policies could make a difference if implemented robustly. On the theme of promoting healthier options, some stakeholders suggested lowering the prices of 'healthy' products and making them more accessible to combat regressivity. There was a potentially surprising level of agreement between policy/advocacy stakeholders and commercial stakeholders, although commercial stakeholders were more likely to advocate for collaboration between government and industry as well as voluntary industry measures. CONCLUSION: While HFSS marketing restrictions have a role to play and send a strong signal - provided they are implemented comprehensively - investment in these policies needs to be part of wider efforts to tackle the underlying drivers of obesity.

Youth's exposure to and engagement with e-cigarette marketing on social media: a UK focus group study.

OBJECTIVE: Electronic-cigarettes (e-cigarette) are promoted creatively through social media and considering the potential influence of social media marketing on young people, we explored young people's exposure to and engagement with social media marketing of e-cigarettes. DESIGN: Semistructured discussion groups. SUBJECTS: Twenty focus groups with 82 young people aged 11-16 living in the Central belt of Scotland. METHODS: Youths were asked about smoking and vaping behaviours, social media use, vaping advertisement exposure and were shown illustrative examples of social media content (eg, images and videos) about different messages, presentations and contextual features. Transcripts were imported into NVivo V.12, coded thematically and analysed. RESULTS: Youths highlighted a variety of tactics e-cigarette companies use, including influencer or celebrity endorsement, attractive youth flavours, bright colours and emotional appeal to advertise and promote their products directly to young people. Social media influencers who advertise e-cigarettes were described as portraying e-cigarettes as 'cool' and 'fashionable' to entice viewers to try the products. Youths considered that there is a need for more restrictions on social media content to protect youths while also still allowing smokers to purchase them as a cessation device. CONCLUSIONS: Our study highlights that the e-cigarette industry is using previously employed tactics similar to the tobacco industry to advertise and promote its products on social media. These findings suggest the growing need for governments to work together to develop and implement policies to restrict the advertising and marketing of e-cigarettes on social media.

Contextual influences on the role of evidence in e-cigarette recommendations: a multi-method analysis of international and national jurisdictions.

Background: E-cigarette policy has varied across jurisdictions, contrasting with the previous coordinated approach of international tobacco control communities. Aims and objectives: A multi-method case study approach was used to understand the role of evidence and external and internal contextual factors in the development of public health recommendations across four purposively selected jurisdictions (WHO, UK, Australia and USA). Methods: Informed by Dobrow et al.'s (2004) conceptual framework for context-based evidencebased decision-making, four data sources were drawn upon: 1) 15 public health bodies' e-cigarette recommendation documents, 2) seven development documents produced by the public health bodies, 3) sources of evidence cited in the public health bodies' recommendation documents and 4) 15 qualitative interviews with experts. Thematic analysis and citation analysis were conducted to aid triangulation of evidence. Findings: We found a complex interplay between internal and external factors which influence the role and use of evidence in the development of e-cigarette recommendations. For example, recommendation documents' remit (internal factor) was influenced by various external factors such as epidemiology and policy history, with decisions made over time having reshaped the external context. Considering the findings with respect to evidence utilisation, we propose a modified version of Dobrow et al.'s (2004) framework, highlighting the important interplay between internal and external contextual factors. Discussion and conclusion: This research suggest internal and external contextual factors mutually interact and influence how evidence is incorporated into recommendations. This dynamic interplay of contextual factors may help explain the why different policy approaches are pursued concerning public health topics, particularly e-cigarettes.

User-generated content and influencer marketing involving e-cigarettes on social media: a scoping review and content analysis of YouTube and Instagram.

BACKGROUND: Evidence suggests that experimentation with e-cigarettes among young people is increasing. Social media is widely used by young people with user-generated content and influencer marketing particularly influential in promoting products. This paper documents a snapshot of online user-generated content and influencer marketing related to e-cigarettes on YouTube and Instagram. METHODS: Scoping review of relevant e-cigarette-related content on two social media platforms popular with youths, YouTube and Instagram, between June and August 2021. Content analysis was undertaken to examine text, audio, and video content, recording age restrictions, health warnings, page characteristics, and post characteristics. Narrative post content was coded using a coding frame that was developed inductively in response to emergent categories. RESULTS: Vaping was portrayed positively on social media; of the posts analysed, 86.5% (n = 90 of 104) of Instagram posts and 66.0% (n = 64 of 97) of YouTube videos. Warnings about age restrictions and health (e.g., nicotine addiction/toxicity) did not feature in the majority of posts; 43.3% (n = 42) of YouTube videos (n = 42) contained an age warning compared to 20.2% of Instagram posts (n = 21). While 25.8% (n = 25) of YouTube videos and 21.2% of Instagram (n = 22) posts contained a health warning. CONCLUSION: Of concern is the fact that the vast majority of YouTube and Instagram content about e-cigarettes promoted their use, and typically the content does not contain age and/or health warnings. These findings may highlight a priority for governmental policy to restrict the ability of marketers to reach youths with social media content promoting e-cigarettes.

Youth's engagement and perceptions of disposable e-cigarettes: a UK focus group study.

OBJECTIVES: Evidence suggests that use of flavoured disposable electronic cigarettes (e-cigarettes) is increasing. Considering the growing popularity and rapid evolution of e-cigarettes, we explored youth's perceptions and engagement with disposable e-cigarettes. DESIGN: Twenty focus groups were conducted between March and May 2022, with 82 youths aged 11-16 living in the Central belt of Scotland. METHODS: Youths were asked about smoking and vaping behaviours and disposable e-cigarettes and were shown vaping-related images and videos from social media which were used to stimulate discussion about different messages, presentations and contextual features. Transcripts were imported into NVivo V.12, coded thematically, and analysed. RESULTS: Youths described disposable e-cigarettes as 'cool', 'fashionable' and enticing and viewed as a modern lifestyle 'accessory'. Tank models were perceived as being used by older adults. Youths stated that disposable e-cigarettes were designed in a way to target youths and the brightly coloured devices and range of flavourings encouraged youths to want to try the products, particularly sweet flavourings. Participants perceived e-cigarettes to be less harmful compared with combustible cigarettes but noted the uncertainty of ingredients in disposable e-cigarettes. CONCLUSIONS: Youths distinguish between e-cigarettes with varying characteristics and social perceptions of users. These findings provide evidence that disposable e-cigarettes are attractive to youths. Future research is needed to understand the factors that contribute to youth perceptions of disposable e-cigarettes. Policymakers should work together to design and implement policies and strategies to prevent youth uptake of vaping.

Alteration of oral microbiome composition in children living with pesticide-exposed farm workers.

Our prior work shows that azinphos-methyl pesticide exposure is associated with altered oral microbiomes in exposed farmworkers. Here we extend this analysis to show the same association pattern is also evident in their children. Oral buccal swab samples were analyzed at two time points, the apple thinning season in spring-summer 2005 for 78 children and 101 adults and the non-spray season in winter 2006 for 62 children and 82 adults. The pesticide exposure for the children were defined by the farmworker occupation of the cohabitating household adult and the blood azinphos-methyl detection of the cohabitating adult. Oral buccal swab 16S rRNA sequencing determined taxonomic microbiota proportional composition from concurrent samples from both adults and children. Analysis of the identified bacteria showed significant proportional changes for 12 of 23 common oral microbiome genera in association with azinphos-methyl detection and farmworker occupation. The most common significantly altered genera had reductions in the abundance of Streptococcus, suggesting an anti-microbial effect of the pesticide. Principal component analysis of the microbiome identified two primary clusters, with association of principal component 1 to azinphos-methyl blood detection and farmworker occupational status of the household. The children's buccal microbiota composition clustered with their household adult in ∼95% of the households. Household adult farmworker occupation and household pesticide exposure is associated with significant alterations in their children's oral microbiome composition. This suggests that parental occupational exposure and pesticide take-home exposure pathways elicit alteration of their children's microbiomes.

Experts' views on how to design a tobacco control fund in the UK.

OBJECTIVE: To explore expert views on the potential value, and approaches to establishing and administering a tobacco control fund in the UK. DESIGN: Semistructured interviews and follow-up discussion groups. SUBJECTS: Twenty-four UK and international experts on tobacco control regulation, public health, economics or law from the academic, public, private and third sector. METHODS: Participants considered the relative merit of (1) general excise tax on retail tobacco sales; (2) ring-fenced hypothecation of excise taxes on retail tobacco sales; and (3) a direct levy on tobacco manufacturers. Preliminary synthesis of interview findings was deliberated on in two follow-up discussion groups to identify key considerations for policy design. RESULT: Most experts agreed that a ring-fenced tobacco control fund would be a valuable method of raising predictable and reliable funds from tobacco producers either using either companies' sales volume or market share as a way to establish the proportion they should pay. Experts predominantly recommended that a fund in the UK should be administered by a government body with devolved nation input and with an independent advisory group. They typically indicated that funding should be allocated yearly with a distribution at local, regional and national levels to support smoking prevention and cessation rather than treatment activities with priority given to measures that tackle smoking-related inequalities. CONCLUSION: There was overwhelming agreement by experts on the need to establish a tobacco control fund to help meet the proposed government tobacco-free targets to reduce adult smoking prevalence to 5% by 2030 (England) and 2034 (Scotland).

Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.

The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, WDR5, RbBp5, Ash2L, and DPY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex.

Development processes for e-cigarette public health recommendations lacked transparency in managing conflicts of interest.

OBJECTIVES: To investigate how guideline development groups collect and manage conflicts of interest (COI) when producing electronic cigarette (e-cigarette) recommendations. STUDY DESIGN AND SETTING: Public health bodies that had produced e-cigarette recommendations were identified from four purposively selected jurisdictions (World Health Organization, United Kingdom, Australia, and United States). We analysed their COI policies and conducted 15 interviews with guideline methodologists, policymakers, and academics in guideline development groups. RESULTS: Only five of 10 public health bodies had a publicly available COI policy. Participants discussed the importance of those involved in the development process declaring COI. However, there were differences in who had to report COI, the time period asked about, and what and how declarations are made. COI policies and participants discussed a range of approaches for managing COI, from limiting involvement to disqualification from the recommendation development process. Participants considered the current processes for collecting and managing COI insufficient due to their open interpretation and possibility for partial declarations of interest. CONCLUSION: The management of COI varies across public health bodies, with little standardization and lack of transparency. To improve the collection and management of COI, and ultimately increase the trustworthiness of recommendations, guideline development groups should draw upon a comprehensive and accessible COI policy.

Evaluation of two collocated federal equivalent method PM2.5 instruments over a wide range of concentrations in Sarajevo, Bosnia and Herzegovina.

Two widely used PM2.5 monitors in the United States (U.S.) designated as federal equivalent methods (FEMs) by the U.S. Environmental Protection Agency were collocated for 15 months in Sarajevo, Bosnia and Herzegovina (BiH) to evaluate their comparability. With differing measurement principles, the FEMs (Met One BAM-1020 and Teledyne API T640) exhibited unique responses to the significant range in PM2.5 over the study period. During the winter months when concentrations greatly increased (e.g., daily PM2.5 > 100 µg m-3), the BAM-1020 had intermittent malfunctioning nozzle contact to the collection tape, resulting in periods of data invalidation. Increased operator observation and doubling the cleaning frequency were required to maintain proper operation. The hourly data from the BAM-1020, which detects PM2.5 via beta-attenuation of particles loaded to the collection tape, indicated higher noise at concentrations below 40 µg m-3 relative to the T640, which detects PM2.5 via an optical method. Above this concentration threshold, the two instruments appear to have comparable hourly fluctuations in the data. Relative to the BAM-1020, the T640 reported higher concentrations when PM2.5 is above 80 µg m-3. A linear regression equation was developed and applied to adjust T640 PM2.5 high concentration values, resulting in 24-hr average T640adj PM2.5 values closely matching that from the BAM-1020 for the full concentration range. Based on the T640adj values, the annual average for Sarajevo was calculated at the site to be 42 µg m-3, with significant seasonality resulting in over 7-fold higher concentrations in the months of December-January compared to June-July.

Examining the sources of evidence in e-cigarette policy recommendations: A citation network analysis of international public health recommendations.

BACKGROUND: Public health policies and recommendations aim to be informed by the best available evidence. Evidence underpinning e-cigarettes policy recommendations has been necessarily limited due to the novelty of the technology and the lack of long-term epidemiological studies and trials. Some public health bodies have actively encouraged e-cigarette use whilst others have raised concerns over introducing new health risks and renormalising tobacco smoking. Using citation network analysis we investigated the author conflicts of interest and study funding statements within sources of evidence used by public health bodies when making recommendations about e-cigarette policy. METHODS: We conducted citation network analysis of public health recommendation documents across four purposively selected diverse jurisdictions: WHO, UK, Australia, and USA. We extracted all citations from 15 public health recommendation documents, with more detailed data collected for influential citations (used in 3+ recommendation documents). We analysed the relationships between the sources of evidence used across jurisdictions using block modelling to determine if similar groups of documents were used across different jurisdictions. We assessed the frequency and nature of conflicts of interest. RESULTS: 1700 unique citations were included across the 15 public health recommendation documents, with zero to 923 citations per document (median = 63, IQR = 7.5-132). The evidence base underpinning public health recommendations did not systematically differ across jurisdictions. Of the 1700 citations included, the majority were journal articles (n = 1179). Across 1081 journal articles published between 1998-2018, 200 declared a conflict of interest, 288 contained no mention of conflicts of interest, and 593 declared none. Conflicts of interest were reported with tobacco (3%; n = 37 journal articles of 1081), e-cigarette (7%; n = 72), and pharmaceutical companies (12%; n = 127), with such conflicts present even in the most recent years. There were 53 influential citations, the most common study type was basic science research without human subjects (e.g. examination of aerosols and e-liquids) (n = 18) followed by systematic review (n = 10); with randomised control trial being least common (n = 4). Network analysis identified clusters of highly-cited articles with a higher prevalence of conflicts of interest. CONCLUSION: Public health bodies across different jurisdictions drew upon similar sources of evidence, despite articulating different policy approaches to e-cigarettes. The evidence drawn upon, including the most influential evidence, contained substantial conflicts of interest (including relationships with e-cigarette and tobacco industries). Processes to explicitly manage conflicts of interest arising from the underlying evidence base may be required when developing public health recommendations.

Recommendations for Assessment of Environmental Exposures in Longitudinal Life Course Studies Such as the National Children's Study.

An important step toward understanding the relationship between the environment and child health and development is the comprehensive cataloging of external environmental factors that may modify health and development over the life course. Our understanding of the environmental influences on health is growing increasingly complex. Significant key questions exist as to what genes, environment, and life stage mean to defining normal variations and altered developmental trajectories throughout the life course and also across generations. With the rapid advances in genetic technology came large-scale genomic studies to search for the genetic etiology of complex diseases. While genome-wide association studies (GWAS) have revealed genetic factors and networks that advance our understanding to some extent, it is increasingly recognized that disease causation is largely non-genetic and reflects interactions between an individual's genetic susceptibility and his or her environment. Thus, the full promise of the human genome project to prevent or treat disease and promote good health arguably depends on a commitment to understanding the interactions between our environment and our genetic makeup and requires a design with prospective environmental data collection that considers critical windows of susceptibility that likely correspond to the expression of specific genes and gene pathways. Unlike the genome, which is static, relevant exposures as well as our response to exposures, change over time. This has fostered the complementary concept of the exposome ideally defined as the measure of all exposures of an individual over a lifetime and how those exposures relate to health. The exposome framework considers multiple external exposures (e.g., chemical, social) and behaviors that may modify exposures (e.g., diet), as well as consequences of environmental exposures indexed via biomarkers of physiological response or measures of behavioral response throughout the lifespan. The exposome concept can be applied in prospective developmental studies such as the National Children's Study (NCS) with the practical understanding that even a partial characterization will bring major advances to health. Lessons learned from the NCS provide an important opportunity to inform future studies that can leverage these evolving paradigms in elucidating the role of environment on health across the life course.

Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1.

Poly-ADP-ribosyltransferases play a critical role in DNA repair and cell death, and poly(ADP-ribosyl) polymerase 1 (PARP1) is a particularly important therapeutic target for the treatment of breast cancer because of its synthetic lethal relationship with breast cancer susceptibility proteins 1 and 2. Numerous PARP1 inhibitors have been developed, and their efficacy in cancer treatment is attributed to both the inhibition of enzymatic activity and their ability to trap PARP1 on to the damaged DNA, which is cytotoxic. Of the clinical PARP inhibitors, talazoparib is the most effective at trapping PARP1 on damaged DNA. Biochemically, talazoparib is also suspected to be a potent inhibitor of PARP5a/b (tankyrase1/2 [TNKS1/2]), which is an important regulator of Wnt/ß-catenin pathway. Here we show using competition experiments in cell lysate that, at a clinically relevant concentration, talazoparib can potentially bind and engage TNKS1. Using surface plasmon resonance, we measured the dissociation constants of talazoparib, olaparib, niraparib, and veliparib for their interaction with PARP1 and TNKS1. The results show that talazoparib has strong affinity for PARP1 as well as uniquely strong affinity for TNKS1. Finally, we used crystallography and hydrogen deuterium exchange mass spectroscopy to dissect the molecular mechanism of differential selectivity of these PARP1 inhibitors. From these data, we conclude that subtle differences between the ligand-binding sites of PARP1 and TNKS1, differences in the electrostatic nature of the ligands, protein dynamics, and ligand conformational energetics contribute to the different pharmacology of these PARP1 inhibitors. These results will help in the design of drugs to treat Wnt/ß-catenin pathway-related cancers, such as colorectal cancers.

Parenting with a disability: exploring the satisfaction and efficacy of the PediaLift wheelchair accessible crib.

PURPOSE: Parents with disabilities face many challenges in fulfilling their daily roles. Previous literature has shown that assistive technology (AT) can be a viable solution to help an individual with a disability participate in everyday roles. Although AT can increase ability of parents with disabilities to care for their children, there are many barriers that prevent them from getting the AT that they need. Some of these barriers include a lack of training and awareness by healthcare providers regarding AT options, a lack of rehabilitation therapists' feeling they are competent to provide AT options for their clients. and funding barriers. One issue that impacts the ability to get funding for AT is the lack of research supporting the efficacy of the technology. An AT device specifically designed for parents with disabilities is an adaptive crib called PediaLift. Health insurance companies are resistant to funding the PediaLift stating that there is no evidence in the literature to support its efficacy. MATERIALS AND METHODS: In this study, we investigated the efficacy of the Pedialift crib by using the Quebec User Evaluation of Satisfaction with Assistive Technology 2.0 (QUEST 2.0) survey and the Canadian Occupational Performance Measure (COPM) with individuals who have already purchased and used the device. RESULTS: Findings revealed that overall users were satisfied with the device and services provided. CONCLUSION: Participants were more able to participate in the role of parenting after obtaining the Pedialift.

Regulation of Persistent Chemicals in Hazardous Waste: A Case Study of Washington State, USA.

Despite ongoing controversy, several strategic frameworks for defining chemicals of concern (e.g., persistent, bioaccumulative, toxic [PBT]; persistent, mobile, toxic [PMT]; persistent organic pollutant [POP]) share persistence as a key criterion. Persistence should be considered over the entire chemical life cycle from production to disposal, including hazardous waste management. As a case study, we evaluate persistence criteria in hazardous waste regulations in Washington state, USA, illustrate impacts on reported waste, and propose refinements in these criteria. Although Washington state defines persistence based on half-life (>1 y) and specific chemical groups that exceed summed concentration thresholds in waste (i.e., >0.01% halogenated organic compounds [HOCs] and >1.0% polycyclic aromatic hydrocarbons [PAHs]), persistence is typically addressed with HOC and PAH evaluation but seldom with half-life estimation. Notably, persistence is considered (with no specific criteria) in corresponding federal regulations in the United States (Resource Conservation and Recovery Act). Consequently, businesses in Washington state report annual amounts of state hazardous waste (including persistent waste) separately from federal hazardous waste. Total state-only waste, and total state and federal waste combined, nearly doubled (by weight) from 2008 to 2018. For the period 2016 to 2018, persistence criteria captured 17% of state-only waste and 2% of total state and federal waste combined. Two recommendations are proposed to improve persistence criteria in hazardous waste regulations. First, Washington state should consider aligning its half-life criterion with federal and European Union PBT definitions (e.g., 60-120 d) for consistency and provide specific methods for half-life estimation. Second, the state should consider expanding its list of persistent chemical groups (e.g., siloxanes, organometallics) with protective concentration thresholds. Ultimately, to the extent possible, Washington state should strive toward harmonizing persistence in hazardous waste regulations with corresponding criteria in global PBT, PMT, and POP frameworks. Integr Environ Assess Manag 2021;17:455-464. © 2020 SETAC.

Molecular Topology of RNA Polymerase I Upstream Activation Factor.

Upstream activation factor (UAF) is a multifunctional transcription factor in Saccharomyces cerevisiae that plays dual roles in activating RNA polymerase I (Pol I) transcription and repression of Pol II. For Pol I, UAF binds to a specific upstream element in the ribosomal DNA (rDNA) promoter and interacts with two other Pol I initiation factors, the TATA-binding protein (TBP) and core factor (CF). We used an integrated combination of chemical cross-linking mass spectrometry (CXMS), molecular genetics, protein biochemistry, and structural modeling to understand the topological framework responsible for UAF complex formation. Here, we report the molecular topology of the UAF complex, describe new structural and functional domains that play roles in UAF complex integrity, assembly, and biological function, and provide roles for previously identified UAF domains that include the Rrn5 SANT and histone fold domains. We highlight the role of new domains in Uaf30 that include an N-terminal winged helix domain and a disordered tethering domain as well as a BORCS6-like domain found in Rrn9. Together, our results reveal a unique network of topological features that coalesce around a histone tetramer-like core to form the dual-function UAF complex.

Characterizing the Neurodevelopmental Pesticide Exposome in a Children's Agricultural Cohort.

The exposome provides a conceptual model for identifying and characterizing lifetime environmental exposures and resultant health effects. In this study, we applied key exposome concepts to look specifically at the neurodevelopmental pesticide exposome, which focuses on exposures to pesticides that have the potential to cause an adverse neurodevelopmental impact. Using household dust samples from a children's agricultural cohort located in the Yakima Valley of Washington state, we identified 87 individual pesticides using liquid chromatography-tandem mass spectrometry. A total of 47 of these have evidence of neurotoxicity included in the Environmental Protection Agency (EPA) (re)registration materials. We used a mixed effects model to model trends in pesticide exposure. Over the two study years (2005 and 2011), we demonstrate a significant decrease in the neurodevelopmental pesticide exposome across the cohort, but particularly among farmworker households. Additional analysis with a non-parametric binomial analysis that weighted the levels of potentially neurotoxic pesticides detected in household dust by their reference doses revealed that the decrease in potentially neurotoxic pesticides was largely a result of decreases in some of the most potent neurotoxicants. Overall, this study provides evidence that the neurodevelopmental pesticide exposome framework is a useful tool in assessing the effectiveness of specific interventions in reducing exposure as well as setting priorities for future targeted actions.