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Background: All forms of asbestos are now banned in 52 countries. Safer products have replaced many materials that once were made with it. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products, and in those that have banned other forms of asbestos, the so-called “controlled use” of chrysotile asbestos is often exempted from the ban. In fact, chrysotile has accounted for > 95% of all the asbestos used globally.
Objective: We examined and evaluated the literature used to support the exemption of chrysotile asbestos from the ban and how its exemption reflects the political and economic influence of the asbestos mining and manufacturing industry.
Discussion: All forms of asbestos, including chrysotile, are proven human carcinogens. All forms cause malignant mesothelioma and lung and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers. No exposure to asbestos is without risk. Illnesses and deaths from asbestos exposure are entirely preventable.
Conclusions: All countries of the world have an obligation to their citizens to join in the international endeavor to ban the mining, manufacture, and use of all forms of asbestos. An international ban is urgently needed. There is no medical or scientific basis to exempt chrysotile from the worldwide ban of asbestos.
Background: The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been implicated in a variety of oxidant-dependent toxicological responses. Unlike ions of other transition metals such as iron, copper, and vanadium, Zn2+ does not generate reactive oxygen species (ROS) through redox cycling.
Objective: To characterize the role of oxidative stress in zinc-induced toxicity.
Methods: We used an integrated imaging approach that employs the hydrogen peroxide (H2O2)-specific fluorophore Peroxy Green 1 (PG1), the mitochondrial potential sensor 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and the mitochondria-targeted form of the redox-sensitive genetically encoded fluorophore MTroGFP1 in living cells.
Results: Zinc treatment in the presence of the Zn2+ ionophore pyrithione of A431 skin carcinoma cells preloaded with the H2O2-specific indicator PG1 resulted in a significant increase in H2O2 production that could be significantly inhibited with the mitochondrial inhibitor carbonyl cyanide 3-chlorophenylhydrazone. Mitochondria were further implicated as the source of zinc-induced H2O2 formation by the observation that exposure to zinc caused a loss of mitochondrial membrane potential. Using MTroGFP1, we showed that zinc exposure of A431 cells induces a rapid loss of reducing redox potential in mitochondria. We also demonstrated that zinc exposure results in rapid swelling of mitochondria isolated from mouse hearts.
Conclusion: Taken together, these findings show a disruption of mitochondrial integrity, H2O2 formation, and a shift toward positive redox potential in cells exposed to zinc. These data demonstrate the utility of real-time, live-cell imaging to study the role of oxidative stress in toxicological responses.
Background: Northward expansion of the tick Ixodes scapularis is driving Lyme disease (LD) emergence in Canada. Information on mechanisms involved is needed to enhance surveillance and identify where LD risk is emerging.
Objectives: We used passive and active surveillance and phylogeographic analysis of Borrelia burgdorferi to investigate LD risk emergence in Quebec.
Methods: In active surveillance, we collected ticks from the environment and from captured rodents. B. burgdorferi transmission was detected by serological analysis of rodents and by polymerase chain reaction assays of ticks. Spatiotemporal trends in passive surveillance data assisted interpretation of active surveillance. Multilocus sequence typing (MLST) of B. burgdorferi in ticks identified likely source locations of B. burgdorferi.
Results: In active surveillance, we found I. scapularis at 55% of sites, and we were more likely to find them at sites with a warmer climate. B. burgdorferi was identified at 13 I. scapularis–positive sites, but infection prevalence in ticks and animal hosts was low. Low infection prevalence in ticks submitted in passive surveillance after 2004—from the tick-positive regions identified in active surveillance—coincided with an exponential increase in tick submissions during this time. MLST analysis suggested recent introduction of B. burgdorferi from the northeastern United States.
Conclusions: These data are consistent with I. scapularis ticks dispersed from the United States by migratory birds, founding populations where the climate is warmest, and then establishment of B. burgdorferi from the United States several years after I. scapularis have established. These observations provide vital information for public health to minimize the impact of LD in Canada.
Background: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by climatic variables. However, few studies have examined the quantitative relationship between climate variation and HFRS transmission.
Objective: We examined the potential impact of climate variability on HFRS transmission and developed climate-based forecasting models for HFRS in northeastern China.
Methods: We obtained data on monthly counts of reported HFRS cases in Elunchun and Molidawahaner counties for 1997–2007 from the Inner Mongolia Center for Disease Control and Prevention and climate data from the Chinese Bureau of Meteorology. Cross-correlations assessed crude associations between climate variables, including rainfall, land surface temperature (LST), relative humidity (RH), and the multivariate El Niño Southern Oscillation (ENSO) index (MEI) and monthly HFRS cases over a range of lags. We used time-series Poisson regression models to examine the independent contribution of climatic variables to HFRS transmission.
Results: Cross-correlation analyses showed that rainfall, LST, RH, and MEI were significantly associated with monthly HFRS cases with lags of 3–5 months in both study areas. The results of Poisson regression indicated that after controlling for the autocorrelation, seasonality, and long-term trend, rainfall, LST, RH, and MEI with lags of 3–5 months were associated with HFRS in both study areas. The final model had good accuracy in forecasting the occurrence of HFRS.
Conclusions: Climate variability plays a significant role in HFRS transmission in northeastern China. The model developed in this study has implications for HFRS control and prevention.
Background: Emerging evidence suggests that the systemic vasculature may be a target of inhaled pollutants of vehicular origin. We have identified several murine markers of vascular toxicity that appear sensitive to inhalation exposures to combustion emissions.
Objective: We sought to examine the relative impact of various pollutant atmospheres and specific individual components on these markers of altered vascular transcription and lipid peroxidation.
Methods: Apolipoprotein E knockout (ApoE−/−) mice were exposed to whole combustion emissions (gasoline, diesel, coal, hardwood), biogenically derived secondary organic aerosols (SOAs), or prominent combustion-source gases [nitric oxide (NO), NO2, carbon monoxide (CO)] for 6 hr/day for 7 days. Aortas were assayed for transcriptional alterations of endothelin-1 (ET-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), and heme oxygenase-1 (HO-1), along with measures of vascular lipid peroxides (LPOs) and gelatinase activity.
Results: We noted transcriptional alterations with exposures to gasoline and diesel emissions. Interestingly, ET-1 and MMP-9 transcriptional effects could be recreated by exposure to CO and NO, but not NO2 or SOAs. Gelatinase activity aligned with levels of volatile hydrocarbons and also monoxide gases. Neither gases nor particles induced vascular LPO despite potent effects from whole vehicular emissions.
Conclusions: In this head-to-head comparison of the effects of several pollutants and pollutant mixtures, we found an important contribution to vascular toxicity from readily bioavailable monoxide gases and possibly from volatile hydrocarbons. These data support a role for traffic-related pollutants in driving cardiopulmonary morbidity and mortality.
Background: Associations between cardiovascular diseases and mercury have been frequently described, but underlying mechanisms are poorly understood.
Objectives: We investigate the procoagulant activation of erythrocytes, an important contributor to thrombosis, by low-level mercury to explore the roles of erythrocytes in mercury-related cardiovascular diseases.
Methods: We used freshly isolated human erythrocytes and ex vivo and in vivo thrombosis models in rats to investigate mercury-induced procoagulant activity.
Results: Prolonged exposure to low-dose mercuric ion (Hg2+; 0.25–5 μM for 1–48 hr) induced erythrocyte shape changes from discocytes to echinocytes to spherocytes, accompanied by microvesicle (MV) generation. These MVs and remnant erythrocytes expressed phosphatidylserine (PS), an important mediator of procoagulant activation. Hg2+ inhibited flippase, an enzyme that recovers PS into the inner leaflet of the cell membrane, and activated scramblase, an enzyme that alters lipid asymmetry in the cell membrane. Consistent with these activity changes, Hg2+ increased intracellular calcium and depleted ATP and protein thiol. A thiol supplement reversed Hg2+-induced MV generation and PS exposure and inhibited the increase in calcium ion (Ca2+) and depletion of ATP, indicating that free-thiol depletion was critical to Hg2+-mediated procoagulant activity. The procoagulant activity of Hg2+-treated erythrocytes was demonstrated by increased thrombin generation and endothelial cell adhesion. We further confirmed Hg2+-mediated procoagulant activation of erythrocytes in ex vivo and in vivo rat thrombosis models, where Hg2+ treatment (0.5–2.5 mg/kg) increased PS exposure and thrombus formation significantly.
Conclusion: This study demonstrated that mercury could provoke procoagulant activity in erythrocytes through protein-thiol depletion–mediated PS exposure and MV generation, ultimately leading to enhanced thrombosis.
Background: Inactivation of p53 is involved in arsenite-induced tumorigenesis; however, the molecular mechanisms remain poorly understood.
Objective: We investigated the molecular mechanisms underlying the inactivation of p53 and neoplastic transformation induced by arsenite in human embryo lung fibroblast (HELF) cells.
Methods: Anchorage-independent growth assays were performed, and tumorigenicity in intact animals was assessed to confirm arsenite-induced neoplastic transformation. We determined the levels and functions of p53, nuclear factor-kappa B (NF-κB; a key transcriptional regulator), and mot-2 (a p53 inhibitor) and their relationships in arsenite-induced transformed HELF cells by two-dimensional electrophoresis, reverse-transcriptase polymerase chain reaction, Western blot, immunofluorescence, and co-immunoprecipitation assays.
Results: Exposure of HELF cells to low levels of arsenite increased their proliferation rate and anchorage-independent growth and disrupted normal contact inhibition. When introduced into nude mice, transformed cells were tumorigenic. We used proteomic analysis to identify proteins with altered expression between untreated and arsenite-exposed cells. We found decreased expression of NF-κB repressing factor (NKRF; an inhibitor of NF-κB–mediated gene transcription), increased expression of mot-2, and increased activation of NF-κB. Changes in cells exposed to 1.0 μM arsenite were more marked than changes in cells exposed to 0.5 or 2.0 μM arsenite. Inactivation of NF-κB prevented malignant transformation induced by 1.0 μM arsenite. Moreover, we also identified a mechanism whereby NF-κB regulated p53. Specifically, activation of NF-κB up-regulated mot-2 expression, which prevented nuclear translocation of p53 and switched the binding preference of the p53 and NF-κB coactivator CBP [cyclic AMP-responsive element binding protein (CREB) binding protein] from p53 to NF-κB.
Conclusions: mot-2–mediated cross talk between NF-κB and p53 appears to be involved in arsenite-induced tumorigenesis of HELF cells.
Background: Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated.
Objectives: We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes.
Methods: Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors.
Results: A 1-SD increase in BC (0.415 μg/m3) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29–3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88–2.67). Interactions modifying BC associations were observed with SNPs in the DICER, GEMIN4, and DiGeorge critical region-8 (DGCR8) genes, and in GEMIN3 and GEMIN4, predicting diastolic and systolic BP, respectively.
Conclusions: We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.
Background: The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized that effects of arsenic on birth weight may be related to effects on myogenic differentiation.
Objective: We investigated the effects of arsenic trioxide (As2O3) on the myogenic differentiation of myoblasts in vitro and muscle regeneration in vivo.
Methods: C2C12 myoblasts and primary mouse and human myoblasts were cultured in differentiation media with or without As2O3 (0.1–0.5 μM) for 4 days. Myogenic differentiation was assessed by myogenin and myosin heavy chain expression and multinucleated myotube formation in vitro; skeletal muscle regeneration was tested using an in vivo mouse model with experimental glycerol myopathy.
Results: A submicromolar concentration of As2O3 dose-dependently inhibited myogenic differentiation without apparent effects on cell viability. As2O3 significantly and dose-dependently decreased phosphorylation of Akt and p70s6k proteins during myogenic differentiation. As2O3-induced inhibition in myotube formation and muscle-specific protein expression was reversed by transfection with the constitutively active form of Akt. Sections of soleus muscles stained with hematoxylin and eosin showed typical changes of injury and regeneration after local glycerol injection in mice. Regeneration of glycerol-injured soleus muscles, myogenin expression, and Akt phosphorylation were suppressed in muscles isolated from As2O3-treated mice compared with untreated mice.
Conclusion: Our results suggest that As2O3 inhibits myogenic differentiation by inhibiting Akt-regulated signaling.
Background: The etiology of rheumatoid arthritis (RA) remains largely unknown, although epidemiologic studies suggest genetic and environmental factors may play a role. Geographic variation in incident RA has been observed at the regional level.
Objective: Spatial analyses are a useful tool for confirming existing exposure hypotheses or generating new ones. To further explore the association between location and RA risk, we analyzed individual-level data from U.S. women in the Nurses’ Health Study, a nationwide cohort study.
Methods: Participants included 461 incident RA cases and 9,220 controls with geocoded addresses; participants were followed from 1988 to 2002. We examined spatial variation using addresses at baseline in 1988 and at the time of case diagnosis or the censoring of controls. Generalized additive models (GAMs) were used to predict a continuous risk surface by smoothing on longitude and latitude while adjusting for known risk factors. Permutation tests were conducted to evaluate the overall importance of location and to identify, within the entire study area, those locations of statistically significant risk.
Results: A statistically significant area of increased RA risk was identified in the northeast United States (p-value = 0.034). Risk was generally higher at northern latitudes, and it increased slightly when we used the nurses’ 1988 locations compared with those at the time of diagnosis or censoring. Crude and adjusted models produced similar results.
Conclusions: Spatial analyses suggest women living in higher latitudes may be at greater risk for RA. Further, RA risk may be greater for locations that occur earlier in residential histories. These results illustrate the usefulness of GAM methods in generating hypotheses for future investigation and supporting existing hypotheses.
Background: Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways.
Objective: We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM.
Methods: This was a cross-sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders.
Results: After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9–10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity.
Conclusions: Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways.
Background: Sulfur dioxide, formed during the combustion of fossil fuels, is a major air pollutant near large cities. Its two ionized forms in aqueous solution, sulfite and (bi)sulfite, are widely used as preservatives and antioxidants to prevent food and beverage spoilage. (Bi)sulfite can be oxidized by peroxidases to form the very reactive sulfur trioxide anion radical (•SO3−). This free radical further reacts with oxygen to form the peroxymonosulfate anion radical (−O3SOO•) and sulfate anion radical (SO4• −).
Objective: To explore the critical role of these radical intermediates in further oxidizing biomolecules, we examined the ability of copper,zinc-superoxide dismutase (Cu,Zn-SOD) to initiate this radical chain reaction, using human serum albumin (HSA) as a model target.
Methods: We used electron paramagnetic resonance, optical spectroscopy, oxygen uptake, and immuno-spin trapping to study the protein oxidations driven by sulfite-derived radicals.
Results: We found that when Cu,Zn-SOD reacted with (bi)sulfite, •SO3− was produced, with the concomitant reduction of SOD-Cu(II) to SOD-Cu(I). Further, we demonstrated that sulfite oxidation mediated by Cu,Zn-SOD induced the formation of radical-derived 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin-trapped HSA radicals.
Conclusions: The present study suggests that protein oxidative damage resulting from (bi)sulfite oxidation promoted by Cu,Zn-SOD could be involved in oxidative damage and tissue injury in (bi)sulfite-exacerbated allergic reactions.
Background: Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants that contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions.
Objective: The aim of the present study was to address the hypothesis that highly chlorinated PCBs can disrupt gut integrity at the level of tight junction (TJ) proteins.
Methods: Caco-2 human colon adenocarcinoma cells were exposed to one of the following PCB congeners: PCB153, PCB118, PCB104, and PCB126. We then assessed NAD(P)H oxidase (NOX) activity and expression and the barrier function of Caco-2 cells. In addition, the integrity of intestinal barrier function and expression of TJ proteins were evaluated in C57BL/6 mice exposed to individual PCBs by oral gavage.
Results: Exposure of Caco-2 cells to individual PCB congeners resulted in activation of NOX and increased permeability of fluorescein isothiocyanate (FITC)-labeled dextran (4 kDa). Treatment with PCB congeners also disrupted expression of TJ proteins zonula occludens-1 (ZO-1) and occludin in Caco-2 cells. Importantly, inhibition of NOX by apocynin significantly protected against PCB-mediated increase in epithelial permeability and alterations of ZO-1 protein expression. Exposure to PCBs also resulted in alterations of gut permeability via decreased expression of TJ proteins in an intact physiological animal model.
Conclusions: These results suggest that oral exposure to highly chlorinated PCBs disrupts intestinal epithelial integrity and may directly contribute to the systemic effects of these toxicants.
Background: Exposure to zinc oxide (ZnO) in environmental and occupational settings causes acute pulmonary responses through the induction of proinflammatory mediators such as interleukin-8 (IL-8).
Objective: We investigated the effect of ZnO nanoparticles on IL-8 expression and the underlying mechanisms in human bronchial epithelial cells.
Methods: We determined IL-8 mRNA and protein expression in primary human bronchial epithelial cells and the BEAS-2B human bronchial epithelial cell line using reverse-transcriptase polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively. Transcriptional activity of IL-8 promoter and nuclear factor kappa B (NFκB) in ZnO-treated BEAS-2B cells was measured using transient gene transfection of the luciferase reporter construct with or without p65 constructs. Phosphorylation and degradation of IκBα, an inhibitor of NF-κB, and phosphorylation of p65 were detected using immunoblotting. Binding of p65 to the IL-8 promoter was examined using the chromatin immunoprecipitation assay.
Results: ZnO exposure (2–8 μg/mL) increased IL-8 mRNA and protein expression. Inhibition of transcription with actinomycin D blocked ZnO-induced IL-8 expression, which was consistent with the observation that ZnO exposure increased IL-8 promoter reporter activity. Further study demonstrated that the κB-binding site in the IL-8 promoter was required for ZnO-induced IL-8 transcriptional activation. ZnO stimulation modestly elevated IκBα phosphorylation and degradation. Moreover, ZnO exposure also increased the binding of p65 to the IL-8 promoter and p65 phosphorylation at serines 276 and 536. Overexpression of p65 constructs mutated at serines 276 or 536 significantly reduced ZnO-induced increase in IL-8 promoter reporter activity.
Conclusion: p65 phosphorylation and IκBα phosphorylation and degradation are the primary mechanisms involved in ZnO nanoparticle-induced IL-8 expression in human bronchial epithelial cells.
Background: About half of the world’s population is exposed to smoke from burning biomass fuels at home. The high airborne particulate levels in these homes and the health burden of exposure to this smoke are well described. Burning unprocessed biological material such as wood and dried animal dung may also produce high indoor endotoxin concentrations.
Objective: In this study we measured airborne endotoxin levels in homes burning different biomass fuels.
Methods: Air sampling was carried out in homes burning wood or dried animal dung in Nepal (n = 31) and wood, charcoal, or crop residues in Malawi (n = 38). Filters were analyzed for endotoxin content expressed as airborne endotoxin concentration and endotoxin per mass of airborne particulate.
Results: Airborne endotoxin concentrations were high. Averaged over 24 hr in Malawian homes, median concentrations of total inhalable endotoxin were 24 endotoxin units (EU)/m3 in charcoal-burning homes and 40 EU/m3 in wood-burning homes. Short cooking-time samples collected in Nepal produced median values of 43 EU/m3 in wood-burning homes and 365 EU/m3 in dung-burning homes, suggesting increasing endotoxin levels with decreasing energy levels in unprocessed solid fuels.
Conclusions: Airborne endotoxin concentrations in homes burning biomass fuels are orders of magnitude higher than those found in homes in developed countries where endotoxin exposure has been linked to respiratory illness in children. There is a need for work to identify the determinants of these high concentrations, interventions to reduce exposure, and health studies to examine the effects of these sustained, near-occupational levels of exposure experienced from early life.
Background: In spite of the application of toxicogenomic (TGx) data to the field of toxicology for the past 10 years, the broad implementation and full impact of TGx for chemical and drug evaluation to improve decision making within organizations and by policy makers has not been achieved.
Objectives: The goal of the Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to Mechanism-based Risk Assessment was to construct and summarize a multisector survey, addressing key issues and perspectives on the current and future practical uses and challenges of implementing TGx data to facilitate discussions for decision making within organizations and by policy makers.
Methods: An online survey to probe the current status and future challenges facing the field of TGx for drug and chemical evaluation in experimental and nonclinical models was taken by scientists and scientific decision/policy makers actively engaged in the field of TGx within industrial, academic, and regulatory sectors of the United States, Europe, and Japan. For this survey, TGx refers specifically to the analysis of gene expression responses to evaluate xenobiotic exposure in experimental and preclinical models.
Results: The survey results are summarized from questions covering broad areas including technology used, organizational capacity and resource allocation, experimental approaches, data storage and exchange, perceptions of benefits and hurdles, and future expectations.
Conclusions: The survey findings provide valuable information on the current state of the science of TGx applications and identify key areas in which TGx will have an impact as well as the key hurdles in applying TGx data to address issues. The findings serve as a public resource to facilitate discussions on the focus of future TGx efforts to ensure that a maximal benefit can be obtained from toxicogenomic studies.
Background: Phthalates are compounds that are used in a wide range of consumer products. However, the contribution of dietary intake to phthalate exposure has not been well defined.
Objective: The objective of this study was to assess the contribution of different food types to phthalate exposure. Phthalates are chemicals of concern because of the high levels measured in people and the environment, as well as the demonstrated toxicity in animal studies and limited epidemiological studies. Previous research, although limited, has suggested that phthalates contaminate food in various countries.
Methods: We conducted an exploratory analysis of data collected as part of the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Associations between dietary intake (assessed by a 24-hr dietary recall) for a range of food types (meat, poultry, fish, fruit, vegetable, and dairy) and phthalate metabolites measured in urine were analyzed using multiple linear regression modeling.
Results: We found that metabolites of di-(2-ethylhexyl) phthalate (DEHP) and high-molecular-weight phthalate metabolites were associated with the consumption of poultry. Monoethyl phthalate, the metabolite of diethyl phthalate (DEP), was associated with vegetable consumption, specifically tomato and potato consumption.
Discussion: These results, combined with results from previous studies, suggest that diet is an important route of intake for phthalates. Further research is needed to determine the sources of food contamination with these toxic chemicals and to describe the levels of contamination of U.S. food in a large, representative U.S. sample.
Background: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. However, it is unclear whether human microbiota display similar As metabolism, especially when present in a contaminated matrix.
Objectives: We evaluated the metabolic potency of in vitro cultured human colon microbiota toward inorganic As (iAs) and As-contaminated soils.
Methods: A colon microbial community was cultured in a dynamic model of the human gut. These colon microbiota were incubated with iAs and with As-contaminated urban soils. We determined As speciation analysis using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry.
Results: We found a high degree of methylation for colon digests both of iAs (10 μg methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 μg/g biomass/hr). Besides the formation of monomethylarsonic acid (MMAV), we detected the highly toxic monomethylarsonous acid (MMAIII). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTAV). MMMTAV, the toxicokinetic properties of which are not well known, was in many cases a major metabolite.
Conclusions: Presystemic As metabolism is a significant process in the human body. Toxicokinetic studies aiming to completely elucidate the As metabolic pathway would therefore benefit from incorporating the metabolic potency of human gut microbiota. This will result in more accurate risk characterization associated with As exposures.
Background: The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood.
Objective: We examined the effects and time course of exposure to fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania.
Methods: The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a high-resolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)-corrected QT measures: QT prolongation index (QTI), Bazett’s HR-corrected QT (QTcB), and Fridericia’s HR-corrected QT (QTcF). A personal PM2.5 monitor was used to measure individual-level real-time PM2.5 exposures for 24 hr. We averaged these data and used 30-min time-specific average PM2.5 exposures.
Results: The mean age of the participants was 56 ± 8 years, with 41% male and 74% white. The means ± SDs for QTI, QTcB, and QTcF were 111 ± 6.6, 438 ± 23 msec, and 422 ± 22 msec, respectively; and for PM2.5, the mean ± SD was 14 ± 22 μg/m3. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (β) between 30-min PM2.5 and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM2.5 exposure occurred within 3–4 hr. The multivariable adjusted β (SE, p-value) due to a 10-μg/m3 increase in lag 7 PM2.5 on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively.
Conclusions: Our results suggest a significant adverse effect of PM2.5 on ventricular repolarization. The time course of the effect is within 3–4 hr of elevated PM2.5.
Background: The presence of pharmaceuticals in aquatic environments and in drinking water has prompted significant public interest regarding potential adverse ecological effects and risks to human health.
Objectives: The Environmental Health Summit held in North Carolina, 10–11 November 2008, explored the issues associated with the presence and relative risk of trace levels of pharmaceuticals in water. More than 150 participants from government organizations and institutions, academia, industry, water utilities, and public interest groups participated in discussions aimed at evaluating the current knowledge on this issue and at identifying research gaps and innovative solution-oriented recommendations.
Discussion: We present different aspects related to the subject that were discussed at the summit, including the source, fate, and transport of pharmaceuticals, their exposure effects and potential risks to human and ecosystems, and the best management practices to address these issues. Recommendations placed emphasis on research needs as well as education, communication, prevention, and intervention programs, and other public health solutions and actions.
Conclusions: Despite rising concerns about the presence of trace amounts of pharmaceuticals in drinking water, little evidence is currently available that associates these chemicals with adverse human health risks. In order to prioritize which pharmaceutical chemicals could potentially pose the highest risk to consumers and the environment, the summit participants concluded that more studies are needed to generate meaningful and accurate data.
Background: Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma.
Objectives: We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools.
Methods: Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children’s Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric.
Results: Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25–1.82] and near schools (HR 1.45; 95% CI, 1.06–1.98). Ambient NO2 measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18–4.01). In models with both NO2 and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO2 was attenuated (HR 1.37; 95% CI, 0.69–2.71).
Conclusions: Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.
Background: Concern over phthalates has emerged because of their potential toxicity to humans.
Objective: We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.
Methods: This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.
Results: We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.
Conclusion: Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.
Background: Libby, Montana, was home to the largest vermiculite ore mine in the United States. The processing, use, and transport of the ore, which was contaminated with amphibole asbestos, led to generalized contamination of the community. The mine closed in 1990.
Objectives: We examined the prevalence of respiratory symptoms in 2000–2001 and their association with history of vermiculite exposure among people who were ≤ 18 years of age when the mine closed.
Methods: Information on respiratory symptoms and exposure history was collected by questionnaire in 2000–2001, at which time participants were 10–29 years old. Logistic regression was used to model the associations between exposures and outcomes adjusted for age, sex, and tobacco smoke exposure.
Results: Of the 1,003 individuals included in the study, 10.8% reported usually having a cough, 14.5% reported experiencing shortness of breath when walking up a slight hill or hurrying on level ground, and 5.9% reported having coughed up bloody phlegm in the past year. These respiratory symptoms were positively associated with frequently handling vermiculite insulation compared with never handling vermiculite insulation. We found no association between vermiculite insulation in the house and respiratory symptoms. Respiratory symptoms were associated with other vermiculite exposures as well, and the number and frequency of these activities showed a positive trend with usually having a cough. We found no association between any of the activities and abnormal spirometry.
Conclusions: These data suggest that residents of Libby, Montana, who were children when the mine closed experienced some respiratory symptoms associated with asbestos-contaminated vermiculite exposure.
Background: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins.
Objectives: We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6–8 years of age at enrollment (2004–2007).
Methods: We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones.
Results: Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88–1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23–1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone.
Conclusions: Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.