Use of Portable Air Cleaners in Washington State Schools: A Qualitative Analysis Based on the Technology Acceptance Model.

BACKGROUND: The US government allocated over $2.5 billion in "Elementary and Secondary School Emergency Relief (ESSER)" funds to Washington State for COVID-19 response and ventilation improvements. Despite available funding, gaps persist in supporting schools to successfully use portable air cleaners (PACs). We evaluated PAC needs within King County, Washington and characterized factors influencing schools' purchase and use of PACs. METHODS: Public Health-Seattle & King County (PHSKC) assessed school's ventilation systems and IAQ improvements through a survey (N = 17). Separately, semi-structured interviews (N = 13) based on the technology acceptance model (TAM) were conducted with school personnel. A thematic analysis using inductive and deductive coding was conducted and logistic regression models assessed the predictive capability of the TAM. RESULTS: The PHSKC survey findings informed our recommendations. Positive attitudes, knowledge, and beliefs in ease of use and effectiveness of PACs were facilitators to PAC use. While barriers included a lack of training, education, and concerns about PAC maintenance and sustainability. TAM constructs of perceived usefulness (PU) and perceived ease of use (PEU) were predictive of having the intention to use PACs in schools. CONCLUSIONS: There is a critical need for solutions to circumvent challenges to implementing PACs in schools. This characterization provides insight for promoting PAC use in IAQ-impacted schools.

Assessing the effectiveness of portable HEPA air cleaners for reducing particulate matter exposure in King County, Washington homeless shelters: Implications for community congregate settings.

Over four thousand portable air cleaners (PACs) with high-efficiency particulate air (HEPA) filters were distributed by Public Health - Seattle & King County to homeless shelters during the COVID-19 pandemic. This study aimed to evaluate the real-world effectiveness of these HEPA PACs in reducing indoor particles and understand the factors that affect their use in homeless shelters. Four rooms across three homeless shelters with varying geographic locations and operating conditions were enrolled in this study. At each shelter, multiple PACs were deployed based on the room volume and PAC's clean air delivery rate rating. The energy consumption of these PACs was measured using energy data loggers at 1-min intervals to allow tracking of their use and fan speed for three two-week sampling rounds, separated by single-week gaps, between February and April 2022. Total optical particle number concentration (OPNC) was measured at 2-min intervals at multiple indoor locations and an outdoor ambient location. The empirical indoor and outdoor total OPNC were compared for each site. Additionally, linear mixed-effects regression models (LMERs) were used to assess the relationship between PAC use time and indoor/outdoor total OPNC ratios (I/OOPNC). Based on the LMER models, a 10 % increase in the hourly, daily, and total time PACs were used significantly reduced I/OOPNC by 0.034 [95 % CI: 0.028, 0.040; p < 0.001], 0.051 [95 % CI: 0.020, 0.078; p < 0.001], and 0.252 [95 % CI: 0.150, 0.328; p < 0.001], respectively, indicating that keeping PACs on resulted in significantly lower I/OOPNC. The survey suggested that keeping PACs on and running was the main challenge when operating them in shelters. These findings suggested that HEPA PACs were an effective short-term strategy to reduce indoor particle levels in community congregate living settings during non-wildfire seasons and the need for formulating practical guidance for using them in such an environment.

Lead Poisoning From Home-Prepared Indian Spices in 3 Families.

Spice consumption, along with other environmental factors, can contribute to pediatric lead poisoning. Although public health efforts have increased awareness of contamination of spices, false assumptions regarding the safety of home-prepared spices have emerged. Here, we present the clinical features, family beliefs, and environmental toxicology of 3 spice-associated pediatric lead poisoning cases.

Update on Activities in Endocrine Disruptor Research and Policy.

For nearly 15 years, the Endocrine Society has engaged in a coordinated effort to engage the issue of endocrine-disrupting chemicals (EDCs). This effort is based on an effective collaboration between scientists and physician members of the Endocrine Society and a competent and professional staff that supports membership efforts to study EDC actions and translate this knowledge to regulatory agencies. This is a brief history of these important efforts to inform the broad readership of Endocrinology.

Correction to: Organochlorine Chemical Residues in Northern Cardinal (Cardinalis cardinalis) Eggs from Greater Washington, DC USA.

The original version of this article contained a mistake. Author name in the text citation and reference in section should be Maldonado et al (2016), it was incorrectly spelled as Maldinado et al (2015).

Organochlorine Chemical Residues in Northern Cardinal (Cardinalis cardinalis) Eggs from Greater Washington, DC USA.

Northern Cardinal eggs from six neighborhoods near Washington DC were analyzed for organochlorine pesticides and PCBs. All compounds were detected more frequently and at higher concentrations in more heavily urbanized neighborhoods. DDT (mostly as p,p'-DDE) was detected in all neighborhoods. p,p'-DDT was typically 0.5‒16 ng/g (ww) in most suburban neighborhoods but was not detected (< 0.1 ng/g) in more rural areas; however, p,p'-DDT was 127‒1130 ng/g in eggs from two suburban Maryland nests and comprised 65.7% of total p,p'-DDT isomers in the most contaminated sample, indicating recent exposure to un-weathered DDT. Total chlordane (sum of 5 compounds) was 2‒70 ng/g; concentrations were greatest in older suburban neighborhoods. Total PCB (sum of detected congeners) was < 5‒21 ng/g. Congener patterns were similar in all neighborhoods and resembled those typical of weathered mixtures. Results indicate that wildlife remains exposed to low concentrations of legacy contaminants in suburban neighborhoods and that cardinal eggs can be used to monitor localized contamination.

Endocrine profiling and prioritization of environmental chemicals using ToxCast data.

BACKGROUND: The prioritization of chemicals for toxicity testing is a primary goal of the U.S. Environmental Protection Agency (EPA) ToxCast™ program. Phase I of ToxCast used a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxicity is endocrine disruption, and the U.S. EPA's Endocrine Disruptor Screening Program (EDSP) has been charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife. OBJECTIVE: The goal of this study was to develop a flexible method to facilitate the rational prioritization of chemicals for further evaluation and demonstrate its application as a candidate decision-support tool for EDSP. METHODS: Focusing on estrogen, androgen, and thyroid pathways, we defined putative endocrine profiles and derived a relative rank or score for the entire ToxCast library of 309 unique chemicals. Effects on other nuclear receptors and xenobiotic metabolizing enzymes were also considered, as were pertinent chemical descriptors and pathways relevant to endocrine-mediated signaling. RESULTS: Combining multiple data sources into an overall, weight-of-evidence Toxicological Priority Index (ToxPi) score for prioritizing further chemical testing resulted in more robust conclusions than any single data source taken alone. CONCLUSIONS: Incorporating data from in vitro assays, chemical descriptors, and biological pathways in this prioritization schema provided a flexible, comprehensive visualization and ranking of each chemical's potential endocrine activity. Importantly, ToxPi profiles provide a transparent visualization of the relative contribution of all information sources to an overall priority ranking. The method developed here is readily adaptable to diverse chemical prioritization tasks.

Assessment of a robust model protocol with accelerated throughput for a human recombinant full length estrogen receptor-alpha binding assay: protocol optimization and intralaboratory assay performance as initial steps towards validation.

Despite about two decades of research in the field of endocrine active compounds, still no validated human recombinant (hr) estrogen receptor-alpha (ERalpha) binding assay is available, although hr-ERalpha is available from several sources. In a joint effort, US EPA and Bayer Schering Pharma with funding from the EU-sponsored 6th framework project, ReProTect, developed a model protocol for such a binding assay. Important features of this assay are the use of a full length hr-ERalpha and performance in a 96-well plate format. A full length hr-ERalpha was chosen, as it was considered to provide the most accurate and human-relevant results, whereas truncated receptors could perform differently. Besides three reference compounds [17beta-estradiol, norethynodrel, dibutylphthalate] nine test compounds with different affinities for the ERalpha [diethylstilbestrol (DES), ethynylestradiol, meso-hexestrol, equol, genistein, o,p'-DDT, nonylphenol, n-butylparaben, and corticosterone] were used to explore the performance of the assay. Three independent experiments per compound were performed on different days, and dilutions of test compounds from deep-frozen stocks, solutions of radiolabeled ligand and receptor preparation were freshly prepared for each experiment. The ERalpha binding properties of reference and test compounds were well detected. As expected dibutylphthalate and corticosterone were non-binders in this assay. In terms of the relative ranking of binding affinities, there was good agreement with published data obtained from experiments using a human recombinant ERalpha ligand binding domain. Irrespective of the chemical nature of the compound, individual IC(50)-values for a given compound varied by not more than a factor of 2.5. Our data demonstrate that the assay was robust and reliably ranked compounds with strong, weak, and no affinity for the ERalpha with high accuracy. It avoids the manipulation and use of animals, i.e., the preparation of uterine cytosol as receptor source from ovariectomized rats, as a recombinant protein is used and thus contributes to the 3R concept (reduce, replace, and refine). Furthermore, in contrast to other assays, this assay could be adjusted to an intermediate/high throughput format. On the whole, this assay is a promising candidate for further validation.

The toxicity data landscape for environmental chemicals.

OBJECTIVE: Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. DATA SOURCES: We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. DATA EXTRACTION: ACToR contains chemical structure information; physical-chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. DATA SYNTHESIS: We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. CONCLUSIONS: Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program.

The endocrine effects of mercury in humans and wildlife.

Mercury (Hg) is well studied and research continues as our knowledge of its health risks increases. One expanding area of research not well emphasized to date is the endocrine effects of Hg. This review summarizes the existing literature on the effects of Hg on the endocrine system and identifies gaps in the knowledge. It focuses on the thyroid, adrenal, and reproductive systems, including the accumulation of Hg in the endocrine system, sex differences that are manifested with Hg exposure, reproductive effects in male and female animals including humans, and Hg effects on the thyroid and adrenal systems. We concluded that there are five main endocrine-related mechanisms of Hg across these systems: (a) accumulation in the endocrine system; (b) specific cytotoxicity in endocrine tissues; (c) changes in hormone concentrations; (d) interactions with sex hormones; and (e) up-regulation or down-regulation of enzymes within the steroidogenesis pathway. Recommendations for key areas of research to better understand how the endocrine effects of Hg affect human and wildlife health were developed, and include increasing the amount of basic biological information available about Hg and wildlife species, exploring the role of Hg in the presence of other stressors and chemicals, understanding sublethal and indirect effects of Hg on adverse outcomes, developing better methods to extrapolate effects across species, and understanding the effects of Hg on multiple organ systems following exposure of an animal. Greater inclusion of endocrine endpoints in epidemiological and field studies on humans and wildlife will also advance the research in this area.

History and genesis of the detailed review of thyroid hormone disruption assays.

This issue presents the detailed review paper (DRP) on thyroid hormone disruption assays that was prepared for the Organization for Economic Cooperation and Development (OECD) and that exists as an OECD monograph. However, this document is now available here in one issue of Critical Reviews in Toxicology as a series of published articles. The original document has been modified in several ways. First, an overview (now article 2) was added to discuss how new data and new directions for thyroid research will play an important role in shaping thyroid assays as they evolve. Second, each of the original chapters of the thyroid DRP have been separated into individual papers. The appendices of the original DRP were removed and will be merged and published separately.

Integrating basic research on thyroid hormone action into screening and testing programs for thyroid disruptors.

Thyroid hormone signaling is highly conserved among all the vertebrates, and appears to be present in some invertebrates. Both the components that comprise the system and its general role in development and physiology are evolutionarily conserved, although specific events regulated by thyroid hormones, such as amphibian metamorphosis, may differ among taxonomic groups. The articles in this issue review the thyroid systems of mammals (specifically humans and rodents), fish, amphibians, and birds, and the states of the assays and endpoints used to detect disruption of the thyroid system within a toxicological paradigm. It must be noted that while reptiles represent an enormously important group, they were excluded because there was not enough information in the literature on thyroid toxicology in reptiles at the time that this series of reviews was drafted. Each review highlights the best assays for current regulatory use and those that may be considered for development for future use and research. However, it is important to remember that thyroid research is moving ahead at a fast pace. New thyroid research will impact the design of future thyroid assays used for the detection of thyroid system disruption in ways that may not be anticipated at the time of this writing. Several new areas of exploration are discussed that reveal potential sites of disruption in the thyroid system, including (1) the importance of the neural drive for TSH upregulation, (2) thyroid hormone transport, including cellular transporters like monocarboxylate anion transporter 8 (MCT8) that can regulate thyroid hormone action at the cellular level, and thyroid hormone-binding proteins in the serum that have been shown to differentially bind to environmental chemicals (e.g., certain PCB congeners), and (3) the deiodinases as a target for disruption of thyroid hormone activity in the peripheral thyroid system. The review papers in this issue represent the current state of thyroid assays and endpoints for detection of chemicals that disrupt the thyroid system.

General background on the hypothalamic-pituitary-thyroid (HPT) axis.

This article reviews the thyroid system, mainly from a mammalian standpoint. However, the thyroid system is highly conserved among vertebrate species, so the general information on thyroid hormone production and feedback through the hypothalamic-pituitary-thyroid (HPT) axis should be considered for all vertebrates, while species-specific differences are highlighted in the individual articles. This background article begins by outlining the HPT axis with its components and functions. For example, it describes the thyroid gland, its structure and development, how thyroid hormones are synthesized and regulated, the role of iodine in thyroid hormone synthesis, and finally how the thyroid hormones are released from the thyroid gland. It then progresses to detail areas within the thyroid system where disruption could occur or is already known to occur. It describes how thyroid hormone is transported in the serum and into the tissues on a cellular level, and how thyroid hormone is metabolized. There is an in-depth description of the alpha and beta thyroid hormone receptors and their functions, including how they are regulated, and what has been learned from the receptor knockout mouse models. The nongenomic actions of thyroid hormone are also described, such as in glucose uptake, mitochondrial effects, and its role in actin polymerization and vesicular recycling. The article discusses the concept of compensation within the HPT axis and how this fits into the paradigms that exist in thyroid toxicology/endocrinology. There is a section on thyroid hormone and its role in mammalian development: specifically, how it affects brain development when there is disruption to the maternal, the fetal, the newborn (congenital), or the infant thyroid system. Thyroid function during pregnancy is critical to normal development of the fetus, and several spontaneous mutant mouse lines are described that provide research tools to understand the mechanisms of thyroid hormone during mammalian brain development. Overall this article provides a basic understanding of the thyroid system and its components. The complexity of the thyroid system is clearly demonstrated, as are new areas of research on thyroid hormone physiology and thyroid hormone action developing within the field of thyroid endocrinology. This review provides the background necessary to review the current assays and endpoints described in the following articles for rodents, fishes, amphibians, and birds.

Current and potential rodent screens and tests for thyroid toxicants.

This article reviews current rodent screens and tests to detect thyroid toxicants. Many points of disruption for thyroid toxicants are outlined and include: (a) changes in serum hormone level; (b) thyroperoxidase inhibitors; (c) the perchlorate discharge test; (d) inhibitors of iodide uptake; (e) effects on iodothyronine deiodinases; (f) effects on thyroid hormone action; and (g) role of binding proteins (e.g., rodent transthyretin). The major thyroid endpoints currently utilized in existing in vivo assay protocols of the Organization for Economic Cooperation and Development (OECD), Japanese researchers, and U.S. Environmental Protection Agency (EPA) include thyroid gland weight, histopathology, circulating thyroid hormone measurements, and circulating thyroid-stimulating hormone (TSH). These endpoints can be added into the existing in vivo assays for reproduction, development, and neurodevelopment that are outlined in this chapter. Strategic endpoints for possible addition to existing protocols to detect effects on developmental and adult thyroid endpoints are discussed. Many of these endpoints for detecting thyroid system disruption require development and additional research before they can be considered in existing assays. Examples of these endpoints under development include computer-assisted morphometry of the brain and evaluation of treatment-related changes in gene expression, thyrotropin-releasing hormone (TRH) and TSH challenge tests, and tests to evaluate thyroid hormone (TH)-dependent developmental events, especially in the rodent brain (e.g., measures of cerebellar and cortical proliferation, differentiation, migration, apoptosis, planimetric measures and gene expression, and oligodendrocyte differentiation). Finally, TH-responsive genes and proteins as well as enzyme activities are being explored. Existing in vitro tests are also reviewed, for example, thyroid hormone (TH) metabolism, receptor binding, and receptor activation assays, and their restrictions are described. The in vivo assays are currently the most appropriate for understanding the potential effects of a thyroid toxicant on the thyroid system. The benefits and potential limitations of the current in vivo assays are listed, and a discussion of the rodent thyroid system in the context of human health is touched upon. Finally, the importance of understanding the relationship between timing of exposure, duration of dose, and time of acquisition of the endpoints in interpreting the results of the in vivo assays is emphasized.

Implications of research on assays to characterize thyroid toxicants.

Many aspects of thyroid endocrinology are very well conserved across vertebrate taxa. These aspects include thyroid hormone chemistry, the mechanism of its synthesis, and the proteins involved in these processes. In addition, the system by which the hormone is delived from the thyroid gland to target cells, including transport and regulation within the hypothalamic-pituitary-thyroid (HPT) axis, and the proteins that regulate the different components of this delivery system appear to be highly conserved across the vertebrates. Finally, the receptors that mediate thyroid hormone action and the roles thyroid hormone plays are very similar among the vertebrates. Thus, the goal of this chapter is to provide a brief synopsis of the literature supporting existing screening and testing strategies in different vertebrate taxa, and to provide insight into the strengths, weaknesses, and likely changes over time. It was determined during this review that, because of the complexity of the thyroid system, it is unlikely that current in vitro assays for thyroid toxicity will be able to sufficiently replace in vivo assays for thyroid toxicants. However, the in vitro assays serve an important purpose in providing mode of action information and could provide potential screening tools, and should continue to be developed for use. Moreover, because in vivo assays are added on to preexisting reproductive or developmental screens and tests, there are no additional animals required for the in vivo assays. Specific in vitro assays were identified for development, including the thyroid receptor binding and activation assays, and in vitro assays to evaluate thyroid hormone action. Some in vivo endpoints suggested for further research included neuronal differentiation and migration, measures of histogenesis, and measures for thyroid gland thyroid hormone content, which may be more sensitive indicators of TSH stimulation. The most commonly used endpoints currently used to monitor thyroid function are thyroid hormone levels (T3 and T4), TSH, thyroid gland weight, and thyroid histology. Thyroid endocrinology is rapidly advancing and new discoveries will certainly warrant incorporation into future assays. The development of additional endpoints that measure thyroid hormone's actions peripheral to the HPT axis and the development of new reagents for nonmammalian vertebrate species will significantly improve the ability of today's assays to detect chemicals that disrupt the thyroid system in multiple vertebrate species. It is our hope that this series of thyroid articles will provide regulators and research scientists the information needed for each individual to identify the assays and endpoints most suited for their specific purposes.

Estimates of exposures to perchlorate from consumption of human milk, dairy milk, and water, and comparison to current reference dose.

To develop an enforceable drinking water standard from a health-based reference dose, sources of exposure and relevant exposure factors across the U.S. population must be considered. Human exposures, expressed as an estimated daily exposure, can be used to evaluate the health protectiveness of a range of potential regulatory values, thus providing a scientific foundation on which decisions can be based. Recent evidence points to detectable levels of perchlorate in milk and other foods. The purpose of this article is to estimate human exposure to perchlorate from ingestion of drinking water, human milk, and dairy milk. Drinking-water exposure was based on a range of possible regulatory values, derived from the recently established reference dose. Exposure to perchlorate from the consumption of milk was based on exploratory Food and Drug Administration dairy milk data, and on additional published perchlorate concentrations in dairy and human milk samples. This effort is exploratory in nature due to the limited data available at this time. However, it is anticipated that these exposure estimates and comparison with the current reference dose will stimulate dialogue and research that will advance the risk assessment for perchlorate.