Potential Mechanisms behind Air Pollution Toxicity: Findings from Real-World Chronic Exposures

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Traffic is one of the major contributors to air pollution in urban areas; the dynamic mixture of gases and particles that results from vehicle exhaust and noncombustion emissions such as road and tire wear is known as traffic-related air pollution (TRAP).1 The impact of TRAP exposure on human health has been the subject of epidemiological studies for two decades, but the mechanisms by which TRAP-associated particulate matter (PM) alters heart and lung function remain to be elucidated. In a recent pilot study reported in Environmental Health Perspectives, investigators sought to address this issue using a real-world model of TRAP exposure in rats.2Worldwide, ambient air pollution is estimated to cause 3.8 million premature deaths per year due to cardiovascular and respiratory diseases.3^,4 Several studies have reported an association between acute exposure to highly concentrated PM and development of cardiopulmonary dysfunction in humans and animals.5^,6^,7^,8^,9Open in a separate windowThe confined air found in highway tunnels contains levels of TRAP comparable to daily exposures for people who commute or live near busy roads. Image: © ddisq/Shutterstock.Tunnel traffic has been used before to characterize single or well-defined mixtures of TRAP pollutants as well as associated health effects in humans and animals.5^,6^,7^,8^,10 The new study, in contrast, examined health effects of chronic exposure to environmentally relevant doses of real-world TRAP. The animals’ average exposures to fine PM roughly approximated the primary National Ambient Air Quality Standard of 12 μg/m3 per day per year set by the U.S. Environmental Protection Agency (EPA).11David Diaz-Sanchez, director of the Public Health and Integrated Toxicology Division at the EPA Center for Public Health and Environmental Assessment, says the inclusion of both males and females is another unique feature of this study. “Some epidemiological studies have looked at [sex-dependent differences on TRAP exposure effects], but their results are often confounded by lifestyle differences between men and women,” notes Diaz-Sanchez, who was not involved in the study. “The majority of animal models and preclinical studies look at male data, so there is a real need to try to understand the differences between male and female responses.”For the new study, researchers created a vivarium beside a heavily traveled tunnel in Northern California, which allowed for collection and delivery of TRAP into chambers housing male and female rats. Starting at 4 weeks of age, animals were exposed continuously to either tunnel air or filtered air. After about 14 months, the investigators performed histological and biochemical assays to evaluate oxidative stress, inflammation, and fibrosis as markers of cardiopulmonary function.Surprisingly, although lungs exposed to TRAP showed formation of black nodules, markers of pulmonary function were not affected. In contrast, cardiac dysfunction markers were elevated in hearts from both males and females exposed to TRAP. “The most important takeaway is that we see pathologic changes in the cardiorespiratory system after chronic exposure to levels of TRAP that are considered safe by the EPA,” says senior author Pamela Lein, a professor in the Department of Molecular Biosciences at the University of California, Davis.Moreover, there were strong sex differences in this response, with female hearts showing greater effects than male hearts. These findings are consistent with emerging epidemiologic data12 that suggest women may be more susceptible to TRAP-related health effects and further support the relevance of this model to the human condition, Lein says.Even though the study presented limitations such as small sample size and lack of direct assessment of cardiopulmonary function, it could open the door for mechanistic studies aimed at understanding the basis for the sex differences observed. Lein concludes that identifying the TRAP constituent that is driving these changes is the logical next step, as it will likely inform necessary changes to air quality regulatory guidelines.     

BPS and Cell Fusion in the Human Placenta: A Separate Mechanism of Action?

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During the past decade, the plasticizer bisphenol S (BPS) has been replacing the endocrine-disrupting chemical bisphenol A (BPA) in numerous consumer products.1^,2 As an example of its prevalence, a survey conducted in the United States and seven Asian countries found BPS in 81% of human urine samples collected.3 Despite the two chemicals’ general similarity, some of their biochemical properties differ.4^,5^,6 This raises the possibility that BPS may affect endocrine organs—including the human placenta—differently than BPA does. Researchers led by Almudena Veiga-Lopez, a visiting associate professor in the Department of Pathology at the University of Illinois at Chicago, explored one such mechanism in a recent in vitro study published in Environmental Health Perspectives.7Open in a separate windowBPS is used in thermal receipt paper and linings of food and beverage cans. It has been found in canned foods, indoor dust, sewage sludge, groundwater, and river sediment. Image: © Robert Hoetink/Shutterstock.Veiga-Lopez and colleagues studied cell fusion processes human placentas collected at the end of healthy pregnancies. The results of their analyses suggest that BPS may interfere with the formation of the syncytiotrophoblast (STB), a layer of epithelial cells in the placenta. The STB prevents the rejection of fetal cells by the maternal immune system, enables the exchange of nutrients and gases between mother and fetus, protects the fetus from some (although not all) harmful chemicals in maternal blood, and secretes its own hormones, such as hCG and progesterone.8The STB is composed of trophoblasts, which are the first cells to differentiate after an egg is fertilized. The authors proposed that BPS interferes with the fusion of trophoblasts into the STB by competing with the epidermal growth factor (EGF) for binding to the EGF receptor (EGFR). EGF is a protein that stimulates cell growth and differentiation throughout the body.9 The researchers analyzed trophoblasts from six term placentas and found that 200ng/mL of BPS blocked EGF-mediated cell fusion in vitro by binding to EGFR. That concentration is at the upper end of the reported urinary range for the U.S. general population.10Importantly, spontaneous cell fusion was not blocked by this dose, suggesting alternative mechanisms may be involved in the interference with STB formation. “Even if BPS were to block all of the cell fusion events that are induced by EGF, cells that were to fuse spontaneously—not through EGF—could still do so,” Veiga-Lopez explains.Although human trophoblasts from term placentas still fuse in vitro, they no longer divide.11^,12 So the researchers also analyzed proliferating breast cancer cells, which are an established model for testing the EGFR-binding activity of environmental chemicals. The results provided additional evidence that BPS acts as an EGFR antagonist.The study raises the possibility that BPS may adversely affect fetal development or increase the risk of pregnancy complications. However, those possibilities hinge on the role of EGF in the cell fusion process in vivo.“The placenta has one of the body’s highest EGFR expression levels, and EGF is among the dominant factors regulating the proliferation, uterine [attachment], and fusion of human trophoblasts,” says Veiga-Lopez. “But other factors are involved as well. Our understanding of these processes is limited, as they are very difficult to study.”EGF likely plays a variety of roles throughout pregnancy.13^,14^,15 In the first trimester, EGF helps the developing placenta attach to the uterus. To nourish the rapidly growing fetus in later pregnancy stages, EGF and other factors primarily control the cell fusion process to keep up with the increasing complexity the villi—the finger-like structures that maximize the embryo’s contact with maternal blood.Any role of BPS in that fusion process is currently uncertain, says R. Michael Roberts, a professor emeritus of reproductive biology at the University of Missouri, who was not involved in the study. “The researchers proposed a new mechanism of action for BPS that is different from alterations of the classical steroid receptor pathway,” he says. “Although intriguing, I think it remains a hypothesis until confirmed by other studies at environmentally relevant doses.”Graham Burton, a professor emeritus of reproductive physiology at the University of Cambridge, United Kingdom, who also was not involved in the study, agrees with the authors’ conclusion that BPS blocks EGF-mediated cell fusion in vitro. However, extrapolating that finding to human pregnancies is difficult, he notes.“BPS may affect trophoblast proliferation early in the course of placental development, but I think it is less likely to affect in vivo syncytialization, as spontaneous fusion was not blocked in their experiments,” says Burton. “At the end of the day, we just don’t know enough about the role of EGF in regulating this complex process.”Recently generated organoid trophoblast cultures16^,17 form structures similar to villi, differentiate into the STB and other cell types, and secrete placenta-specific peptides and hormones. These cultures closely resemble first-trimester placentas and may help clarify the regulation of cell fusion, says Burton.     

Uptake of Chemicals through the Skin: An Important Role of Filaggrin Gene Variants

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Environmental chemicals can enter the human body through oral consumption, inhalation, or skin absorption. The latter exposure route may have been underappreciated, according to Karin Broberg, a professor of environmental medicine at the Karolinska Institute and Lund University, Sweden. That is one reason she decided to study the genetic effects on skin permeability for selected chemicals. Broberg and her colleagues recently published the results of their research in Environmental Health Perspectives.1 They reported that common variants of the filaggrin-expressing gene, FLG, were associated with an increased uptake of chemicals through the skin of human volunteers.The variants studied included the four most common “loss of function” (LOF) mutations in northern Europeans, mutations that prevent the proper assembly of filaggrin.2 The researchers also quantified copy number variants (CNVs), or nearly identical repeat sequences (high versus low), in one part of the FLG gene. CNVs may influence filaggrin function even in people who do not carry LOF mutations.3Open in a separate windowFilament-aggregating protein—or filaggrin—plays an important role in the skin’s ability to maintain a strong barrier. Loss-of-function gene mutations can make carriers vulnerable to the transfer of allergens through the skin.4 The same may hold true for the transfer of environmental chemicals. Image: © zefart/Shutterstock.Filaggrin is a large structural protein that contributes to the skin’s barrier role. Its smaller constituent amino acids act as skin softeners and moisturizers and regulate pH levels and water resistance.4 An effect of the FLG gene on dermal uptake of chemicals is supported by observational studies. For example, cross-sectional studies of Danish men have associated LOF mutations in FLG with higher urinary concentrations of phthalates5 and of phenols, parabens, and ultraviolet filters.6 A case–control study of Swedish chimney sweeps associated high CNVs with lower urinary levels of polycyclic aromatic hydrocarbons (PAHs) from soot.7In the new study, 6.5% of 432 genotyped volunteers carried an LOF mutation and were invited to participate in the dermal exposure experiment, along with age-matched controls. The researchers collected preexposure blood and urine samples from 54 individuals (23 FLG mutation carriers, 31 “typical” wild-type carriers). Next, they applied solutions of three chemicals of interest to different areas of the volunteers’ arms. These chemicals were pyrene (a PAH formed by the combustion of organic material8^,9), pyrimethanil (a fungicide commonly used in fruit farming10), and oxybenzone (an ultraviolet light absorber found in many sunscreen products11^,12). After 4 hours of exposure, the participants again provided blood samples and were asked to collect all urine excreted for 48 hours.Wild-type carriers were distinguished by whether they had low or high CNVs. Urinary biomarkers of the three chemicals were analyzed by liquid chromatography–mass spectrometry. The three genotype groups differed widely in the lag time between absorption of each chemical via the skin and excretion in urine. In both mutation and wild-type/low CNV carriers, the lag time was shorter than in wild-type/high CNV carriers.“Our results show that FLG genotypes influence the levels of chemicals that [enter] our body,” says Broberg. “This example of gene–environment interaction requires validation in independent studies but suggests that low CNV carriers may be as susceptible as mutation carriers to a higher uptake.”With up to 10% of European individuals carrying an FLG LOF mutation13 and 30% having low CNVs,3 this is a surprisingly powerful result, says Sara Brown, a professor of dermatology at the University of Edinburgh, United Kingdom, who was not involved in the study.“This is a high-quality, carefully conducted study,” says Brown. The finding is especially compelling, she says, because not only LOF mutations but also the CNV appears to affect uptake of chemicals through the skin. She adds that important next steps include studying non-White ethnicities and testing whether other genes that control the skin’s also affect the penetration of chemicals.Jacob Pontoppidan Thyssen, a professor of dermatology at the University of Copenhagen, Denmark, agrees with Brown on the high quality of the work, although he notes the lack of measured filaggrin levels in the skin. “Future risk assessment should take into account that individuals with genetically impaired skin barriers are more susceptible to the effects of environmental chemicals,” says Thyssen, who also was not involved in the research. “We should also study if and how FLG mutations affect the penetration of topical drugs.”FLG mutations are powerful risk factors for atopic dermatitis3^,14 and related systemic atopic diseases, such as asthma,15 hay fever,16 and food allergies.17 If this gene also modulates the uptake of environmental chemicals during years of exposure, its potentially even broader systemic effects deserve further study, says Brown. She concludes, “This new research provides convincing evidence that common differences in [skin barrier function] affect the absorption of chemicals that are all around us.”     

Reframing the Question: Does Mitochondrial Damage Set the Stage for Future Inflammation?

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In the 1970s, evidence emerged that environmental exposures could damage mitochondria, the primary regulators of cellular energetics.1^,2 More recently, researchers are studying how stressed mitochondria may initiate a signaling cascade that culminates in inflammation. At the center of this increased investigation is a multiprotein complex called the NLRP3 inflammasome.3^,4 The elusive link between environmentally induced mitotoxicity and inflammasome activation is the subject of a new study published in Environmental Health Perspectives.5Inflammation is a vital physiological response to invading agents or stressors, and inflammasomes are major players in this response. These multiprotein complexes sense pathogen- or damage-associated molecular patterns and trigger the release of proinflammatory cytokines that enhance and sustain inflammation.3 Most inflammasomes contain proteins in the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family; among these, the NLRP3 inflammasome is sensitive to the broadest variety of stimuli and has therefore sparked the most research interest.6 Abnormal activation of NLRP3 has been implicated in disorders such as Alzheimer’s and Parkinson’s diseases, diabetes, and atherosclerosis,4 raising huge clinical interest as a drug development target.7Open in a separate windowAn inflammasome is a complex molecule made up of different proteins. Inflammasomes are activated by sensing the presence of viruses, bacteria, particulate matter, and molecules produced by tissue stress. On activation, they mediate the release of proinflammatory cytokines, which help the body clear foreign substances and repair tissue. Abnormal activation of inflammasomes is implicated in a variety of human diseases. Image: © RAMON ANDRADE 3DCIENCIA/Science Source.“This study may lay the foundation for new directions in research examining agents that contribute to disease via mitochondrial function and inflammasome modulation,” says EHP deputy editor B. Paige Lawrence, a professor at the University of Rochester Medical Center. “Being able to connect exposures with specific, measurable molecular pathways helps to inform our understanding of pathways that lead from exposure to disease.”Previous research has linked inflammasome activation to by-products of mitochondrial damage, such as production of reactive oxygen species (ROS) and loss of membrane potential.8^,9^,10 However, it remains unclear whether pollutant exposures directly alter mitochondria or indirectly affect them by other injury to the cell.11National Institute of Environmental Health Sciences (NIEHS) neurotoxicologist Jean Harry, senior author of the present report, says her team set out to clarify this link. “We wanted to separate biological responses from toxicological ones by looking at a specific shift in the ability of the cell to respond to a secondary hit,” she says. To do this, the investigators exposed specialized immune cells called macrophages to tri-organotins, which are prevalent environmental contaminants that have been shown to alter mitochondrial function.12^,13^,14^,15^,16^,17One group of macrophages was activated, or primed, by exposure to bacterial lipopolysaccharide (LPS), and then both primed and unprimed groups were treated with tri-organotin compounds. Two known neurotoxicants, triethyltin bromide (TETBr) and trimethyltin hydroxide (TMTOH), enhanced formation of inflammasome aggregates and release of proinflammatory cytokines in LPS-primed macrophages. These compounds suppressed mitochondrial bioenergetics but did not alter ROS production, demonstrating that inflammasome activation can occur independently of ROS release. In the reverse scenario, however, pre-exposure to TETBr and TMTOH blunted the appropriate macrophage response to proinflammatory LPS.“Overall, I think the study demonstrates that, rather than looking at apical end points, we should reframe the environmental and public health question: How does an exposure modify the system such that we may change a relative risk to something else coming down the pike later?” says Harry. The environmental toxicants were tested at sublethal levels—not high enough to elicit cell death, but sufficient to change the cells’ responses to a secondary insult. Harry says such changes could manifest as an earlier onset of disease, progression of a disease process, or—of particular interest in the context of the current global pandemic—reduced vaccine response. These effects may be seen as two sides of the same coin.“On the one hand, having an underlying chronic inflammatory condition might change my susceptibility to [any] environmental exposures that might act upon the immune system,” Harry says. “On the other hand, a low-level environmental exposure could change how I respond to an immune challenge later.”Matthew Havrda, an assistant professor at the Geisel School of Medicine at Dartmouth, cautions that the generalized suppression of metabolism observed in exposed macrophages may suggest general distress due to lack of adenosine triphosphate (ATP; the energy currency of the cell) and that inflammasome activation could therefore be part of a bigger stress response. Havrda, who was not involved in the current study, suggests that to find the direct link—the molecular smoking gun—scientists should look at whether the response elicited by tri-organotin exposure is specific to NLRP3. “[NLRP3] drugs and biomarker assays are out there, so if [NLRP3 activation is] specific for this type of toxic exposure, you could potentially screen and treat people to circumvent the deleterious effects,” he says.Harry agrees, noting that inflammasome-blocking drugs currently in development may simply be blocking ATP release and that the specificity of the inflammasome response calls for further studies. She adds that the role of inflammasome aggregate formation should also be clarified. “These aggregates are very sticky and hard to break up, and they have a major stimulatory effect on [surrounding] macrophages, so the acute inflammatory response elicited by environmental exposures may have long-term consequences through the release of those aggregates,” she says. Recent studies18 have proposed these aggregates may act as scaffolds in the formation of plaques in Alzheimer’s disease, supporting the need for further investigation.     

From the Ground up: Assessing Bacterial Diversity in the Air Space of an Urban Park

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Emerging research has linked exposure to diverse airborne microbial communities to healthy human immune systems.1 But few studies have examined how communities of airborne microbes (aerobiomes) vary over time and space2; none are known to have investigated whether these communities change with height from the ground. A recent proof-of-concept study in Environmental Health Perspectives described how the diversity of airborne bacterial communities decreased from ground level to 2m in height in an urban park, noting that the makeup of the communities also varied, depending on height.3“Exposure to a diverse set of microbes from our environment trains our immune systems to respond appropriately to pathogens,” says Graham Rook, a professor of medical microbiology at University College London who was not involved in the study. Lack of exposure to bacterial diversity has been associated with autoimmune diseases,4 allergies,5 Alzheimer’s disease,6 and inflammatory bowel disease.7Open in a separate windowVertical stratification sampling stations captured a snapshot of bacterial diversity at different heights from the ground. Image: Robinson et al. (2020); DOI: 10.1289/EHP7807.Airborne microbial communities are important for human health because our skin and mucous membranes are exposed to them every day.8 Yet the community structure of the aerobiome remains little known, says lead study author Jake Robinson, a doctoral student in microbial ecology at England’s University of Sheffield. An earlier study comparing forest and grassland areas found that elements of the local environment likely drive aerobiome structure.9 “But we wanted to know how the airborne bacterial communities varied over vertical space because, due to height differences, children may be exposed to different microbes than adults,” Robinson says.He and his team chose an urban park in Adelaide, Australia, that consists of about 700 hectares of gardens, woodlands, and playing fields. The researchers set up sampling stations in three randomly selected plots of scrub habitat, defined as parkland with semi-mature trees. At each station, they constructed a stand resembling a hat rack with petri dishes mounted at ground level and at 0.5, 1, and 2m above the ground. These levels were chosen to roughly represent the height of a jogging stroller, a 4-year-old child, and an adult, respectively.On three different days the team left the petri dishes open for 6–8 hours to passively sample the aerobiome. They also collected soil samples. The environmental conditions during the sampling were warm and dry.Back in the lab, the researchers extracted DNA from the samples and amplified the region coding for the 16S rRNA gene. This gene is present across all bacteria and can be used to distinguish between different organisms.10 Software tools clustered the millions of gene sequences and taxonomically identified sequences down to the level of bacterial genus. To quantify bacterial diversity, the team used the Shannon Diversity Index, which uses both species richness (the number of species in a population) and species evenness (the abundance of each species in a population).11The index scores declined by roughly one-third from soil level to 2m above ground. The highest score was found in one of the soil samples. Genera that occurred in both air and soil tended to decline with height above ground. Approximately 84% of taxa in the lower air samples and 76% of upper air taxa were also found in soil. In addition, the community composition of bacterial genera varied widely at different heights. The investigators estimated that sampling height explained 22% of the variation in aerobiome makeup in the study.Notably, this study sampled a small area for only 3 days and did not analyze bacterial DNA down to the level of species and strain. That information would be important “in order to determine whether the organisms they were looking at are the ones that might end up in our guts,” Rook says. In addition, aerobiomes vary across habitat types, different weather conditions (e.g., windy vs. calm days), and concurrent activity levels (e.g., kicking a ball vs. sitting).“The finding that microbial communities vary with height is important because we breathe hundreds of millions of microbes every day,” says Emily Flies, a research fellow in health ecology at the University of Tasmania in Australia. “That exposure during early development is crucial to children’s immune systems. But most aerobiome sampling is done at two meters above ground, so this study indicates that if we want to research what kids are breathing, we need to be sampling at half a meter above ground.”Flies adds that, with more research on how microbial exposure translates to health, investigators may find ways to optimize human exposure to health-promoting biodiverse microbes in greenspaces. This study suggests that greenspaces where people can sit or lie on the ground might facilitate more biodiverse microbial exposures, she says, but further research is needed to confirm these findings and to determine whether and how those microbial exposures affect human health.     

The P-Sufficient Approach: A Strategy for Regulating PFAS as a Class

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Because of concerns about their persistence and potential toxicity, certain per- and polyfluoroalkyl substances (PFAS) have been targeted for regulation or removal from commerce.1^,2 Yet experts worry that regulations aimed at specific PFAS will lead to problems with “regrettable substitutions” in which a regulated chemical is replaced with an unregulated one that may be equally or even more toxic.1 In a commentary published in Environmental Health Perspectives, members of the Safer Consumer Products Program at the California Department of Toxic Substances Control (DTSC) elucidated the scientific rationale for a novel regulatory approach—regulating PFAS chemicals as a class.3PFAS are a group of manmade chemicals that have been used widely over the past several decades in industrial applications, commercial household products, and food packaging.4 Numerous studies suggest that exposure to certain PFAS may be harmful to human health and the health of other organisms, although much remains to be learned.5 “There are six thousand or so PFAS chemicals,6 and the majority have not been thoroughly evaluated for ecological and human toxicity,” says André Algazi, senior study author and chief of the DTSC Chemical-Product Evaluation Section.Open in a separate windowGreaseproof paper food packaging can expose people to PFAS if the chemicals migrate into the packaged food. But discarded products present other exposure opportunities. For instance, depending on the disposal method, packaging can release PFAS into compost, landfill leachate, or (if incinerated) the air. In addition, recycled products made from PFAS-treated paper can be a source of PFAS exposure.10 Image: © onajourney/Shutterstock.PFAS are an extremely diverse group of substances with a wide range of properties and applications, but they all have one thing in common: Somewhere in their chemical structure, each contains at least one carbon chain that is fully fluorinated, meaning it contains only carbon–fluorine bonds. A carbon–fluorine bond is one of the strongest chemical bonds known and thus one of the hardest to break. It is what makes PFAS so resistant to degradation in the environment, explains Ian Cousins, an environmental chemist at Stockholm University in Sweden, who was not involved in the new commentary.Cousins and other environmental scientists have advocated for a persistence-sufficient, or “P-sufficient,” approach to regulating PFAS.7 The idea behind the P-sufficient approach is that the persistence of PFAS is a sufficient basis to warrant regulation regardless of, say, the chemicals’ bioaccumulation potential or toxicity.7 That is different from most chemical regulatory approaches, which tend to focus on hazard traits, such as whether a chemical is suspected or known to cause adverse health effects, Cousins explains. “We know that if we keep emitting PFAS, their concentrations in the environment will increase, because they do not degrade, and ultimately some known or unknown ‘effects threshold’ will be breached. But because there are thousands of PFAS chemicals and we have inadequate toxicity data on most of them, we do not know what the long-term effects will be,” he says.Lead commentary author Simona Bălan, senior environmental scientist at the DTSC, says the California agency is the first in the world to adopt a P-sufficient approach to PFAS. The DTSC has proposed using this new approach to regulate PFAS specifically in food packaging, carpets and rugs, and stain-proofing treatments used on clothing, upholstery, and other consumer textiles.8 Bălan explains these product categories represent some of the biggest sources of documented PFAS exposure. The regulations are expected to be finalized by July 2021. Industry trade groups, including the American Chemistry Council (ACC), argue against a class approach to regulation. Although the total number of PFAS may be large, only a “small fraction” of these substances are actually used in a given application, such as textile treatment products, wrote ACC representative Renée M. Lani in comments to the DTSC on the proposed regulations.9Under the new regulations, manufacturers selling those products on the California market will notify the DTSC of any PFAS used in the product. If a product contains PFAS, the manufacturer will perform an alternatives analysis to determine if a non-PFAS chemical could serve the same function in the product. If a suitable alternative does not exist, the product may continue to be sold, but it will carry a warning label for consumers. “The purpose of the new regulations is to [help] prevent regrettable substitutions, not to put an immediate ban on PFAS in those products,” Bălan says.She and Algazi say these state regulations are just one small step to moving the consumer products market away from persistent chemicals. A P-sufficient approach to PFAS could also be feasible in regulations of drinking water and other environmental media, Algazi adds—for instance, by setting a limit for total allowable PFAS in drinking water. In addition, the authors wrote that other chemical classes may lend themselves to the P-sufficient approach, including nonylphenol ethoxylates in laundry detergents and microplastics.3Although many environmental scientists believe a P-sufficient approach is a step in the right direction when it comes to PFAS,7 it does not completely solve the problem of regrettable substitutions. “Just because something is nonpersistent, doesn’t mean that it is safe,” Cousins says. “A lot more research is needed to determine whether alternatives are better and safer, and what ‘better and safer’ means.”     

Walking on a Redline: Did Discriminatory U.S. Housing Policies Affect Greenspace Development?

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Nearly a century ago, a New Deal–era U.S. federal agency developed a color-coding method for mortgage lenders to evaluate the worthiness of neighborhoods across the country. The Home Owners’ Loan Corporation (HOLC) considered characteristics such as racial/ethnic makeup of neighborhoods, age and condition of housing, and access to public services when they evaluated the possible risk to lenders.1 People were systematically denied loans to buy homes or businesses in high-risk “redlined” neighborhoods, and what followed were decades of neglect and disinvestment. Even though redlining as a policy was outlawed in the late 1960s,2 it continues to have not only a social and economic impact on communities, but also an environmental health one.3 A recent study in Environmental Health Perspectives offers new data about the legacy of redlining in American cities and its relationship to greenspace development.4Open in a separate windowThis 1933 map of Birmingham, Alabama, demonstrates the color-coding system10 used by the HOLC to determine the riskiness of making loans for properties in certain neighborhoods. Wealthy White neighborhoods were marked in green and given an A (“best”) grade as the safest investments. Blue B neighborhoods were deemed “still desirable,” although less so, whereas neighborhoods with a lot of recent immigrants might get a yellow C (“declining”) grade. Low-income, ethnically diverse neighborhoods were outlined in red and rated D (“hazardous” to lenders). This particular map includes an additional designation separate from the HOLC system: solid gray for areas with a “Negro concentration.” Cross-hatching indicates industrial and commercial areas, and diagonal lines indicate undeveloped property. Image: Courtesy U.S. National Archives.Anthony Nardone, lead author of the new study and a student in the Joint Medical Program at the University of California, Berkeley, and University of California, San Francisco, says the paper emerged from research that he and his colleagues were conducting on asthma5 and birth outcomes6 in historically redlined communities. “When we were hypothesizing the reasons as to why current outcomes are worse in these places today, one of the things that kept coming up was just the actual physical built environment,” says Nardone. In many of the historically redlined areas, the land was more often covered by impervious surfaces like asphalt and sidewalks, and the neighborhoods had a dearth of parks and trees.7Nardone and his colleagues knew they could simply overlay the original HOLC maps with more recent satellite imagery of neighborhood vegetation, but they wanted to probe any potential associations more deeply by controlling for other sociodemographic factors, such as the racial composition of neighborhoods, median home values, and number of employed people. They mined demographic data from the 1940 U.S. Census and used machine learning to calculate multiple propensity scores to estimate the likelihood that a neighborhood would have been assigned a particular grade.“We tried to compare groups that were similar like you would in a randomized controlled trial, where you try to take two groups that are essentially identical in every which way except for the treatment,” says Nardone. In this way, they could compare C neighborhoods that could have just as well been graded D, or B neighborhoods that might have been graded A.The results showed that neighborhoods that had lower HOLC grades in the past tended to have fewer green resources like parks and trees in the present day. This was true even when controlling for historical demographic factors. Nardone says the results help quantify how the federal government and the banking industry were “able to use their power to funnel well-being and health-generating resources to predominantly White neighborhoods.”That argument piques the interest of Lonnie Hannon, an associate professor of sociology at Tuskegee University who was not involved in the new study. He says this new study is useful in making a case that past discriminatory policies are still having a deleterious impact on Black communities decades later. “If we start with the premise that greenspace enhances health behavior,” he says, “this historical racism that has occurred over the years also leads to deficits in health behavior among current residents of these areas.” In other words, people with reduced access to greenspaces today are typically from the same racial/ethnic groups that experienced redlining. He concludes, “These ‘consequences of place’ manifest as poor health outcomes.”Vivek Shandas, a professor of urban studies and planning at Portland State University who coauthored a study8 on redlining and urban heat in 2020, says that although we have long known that there is a general association between redlining and greenspace, this study offers more proof. “This paper helps us validate and more explicitly articulate the impacts of HOLC redlining policies on the presence of greenspace across these grades,” says Shandas, who was not involved in the new work. “It has the kind of systematic analysis that would help anybody make a clear case that redlining had an effect on the presence of anything green in those specific neighborhoods.”Mixed evidence suggests associations between access to greenspace and improvements in mental health, cardiovascular health, birth outcomes, and child development.9 For Nardone, the issue of greenspace access is a key part of his other health-related research. “We know there are racial health disparities here in the United States, some quite drastic,” he says. He hopes that as policy makers see more evidence for how historical policies of discrimination contributed to these problems, they will be more willing to find solutions.     

A Different Kind of Storm: Natech Events in Houston’s Fenceline Communities

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Puffy plumes of steam rise from the Valero refinery in the Houston community of Manchester, merging into the cloudy August sky. An older Hispanic couple sit in their front yard just across from the refinery, eating their lunch, while two scientists sample the air and soil nearby. It is August 2020, one week after Category 4 Hurricane Laura veered right, sparing Houston, the “Energy Capital of the World,” from the devastation Hurricane Harvey wrought 3 years before. But the residents are perpetually in the path of a different kind of storm.Garett Sansom, a research assistant professor of epidemiology at Texas A&M University (TAMU), is here with graduate student Leanne Fawkes. Working closely with local partner Texas Environmental Justice Advocacy Services, their goal is to find out what chemicals the residents of this community are exposed to and how exposures change before and after storm events. “Most of the visual stuff is steam,” Sansom says of Valero’s smokestacks. “It’s the invisible stuff that’s a problem.”Open in a separate windowIn the days following Hurricane Laura, Garett Sansom and Leanne Fawkes of TAMU collected air and soil samples along the streets of Manchester, across the street from Valero’s Houston Refinery. TAMU investigators are working closely with local partner Texas Environmental Justice Advocacy Services to study chemical exposures in the community. All images: © Wendee Nicole.Manchester is one of several majority Hispanic and Black “fenceline” communities along the Houston Ship Channel, home to one-fourth of the world’s refining capacity.1 Fenceline communities lie adjacent to industrial facilities and live with excess pollution levels, health disparities, and often lower-than-average incomes.2 A history of redlining and segregation, along with a lack of zoning laws, has led many people of color to live in the shadow of industry.3^,4^,5Proximity to industrial neighbors puts fenceline communities in a double bind. They not only deal with daily exposure to potentially toxic emissions but also face increased risk of experiencing a so-called natech (“nay-teck”) event.6 Natech events—short for natural hazard–triggered technological disasters—occur when a natural occurrence such as a hurricane or flood leads to infrastructural failures such as a chemical spill or nuclear reactor meltdown.7 Experts interviewed for this story say neither government regulations nor companies’ planning documents are protecting public health from natech events.The TAMU investigators frequently detect benzene—rare in a typical neighborhood—when they sample in Manchester. Today Fawkes gets a benzene reading of 0.036 ppm along with a total volatile organic compound (VOC) reading of 0.5 ppm. VOC levels rise and fall—these chemicals are volatile, after all—but 0.5 ppm “is weird in neighborhoods,” says Sansom.Most of the available health data for benzene have come from occupational settings, Sansom says, where workers are typically healthy, have access to personal protective equipment, and stay on site for a maximum of 8 hours per workday. On the other hand, he says, “If you live in Manchester, you’re a child, and you’re exposed to it twenty-four seven, what does that mean? The truth is, there are no good toxicological models that can totally explain this situation.”Before Laura, chemical facilities in the Greater Houston area had released an estimated 4,400 tons of air pollutants8 beyond what their Clean Air Act permits allow during normal operations. Such “excess emissions” routinely occur as facilities shut down and start back up before and after major weather events.9 And during storms—whether a hurricane or Texas’s February 2021 historic winter storm—fenceline communities stand a greater chance of suffering the harmful consequences of a natech event due to their proximity.Dealing with hazardous emissions and the fear of leaks and explosions are par for the course for Manchester and other fenceline neighborhoods.10 “Do we get scared sometimes? Of course we do. We live next to a refinery,” Cesareo Torres, the older man sitting in the front yard with his wife, says in Spanish. “But what are you going to do? We have a lifetime here. You kind of get acclimated to it.”Open in a separate windowOne of several fenceline communities along the Houston Ship Channel, Manchester is home to 19 facilities representing numerous industries. However, only 7 of these facilities are required to report potential or actual hazardous releases to the U.S. EPA—the others do not reach the reporting threshold set by the agency, although they are very likely emitting hazardous pollutants. Image: Courtesy Union of Concerned Scientists.     

Microplastics in Seafood: How Much Are People Eating?

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With discarded plastics making up more than 80% of the trash that accumulates in some locations,1 microplastics (MPs) have become ubiquitous in the environment. Generally defined as synthetic polymers less than 5mm in diameter,2 MPs have been found in fish, shellfish, crustaceans, mollusks, and even mammals.3 In a systematic review and meta-analysis recently reported in Environmental Health Perspectives, investigators estimated the level of MP contamination in seafood and, consequently, how much people may ingest each year.3It is not clear whether MP consumption harms human health, although particles may carry potential hazardous plastic constituents, microorganisms, and adsorbed chemicals.3 “In order to assess whether the uptake of microplastics via food can indeed pose a risk to our health, first we need to quantify this exposure, and, second, determine whether this exposure is high enough to have a detrimental effect,” says lead study author Evangelos Danopoulos, a doctoral student at Hull York Medical School in England. “Systematic reviews and meta-analyses can play a key function in the risk assessment process.”Open in a separate windowInvestigators used a novel risk of bias tool to identify high-quality studies of microplastics in crustaceans, mollusks, echinoderms, and fish. Images, left to right: © iStockphoto/Kateryna Kukota, © iStockphoto/Don White, © iStockphoto/79mtk, © iStockphoto/Photosiber.The systematic review included 50 primary peer-reviewed papers—all field studies that sampled mollusks, crustaceans, fish, and echinoderms for MP contamination—and 19 studies were used in the meta-analysis. The authors developed a novel risk of bias (RoB) quality assessment tool to evaluate all aspects of experimental design, execution, and reporting for each paper. Among other inclusion criteria, studies must have sampled commercially relevant seafood species and used one of four validated procedures to assess the chemical composition of MPs.The studies measured contamination in terms of MP particles per gram of organism wet weight or per individual organism. Over half the reviewed studies sampled mollusks, reporting a range of 0–10.5 MPs/g. Mollusks collected in Asia tended to be the most contaminated. In addition, mollusks collected directly from fishing waters were more contaminated than those purchased from markets. The reasons for this finding are not entirely clear, Danopoulos says, but one possibility is that harvested mollusks are sometimes put through a flushing process known as depuration before they are commercially available.For crustaceans, the range was 0.14–8.6 MPs/g, but there were many gaps in the study data. Among fish, anchovies had a range of 0.35–2.3 MPs/individual, and sardines had 0.23–4.63 MPs/individual. Four studies analyzed larger fish; two reported the absence of MPs, one did not find contents that were significantly different from the control samples, and only one found MPs, reporting a content of 2.9 MPs/g. However, the authors rated the latter study as having a high RoB, meaning it was not rigorously conducted, according to the RoB matrix. One study on echinoderms found 0.82 MPs/individual or 1 MP/g in edible tissue.The investigators estimated a maximum human uptake of MPs from seafood to be a maximum of 53,864 particles annually. They based this calculation on global consumption estimates4 of 15.21kg/person per year for fish, 2.65kg/person per year for mollusks, and 2.06kg/person per year for crustaceans (echinoderms were not listed in the consumption data set they used). The authors acknowledge that seafood consumption varies widely by country, depending on geography and culture. Given the variation in MPs’ sizes, the authors did not attempt to estimate the total mass consumed.“The most striking finding for me was that every single study identified the presence of microplastics in [at least part of] their samples,” Danopoulos says. With samples coming from four phyla comprising more than 20 families collected from all around the world, living in different habitats and different environmental compartments—all were found to be positive, at some level, for MP contamination. “Microplastics contamination is indeed ubiquitous,” he says. He also notes that the most abundant polymers identified in seafood (polyethylene and polypropylene) are the ones that have been most heavily produced in the last 15 years.“This is an interesting analysis,” says Thavamani Palanisami, a senior lecturer at Australia’s University of Newcastle. “The maximum uptake … is very high and could be due to methodological issues. Nevertheless, if I am a fish eater, I would be worried [about] even one MP in my diet.” Palanisami, who was not involved in the current study, recently published an analysis of MP consumption from all dietary sources in which he estimated humans could be eating up 5g per week.5“This is the first systematic review of the literature on microplastics in seafood, which is important in its own right,” says Dave Love, an associate scientist at the Johns Hopkins Bloomberg School of Public Health who also was not involved in the study. “If regulatory agencies were to inspect seafood for microplastics—which they do not currently do as part of routine testing—there would need to be expert guidance on where to set the bar or the numbers of microparticles per gram of tissue allowable. Before that, however, we probably need more health effects studies to decide if microplastic exposure warrants any regulatory action.”Danopoulos and colleagues also recently published systematic reviews of microplastics exposure from salt6 and drinking water.7 They estimated potential human exposures via salt at 0–6,110 MPs/year.6 For drinking water, they estimated that people might be consuming up to 458,000 MPs/year for tap water and 3,569,000 MPs/year for bottled water, based on average water consumption.7 “The results of all three systematic reviews,” Danopoulos says, “can be used in an aggregate exposure framework from all three mediums, which will give us an estimate of high confidence on human microplastics exposures.”     

Linking Pollutants and Therapeutics to Heart Health: Key Characteristics of Cardiovascular Toxicants

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Categorizing chemicals that affect human health according to their key characteristics (KCs) has proven useful for carcinogens,1 endocrine-disrupting chemicals,2 and reproductive toxicants.3^,4 The term “key characteristics” refers to shared properties of chemicals that are known to cause a particular human health outcome. The KC concept has been applied by researchers, regulatory agencies, and bodies such as the International Agency for Research on Cancer to better understand disease mechanisms and to help prioritize the development of new in vitro or in vivo chemical testing assays.5^,6 The authors of a commentary recently published in Environmental Health Perspectives extend this work to chemicals with cardiovascular toxicity.7Open in a separate windowBy understanding the key characteristics of cardiovascular toxicants, researchers and regulators can better identify chemicals that may contribute to cardiovascular diseases as well as assess their mechanisms of action. Image: © iStock/andresr.A diverse panel of 19 experts identified and grouped cardiovascular toxicants based on mechanistic similarities between therapeutics and environmental chemicals, such as air pollutants, arsenic, and lead. “We used textbook lists of drugs and chemicals that cause cardiovascular toxicity and also made a list of probable mechanisms,” says Martyn Smith, a professor of toxicology at the University of California, Berkeley, and the commentary’s senior author. “Since we typically have a better understanding of drug mechanisms, we wanted to apply that information to environmental pollutants that affect the cardiovascular system in similar ways.”The panel identified 12 KCs, which they divided into three groups: those that primarily affect cardiac tissue (KC1–KC4), those that primarily affect vascular tissue (KC5–KC7), and those that affect both tissue types (KC8–KC12). The first group includes “KC1: impairs regulation of cardiac excitability,” which describes disruptions of ion channels that balance cardiac excitation and contraction. Abnormal ion channel activity can lead to cardiac arrhythmias and sudden cardiac death.7 Antiarrhythmic drugs8 and the environmental chemical bisphenol A9 are example compounds with KC1.The second group includes “KC5: impacts endothelial and vascular function,” which describes damage to endothelial or smooth muscle cells in blood vessels. Impairments in these cells, which ensure proper blood flow and nutrient delivery to all organs, may result in atherosclerotic disease, hypertension, myocardial infarction, or other conditions.10 Chemicals with KC5 include antihypertensive drugs,11 arsenic,12 cadmium,13 and organophosphate pesticides.14The third group includes “KC8: impairs mitochondrial function.” As the cell’s power factories, mitochondria regulate several important processes in both heart and vascular tissue. Their impairment may reduce energy metabolism, increase oxidative stress, or disturb ion channel function. Drugs with KC8 include anthracyclines,15 a class of cancer chemotherapeutic agents. Environmental chemicals with similar features include fine particulate matter (PM2.5)16 and nitrogen dioxide.17Matthew Campen, a professor of environmental health at the University of New Mexico, who was not involved in this project, says it makes sense to treat cardiac and vascular tissue both separately and together. “The cardiac muscle is exquisitely protected from many harmful impacts, [whereas] the blood vessels have received chronic insults from different toxicants for most of human history,” he explains.Campen also appreciates that the KCs are broad enough to capture viruses, other nonchemical agents, and indirect mechanisms involving other organs. For example, kidney disease may contribute to cardiovascular disorders when the impaired ability to remove toxicants causes their accumulation in blood vessels.18For Ana Navas-Acien, a professor of environmental health sciences at Columbia University, highlighting the shared KCs of therapeutics and environmental toxicants is especially important for the project’s diverse target audiences of epidemiologists, physicians, and basic, pharmaceutical, and regulatory scientists. “Drinking low levels of arsenic in your daily water is comparable to swallowing a daily pill of arsenic to treat certain diseases [i.e., African sleeping sickness and a rare form of leukemia],” says Navas-Acien, who was not involved in the project. “This helps people understand that some chemicals in the environment function exactly like drugs.”PM2.5, which exhibits seven KCs,7 illustrates the evolution of environmental cardiology,19^,20^,21 adds Navas-Acien. Early reports of acute cardiac events requiring hospitalization on days with high exposures to PM2.5 were followed by studies of chronic low-level exposures.22 A 2016 longitudinal study,23 for example, associated PM2.5 and nitrogen oxide exposures with coronary artery calcification as a marker of increased cardiovascular risk. “Cardiologists are beginning to recognize that air pollution and other environmental hazards can increase risk as much as smoking, lack of physical activity, and other lifestyle factors,” says Navas-Acien.Air pollution also affects the lungs, brain, and other organs.24 Similarly, arsenic is a reproductive and cardiovascular toxicant and a carcinogen.25 This, says Smith, illustrates that some KCs apply to multiple systems, whereas others describe organ-specific pathways.“KCs provide a systematic framework for improving our understanding of disease mechanisms,” adds Smith. That, he hopes, will benefit both drug development and efforts to reduce human exposure to environmental hazards.     

Tropical Cyclone Exposures and Health: A New Data Set to Assess Associations over Time

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When a tropical cyclone strikes a region, some deaths and injuries may be directly tied to the storm. Drownings may be caused by flooding, and crushing injuries can result from high winds. However, disasters may also impact health through less apparent routes. For example, the psychological stress of losing one’s home could trigger a heart attack in a person with traditional cardiovascular risk factors, says Brooke Anderson, an associate professor of epidemiology at Colorado State University. In a recent paper published in Environmental Health Perspectives, Anderson and colleagues presented an open-source data set to help epidemiologists understand the health risks associated with tropical cyclones across the eastern half of the United States.1Open in a separate windowA new open-source data set will help epidemiologists better estimate excess mortality and morbidity related to cyclone-related hazards, including flooding, high winds, heavy rains, and tornadoes. Image: © iStockphoto/Shmenny50.Forecasting technologies developed over the last several decades have led to better warning and evacuation systems. These systems have dramatically lowered deaths and injuries from direct causes when a terrible storm hits, Anderson says. “What’s been harder to study is how those disasters might affect health through an indirect path, especially when looking at health outcomes—such as a heart attack—that are pretty common outside of the storm,” she says.Some investigators have already begun to study the indirect health impacts of specific tropical cyclones, including Hurricane Maria,2 which struck Puerto Rico and several Caribbean islands in 2017, and Hurricane Sandy,3 which caused damage in the Caribbean and along the U.S. and Canadian coasts in 2012. Similar data sets have been developed for heat waves to compare how community-wide rates of health outcomes change during or after a heat event.4 “We know a fraction of the health impacts of single large hurricanes,” says Marianthi-Anna Kioumourtzoglou, an epidemiologist at Columbia University, “[but] what is the impact on the health of the cumulative exposure to smaller storms for people living in coastal communities?” Kioumourtzoglou was not involved in the study.To create the new cyclone-specific data set, Anderson and colleagues compiled county-level exposure data for four tropical cyclone hazards: peak sustained wind, rainfall, flooding, and tornadoes. The data cover all counties in the eastern half of the United States for all land-falling or near-land Atlantic basin storms between 1988 and 2018. The researchers chose to aggregate exposure data at the county level to facilitate joining them with other county-level health data such as deaths, hospitalizations, and birth outcomes. The county level is also where decisions and policies around disaster preparation and response are often undertaken.As part of a separate research team, Anderson used the open-source package to assess whether tropical cyclone exposures are linked to adverse birth outcomes5 and is currently studying hospitalization risk among the elderly. Kioumourtzoglou is using the data set to study whether health outcomes such as hospitalizations for asthma attacks, heart attacks, or infections go up or down with exposure to tropical cyclone hazards. “There is the potential to take tropical cyclone epidemiology in a powerful new direction,” Kioumourtzoglou says.Yet, there are certain limitations. Some tropical cyclone exposures may be more consistent over large areas than others.6 High winds and rainfall totals, for instance, may be consistent across a county, tornadoes or flooding may be much more localized.1 If a county is very large, maybe only one part of it experiences flooding. Maybe houses in only a few neighborhoods are destroyed by a tornado. “This could lead to issues with exposure misclassification,” Kioumourtzoglou says.This type of big data approach also may not fully account for social vulnerability, says Jennifer Horney, a disaster epidemiologist at the University of Delaware who was not involved in the study. She explains that factors such as people’s housing, their ability to understand warnings and alerts, and access to vehicles should be part of the equation. “Even at the county level,” she says, “disasters impact different groups differently.”     

Making It Count: How to Achieve Structural Change with Community-Based Participatory Research Projects

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Low-income communities of color are inequitably burdened with pollution and its related health effects.1 Environmental health researchers sometimes conduct community-based participatory research projects in which residents help design research questions, collect data, and interpret results.2 Such collaboration often improves the academic rigor of these studies3 and helps inform residents of health risks.4 But does it actually bring about systemic change to economic, social, and political structures? The authors of a review in Environmental Health Perspectives sought to answer that question.5Open in a separate windowThe authors of the new review discussed examples of community-based participatory research projects that successfully effected change. In one, members of the Crow Environmental Health Steering Committee at Little Big Horn College partnered with Montana State University to study contaminants in well water on the Apsaálooke (Crow) Reservation. Crow members of the team (including graduate student Emery Three Irons, shown sampling tap water) used culturally appropriate methods to collect samples and educate fellow Tribal members about the risks of drinking contaminated water. Ultimately, says investigator Margaret Eggers, the best intervention has been to provide free home water coolers that dispense safe drinking water from 5-gallon refillable jugs. Image: Courtesy John Doyle (Apsaálooke)/Little Big Horn College.“I was interviewing community members, and some of their stories just kind of got to me,” says Leona Davis, the lead author of the review. A graduate student in environmental education, Davis was helping Mónica Ramírez-Andreotta, an environmental health science professor and one of her advisors at the University of Arizona, evaluate learning and outcomes of a cocreated citizen science program with disadvantaged communities in Arizona. One of these was Hayden, Arizona, a majority Latino town that is home to a copper smelter and piles of mine tailings.6 Although Davis recognized the residents’ environmental science literacy, she was struck by the glaring injustice of their situation. “I just remember … reflecting that this is a bigger issue than a lack of understanding of science,” says Davis.Davis and Ramírez-Andreotta reviewed the literature to investigate which specific study design elements prompt structural change to benefit overburdened communities. They found that 26 of the 154 case studies they examined resulted in structural change, which they defined as “affecting macro- or meso-level determinants of health, such as zoning policy, economic policy, political power, built environment, public service provision, or environmental policy enforcement.”Within those successful case studies, they found policy change was rarely a clear win, Davis says. For instance, in one case study,7 residents were unable to prevent a new waste facility from being built in their neighborhood. Still, they were able to negotiate a reduction in how much waste the facility handled and the removal of a diesel fueling station from the project. They also obtained guarantees that fleet vehicles would run on alternative fuels.The investigators also found that successful projects shared certain characteristics. During initial planning, these projects examined the structures already in place. They were community-directed, and they adopted governance models where community members held formal leadership roles. Hiring community members to serve as project leaders whenever possible is critical, says Ramírez-Andreotta. She explains that by providing a salary and funding for expenses, financial support for grassroots leadership makes it easier for residents—who are often grappling with poverty, illness, and other stressors—to work toward the changes they want to see.In projects that managed to bring about structural change, investigators had also valued the local knowledge and the lived experience of the community residents. They carefully translated the resulting data into a form that was understandable and useful for community members and other stakeholders. They also set policy change as a goal from the outset. Another key characteristic was commitment to a long-term presence in the community, which the authors defined as longer than 4 years. One case study8 examined the Detroit Community–Academic Urban Research Center, which has existed for more than 25 years and engaged in partnerships to address asthma, air quality, heart health, and other environmental health issues.9Those long-term commitments help build trust, something that can be sorely lacking between community members and academics, says Yanna Lambrinidou, co-organizer of the Engineering Ethics and Community Rights Collaborative, a national initiative to institute community rights in participatory research. “I think [the review] holds a mirror up to academics, asking us to reflect on our trustworthiness—on whether our educational, research, and funding structures are adequately designed to support community-led, systemic solutions or if they may at times even stand in the way,” says Lambrinidou, who was not involved with the review. “Environmental justice communities have been voicing concerns for a long time about academics who show up to help,” she continues. “Yet to this day, academia provides no space for these communities to report problems and no mechanism for protecting them from harm.”Davis and Ramírez-Andreotta hope their work will inform a new generation of investigators while acknowledging the steep systemic barriers to structural change. They point to one case study that involved the Aamjiwnaang First Nation community in Canada. For years, the group has collected data and filed numerous complaints about the dozens of surrounding petrochemical and polymer industrial facilities.10 Yet “despite years of formal complaints supported by empirical evidence,” the authors wrote, “the Canadian Ministry of the Environment continues to approve permits for local polluting industries.”Looking at such cases, the two researchers say, raises a deeply troubling reality: “[Injustice] isn’t because [these communities] lack understanding or education or resources,” says Davis. “It’s the belief that … some people deserve to be the dumping grounds of others. And so even the most robust data set or the snazziest data communication campaign is not going to shake that. You need additional tools.” The authors conclude that project designs that include decision makers and policy goals, as well as increased hiring of faculty of color who can potentially serve as “cultural knowledge brokers,” may be just such tools.     

A New View of the Things We Use: Using Purchasing Data to Predict Common Mixture Exposures

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Humans are exposed to a multitude of chemicals,1 typically in mixtures. Testing substances individually using traditional methods can be time consuming and cost prohibitive;2 the number of possible chemical combinations makes this type of testing unrealistic for mixtures.3 To circumvent these challenges, scientists at the U.S. Environmental Protection Agency (EPA) used a data-driven approach to identify and prioritize relevant chemical combinations, as reported recently in Environmental Health Perspectives.3Open in a separate windowBy identifying patterns in purchasing data, investigators can estimate common ingredient combinations that consumers are exposed to in the products they use regularly. Knowledge of common co-exposures could help direct experimental toxicology assessments. Image: © iStock/Prostock-Studio.Other efforts to identify high-priority co-exposures have not captured the full spectrum of chemical combinations because of either the lack of ingredient information or insufficient purchase and use data.2^,4^,5 “This study is unique because of the way we were able to integrate multiple data sets to improve our overall understanding of human exposure,” says Zachary Stanfield, a postdoctoral researcher at the U.S. EPA and first author of the study.Stanfield and colleagues matched consumer purchasing data from a marketing database compiled in 2012 with ingredient data obtained from the U.S. EPA’s Chemical and Product Database.6 The combined data streams included approximately 2.4 million purchases by about 53,000 households of 31,000 products. Using frequent item set mining,7 a well-established method for identifying patterns in behavior, the group sifted through the extremely high number of theoretical chemical combinations to identify the truly relevant ones.“Our findings show that, from a risk standpoint, we don’t need to concern ourselves with all possible chemical combinations,” notes Kristin Isaacs, senior author of the study. “This ‘top-down’ approach can supplement others that ‘look under the lamppost’ at specific chemicals.”“This is an important start,” says Julia Brody, executive director of the Silent Spring Institute. “It creates a resource so we can evaluate the combined effects on health [of specific chemicals].” She notes that products’ ingredient data were incomplete and calls for additional ingredient disclosure. “In the U.S., manufacturers can use ingredients without testing first for effects on health, and they don’t have to list all the ingredients on product labels, so we’re always playing catch-up to understand how [products] affect people’s health,” she explains. Brody was not involved in the study.The study revealed exposure variations across demographic groups. Focused analysis comparing predominant purchases and demographic patterns showed several distinct patterns. For example, chemical mixtures most frequently encountered by households with children, households headed by women of color, and lower-income households diverged from those encountered by the rest of the study households.“This suggests a need for further study of the product chemical combinations, such as from hair products used by Black women, that may be contributing to health inequalities,” says Brody. More in-depth studies should look at the factors underlying differences in purchasing behavior within households and communities—for example, how choice, brand, or product availability influences chemical mixture exposures. Brody says information like this can better inform public health policy aimed at eliminating racial inequities in environmental health.     

[... formula ...] and Lung Function: An in Vivo Exploration of Potential Climate Change Implications

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Atmospheric carbon dioxide (CO2) hit a milestone in 2015, when global average concentrations reached 400ppm for the first time in recorded history.1 By 2100, the global average could more than double if emissions remain unabated, according to the RCP8.5 (“business as usual”) scenario used by the Intergovernmental Panel on Climate Change in its assessments.2 Although much attention has been paid to the effect of CO2 as a climate forcing agent, multiple reports suggest this greenhouse gas also may have direct health effects.3 A recent report in Environmental Health Perspectives used a mouse model to assess the pulmonary effects of chronic exposure to ambient CO2 at concentrations comparable to those projected by climate modeling.4Open in a separate windowHumans have been exposed to atmospheric CO2 concentrations averaging roughly 230ppm since the time of our earliest ancestor.9^,10 However, intensified human activity and associated CO2 emissions have led to increases of 2–3ppm per year for the past 50 years. In its most recent update as of this writing, Hawaii’s Mauna Loa Observatory reported a seasonally adjusted CO2 concentration of 414.88ppm for the month of December 2020.11 Image: National Aeronautics and Space Administration. Based on data from Lüthi et al. (2008).12A 2019 review in Nature Sustainability summarized evidence on the effects on lung function of very high (>1,000ppm), acute CO2 exposures.3 In contrast, current report is the first known study to directly assess the physiological impact of long-term exposure to CO2 concentrations that are realistically possible in the near future, says first author Alexander Larcombe, an associate professor at the Telethon Kids Institute and Wal-yan Respiratory Research Center in Nedlands, Australia.In the new study, investigators exposed adult female mice and their offspring to either control (approximately465ppm) or elevated (approximately890ppm) concentrations of CO2. Dams began exposure with a 1-week acclimation period before mating, and offspring were exposed from preconception to adulthood. At postnatal week 12, the investigators assessed the offspring’s respiratory function and lung structure. To compare the effects of exposure during lung development versus exposure during adulthood, they also examined the dams’ lung function.Their results indicate that, among female offspring, exposures to high ambient CO2 caused modest measurable changes in lung function and structure compared with exposure to control CO2 levels. The fact that deficits were seen only in offspring suggests the differences were developmental rather than adaptational.Lung development impairment is well documented to occur in a low-oxygen environment (hypoxia);5 however, the exposure model used in this study did not mimic hypoxic conditions, where oxygen levels are significantly lower while CO2 levels remain unchanged. In the lung, gas exchange occurs in tiny air sacs called alveoli, and perturbations in ambient CO2 levels would be expected to result in increased lung area through alveolarization,6 which in the mouse develops almost exclusively after birth.7 Consistent with this notion, male mice exhibited higher numbers of alveoli; conversely, females showed decreased alveolarization. Other markers of lung function suggested that high CO2 exposure affected female mice exclusively.The authors proposed respiratory acidosis, a change in blood chemistry that results from CO2 exposure, as a possible basis for impaired lung function in female mice. However, they explored no foundation for the sex-specific effects.The findings reported by the authors might not rule out an effect on male mice given the relatively small sample size and inherent animal-to-animal variability, cautions Darryl Zeldin, head of the Environmental Cardiopulmonary Disease Group and scientific director of the National Institute of Environmental Health Sciences. Zeldin was not involved in the study.An additional caveat to the study is the choice of animal model. As burrowing animals, mice are more tolerant to elevated CO2 than animals that stay aboveground.8 Larcombe suggests that future studies should address whether similar outcomes occur in larger, nonburrowing mammals, which would help to give further insight into potential implications for human health.     

A Framework for Cumulative Risk Assessment: Exploring the Carcinogenic Effects of Chemical Mixtures

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Humans are commonly exposed to mixtures of chemicals in their environments, rather than to one compound at a time. Accordingly, researchers have long been interested in the complex task of studying how mixtures affect disease end points.1 Cynthia Rider and colleagues recently proposed in Environmental Health Perspectives2 a research program on mixtures and cancer based on the key characteristics of carcinogenic chemicals.3“We wanted to apply what we have learned from studying outcomes with shorter exposure periods to a more complex scenario,” says Rider, a toxicologist at the National Institute of Environmental Health Sciences and first author of the new paper. “Because cancer results from the cumulative impact of multiple low-dose hits in several pathways during a long period of latency, the analysis of mixture effects is especially challenging.”Open in a separate windowAlthough people are exposed to many chemicals over their lifetimes—in food, water, personal care products, air, and other media—toxicology has historically studied agents individually. The authors of a new commentary recommend strategies for studying exposures to chemical mixtures. Image: © iStock/NoSystem Images.Based on literature reviews and expert workshops, the team, organized by Martyn Smith at the University of California, Berkeley, proposed to anchor mixture analyses to a single carcinogen with a known effect. This approach allows researchers to use in vitro or in vivo assays to test specific hypotheses about changes in the dose–response curve when an organism is exposed to other chemicals in combination with the known carcinogen.The proposal’s central tenet is that cancer results from a sequence of exposures to several carcinogens that affect the initiation, promotion, or progression of a slowly unfolding disease process.4^,5 Thus, an appropriate research plan should build on both the key characteristics of carcinogenic chemicals and the hallmarks of cancer. “Key characteristics” refers to qualities or capabilities of a carcinogen that can lead to cancer, such as the ability to induce DNA damage or chronic inflammation, cause genomic instability, or suppress the immune system.3 “Hallmarks” refers to properties of cancer cells that are acquired during tumor formation, such as the ability to proliferate limitlessly and control formation of new blood vessels.6The authors of the new paper proposed three strategies for studying how mixtures affect cancer outcomes. The first, a chemical screening, complements the other two approaches but may also stand alone. This approach involves mining existing data sets to select chemicals with some known link to cancer.The second strategy is a transgenic model-based approach, for which the authors propose the rasH2 mouse 26-week bioassay. Animal models allow researchers to include nonchemical stressors, such as a high-fat diet, and better mimic the complexity of human cancers. “The critical piece for mixture studies is knowing what to expect,” says Rider. “The rasH2 mouse is [a Food and Drug Administration]-approved model with rich historical data for multiple cancers that provides expected joint effects as a benchmark for observed data.”The third strategy, a disease-centered approach, may employ either an animal or in vitro organoid model. Organoid models, which may also be used in the screening approach, are well suited for testing how chemical mixtures affect cancer-relevant pathways or biomarkers.7^,8The authors also recommend experimental designs. For studying poorly understood cancers, they suggest starting with single-compound testing in an in vivo or in vitro screen, followed by high-throughput testing of multiple ratios of two chemicals along a single predicted response plane.9 For mixtures of more than two substances, the authors recommend the fixed ratio ray design,10 which focuses on a single fixed ratio of chemicals.Alan Boobis, an emeritus professor of toxicology at Imperial College London, applauds the authors for addressing a topic whose importance has long been recognized by researchers and funding agencies. He agrees with anchoring mixture tests to a known carcinogen but would not limit animal models to the rasH2 just because it has extensive historical data.“We have seen fantastic advances in systems biology and high-throughput screening technology,” says Boobis, who was not involved in the project. “I consider the rasH2 model a rather blunt instrument that may not provide sufficient power to detect low-dose effects and would prefer newer models that are better suited for proof-of-principle studies.”For Susan Tilton, an associate professor of environmental and molecular toxicology at Oregon State University, the rasH2 model is a reasonable starting point that can be followed up with other models, perhaps designed for nonchemical stressors. “Evaluating mixtures is a challenging task,” she says. “To tackle this complex problem, leveraging a data-rich environment of existing models and toxicity information for individual chemicals is important.” Tilton also was not involved in the project.Andreas Kortenkamp, a professor of human molecular toxicology at Brunel University London, hopes that carcinogenic effects of mixtures can eventually be predicted by modeling approaches alone, without further experiments. Kortenkamp, who also was not involved in the project, says, “This would be particularly attractive for risk assessment by regulatory agencies.”     

A Fix for Fixtures: Addressing Lead Contamination in West African Drinking Water

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Lead in drinking water is an issue of global concern.1 New research published in Environmental Health Perspectives documents the problem in previously unexamined areas of rural West Africa,1 further indicating the wide reach of this harmful contaminant.Lead rarely occurs naturally in drinking water; most often it leaches from lead-bearing plumbing components, such as pipes, solder, or brass fittings. Characteristics of the piped water, such as low pH level or low phosphate content, can cause these components to corrode over time, allowing the metal to contaminate drinking water.2Open in a separate windowThe new study of drinking water in three West African countries pinpoints plumbing fixtures, such as brass taps, as a source of high lead levels. Image: © Riccardo Mayer/Shutterstock.Health scientists have not identified a safe level of lead exposure.3 In children, even low-level exposures may cause nervous system damage, learning disabilities, shorter stature, hearing loss, and impaired formation and function of blood cells.4 Worldwide, an estimated 800,000 children have blood lead levels at or above 5μg/dL,5 the concentration at which the U.S. Centers for Disease Control and Prevention recommend intervention.6In the new study, a team of researchers based at the University of North Carolina (UNC) Water Institute sampled 261 community water systems (hand pumps and public taps) in rural areas of Ghana, Mali, and Niger.In 9% of drinking water samples, lead concentrations exceeded the World Health Organization (WHO) guideline value of 10μg/L.4 Additional testing of metal scrapings obtained from plumbing system components identified lead-containing brass fittings as an important source of contamination, with galvanized steel and other lead-containing materials as secondary sources. The authors concluded that their results are broadly comparable to those obtained from studies in many high-income countries.7^,8^,9 In 2019, the U.S. Geological Survey National Water Quality Program reported analyses of water from more than 8,300 wells across the United States. In about one-third of the wells—concentrated in eastern and southeastern states—they identified characteristics that could cause lead in plumbing components to leach into tap water.10 Similarly, a study of private drinking water systems in Virginia found that 20% of 2,146 tap water samples had lead concentrations exceeding 15μg/L.7Even though the samples from Ghana, Mali, and Niger exceeded regulatory guidelines less frequently than those in the Virginia study, the same underlying issues are responsible: corrosion of lead-containing plumbing components, says Michael Fisher, an assistant professor of environmental sciences and engineering at UNC–Chapel Hill and first author of the new article. “If you look at occurrence and concentrations, I think a strong case can be made that these are qualitatively similar stories about a qualitatively similar process in Virginia and largely rural West Africa settings,” Fisher says. In both settings, testing also revealed an association in tap water between levels of lead and copper, often found together in brass fittings.11Kelsey Pieper, an assistant professor at Northeastern University in Boston, Massachusetts, who served as lead author of the Virginia study, says the new paper is notable for drawing a connection between two seemingly disparate settings and calling attention to lead contamination in a previously understudied context. “I think this paper does a great job of starting a new dialog about lead in drinking water in sub-Saharan Africa. It is starting a discussion that really hasn’t been had before,” she says. Pieper was not involved in the new study.University of South Florida associate professor Jeffrey Cunningham, also not involved in the new study, says the article broadens researchers’ and public health authorities’ understanding of not only where leaded plumbing components are contaminating drinking water sources but also how. Cunningham worked on a 2015 study in Madagascar that found 67% of drinking water samples drawn from household wells had lead concentrations exceeding WHO guidelines.12“One of the big things that I took away from [the new study] is the importance of brass,” Cunningham says, noting that much of the contamination in the Malagasy communities he studied derived from all-lead components fashioned from melted-down car batteries. “As we proceed in our own research,” he says, “I think that’s one of the things that’s going to be important for us to look at.”Fisher suggests that risk of lead exposure can be reduced by using lead-free components when replacing existing fixtures or installing new systems. Getting these components to rural areas that lack easy access, from the United States to Africa and beyond, may require addressing global supply chains. “If the wrong parts are getting into the supply chain and used for drinking water systems in our backyard,” Fisher says, “there may well be an issue globally.”     

A Better Way to Boil: Comparing Methods of Purifying Water at Home

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Despite major gains in access to water, sanitation, and hygiene services around the world, an estimated 2.2billion people still lack access to safe drinking water.1 In places without a potable supply, some households treat their own water, often by boiling. Others use bottled water. But little is known about the relative effectiveness of different boiling methods, the microbiological safety of bottled water compared with public water sources, and the relationship between home water treatment and indoor air pollution. A study recently published in Environmental Health Perspectives explored these questions in rural Chinese communities.2Looking at a representative cross section of households in 15 villages each in Guangxi and Henan Provinces, the authors of the new study collected a variety of data around water sources, sanitation, health, and gender equity. They measured thermotolerant coliforms (TTCs) in samples of drinking water as an indicator of fecal contamination. As TTC counts increase, generally speaking, so too does the expected risk of pathogenic infection.3Open in a separate windowProper sterilization requires bringing water to a rolling boil—not a simmer—for one full minute, or three minutes at elevations above 6,500 feet. Water should then be allowed to cool and stored in a sanitized container with a tight lid.4 Image: © Salineekapui/Shutterstock.The researchers placed temperature sensors on pots and kettles to corroborate self-reported data on boiling times. These data, in turn, were used to estimate household exposure to fine particulate matter (PM2.5) released by burning biomass to heat the water.Approximately 61% of the survey participants boiled their water, 30% used bottled water, and 9% drank untreated water. Overall, some level of TTC was detected in 13.6% of the households using electric kettles and 11.6% of those using open pots, compared with approximately half of both the households using bottled water and those consuming untreated water. Cohen says the frequency of TTC contamination in bottled water suggests the water may be coming from contaminated sources.Electric kettles appeared to be more effective at purifying water than boiling in pots. “Most electric kettles heat the water until the boiling point, so this method typically ensures full inactivation of pathogens,” explains lead author Alasdair Cohen, an assistant professor of Environmental Epidemiology at the Virginia Polytechnic Institute and State University. Kettles also typically have a built-in top that reduces the opportunity for post-boiling secondary contamination. Water in pots, on the other hand, may not be fully brought to boiling because users may mistake a vigorous simmer for a full boil. Pot-boiled water also may become contaminated after treatment.The researchers found it took twice as long to boil water in pots compared with kettles. In most cases, Cohen says, this was due to comparative heating efficiency in biomass- versus electricity-fueled boiling. Across both provinces, the researchers estimated that boiling water in pots resulted in an average household PM2.5 concentration of 79μg/m3. In Guangxi households, where data were available for multiple seasons, average concentrations were much higher in winter than in summer.“This paper brings together primary data and analysis on safe water and household air pollution, fields that are often discussed in completely different literatures,” says Karen Levy, an associate professor of public health at the University of Washington who was not involved in the research.” It is important to break down the silos between these two fields of study because water and energy are so highly interconnected.”“Use of temperature sensors for verification of self-reported boiling data is a new and interesting approach,” Levy adds. “Sensors can add objective, quantitative estimates to study phenomena that are hard to get at with self-reported survey data.” She cautions that some characteristics of the study region—such as near-universal electricity access and common access to piped water—may not apply to other low- and middle-income countries or even other regions in China.“This paper tackles an important topic. Boiling with electric kettles provides a viable alternative with built-in safe water storage for many settings, such as urban slums, where electricity is available but water quality is poor,” says Ayse Ercumen, an assistant professor of Global Water, Sanitation, and Hygiene at North Carolina State University who also was not involved with the study. “Boiling is already practiced for water treatment in many parts of the world, but there have been few efforts to capitalize on this existing practice or rigorously study its impact on health, including trade-offs with household air quality.” Ercumen says a follow-up randomized controlled trial would strengthen the findings.The high level of TTC contamination found in the bottled water has important public health implications for populations that use this commodity. “We were surprised by the relatively high proportion of rural households that used bottled water as their primary source of drinking water,” Cohen says. “International agencies and governments focused on expanding safe drinking water access need to address the various negative impacts associated with increasing bottled water use in China and in other low- and middle-income countries.”     

Cleaning Up after the Cold War: Experts Call for Action on Abandoned Uranium Mines on the Navajo Nation

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An estimated 4,225 abandoned uranium mines formerly operated by the federal government and its contractors in support of Cold War weapons development remain on tribal lands across the U.S. West.1 In light of the significant threats to human health posed by these former mines, particularly via ongoing contamination of surface and groundwater sources,2^,3^,4 a group of experts in Tribal environmental health has proposed a more comprehensive path forward. In a recent commentary in Environmental Health Perspectives, the five authors—four of whom represent different Indigenous North American communities—propose a series of specific policy recommendations for improving upon current approaches toward the enormous and challenging issue of uranium-contaminated water sources.5Open in a separate windowAbandoned uranium mine in Cameron, Arizona, on the Navajo Nation. Photographer Jacqueline Keeler writes that the mine is just 100 yards from Navajo homes. The groundwater in this area is contaminated with uranium. Although safe treated water is available at public watering points, residents must drive about an hour each way to fill up.9 Image: © Jacqueline Keeler.“Flint was the red flag for toxic metals in urban drinking water, but if you look in Indian Country, there are Flints everywhere,” says coauthor Ann Marie Chischilly (Navajo Nation), director of the Institute for Tribal Environmental Professionals at Northern Arizona University and a member of the U.S. Environmental Protection Agency’s National Drinking Water Advisory Council. “But no one knows about all those situations because no one is monitoring, and no one sees the level of toxic metals that our Indigenous peoples are consuming.”As is often the case with environmental remediation, inadequate funding represents a key hurdle, the authors note. Their first recommendation is to increase federal funding for drinking water monitoring and infrastructure on Tribal lands. This call is anchored not only to U.S. Government programs and provisions that protect water quality nationwide, such as the Clean Water Act, but also to a broader United Nations resolution6 recognizing the human right to clean drinking water.The authors’ reminder of a governmental obligation to the general public, however, is followed by another that is specific to the American Indian population: treaty rights dating to the establishment of the reservations themselves that generally ensure safe access to drinking water, among other protections to land, water, and people.Tribes can seek federal grants to help build critical infrastructure for producing and distributing clean water. However, as of 2019, American Indian communities had the highest poverty rate of all census groups.7 Thus, the authors explain, Tribal governments often do not have the resources to apply for grants and provide required financial matches. This financial requirement is not only inequitable, they argue, but also a direct violation of treaty rights.“Treaties are the original bilateral agreements between Indigenous communities and government, which came with a number of points on them,” says lead author Nicole Redvers (Deninu K’ue First Nation), an assistant professor at the University of North Dakota and chair of the Canada-based Arctic Indigenous Wellness Foundation. “Communities definitely still go back to those original treaty agreements as being incredibly important for federal government responsibilities to be upheld, which hasn’t been the case, unfortunately.”In addition to improving funding for monitoring and infrastructure and no longer requiring matching funds for water-related grants, the authors also recommend lowering guideline values for uranium on tribal lands and increasing research on the health effects of uranium ingestion in Indigenous populations.A 2017 study of mining and environmental health disparities in Indigenous communities estimated that approximately 300,000 American Indian people live within 10 km of a uranium mine.8 Abandoned uranium mines can also be a source of arsenic, copper, nickel, and selenium says Johnnye Lewis, lead author of that paper and director of the University of New Mexico METALS Superfund Research Program Center.“These mine wastes are so complex. They’re not even primarily uranium; uranium doesn’t live alone in rock,” says Lewis, who was not involved in the new commentary. “The patterns are a little bit different everywhere you go. Wind and rain can move these metals through air and water and affect resources relied on locally, but [the metals] can also travel to distant communities both on and off Indigenous lands.”The impacts of the abandoned mines are felt most profoundly by those who have lived for decades in their shadow, says Chischilly, who has a homestead on the Navajo Nation. “My hope for this paper,” she says, “is to shed some light on this area that’s not seen, and really advocate and say, ‘Indian Tribes have treaties. Honor them, respect them, and be responsible.’”