Tampons as a source of exposure to metal(loid)s.

BACKGROUND: Between 52-86% of people who menstruate in the United States use tampons-cotton and/or rayon/viscose 'plugs'-to absorb menstrual blood in the vagina. Tampons may contain metals from agricultural or manufacturing processes, which could be absorbed by the vagina's highly absorptive tissue, resulting in systemic exposure. To our knowledge, no previous studies have measured metals in tampons. OBJECTIVES: We evaluated the concentrations of 16 metal(loid)s in 30 tampons from 14 tampon brands and 18 product lines and compared the concentrations by tampon characteristics. METHODS: About 0.2 - 0.3 g from each tampon (n = 60 samples) were microwave-acid digested and analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine concentrations of arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, manganese, mercury, nickel, lead, selenium, strontium, vanadium, and zinc. We compared concentrations by several tampon characteristics (region of purchase, organic material, brand type) using median quantile mixed models. RESULTS: We found measurable concentrations of all 16 metals assessed. We detected concentrations of several toxic metals, including elevated mean concentrations of lead (geometric mean [GM] = 120 ng/g), cadmium (GM = 6.74 ng/g), and arsenic (GM = 2.56 ng/g). Metal concentrations differed by region of tampon purchase (US versus European Union/United Kingdom), by organic versus non-organic material, and for store- versus name-brand tampons. Most metals differed by organic status; lead concentrations were higher in non-organic tampons while arsenic was higher in organic tampons. No categoriy had consistently lower concentrations of all or most metals. DISCUSSION: Tampon use is a potential source of metal exposure. We detected all 16 metals in at least one sampled tampon, including some toxic metals like lead that has no "safe" exposure level. Future research is needed to replicate our findings and determine whether metals can leach out of tampons and cross the vaginal epithelium into systemic circulation.

Regulation-driven changes in PM2.5 sources in China from 2013 to 2019, a critical review and trend analysis.

Identifying changes in source-specific fine particles (PM2.5) over time is essential for evaluating the effectiveness of regulatory measures and informing future policy decisions. After the extreme haze events in China during 2013-14, more comprehensive and stringent policies were implemented to combat PM2.5 pollution. To determine the effectiveness of these policies, it is necessary to assess the changes in the specific source types to which the regulations pertain. Multiple studies have been conducted over the past decade to apportion PM2.5. The purpose of this study was to explore the available literature and conduct a critical review of the reliable results. In total, 5008 articles were screened, but only 48 studies were included for further analysis given our inclusion criteria including covering a monitoring period of ≥1 year and having enough speciation data to provide mass closure. Using these studies, we analyzed temporal and spatial trends across China from 2013 to 2019. We observed the overall decrease in the concentration contributions from all main source categories. The reductions from industry, coal and heavy oil combustion, and the related secondary sulfate were more notable, especially from 2013 to 2016-17. The contributions from biomass burning initially decreased but then increased slightly after 2016 in some locations despite new constraints on agricultural and household burning practices. Although the contributions from vehicle emissions and related secondary nitrate decreased, they gradually became the primary contributors to PM2.5 by ∼2017. Despite the substantial improvements achieved by the air pollution regulation implementations, further improvements in air quality will require additional aggressive actions, especially those targeting vehicular emissions. Ultimately, source apportionment studies based on extended duration, fixed-site sampling are recommended to provide a more thorough understanding of the sources impacting areas and transformations in PM2.5 sources prompted by regulatory actions.

Rapid single-particle chemical imaging of nanoplastics by SRS microscopy.

Plastics are now omnipresent in our daily lives. The existence of microplastics (1 µm to 5 mm in length) and possibly even nanoplastics (<1 µm) has recently raised health concerns. In particular, nanoplastics are believed to be more toxic since their smaller size renders them much more amenable, compared to microplastics, to enter the human body. However, detecting nanoplastics imposes tremendous analytical challenges on both the nano-level sensitivity and the plastic-identifying specificity, leading to a knowledge gap in this mysterious nanoworld surrounding us. To address these challenges, we developed a hyperspectral stimulated Raman scattering (SRS) imaging platform with an automated plastic identification algorithm that allows micro-nano plastic analysis at the single-particle level with high chemical specificity and throughput. We first validated the sensitivity enhancement of the narrow band of SRS to enable high-speed single nanoplastic detection below 100 nm. We then devised a data-driven spectral matching algorithm to address spectral identification challenges imposed by sensitive narrow-band hyperspectral imaging and achieve robust determination of common plastic polymers. With the established technique, we studied the micro-nano plastics from bottled water as a model system. We successfully detected and identified nanoplastics from major plastic types. Micro-nano plastics concentrations were estimated to be about 2.4 ± 1.3 × 105 particles per liter of bottled water, about 90% of which are nanoplastics. This is orders of magnitude more than the microplastic abundance reported previously in bottled water. High-throughput single-particle counting revealed extraordinary particle heterogeneity and nonorthogonality between plastic composition and morphologies; the resulting multidimensional profiling sheds light on the science of nanoplastics.

Molecular Imaging Reveals Two Distinct Mixing States of PM2.5 Particles Sampled in a Typical Beijing Winter Pollution Case.

Mixing states of aerosol particles are crucial for understanding the role of aerosols in influencing air quality and climate. However, a fundamental understanding of the complex mixing states is still lacking because most traditional analysis techniques only reveal bulk chemical and physical properties with limited surface and 3-D information. In this research, 3-D molecular imaging enabled by ToF-SIMS was used to elucidate the mixing states of PM2.5 samples obtained from a typical Beijing winter haze event. In light pollution cases, a thin organic layer covers separated inorganic particles; while in serious pollution cases, ion exchange and an organic-inorganic mixing surface on large-area particles were observed. The new results provide key 3-D molecular information of mixing states, which is highly potential for reducing uncertainty and bias in representing aerosol-cloud interactions in current Earth System Models and improving the understanding of aerosols on air quality and human health.

Trends of source apportioned PM2.5 in Tianjin over 2013-2019: Impacts of Clean Air Actions.

A long-term (2013-2019) PM2.5 speciation dataset measured in Tianjin, the largest industrial city in northern China, was analyzed with dispersion normalized positive matrix factorization (DN-PMF). The trends of source apportioned PM2.5 were used to assess the effectiveness of source-specific control policies and measures in support of the two China's Clean Air Actions implemented nationwide in 2013-2017 and 2018-2020, respectively. Eight sources were resolved from the DN-PMF analysis: coal combustion (CC), biomass burning (BB), vehicular emissions, dust, steelmaking and galvanizing emissions, a mixed sulfate-rich factor and secondary nitrate. After adjustment for meteorological fluctuations, a substantial improvement in PM2.5 air quality was observed in Tianjin with decreases in PM2.5 at an annual rate of 6.6%/y. PM2.5 from CC decreased by 4.1%/y. The reductions in SO2 concentration, PM2.5 contributed by CC, and sulfate demonstrated the improved control of CC-related emissions and fuel quality. Policies aimed at eliminating winter-heating pollution have had substantial success as shown by reduced heating-related SO2, CC, and sulfate from 2013 to 2019. The two industrial source types showed sharp drops after the 2013 mandated controls went into effect to phaseout outdated iron/steel production and enforce tighter emission standards for these industries. BB reduced significantly by 2016 and remained low due to the no open field burning policy. Vehicular emissions and road/soil dust declined over the Action's first phase followed by positive upward trends, showing that further emission controls are needed. Nitrate concentrations remained constant although NOX emissions dropped significantly. The lack of a decrease in nitrate may result from increased ammonia emissions from enhanced vehicular NOX controls. The port and shipping emissions were evident implying their impacts on coastal air quality. These results affirm the effectiveness of the Clean Air Actions in reducing primary anthropogenic emissions. However, further emission reductions are needed to meet global health-based air quality standards.

A Systematic Review of the Placental Translocation of Micro- and Nanoplastics.

PURPOSE OF REVIEW: Despite increasing awareness of the ubiquity of microplastics (MPs) in our environments, little is known about their risk of developmental toxicity. Even less is known about the environmental distribution and associated toxicity of nanoplastics (NPs). Here, we review the current literature on the capacity for MPs and NPs to be transported across the placental barrier and the potential to exert toxicity on the developing fetus. RECENT FINDINGS: This review includes 11 research articles covering in vitro, in vivo, and ex vivo models, and observational studies. The current literature confirms the placental translocation of MPs and NPs, depending on physicochemical properties such as size, charge, and chemical modification as well as protein corona formation. Specific transport mechanisms for translocation remain unclear. There is emerging evidence of placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Nine out of eleven studies examined in this review found that plastic particles were capable of placental translocation. In the future, more studies are needed to confirm and quantify the existence of MPs and NPs in human placentas. Additionally, translocation of different plastic particle types and heterogenous mixtures across the placenta, exposure at different periods of gestation, and associations with adverse birth and other developmental outcomes should also be investigated.

Rapid LC-MS/MS quantification of Organophosphate non-specific metabolites in hair using alkaline extraction approach.

Assessing human exposure to commonly used, highly toxic, but non-persistent organophosphates (OPs) is challenging because these toxicants are readily biotransformed into dialkyl phosphates (DAPs) and other metabolites. Growing hair accumulates toxicants and their metabolites, which makes hair a valuable non-invasively sampled matrix that can be used to retrospectively examine chemical exposure. However, the efficient quantification of hydrophilic DAP compounds in hair is challenging due to complex hair matrix effects. To improve upon existing methods, we first examined the acid dissociation constants (pKa) of DAPs and amino acids (major components in hair) and identified the best pH conditions for minimizing matrix effects. We hypothesized that under basic pH conditions DAPs and amino acids would be negatively charged and have weak interactions favorable to DAP dissociation from the matrix. To test this, we compared the efficiency of various pH conditions of suitable solvents to extract six DAPs from hair samples, and we quantified these DAPs using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). As expected, a basic extraction (methanol with 2% NH4OH) approach had the highest extraction efficiency and yielded satisfactory recoveries for all six DAPs (72%-152%) without matrix effects. Additionally, the alkaline extract can be directly injected into the LC-MS/MS. This relatively rapid and simple procedure allowed us to process up to 90 samples per week with reproducible results. To our knowledge, this is the first method to quantify all six DAPs simultaneously in hair using LC-MS/MS with electrospray ionization (ESI) in negative ion mode. Finally, we demonstrated the feasibility of measuring DAP levels in hair samples from patients affected with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease potentially linked to OP exposure. Due to our optimized solvent extraction process, the method we have developed is compatible with the rapidity and sensitivity needed for hair analysis applied to population biomonitoring.

Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.

Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons and Timing of Pubertal Development: The California PAH Study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals. Few studies have evaluated the association between pubertal development in girls and PAH exposures quantified by urinary biomarkers. METHODS: We examined associations of urinary PAH metabolites with pubertal development in 358 girls 6-16 years of age from the San Francisco Bay Area enrolled in a prospective cohort from 2011 to 2013 and followed until 2020. Using baseline data, we assessed associations of urinary PAH metabolites with pubertal development stage. In prospective analyses limited to girls who at baseline had not yet started breast (N = 176) or pubic hair (N = 179) development or menstruation (N = 267), we used multivariable Cox proportional hazards regression to assess associations of urinary PAH metabolites with the onset of breast and pubic hair development, menstruation, and pubertal tempo (interval between the onset of breast development and menstruation). RESULTS: We detected PAH metabolites in >98% of girls. In cross-sectional analyses using baseline data, PAH metabolites were not associated with the pubertal development stage. In prospective analyses, higher concentrations (≥ median) of some PAH metabolites were associated with two-fold higher odds of earlier breast development (2-hydroxy naphthalene, 1-hydroxy phenanthrene, summed hydroxy phenanthrenes) or pubic hair development (1-hydroxy naphthalene) among girls overweight at baseline (body mass index-for-age percentile ≥85) compared with nonoverweight girls with lower metabolites concentrations. PAH metabolites were not associated with age at menarche or pubertal tempo. CONCLUSIONS: PAH exposures were widespread in our sample. Our results support the hypothesis that, in overweight girls, PAHs impact the timing of pubertal development, an important risk factor for breast cancer.

Risk of illness-related school absenteeism for elementary students with exposure to PM2.5 and O3.

Air pollution addresses short-term health effects on morbidity, especially for children. Assessing the impacts of air pollution on elementary students is critical for developing preparedness response strategies for this sensitive group. In the 2016-17 academic year, up to 687,748 groups of illness-related absence records and the information on whether the absentee had gone to a hospital or not were collected from 2564 elementary schools across Jiangsu Province China. We explored the associations between air pollution and illness-related records using a time-stratified case-crossover analysis with distributed lag non-linear design. An increase of 10 µg/m3 in the current-day concentration of PM2.5 and O3 was positively associated with illness-related absenteeism overall. The excess risk of absenteeism was 4.52 % (95%CI 4.37-4.67 %) for PM2.5 and 0.25 % (95%CI 0.01-0.36 %) for O3. The risk associated with O3 was boosted for the frequent absentees who tended to have basic diseases or were more vulnerable to infectious diseases. Students in 43.1 % illness-related absenteeism, mainly due to highly infectious diseases, only received home nursing without going to a hospital. The increase in the number of illness cases associated with PM2.5 and O3 estimated based on the illness-related absence data was 41.5 % and 18.6 % higher than that evaluated based on hospital visit records. Such underestimations persisted in sensitivity analyses and persisted in subgroups classified by gender or grade. Together, the performance of illness-related absence records far outweighed that of hospital visit data regarding the thorough evaluation of air pollution-related illness cases for elementary students. Improvement in air quality and home health care education are warranted as well for the health benefits of children.

Improvement on recovery and reproducibility for quantifying urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs).

Efficient and reproducible measurements of multiple polycyclic aromatic hydrocarbon (PAH) metabolites in urinary samples are required to evaluate the complex health effects of PAH exposure. Here, we demonstrate a highly practical, automated off-line solid-phase extraction (SPE) of deconjugated hydroxylated PAHs followed by LC-MS/MS to simultaneously measure eight mono-hydroxylated PAH compounds: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 2&3-hydroxyphenanthrene, 4-hydroxyphenanthrene and 1-hydroxypyrene. Initially, we observed low recovery rates (e.g., 16% for 1-hydroxypyrene) when using previously published methods. We optimized the procedure by choosing polymeric absorbent-based cartridges, automating the sample loading step by diluting samples with 15% methanol/sodium acetate, and most importantly, replacing acetonitrile with methanol as the eluting solvent. Optimized sample preparation has improved the recovery rates to more than 69% for analytes of interest. This improvement led to higher method sensitivity and detection frequency, especially for 1-hydroxypyrene, in all of 100 urine samples collected in the New York City site of the Legacy Girls Study. The limits of detection ranged from 7.6 pg/mL to 20.3 pg/mL using 1 mL of urine, compared to the 2 mL required in CDC, method 09-OD. The average coefficients of variance of quality control samples (n = 60) ranged between 7 and 21%; variance of repeated measurements (n = 45) was less than 10%. This efficient and reliable method for measuring PAH metabolites will greatly benefit epidemiology studies and biomonitoring programs.

A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk.

Multiple studies indicate that United States veterans have an increased risk of developing amyotrophic lateral sclerosis (ALS) compared to civilians. However, the responsible etiological factors are unknown. In the general population, specific occupational (e.g. truck drivers, airline pilots) and environmental exposures (e.g. metals, pesticides) are associated with an increased ALS risk. As such, the increased prevalence of ALS in veterans strongly suggests that there are exposures experienced by military personnel that are disproportionate to civilians. During service, veterans may encounter numerous neurotoxic exposures (e.g. burn pits, engine exhaust, firing ranges). So far, however, there is a paucity of studies investigating environmental factors contributing to ALS in veterans and even fewer assessing their exposure using biomarkers. Herein, we discuss ALS pathogenesis in relation to a series of persistent neurotoxicants (often emitted as mixtures) including: chemical elements, nanoparticles and lipophilic toxicants such as dioxins, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. We propose these toxicants should be directly measured in veteran central nervous system tissue, where they may have accumulated for decades. Specific toxicants (or mixtures thereof) may accelerate ALS development following a multistep hypothesis or act synergistically with other service-linked exposures (e.g. head trauma/concussions). Such possibilities could explain the lower age of onset observed in veterans compared to civilians. Identifying high-risk exposures within vulnerable populations is key to understanding ALS etiopathogenesis and is urgently needed to act upon modifiable risk factors for military personnel who deserve enhanced protection during their years of service, not only for their short-term, but also long-term health.

Predictors of urinary polycyclic aromatic hydrocarbon metabolites in girls from the San Francisco Bay Area.

BACKGROUND: Polycyclic aromatic hydrocarbon (PAH) exposures from tobacco smoke, automobile exhaust, grilled or smoked meat and other sources are widespread and are a public health concern, as many are classified as probable carcinogens and suspected endocrine-disrupting chemicals. PAH exposures can be quantified using urinary biomarkers. METHODS: Seven urinary metabolites of naphthalene, fluorene, phenanthrene, and pyrene were measured in two samples collected from girls aged 6-16 years from the San Francisco Bay Area. We used Spearman correlation coefficients (SCC) to assess correlations among metabolite concentrations (corrected for specific gravity) separately in first (n = 359) and last (N = 349) samples, and to assess consistency of measurements in samples collected up to 72 months apart. Using multivariable linear regression, we assessed variation in mean metabolites across categories of participant characteristics and potential outdoor, indoor, and dietary sources of PAH exposures. RESULTS: The detection rate of PAH metabolites was high (4 metabolites in ≥98% of first samples; 5 metabolites in ≥95% of last samples). Correlations were moderate to strong between fluorene, phenanthrene and pyrene metabolites (SCC 0.43-0.82), but weaker between naphthalene and the other metabolites (SCC 0.18-0.36). SCC between metabolites in first and last samples ranged from 0.15 to 0.49. When classifying metabolite concentrations into tertiles based on single samples (first or last samples) vs. the average of the two samples, agreement was moderate to substantial (weighted kappa statistics 0.52-0.65). For specific metabolites, concentrations varied by age, race/ethnicity, and body mass index percentile, as well as by outdoor sources (season of sample collection, street traffic), indoor sources (heating with gas, cigarette smoke), and dietary sources (frequent use of grill, consumption of smoked meat or fish) of PAH exposures. CONCLUSIONS: Urinary PAH exposure was widespread in girls aged 6-16 years and associated with several sources of exposure. Tertile classification of a single urine sample provides reliable PAH exposure ranking.

Composition of fine particulate matter and risk of preterm birth: A nationwide birth cohort study in 336 Chinese cities.

BACKGROUND: Potential hazards of fine particulate matter (PM2.5) constituents on preterm birth (PTB) have rarely been explored in China. OBJECTIVE: To quantify the associations of PM2.5 constituents with PTB. METHODS: This study was based on a nationwide cohort of 3,723,169 live singleton births delivered between January 2010 and December 2015 in China. We applied satellite-based estimates of 5 PM2.5 constituents (organic carbon; black carbon; sulfate; ammonium; and nitrate). We used Cox proportional hazards regression models adjusted for individual covariates, temperature, humidity, and seasonality to evaluate the associations. RESULTS: During the entire pregnancy, each interquartile range (29 µg/m3) increase in PM2.5 concentrations was associated with a 7% increase in PTB risk [hazard ratio (HR): 1.07; 95% confidence interval (CI): 1.07-1.08). We observed the largest effect estimates on carbonaceous components (HR: 1.09; 95% CI: 1.08-1.10 for organic carbon and black carbon). Early pregnancy appeared to be the critical exposure window for most constituents. Women who were older, exposed to second-hand smoke, overweight or obese before pregnancy, conceived during winter, and living in northern China or rural areas were more susceptible. CONCLUSIONS: Carbonaceous components of PM2.5 were associated with higher PTB risk. Findings on characteristics of vulnerability underlined targeted protections on susceptible subgroups.

Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with M1-type macrophage activation. Mesenchymal stem cells (MSCs) therapies have shown promise in models of pathologies relevant to SLE, while the function and mechanism of MSC-derived exosomes (MSC-exo) were still unclear. We aimed to interrogate the effect of MSC-exo on M1-type polarization of macrophage and investigate mechanisms underlying MSC-exo. Exosomes were isolated from MSC and the effect of MSC-exo on macrophage polarization was evaluated. The key tRNA-derived fragments (tRFs) carried by exosomes were identified by small RNA sequencing and verified in clinical samples. The effect of exosomal-tRFs on macrophage polarization was examined. In this study, MSC-exo dramatically suppressed expression of M1 markers, and reduced the levels of TNF-α and IL-1ß, while increased M2 markers in macrophages. A total of 243 differently expressed tRFs (DEtRFs) were identified between MSC-exo treated and untreated macrophage, among which 103 DEtRFs were up-regulated in response to MSC-exo treatment, including tsRNA-21109. The target genes of tsRNA-21109 were mainly enriched in DNA transcription-related GO function, and mainly involved in inflammatory-related pathways, including Rap1, Ras, Hippo, Wnt, MAPK, TGF-beta signaling pathway. The tsRNA-21109 was lowly expressed in clinical samples and was associated with the patient data in SLE. Compared to the normal MSC-exo, the tsRNA-21109-privative MSC-exo up-regulated M1 marker (CD80, NOS2, MCP1) and down-regulated M2 marker (CD206, ARG1, MRC2), also increased the levels of TNF-α and IL-1ß in macrophages. Western blot and immunofluorescence confirmed that the proportion of CD80/ARG-1 was increased in macrophages treated with tsRNA-21109-privatived MSC-exo compared to that with control MSC-exo. In conclusion, MSC-exo inhibited the M1-type polarization of macrophages, possibly through transferring tsRNA-21109, which may develop as a novel therapeutic target for SLE.

Identification of newly formed toxic chemicals in E-cigarette aerosols with Orbitrap mass spectrometry and implications on E-cigarette control.

The increasing use of electronic nicotine delivery systems (ENDS) is of concern due to multiple emerging adverse health effects. Most analyses of the harmful chemicals of ENDS have targeted metals or carbonyls generated by thermal decomposition of carrier liquids such as propylene glycol. However, new complex compounds not routinely identified and with unknown health consequences could be formed. ENDS aerosol samples were collected by the direct aerosol droplet deposition method. Untargeted analysis was performed using Orbitrap mass spectrometry with high mass accuracy. We identified more than 30 "features" in the aerosol characterized by pairs of the mass-to-charge ratio "m/z" of the compound and the retention time. We identified several compounds containing nicotine and propylene glycol (NIC-PG), whose abundance relative to nicotine increased along with vaping power used. On the basis of the prediction by the Environmental Protection Agency Toxicity Estimation Software Tool, these compounds exert developmental toxicity. In addition, a nitrogen-containing compound, likely tributylamine (a known lung irritant), was identified based on the molecular weight. This compound has not been previously identified in ENDS e-liquids and aerosols. ENDS produce not only small toxic compounds such as aldehydes, but also large complex toxic compounds such as NIC-PG. Predicted development toxicity for NIC-PG is concerning for fetal development in pregnant women who use ENDS, children exposed to secondhand or thirdhand ENDS aerosols, and teenage ENDS users whose brains are still developing. The strong positive association between NIC-PG levels and ENDS power output supports regulating high-powered ENDS.

Exposure to e-cigarette aerosol over two months induces accumulation of neurotoxic metals and alteration of essential metals in mouse brain.

Despite a recent increase in e-cigarette use, the adverse human health effects of exposure to e-cigarette aerosol, especially on the central nervous system (CNS), remain unclear. Multiple neurotoxic metals have been identified in e-cigarette aerosol. However, it is unknown whether those metals accumulate in the CNS at biologically meaningful levels. To answer this question, two groups of mice were whole-body exposed twice a day, 5 days a week, for two months, to either a dose of e-cigarette aerosol equivalent to human secondhand exposure, or a 5-fold higher dose. After the last exposure, the olfactory bulb, anterior and posterior frontal cortex, striatum, ventral midbrain, cerebellum, brainstem, remaining brain tissue and spinal cord were collected for metal quantification by inductively coupled plasma mass spectrometry and compared to tissues from unexposed control mice. The two-month exposure caused significant accumulation of several neurotoxic metals in various brain areas - for some metals even at the low exposure dose. The most striking increases were measured in the striatum. For several metals, including Cr, Cu, Fe, Mn, and Pb, similar accumulations are known to be neurotoxic in mice. Decreases in some essential metals were observed across the CNS. Our findings suggest that chronic exposure to e-cigarette aerosol could lead to CNS neurotoxic metal deposition and endogenous metal dyshomeostasis, including potential neurotoxicity. We conclude that e-cigarette-mediated metal neurotoxicity may pose long-term neurotoxic and neurodegenerative risks for e-cigarette users and bystanders.

Personal exposure to fine particulate matter and blood pressure: Variations by particulate sources.

Fine particulate matter (PM2.5) is a complex mixture of components which has been associated with various cardiovascular effects, such as elevated blood pressure (BP). However, evidences on specific sources behind these effects remain uncertain. Based on 140 72-h personal measurements among a panel of 36 health college students in Shanghai, China, we assessed associations between source-apportioned PM2.5 exposure and BP changes. Based on personal filter samples, PM2.5 source apportionment was conducted using Positive Matrix Factorization (PMF) model. Linear mixed-effects models were applied to evaluate associations of source-specific PM2.5 exposure with BP changes. Seven sources were identified in PMF analysis. Among them, secondary sulfate (41%) and nitrate (24%) sources contributed most to personal PM2.5, followed by industrial emissions (15%), traffic-related source (10%), coal combustion (6.2%), dust (2.4%) and aged sea salt (1.1%). We found nitrate, traffic-related source and coal combustion were significantly associated with increased BP. For example, an interquartile range increase in PM2.5 from traffic-related source was significantly associated with increase in systolic BP [1.5 (95% CI: 0.26, 2.7) mmHg], diastolic BP [1.2 (95% CI: 0.10, 2.2) mmHg] and mean arterial pressure [1.2 (95% CI: 0.15, 2.2) mmHg]. This is the first investigation linking personal PM2.5 source profile and BP changes. This study provides evidence that several anthropogenic emissions (especially traffic-related emission) may be particularly responsible for BP increases, and highlights that the importance of development of health-oriented PM2.5 source control strategies.

Prenatal polycyclic aromatic hydrocarbons, altered ERα pathway-related methylation and expression, and mammary epithelial cell proliferation in offspring and grandoffspring adult mice.

BACKGROUND: Airborne polycyclic aromatic hydrocarbons (PAH) possess carcinogenic and endocrine disrupting properties linked to mammary tumorigenesis. These effects may be initiated during a prenatal period of susceptibility to PAH activation of the aryl hydrocarbon receptor (Ahr) and through downstream effects on estrogen receptor (Er) α. PURPOSE: We hypothesized prenatal airborne PAH exposure induces sustained effects in female adult wild type BALB/cByj mice detected in the offspring (F1) and grandoffspring (F2) generation. We hypothesized these effects would include altered expression and epigenetic regulation of Erα and altered expression of aryl hydrocarbon receptor repressor (Ahrr, Ahrr/aryl hydrocarbon receptor nuclear translocator (Arnt), and breast cancer type 1 susceptibility (Brca1). Further, we hypothesized that PAH would induce precancerous outcomes such as epithelial cell proliferation and epithelial cell hyperplasia in mammary glands of adult female offspring and grandoffspring. RESULTS: Prenatal ambient PAH exposure lowered Erα mRNA expression (F1 and F2: p<0.001 for each) and induced methylation in the Erα promoter in mammary tissue in offspring and grandoffspring mice on postnatal day (PND) 60. Prenatal PAH lowered Brca1 mRNA (F1: p=0.002, F2: p=0.02); Erα mRNA was correlated with Brca1 (F1: r=0.42, p=0.02; F2: r=0.53, p=0.005). Prenatal PAH lowered Ahrr (F1: p=0.03, F2: p=0.009) and raised Arnt mRNA expression (F1: p=0.01, F2: p=0.03). Alterations in Erα mRNA (F2: p<0.0001) and Ahrr (F2: p=0.02) in the grandoffspring mice also occured by PND 28, and similarly occurred in the dam on postpartum day (PPD) 28. Finally, prenatal PAH was associated with higher mammary epithelial cell proliferation in the offspring (p=0.02), but not grandoffspring mice, without differences in the frequency of mammary cell hyperplasia. These results did not differ after adjustment by each candidate gene expression level. CONCLUSIONS: Prenatal PAH exposure induces DNA methylation and alters gene expression in the Erα-mediated pathway across generations, and suggests that functional outcomes such as mammary cell proliferation also may occur in offspring as a result.

PAEs and PBDEs in plastic fragments and wetland sediments in Yangtze estuary.

Phthalates (PAEs) and polybrominated diphenyl ethers (PBDEs) are widely used as additives in various plastic products. Because of their ubiquity and potential hazards to the environment, they have attracted widespread attention. This research supports the addition critical data of the concentration and distribution of PAEs and PBDEs in the plastic fragments and wetland sediments in Yangtze Estuary. The concentrations of Σ7PAEs and Σ9PBDEs in the plastic samples in Yangtze Estuary wetlands were 26.8-4241.8 µg/g and n.d. (no detectable) to 250.1 µg/g, respectively. The sixteen PAEs and eight PBDEs varied from 35.9 to 36225.2 ng/g and 3.9-253.0 ng/g in sediment samples. The dominant types of these chemicals in plastic and sediment samples were diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), dioctyl phthalate (DEHP) and BDE-209. According to correlation analysis and principal component analysis, the major sources of additives in sediment were associated with the leak from plastic fragment and microplastic. Based on the equilibrium partitioning theory and Sediment Quality Guidelines (SeQGs), the ecological risk of PAEs (high risk) and PBDEs (moderate risk) were evaluated. Overall, the investigated area has been moderately polluted by additives and microplastics; therefore, it is necessary to strengthen the control of environmental input of plastic waste.