National Health and Environmental Effects Research Laboratory
National Health and Environmental Effects Research Laboratory
News Article | May 8, 2017
Nationwide, counties with the poorest quality across five domains - air, water, land, the built environment and sociodemographic - had the highest incidence of cancer, according to a new study published in the journal Cancer. Poor air quality and factors of the built environment -- such as the presence of major highways and the availability of public transit and housing - - were the most strongly associated with high cancer rates, while water quality and land pollution had no measurable effect. The findings may help reduce cancer by driving policy to lower pollution in areas with high cancer rates linked to the environment. Previous research has shown that genetics can be blamed for only about half of all cancers, suggesting that exposure to environmental toxins or socioeconomic factors may also play a role. "Most research has focused on single environmental factors like air pollution or toxins in water," said Jyotsna Jagai, research assistant professor of environmental and occupational health in the University of Illinois at Chicago School of Public Health and lead author of the study. "But these single factors don't paint a comprehensive picture of what a person is exposed to in their environment -- and may not be as helpful in predicting cancer risk, which is impacted by multiple factors including the air you breathe, the water you drink, the neighborhood you live in, and your exposure to myriad toxins, chemicals and pollutants." To investigate the effects of overall environmental quality, the researchers looked at hundreds of variables, including air and water pollution, pesticide and radon levels, neighborhood safety, access to health services and healthy food, presence of heavily-trafficked highways and roads, and sociodemographic factors, such as poverty. Jagai and her colleagues used the U.S. EPA's Environmental Quality Index, a county-level measure incorporating more than 200 of these environmental variables and obtained cancer incidence rates from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program State Cancer Profiles. Cancer data were available for 85 percent of the 3,142 U.S. counties. The average age-adjusted rate for all types of cancer was 451 cases per 100,000 people. Counties with poor environmental quality had higher incidence of cancer--on average, 39 more cases per 100,000 people--than counties with high environmental quality. Increased rates were seen for both males and females, and prostate and breast cancer demonstrated the strongest association with poor environmental quality. The researchers found that high levels of air pollution, poor quality in the built environment and high levels of sociodemographic risk factors were most strongly associated with increased cancer rates in men and women. The strongest associations were seen in urban areas, especially for the air and built environment domains. Breast and prostate cancer were most strongly associated with poor air quality. "Some of the counties we looked at were very large, with both urban and rural areas in a single county, so to tease apart the interplay between the measures of quality in our five domains and how they impact urban and rural areas," Jagai said, "we will need to look at geographic areas smaller than counties." Co-authors on the study are Lynne Messer of Portland State University; Kristen Rappazzo and Danelle Lobdell of the U.S. Environmental Protection Agency; and Chris Gray and Shannon Grabich of the University of North Carolina, Chapel Hill and the Oak Ridge Institute for Science and Education. This research was funded in part by contracts EP09D000003 and EP12D000264 from the EPA Office of Research and Development and by an appointment to the Internship/Research Participation Program Office of Research and Development (National Health and Environmental Effects Research Laboratory) of the EPA, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the EPA and the Department of Energy.
Selgrade M.K.,National Health and Environmental Effects Research Laboratory |
Gilmour M.I.,National Health and Environmental Effects Research Laboratory
Journal of Immunotoxicology | Year: 2010
Numerous epidemiological studies have associated episodes of increased air pollution with increased incidence of respiratory disease, including pneumonia, croup, and bronchitis. Trichloroethylene (TCE) and chloroform are among 33 hazardous air pollutants identified by the U.S. Environmental Protection Agency as presenting the greatest threat to public health in the largest number of urban areas. Also, both are common indoor air pollutants. Here, we assessed the potential effects of TCE and chloroform on resistance to pulmonary bacterial infection and related alveolar macrophage (AM) function. CD-1 mice were exposed by inhalation to filtered air (control) or concentrations of TCE ranging from 5 to 200ppm, or concentrations of chloroform ranging from 100 to 2000ppm. Immediately following exposure, mice were challenged with an aerosol of Streptococcus zooepidemicus and monitored for clearance of bacteria from the lung and mortality. In separate experiments, exposed mice were injected intratracheally with viable bacteria and phagocytic function was evaluated in macrophages obtained from lung washes 30min later. The NOEL for enhanced mortality to infection was 25ppm for TCE and 500ppm for chloroform. Relative to the air controls, differences in clearance of bacteria from the lung were noted in mice exposed to TCE (NOEL = 50ppm) and to chloroform (NOEL 100ppm), and differences in AM phagocytic index were noted for TCE (NOEL = 100ppm) and for chloroform (NOEL < 100ppm). The data support the utility of the S. zooepidemicus infectivity model in assessing potential increased risk of respiratory infection and suggest that delayed clearance of bacteria from the lung or decreased phagocytosis are viable alternatives to mortality as an endpoint. Collectively, these endpoints are among the most sensitive health effects reported for TCE. © 2010 Informa Healthcare USA, Inc.
Veeramachaneni D.N.R.,Colorado State University |
Klinefelter G.R.,National Health and Environmental Effects Research Laboratory
Reproduction | Year: 2014
Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have been noted; e.g., following foetal exposure, abnormal clustering of Leydig cells or decreased production of testosterone that is manifested in rats does not occur in mice or humans. Nonetheless, other facets of testicular dysgenesis occur in both rats and mice as well as in some other species tested. We recently published a comprehensive evaluation of the foetal rat testis proteome, following in utero exposure to diethylhexyl phthalate (DEHP), which revealed changes in individual proteins that are known to be factors in cellular differentiation and migration or related to the capacity of the foetal Leydig cell to produce testosterone and fit a pathway network in which each is regulated directly or indirectly by oestradiol. Plasma oestradiol indeed was found to be elevated approximately twofold in 19-day-old DEHP-exposed foetal male rats. In this brief review, we discuss our new findings vis-à-vis 'oestrogen hypothesis' as a cause for testicular dysgenesis syndrome. © 2014 Society for Reproduction and Fertility.
Schreinemachers D.M.,National Health and Environmental Effects Research Laboratory
Biomarker Insights | Year: 2011
Background: A previous study based on NHANES 2001-2002 observed that increased levels of urinary perchlorate were associated with increased levels of thyroid stimulating hormone among all women, and with decreased levels of thyroxine among women with low urinary iodine. No associations were observed for men. Methods: Using the same NHANES 2001-2002 data, associations of urinary perchlorate with indirect biomarkers of thyroid hormone disruption were investigated. Decreased levels of hemoglobin (HGB), hematocrit (HCT), and high density lipoprotein (HDL) have been observed among subjects with subclinical hypothyroidism. To investigate the suitability of these indicators for use in observational studies, subjects were divided into six groups: boys, age 6-19; men, age 20-85; girls, age 6-14; non-pregnant women, age 15-49; women, age 50-85; and pregnant women. Use of perchlorate quintiles (Q1-Q5) and continuous log-transformed perchlorate in the regression models allowed investigation of both non-linear and linear associations. Adjustments were made for age, urinary creatinine, race/ethnicity, body mass index, cotinine, poverty index, hours of fasting, thiocyanate, nitrate, daily kcal intake, C-reactive protein. Adjustment for alcohol consumption depended on availability. Adjustment for prescription drugs (beta-blockers, sex hormones, antihyperlipidemic and antidiabetic drugs) was made if it changed the perchlorate estimate by ≥ 10%. Results: Statistically significant decreases were observed for HGB and HCT among boys, men, women age 15-49, and pregnant women, and for HDL among men. Conclusions: Although the mean response biomarkers were within normal range, their association with urinary perchlorate is of interest. HGB and HCT among pregnant women showed a stronger association with urinary perchlorate than non-pregnant women age 15-49. Statistically significant associations were observed for individual perchlorate quintiles. Assumption of linearity of log-transformed perchlorate may result in underestimation of some associations. © the author(s), publisher and licensee Libertas Academica Ltd.
Ghio A.J.,National Health and Environmental Effects Research Laboratory
Infection | Year: 2014
Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Cigarette smoking, burning of biomass, dust storms, mining, agricultural work, environmental tobacco smoke (ETS), wood stoves, traffic-related emissions, gas stoves, and ambient air pollution are all particle-related exposures associated with an increased risk for respiratory infections. In addition, cigarette smoking, burning of biomass, dust storms, mining, and ETS can result in an elevated risk for tuberculosis, atypical mycobacterial infections, and meningitis. One of the mechanisms for particle-related infections includes an accumulation of iron by surface functional groups of particulate matter (PM). Since elevations in metal availability are common to every particle exposure, all PM potentially contributes to these infections. Therefore, exposures to wood stove emissions, diesel exhaust, and air pollution particles are predicted to increase the incidence and prevalence of tuberculosis, atypical mycobacterial infections, and meningitis, albeit these elevations are likely to be small and detectable only in large population studies. Since iron accumulation correlates with the presence of surface functional groups and dependent metal coordination by the PM, the risk for infection continues as long as the particle is retained. Subsequently, it is expected that the cessation of exposure will diminish, but not totally reverse, the elevated risk for infection. © 2014 Springer-Verlag.
Madden M.C.,National Health and Environmental Effects Research Laboratory
Biochimica et Biophysica Acta - General Subjects | Year: 2016
Background Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biological responses or health effects or at a minimum reduce the effects relative to other fuels. In evaluating the overall environmental and health effects of biodiesel production to end use scenario, empirical data or modeling data based on such data are needed. Scope of review This manuscript examines the available toxicology reports examining combustion derived biodiesel emissions since approximately 2007, when our last review of the topic occurred. Toxicity derived from other end uses of biodiesel - e.g., spills, dermal absorption, etc. - are not examined. Findings from biodiesel emissions are roughly divided into three areas: whole non-human animal model exposures; in vitro exposures of mammalian and bacterial cells (used for mutation studies primarily); and human exposures in controlled or other exposure fashions. Major conclusions Overall, these more current studies clearly demonstrate that biodiesel combustion emission exposure- to either 100% biodiesel or a blend in petroleum diesel- can induce biological effects. There are reports that show biodiesel exposure generally induces more effects or a greater magnitude of effect than petroleum diesel, however there are also a similar number of reports showing the opposite trend. It is unclear whether effects induced by exposure to a blend are greater than exposure to 100% biodiesel. Taken together, the evidence suggest biodiesel emissions can have some similar effects as diesel emissions on inflammatory, vascular, mutagenic, and other responses. General significance While acute biodiesel exposures can show toxicity with a variety of endpoints, the potential effects on human health need further validation. Additionally there are few or no findings to date on whether biodiesel emissions can induce effects or even a weaker response that petroleum diesel with repeated exposure scenarios such as in an occupational setting. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. © 2016
Shannahan J.H.,East Carolina University |
Kodavanti U.P.,National Health and Environmental Effects Research Laboratory |
Brown J.M.,East Carolina University
Inhalation Toxicology | Year: 2012
Human inhalation exposures to manufactured nanoparticles (NP) and airborne ultrafine particles (UFP) continues to increase in both occupational and environmental settings. UFP exposures have been associated with increased cardiovascular mortality and morbidity, while ongoing research supports adverse systemic and cardiovascular health effects after NP exposures. Adverse cardiovascular health effects include alterations in heart rate variability, hypertension, thrombosis, arrhythmias, increased myocardial infarction, and atherosclerosis. Exactly how UFP and NP cause these negative cardiovascular effects is poorly understood, however a variety of mediators and mechanisms have been proposed. UFP and NP, as well as their soluble components, are known to systemically translocate from the lung. Translocated particles could mediate cardiovascular toxicity through direct interactions with the vasculature, blood, and heart. Recent study suggests that sensory nerve stimulation within the lung may also contribute to UFP- and NP-induced acute cardiovascular alterations. Activation of sensory nerves, such as C-fibers, within the lung may result in altered cardiac rhythm and function. Lastly, release of pulmonary-derived mediators into systemic circulation has been proposed to facilitate cardiovascular effects. In general, these proposed pulmonary-derived mediators include proinflammatory cytokines, oxidatively modified macromolecules, vasoactive proteins, and prothrombotic factors. These pulmonary-derived mediators have been postulated to contribute to the subsequent prothrombotic, atherogenic, and inflammatory effects after exposure. This review will evaluate the potential contribution of individual mediators and mechanisms in facilitating cardiopulmonary toxicity following inhalation of UFP and NP. Lastly, we will appraise the literature and propose a hypothesis regarding the possible role of mast cells in contributing to these systemic effects. © 2012 Informa Healthcare USA, Inc.
Wu W.,Xinxiang Medical University |
Wu W.,University of North Carolina at Chapel Hill |
Bromberg P.A.,University of North Carolina at Chapel Hill |
Samet J.M.,National Health and Environmental Effects Research Laboratory
Free Radical Biology and Medicine | Year: 2013
The redox-inert transition metal Zn is a micronutrient that plays essential roles in protein structure, catalysis, and regulation of function. Inhalational exposure to ZnO or to soluble Zn salts in occupational and environmental settings leads to adverse health effects, the severity of which appears dependent on the flux of Zn2+ presented to the airway and alveolar cells. The cellular toxicity of exogenous Zn2+ exposure is chazracterized by cellular responses that include mitochondrial dysfunction, elevated production of reactive oxygen species, and loss of signaling quiescence leading to cell death and increased expression of adaptive and inflammatory genes. Central to the molecular effects of Zn2+ are its interactions with cysteinyl thiols, which alters their functionality by modulating their reactivity and participation in redox reactions. Ongoing studies aimed at elucidating the molecular toxicology of Zn2+ in the lung are contributing valuable information about its role in redox biology and cellular homeostasis in normal and pathophysiology. © 2013 Elsevier B.V. All rights reserved.
Cao D.,University of North Carolina at Chapel Hill |
Bromberg P.A.,University of North Carolina at Chapel Hill |
Samet J.M.,National Health and Environmental Effects Research Laboratory
American Journal of Respiratory Cell and Molecular Biology | Year: 2010
Exposure to diesel exhaust particles (DEP) has been associated with adverse health outcomes such as inflammation, adjuvancy, and mutagenesis. However, the molecular mechanisms by which DEP inhalation exerts these effects are still largely unknown. We previously reported that exposure to DEP activates the transcription factor Stat3 in airway epithelial cells, a primary target cell of inhaled DEP. To elucidate the functional role of Stat3 activation in these cells, we investigated the function of Stat3 in DEP-induced expression of the p21 gene in the human bronchial epithelial cell line BEAS-2B. We report that DEP exposure induces increased levels of p21 mRNA and protein in a manner that is independent of p53 and Sp1 expression or DNA binding to the p21 gene. Using chromatin immunoprecipitation assays and expression of a dominant-negative Stat3 mutant, we show that activation of Stat3 and its binding to the p21 promoter are required for DEP-induced expression of p21, suggesting that Stat3 plays an essential role in the induction of p21 by DEP. Additional experiments demonstrated that activation of p21 gene expression is dependent on the activation of epidermal growth factor receptor and Src kinase activities. Finally, we provide evidence suggesting that DEP exposure can inhibit the proliferation of human bronchial epithelial cells, suggesting a functional role of p21 activation airway epithelial cells exposed to DEP.
News Article | December 14, 2016
Nearly everything people do, eat or come into contact with can change them in little ways — sometimes with big consequences. Exposure to some chemicals can damage DNA, leading to cancer and other problems. Other molecular changes—chemical tags added to DNA or to proteins called histones — may affect health without injuring DNA. There are more than 100 varieties of these chemical tags, collectively known as epigenetic marks. While they may help humans and other organisms respond to their environments, the tags can also alter development and body functions in unhelpful, even harmful, ways. Yet people who make decisions about safe levels of exposure to chemicals, heavy metals and other environmental factors generally aren’t including epigenetic alterations in their deliberations. Risk assessors take a wide variety of scientific data into account when making recommendations for preventing overexposure to chemicals. When it comes to epigenetic information, though, “honestly, we don’t know what to do with it,” says Marie Fortin, a toxicologist and risk assessor for Colgate-Palmolive Co. “We don’t have a framework to interpret it,” she said at the Society of Toxicology’s ToxicoEpigenetics meeting in Tysons Corner, Va., in November. Even researchers studying how environmental factors write, erase and tweak epigenetic marks admit that the field is in its infancy and still has a long way to go before it can be used to make public health decisions. Epigenetics is “a science that offers enormous opportunities for research, and maybe in a long time it will be useful for risk assessment, but right now we don’t know enough,” says neurotoxicologist Deborah Cory-Slechta of Rochester University Medical Center in New York. Cory-Slechta coauthored a paper describing the epigenetic effects of lead and stress on developing mouse brains. Studying those changes may help scientists learn how lead impairs human brain function and may suggest ways to counteract the heavy metal’s effects, she says. Stressed mouse moms that drank water laced with lead during pregnancy had offspring in which two important epigenetic marks differed in parts of their brains, Cory-Slechta and colleagues reported in the May NeuroToxicology. At various times during development, male and female pups had different changes in the hippocampus, a brain structure involved in learning and memory. Those findings could indicate that males are at higher risk of developing learning problems when their mothers are exposed to lead and are under stress. Other epigenetic studies have indicated that high-fat diets, smoking, exposure to pesticides or to estrogen-mimicking chemicals could have health effects — including increased risk of breast and other cancers—that last for generations (SN: 4/6/13, p. 18). A study published in Scientific Reports in 2015 indicated that grandchildren could inherit epigenetic marks if their grandmothers were exposed to lead (SN: 3/19/16, p. 8). And researchers regularly publish new studies showing that epigenetic marks can be altered by exposure to air pollution, arsenic in drinking water or chemicals such as bisphenol A that are found in products including plastics, canned food and cash register receipts. Yet there are limits to applying the conclusions to human risk assessment. For one thing, most of what scientists know about environmental effects on epigenetic marks comes from animal studies. Such studies will always be imperfect mimics of what goes on in humans. One obstacle to using lab animals as stand-ins for humans is that the animals aren’t living in the real world. Researchers give lead to mice for only a short time, for example; humans typically face long-term exposures, Cory-Slechta says. Her mouse studies indicate that stress can make lead’s effects worse, but lab mice don’t deal with the same sort of social and economic stress that people do. Those types of chronic stress may have different epigenetic consequences than those produced by the short-lived physical challenges mice are usually subjected to. Another major roadblock to determining whether mice and people respond similarly to lead exposure is that Cory-Slechta and her colleagues can’t get samples of people’s brains. The closest the researchers might get is examining epigenetic marks in people’s white blood cells, but lead is likely to affect those cells differently than it does brain cells. Researchers also don’t agree on which epigenetic marks they should track. Some scientists favor DNA methylation, an alteration in which molecules called methyl groups are attached to the DNA building block cytosine. That mark usually signals that gene activity has been turned down. Other researchers concentrate on chemical modifications of histones. Histones are proteins that form spools around which DNA is wound to fit into a cell. A dizzying array of chemical changes at various spots on the histones are associated with more or less gene activity. For instance, tacking an acetyl group onto the histone H3 protein at a specific spot is associated with increased gene activity, but switching the acetyl group for a couple of methyl groups can reduce gene activity. Researchers may not be able to get away with choosing just one of these epigenetic marks to predict how a chemical exposure, diet, exercise and stress might combine with a person’s age, sex and genetic makeup to affect them, says molecular toxicologist Shaun McCullough. Each epigenetic mark is like a letter in a language, says McCullough, of the U.S. Environmental Protection Agency’s National Health and Environmental Effects Research Laboratory in Chapel Hill, N.C. If researchers look at only one type of modification, “it’s like trying to get something out of reading a book in which you can only see one of the letters. You’re not going to get the full story.” Filling in all of the letters may not be necessary. Like contestants on Wheel of Fortune, researchers may be able to guess at the meaning of a particular epigenetic change with a few key letters. To play the guessing game, researchers may have to construct a database compiling all the epigenetic changes in response to particular chemicals and how these changes influence the activity of many genes. Such a project is still a dream; most researchers are still concentrating on only one mark at a time and its effect on a few genes. Even if researchers learn to read the epigenetic language, they still need to establish whether changes cause disease, are merely indicators that something has gone wrong, or are neutral, says environmental epigeneticist Dana Dolinoy. Dolinoy, of the University of Michigan School of Public Health in Ann Arbor, and McCullough co-organized the Toxico-Epigenetics meeting. Their goal was to bring policy makers and research scientists together to learn how epigenetics might be incorporated in risk assessment. Even though participants walked away from the conference with no definite answer, they have begun talking about the steps needed to determine whether epigenetic marks are reliable predictors of chemical exposure safety. Regulators shouldn’t wait for epigenetics to mature as a field before making a ruling on safety, says Ivan Rusyn, a toxicologist at Texas A&M University in College Station. But they should keep the door open for revising decisions as more data become available. Rusyn is one of 46 authors of a report in the November issue of Environmental Health Perspectives on the promise and challenges of incorporating new technology into risk assessment. He’s optimistic that epigenetics can one day contribute valuable data about health risks, but that day won’t come soon. “Right now this is not an airplane we can fly,” he says. “It’s an airplane that’s still in the drawing stage.”