Background:

Projected increases in extreme weather may change relationships between rain-related climate exposures and diarrheal disease. Whether rainfall increases or decreases diarrhea rates is unclear based on prior literature. The concentration-dilution hypothesis suggests that these conflicting results are explained by the background level of rain: Rainfall following dry periods can flush pathogens into surface water, increasing diarrhea incidence, whereas rainfall following wet periods can dilute pathogen concentrations in surface water, thereby decreasing diarrhea incidence.

Objectives:

In this analysis, we explored the extent to which the concentration-dilution hypothesis is supported by published literature.

Methods:

To this end, we conducted a systematic search for articles assessing the relationship between rain, extreme rain, flood, drought, and season (rainy vs. dry) and diarrheal illness.

Results:

A total of 111 articles met our inclusion criteria. Overall, the literature largely supports the concentration-dilution hypothesis. In particular, extreme rain was associated with increased diarrhea when it followed a dry period [incidence rate ratio (IRR)=1.26; 95% confidence interval (CI): 1.05, 1.51], with a tendency toward an inverse association for extreme rain following wet periods, albeit nonsignificant, with one of four relevant studies showing a significant inverse association (IRR=0.911; 95% CI: 0.771, 1.08). Incidences of bacterial and parasitic diarrhea were more common during rainy seasons, providing pathogen-specific support for a concentration mechanism, but rotavirus diarrhea showed the opposite association. Information on timing of cases within the rainy season (e.g., early vs. late) was lacking, limiting further analysis. We did not find a linear association between nonextreme rain exposures and diarrheal disease, but several studies found a nonlinear association with low and high rain both being associated with diarrhea.

Discussion:

Our meta-analysis suggests that the effect of rainfall depends on the antecedent conditions. Future studies should use standard, clearly defined exposure variables to strengthen understanding of the relationship between rainfall and diarrheal illness. https://doi.org/10.1289/EHP6181

Background:

In the United States, nationwide estimates of public drinking water arsenic exposure are not readily available. We used the U.S. Environmental Protection Agency’s (EPA) Six-Year Review contaminant occurrence data set to estimate public water arsenic exposure. We compared community water system (CWS) arsenic concentrations during 2006–2008 vs. after 2009–2011, the initial monitoring period for compliance with the U.S. EPA’s 10 μg/L arsenic maximum contaminant level (MCL).

Objective:

Our objective was to characterize potential inequalities in CWS arsenic exposure over time and across sociodemographic subgroups.

Methods:

We estimated 3-y average arsenic concentrations for 36,406 CWSs (98%) and 2,740 counties (87%) and compared differences in means and quantiles of water arsenic (via quantile regression) between both 3-y periods for U.S. regions and sociodemographic subgroups. We assigned CWSs and counties MCL compliance categories (High if above the MCL; Low if below) for each 3-y period.

Results:

From 2006–2008 to 2009–2011, mean and 95th percentile CWS arsenic (in micrograms per liter) declined by 10.3% (95% CI: 6.5%, 14.1%) and 11.5% (8.3%, 14.8%) nationwide, by 11.4% (4.7%, 18.1%) and 16.3% (8.1%, 24.5%) for the Southwest, and by 36.8% (7.4%, 66.1%) and 26.5% (12.1%, 40.8%) for New England, respectively. CWSs in the High/High compliance category (not MCL compliant) were more likely in the Southwest (61.1%), served by groundwater (94.7%), serving smaller populations (mean 1,102 persons), and serving Hispanic communities (38.3%).

Discussion:

Larger absolute declines in CWS arsenic concentrations at higher water arsenic quantiles indicate declines are related to MCL implementation. CWSs reliant on groundwater, serving smaller populations, located in the Southwest, and serving Hispanic communities were more likely to continue exceeding the arsenic MCL, raising environmental justice concerns. These estimates of public drinking water arsenic exposure can enable further surveillance and epidemiologic research, including assessing whether differential declines in water arsenic exposure resulted in differential declines in arsenic-associated disease. https://doi.org/10.1289/EHP7313

Background:

Inadequate access to safe drinking water remains a global health problem, particularly in rural areas. Boiling is the most commonly used form of point-of-use household water treatment (HWT) globally, although the use of bottled water in low- and middle-income countries (LMICs) is increasing rapidly.

Objectives:

We assessed the regional and seasonal prevalence of HWT practices (including bottled water use) in low-income rural areas in two Chinese provinces, evaluated the microbiological safety of drinking water and associated health outcomes, and estimated the air pollution burden associated with the use of solid fuels for boiling.

Methods:

We conducted cross-sectional surveys and collected drinking water samples from 1,033 rural households in Guangxi and Henan provinces. Temperature sensors affixed to pots and electric kettles were used to corroborate self-reported boiling frequencies and durations, which were used to model household air pollution (HAP) in terms of estimated particulate matter ≤2.5μm in aerodynamic diameter (PM2.5) concentrations.

Results:

Based on summer data collection in both provinces, after controlling for covariates, boiling with electric kettles was associated with the largest log reduction in thermotolerant coliforms (TTCs) (−0.66 log10 TTC most probable number/100mL), followed by boiling with pots (−0.58), and bottled water use (−0.39); all were statistically significant (p<0.001). Boiling with electric kettles was associated with a reduced risk of TTC contamination [risk ratio (RR)=0.25, p<0.001] and reported diarrhea (RR=0.80, p=0.672). TTCs were detected in 51% (n=136) of bottled water samples. For households boiling with biomass, modeled PM2.5 concentrations averaged 79 μg/m3 (standard deviation=21).

Discussion:

Our findings suggest that where boiling is already common and electricity access is widespread, the promotion of electricity-based boiling may represent a pragmatic stop-gap means of expanding safe water access until centralized, or decentralized, treated drinking water is available; displacing biomass use for water boiling could also reduce HAP concentrations and exposures. Our results also highlight the risks of increasing bottled water use in rural areas, and its potential to displace other sources of safe drinking water, which could in turn hamper efforts in China and other LMICs toward universal and affordable safe water access. https://doi.org/10.1289/EHP7124

Background:

Traffic-related air pollution (TRAP) is made up of complex mixtures of particulate matter, gases and volatile compounds. However, the effects of TRAP on the cardiopulmonary system in most animal studies have been tested using acute exposure to singular pollutants. The cardiopulmonary effects and molecular mechanisms in animals that are chronically exposed to unmodified air pollution as a whole have yet to be studied. Additionally, sex-dependent toxicity of TRAP exposure has rarely been evaluated.

Objectives:

This study sought to assess the cardiopulmonary effect of chronic exposure to unmodified, real-world TRAP in both female and male rats.

Methods:

Four-week-old male and female rats were exposed to TRAP or filtered air for 14 months in a novel facility drawing air from a major freeway tunnel system in Northern California. Inflammation and oxidative stress markers were examined in the lung, heart, spleen, and plasma, and TRAP deposits were quantified in the lungs of both male and female rats.

Results:

Elemental analysis showed higher levels of eight elements in the female lungs and one element in the male lungs. Expression of genes related to fibrosis, aging, oxidative stress, and inflammation were higher in the rat hearts exposed to TRAP, with female rats being more susceptible than males. Enhanced collagen accumulation was found only in the TRAP-exposed female hearts. Plasma cytokine secretion was higher in both female and male rats, but inflammatory macrophages were higher only in TRAP-exposed male spleens.

Discussion:

Our results in rats suggest pathological consequences from chronic TRAP exposure, including sex differences indicating females may be more susceptible to TRAP-induced cardiac fibrosis. https://doi.org/10.1289/EHP7045

Background:

Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus.

Objectives:

We examined the association of cadmium burden with mortality related to influenza or pneumonia.

Methods:

This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants ≥45 years of age enrolled in NHANES-III and NHANES 1999–2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999–2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations.

Results:

In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p=0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p=0.002) among never smokers. In NHANES 1999–2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p=0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p=0.07) in never smokers.

Discussion:

Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections. https://doi.org/10.1289/EHP7598

Background:

Bisphenol A (BPA) is known to be biologically active in experimental models even at low levels of exposure. However, its impact on endometrial cancer remains unclear.

Objectives:

This study aimed to investigate whether lifelong exposure to different doses of BPA induced uterine abnormalities and molecular changes in a rat model.

Methods:

Sprague-Dawley rats were exposed to 5 doses of BPA [0, 25, 250, 2,500, or 25,000μg/kg body weight (BW)/d] or 2 doses of 17α−ethynylestradiol (EE2) (0.05 and 0.5μg/kg BW/d) starting from gestational day 6 up to 1 y old according to the CLARITY-BPA consortium protocol. The BW, uterus weight, and histopathology end points of the uteri were analyzed at postnatal (PND) day 21, 90, and 365. Estrous cycling status was evaluated in PND90 and PND365 rats. Transcriptomic analyses of estrus stage uteri were conducted on PND365 rats.

Results:

Based on the analysis of the combined effects of all testing outcomes (including immunohistological, morphological, and estrous cycle data) in a semiblinded fashion, using statistical models, 25μg/kg BW/d BPA [BPA(25)], or 250μg/kg BW/d BPA [BPA(250)] exerted effects similar to that of EE2 at 0.5μg/kg BW/d in 1-y-old rats. Transcriptome analyses of estrus stage uteri revealed a set of 710 genes shared only between the BPA(25) and BPA(250) groups, with 115 of them predicted to be regulated by estradiol and 57 associated with female cancers. An interesting finding is that the expression of 476 human orthologous genes in this rat BPA signature robustly predicted the overall survival (p=1.68×10−5, hazard ratio=2.62) of endometrial cancer patients.

Discussion:

Lifelong exposure of rats to low-dose BPA at 25 and 250μg/kg BW/d altered the estrous cycle and uterine pathology with similarity to EE2. The exposure also disrupted a unique low-dose BPA-gene signature with predictive value for survival outcomes in patients with endometrial cancer. https://doi.org/10.1289/EHP6875

Background:

Aryl phosphate esters (APEs) are widely used and commonly present in the environment. Health hazards associated with these compounds remain largely unknown and the effects of diphenyl phosphate (DPhP), one of their most frequent derivatives, are poorly characterized.

Objective:

Our aim was to investigate whether DPhP per se may represent a more relevant marker of exposure to APEs than direct assessment of their concentration and determine its potential deleterious biological effects in chronically exposed mice.

Methods:

Conventional animals (FVB mice) were acutely or chronically exposed to relevant doses of DPhP or to triphenyl phosphate (TPhP), one of its main precursors. Both molecules were measured in blood and other tissues by liquid chromatography–mass spectrometry (LC-MS). Effects of chronic DPhP exposure were addressed through liver multi-omics analysis to determine the corresponding metabolic profile. Deep statistical exploration was performed to extract correlated information, guiding further physiological analyses.

Results:

Multi-omics analysis confirmed the existence of biological effects of DPhP, even at a very low dose of 0.1mg/mL in drinking water. Chemical structural homology and pathway mapping demonstrated a clear reduction of the fatty acid catabolic processes centered on acylcarnitine and mitochondrial β-oxidation in mice exposed to DPhP in comparison with those treated with vehicle. An interesting finding was that in mice exposed to DPhP, mRNA, expression of genes involved in lipid catabolic processes and regulated by peroxisome proliferator–activated receptor alpha (PPARα) was lower than that in vehicle-treated mice. Immunohistochemistry analysis showed a specific down-regulation of HMGCS2, a kernel target gene of PPARα. Overall, DPhP absorption disrupted body weight–gain processes.

Conclusions:

Our results suggest that in mice, the effects of chronic exposure to DPhP, even at a low dose, are not negligible. Fatty acid metabolism in the liver is essential for controlling fast and feast periods, with adverse consequences on the overall physiology. Therefore, the impact of DPhP on circulating fat, cardiovascular pathologies and metabolic disease incidence deserves, in light of our results, further investigations. https://doi.org/10.1289/EHP6826

Background:

Despite the substantial role indoor exposure has played in heat wave–related mortality, few epidemiological studies have examined the health effects of exposure to indoor heat. As a result, knowledge gaps regarding indoor heat–health thresholds, vulnerability, and adaptive capacity persist.

Objective:

We evaluated the role of indoor heat exposure on mortality and morbidity among the elderly (≥65 years of age) in Houston, Texas.

Methods:

Mortality and emergency hospital admission data were obtained through the Texas Department of State Health Services. Summer indoor heat exposure was modeled at the U.S. Census block group (CBG) level using building energy models, outdoor weather data, and building characteristic data. Indoor heat–health associations were examined using time-stratified case-crossover models, controlling for temporal trends and meteorology, and matching on CBG of residence, year, month, and weekday of the adverse health event. Separate models were fitted for three indoor exposure metrics, for individual lag days 0–6, and for 3-d moving averages (lag 0–2). Effect measure modification was explored via stratification on individual- and area-level vulnerability factors.

Results:

We estimated positive associations between short-term changes in indoor heat exposure and cause-specific mortality and morbidity [e.g., circulatory deaths, odds ratio per 5°C increase=1.16 (95% CI: 1.03, 1.30)]. Associations were generally positive for earlier lag periods and weaker across later lag periods. Stratified analyses suggest stronger associations between indoor heat and emergency hospital admissions among African Americans compared with Whites.

Discussion:

Findings suggest excess mortality among certain elderly populations in Houston who are likely exposed to high indoor heat. We developed a novel methodology to estimate indoor heat exposure that can be adapted to other U.S. locations. In locations with high air conditioning prevalence, simplified modeling approaches may adequately account for indoor heat exposure in vulnerable neighborhoods. Accounting for indoor heat exposure may improve the estimation of the total impact of heat on health. https://doi.org/10.1289/EHP6340

Background:

Humans are constantly being exposed to various xenobiotics at relatively low concentrations. To date, limited evidence is available to ascertain whether a complex xenobiotic mixture at human-relevant levels causes any health effect. Moreover, there is no effective method to pinpoint the contribution of each chemical toward such an effect.

Objectives:

This study aims to understand the responses of cells to a mixture containing 23 xenobiotics at human-relevant levels and develop a feasible method to decipher the chemical(s) that contribute significantly to the observed effect.

Methods:

We characterized the metabolome and transcriptome of breast cancer cells (MCF-7) before and after exposure to the mixture at human-relevant levels; preexposure levels were derived from existing large-scale biomonitoring data. A high-throughput metabolomics-based “leave-one-out” method was proposed to understand the relative contribution of each component by comparing the metabolome with and without the particular chemical in the mixture.

Results:

The metabolomic analysis suggested that the mixture altered metabolites associated with cell proliferation and oxidative stress. For the transcriptomes, gene ontology terms and pathways including “cell cycle,” “cell proliferation,” and “cell division” were significantly altered after mixture exposure. The mixture altered genes associated with pathways such as “genotoxicity” and “nuclear factor erythroid 2-related factor 2 (Nrf2).” Through joint pathways analysis, metabolites and genes were observed to be well-aligned in pyrimidine and purine metabolisms. The leave-one-out results showed that many chemicals made their contributions to specific metabolic pathways. The overall metabolome pattern of the absence of 2,4-dihyroxybenzophenone (DHB) or bisphenol A (BPA) showed great resemblance to controls, suggesting their higher relative contribution to the observed effect.

Discussion:

The omics results showed that exposure to the mixture at human-relevant levels can induce significant in vitro cellular changes. Also, the leave one out method offers an effective approach for deconvoluting the effects of the mixture. https://doi.org/10.1289/EHP6641

Background:

Arsenic and cadmium are known cardiovascular toxicants that pose disproportionate risk to rural communities where environmental exposures are high. American Indians have high vascular risk, which may be attributable in part to these exposures.

Objective:

We examined urine metal concentrations in association with magnetic resonance imaging findings of vascular brain injury or cerebral atrophy in adult American Indians.

Methods:

We measured arsenic and cadmium in American Indian participants from the Strong Heart Study (1989–1991) and evaluated these associations with later (2010–2013) measures of infarct, hemorrhage, white matter hyperintensity (WMH) grade, brain and hippocampal volume, and sulcal and ventricle atrophy using nested multivariate regression analyses.

Results:

Among participants with available data (N=687), the median urine arsenic:creatinine ratio was 7.54μg/g [interquartile range (IQR): 4.90–11.93] and the cadmium:creatinine ratio was 0.96μg/g (IQR: 0.61–1.51). Median time between metal measurement and brain imaging was 21 y (range: 18–25 y). Statistical models detected significant associations between arsenic and higher burden of WMH [grade increase=0.014 (95% CI: 0.000, 0.028) per 10% increase in arsenic]; and between cadmium and presence of lacunar infarcts [relative risk (RR)=1.024 (95% CI: 1.004, 1.045) per 10% increase in cadmium].

Discussion:

This population-based cohort of American Indian elders had measured values of urine arsenic and cadmium several times higher than previous population- and clinic-based studies in the United States and Mexico, and comparable values with European industrial workers. Our findings of associations for arsenic and cadmium exposures with vascular brain injury are consistent with established literature. Environmental toxicant accumulation is modifiable; public health policy may benefit from focusing on reductions in environmental metals. https://doi.org/10.1289/EHP6930