National Institute Of Environmental Health Sciences Research Articles

Evolution of DOHaD: the impact of environmental health sciences.

Environmental exposures have a significant influence on the chronic health conditions plaguing children and adults. Although the Developmental Origins of Health and Disease (DOHaD) paradigm historically has focused on nutrition, an expanding body of research specifically communicates the effects of chemical exposures on early-life development and the propagation of non-communicable disease across the lifespan. This paper provides an overview of 20 years of research efforts aimed at identifying critical windows of susceptibility to environmental exposures and the signaling changes and epigenetic influences associated with disease progression. DOHaD grants funded by the National Institute of Environmental Health Sciences (NIEHS) in 1991, 2001 and 2011 are identified by grant-analysis software, and each portfolio is analyzed for exposures, disease endpoints, windows of exposure, study design and impact on the field based on publication data. Results show that the 1991 and 2001 portfolios comprised metals, PCBs and air pollutants; however, by 2011, the portfolio has evolved to include or expand the variety of endocrine disruptors, pesticides/persistent organic pollutants and metals. An assortment of brain-health endpoints is most targeted across the portfolios, whereas reproduction and cancer increase steadily over the same time period, and new endpoints like obesity are introduced by 2011. With mounting evidence connecting early-life exposures to later-life disease, we conclude that it is critical to expand the original DOHaD concept to include environmental chemical exposures, and to continue a research agenda that emphasizes defining sensitive windows of exposure and the mechanisms that cause disease.

Transparency of Values in Science: Elliott and Resnik Respond

We thank Schwartz for his thoughtful comments, which provide an opportunity for us to clarify some of the points in our commentary, in which we called for greater transparency about the values that influence policy-relevant research (Elliott and Resnik 2014). His first concern is that even though we call for employing different standards of evidence in various social contexts, the evidence itself remains the same. We agree; in our commentary we were not claiming that the evidence itself changes but only that the form of evidence required for different decisions depends on the social context. Nevertheless, it is important to recognize that although the evidence itself does not change, it has to be interpreted and weighed, and many contemporary science policy disputes stem from disagreements about how to do so (Douglas 2012). Therefore, our view is that conflicts over public policies often stem from value judgments about both the nature of the evidence and standards of evidence. We agree with Schwartz about the solution: Transparency is essential. The more scientists acknowledge the assumptions and values that influence their interpretations of evidence and their decisions about how to weigh it, the better. Schwartz’s second point is that it is problematic for us to treat tort law and chemical regulations as equivalent contexts, in which weaker standards of evidence can appropriately inform policy. We agree that different standards of evidence may be appropriate in the two contexts. However, we caution against equating the standards of evidence expected in tort law with those expected in more traditional scientific contexts. The tort system requires only a preponderance of evidence (> 50% likelihood) to win a case; this is much weaker evidence than scientists typically demand when presenting or publishing results, and confusion about these differing standards has led to significant legal controversies (Cranor 2006). Schwartz’s third point is that other conflicts of interest, such as “ideological ties to advocacy organizations,” are important to disclose in addition to financial ties to industry. We heartily agree; indeed, in our commentary (Elliott and Resnik 2014) we stated that “Disclosures of competing financial interests and nonfinancial interests (such as professional or political allegiances) also provide opportunities for more transparent discussions” (Elliott and Resnik 2014). One of the aims of our commentary was to encourage more careful thinking about how to promote transparency regarding a wide range of different factors that could influence scientists’ reasoning, including ideology. Nevertheless, there are at least two reasons that financial connections to industry groups should continue to receive careful attention: a) Advocacy organizations typically have much fewer resources than industry to generate policy-relevant research that serves their interests (Elliott 2011); and b) a large body of evidence indicates that industry funding has important effects on research outcomes, whereas there is less information about how ideological ties affect research (e.g., Lundh et al. 2012). Schwartz’s fourth concern is that it is important to think about risk–benefit relationships when applying science to public policy. This is a very good point, but it needs to be considered in conjunction with the fact that scientists’ values and assumptions may influence their assessments of the evidence. It would be ideal if scientists could provide perfectly unbiased risk assessments to policy makers, who could then evaluate the risks versus the benefits in order to make policy decisions. Unfortunately, this picture is unrealistic; scientists’ views about the benefits associated with new technologies likely have implicit influences on their risk assessments. For example, evidence from the literature on risk perception indicates that people’s perceptions of risk are influenced by a number of factors, including the voluntariness of the risks, the fairness of their distribution, their familiarity, and the perceived benefits associated with them (Fischhoff et al. 1981). Scientists are subject to these same influences, especially when they have limited data or are forced to weigh multiple forms of evidence (Cooke 1991). This provides further support for our central claim, namely, that scientists should explore ways to acknowledge the values that may influence them rather than denying the presence of these influences.

The NIEHS Superfund Research Program: Epidemiological Research to Address the Complexity of Environmental Exposures and Improve Public Health

The National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program (SRP) funds a wide range of university-based research to address public health concerns arising from hazardous substances in the environment. Since its inception in 1987, the SRP has applied a multidisciplinary approach that combines laboratory-based and population-based studies, as well as community engagement and research translation, to improve our understanding of and minimize the health effects associated with exposures to contaminants. For example, SRP-funded researchers are investigating (1) associations between phthalates and preterm birth, (2) prenatal and early-life exposure to chlorinated compounds and adverse neurological effects in later childhood and adulthood, (3) the links between arsenic in drinking water and various cancers, birth outcomes, and adverse effects on intelligence and motor function in children, and (4) associations between metal mixtures and neurodevelopment. Innovative research from SRP-funded investigators is also addressing challenges in environmental epidemiology through the validation of relevant biomarkers and development of immunoassay-based and field-deployable exposure assessment devices. Moving forward, SRP-funded researchers are focusing on the health effects of complex chemical mixtures, determining relevant chemical exposures, identifying developmental windows of susceptibility, analyzing patterns in epidemiologic and toxicologic data to assess risks to human health presented by hazardous substances, and development of tools to facilitate assessment of exposure and toxicity. This presentation will summarize results from SRP epidemiological studies that have linked hazardous substances to health effects, the impact that these studies have had in human health risk assessment, as well as future projects that will address research priority areas in environmental epidemiology.

The EPA/NIEHS Children’s Environmental Health and Disease Prevention Research Centers: More Than 15 Years of Innovative Research on Important Challenges in Children’s Environmental Health

The EPA/NIEHS Children’s Environmental Health and Disease Prevention Research Centers: More Than 15 Years of Innovative Research on Important Challenges in Children’s Environmental HealthAbstract Number:2798 Kimberly Gray* and Nica Louie* Kimberly Gray* U.S. Environmental Protection Agency, United States, E-mail Address: [email protected] Search for more papers by this author and Nica Louie* U.S. Environmental Protection Agency, United States, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: The U.S. Environmental Protection Agency (EPA) and the National Institute of Environmental Health Sciences (NIEHS) have jointly supported the Children's Environmental Health and Disease Prevention Research Centers (‘Children’s Centers’) program since 1998, forming a highly successful and collaborative, interdisciplinary research network.Methods: These multidisciplinary, translational research centers are investigating the role of a wide range of environmental exposures in adverse children's health outcomes and how to protect children's health. Studies include how exposure to chemicals such as ambient air pollutants, arsenic in water and food, endocrine-disrupting compounds (EDCs) including bisphenol A (BPA), manganese, organophosphate pesticides and polybrominated flame retardants may, in combination with other factors such as social and behavioral factors and genetic susceptibility, result in adverse birth and health outcomes including asthma, autism, childhood leukemia, changes in epigenetics/gene expression, changes in neurodevelopment and immune system function -- and how to prevent adverse health outcomes. The Children's Centers are using approaches including longitudinal cohort and case-control studies and environmental epidemiology in conjunction with laboratory-based studies to find novel biomarkers of exposure, early developmental and pubertal effects and gene-environment interactions. Community engagement is a key part of the program.Results: This presentation will review some of the important findings from the program over the past 15 years and summarize some of the research currently being funded.Conclusion: Program grantees have published over 1,000 peer-reviewed publications, some highly cited in high-impact journals and cited in environmental policy. Research from the EPA/NIEHS Children’s Centers program is having a significant impact on the field of children’s environmental health and in protecting children's health.

Retirement of Hugh A. Tilson

Vol. 122, No. 8 EditorialOpen AccessRetirement of Hugh A. Tilson Linda S. Birnbaum, and Rick Woychik Linda S. Birnbaum Search for more papers by this author and Rick Woychik Search for more papers by this author Published:1 August 2014https://doi.org/10.1289/ehp.1408939AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Linda S. BirnbaumRick WoychikAs announced in the April 2014 issue (Tilson 2014), Hugh A. Tilson will be stepping down as Editor-in-Chief of Environmental Health Perspectives (EHP) on 1 August 2014. With his departure, the National Institute of Environmental Health Sciences (NIEHS) is now actively recruiting for a new Editor-in-Chief. Dr. Tilson is generously offering to continue to stay involved with the journal during the period of transition until his successor can be identified. A search committee has been formed and is actively seeking to identify world-class environmental health scientists who have the qualifications and interests to serve in this role. If you are interested in learning more about the position, please send an e-mail to either of us (see e-mail addresses below). For information on how to apply for the position, contact Angela Davis in the National Institutes of Health Office of Human Resources ([email protected]).On behalf of the NIEHS and the National Toxicology Program, we want to express appreciation for Dr. Tilson’s efforts over the past 6.5 years. Since January 2008, when he assumed the role of Editor-in-Chief, Dr. Tilson has played a significant role in moving the journal to where it is today—one of the premier peer-reviewed journals in environmental health sciences. Dr. Tilson has worked diligently to improve the quality of the journal. The impact factor has moved steadily upward—from 5.86 in 2008 to 7.26 in 2013. He has also worked hard to ensure a more diverse readership. The submission of papers from Asia, particularly from China, has almost quadrupled over the past 6 years, and EHP has further expanded its accessibility by disseminating news and research to readers via social media such as Twitter and Facebook. EHP, one of the first scientific journals to move to an open access format, continued to demonstrate its leadership by becoming one of the first scientific journals to go to an online-only version in January 2013. Hugh Tilson has done a remarkable job and has much to be proud of during his tenure as Editor-in-Chief of EHP!ReferenceTilson HA. 2014. Letter from the Editor-in-Chief.Environ Health Perspect 122:A88; doi:10.1289/ehp.1408430. Link, Google ScholarFiguresReferencesRelatedDetails Vol. 122, No. 8 August 2014Metrics About Article Metrics Publication History Originally published1 August 2014Published in print1 August 2014 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Environmental health research recommendations from the Inter-Environmental Health Sciences Core Center Working Group on unconventional natural gas drilling operations.

Background: Unconventional natural gas drilling operations (UNGDO) (which include hydraulic fracturing and horizontal drilling) supply an energy source that is potentially cleaner than liquid or solid fossil fuels and may provide a route to energy independence. However, significant concerns have arisen due to the lack of research on the public health impact of UNGDO.Objectives: Environmental Health Sciences Core Centers (EHSCCs), funded by the National Institute of Environmental Health Sciences (NIEHS), formed a working group to review the literature on the potential public health impact of UNGDO and to make recommendations for needed research.Discussion: The Inter-EHSCC Working Group concluded that a potential for water and air pollution exists that might endanger public health, and that the social fabric of communities could be impacted by the rapid emergence of drilling operations. The working group recommends research to inform how potential risks could be mitigated.Conclusions: Research on exposure and health outcomes related to UNGDO is urgently needed, and community engagement is essential in the design of such studies.Citation: Penning TM, Breysse PN, Gray K, Howarth M, Yan B. 2014. Environmental health research recommendations from the Inter-Environmental Health Sciences Core Center Working Group on Unconventional Natural Gas Drilling Operations. Environ Health Perspect 122:1155–1159; http://dx.doi.org/10.1289/ehp.1408207

Letter from the Editor-in-Chief

Vol. 122, No. 4 EditorialOpen AccessLetter from the Editor-in-Chief Hugh A. Tilson Hugh A. Tilson Search for more papers by this author Published:1 April 2014https://doi.org/10.1289/ehp.1408430Cited by:3View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit The first day of August 2014 will be a big day for me. I have decided to retire after nearly 40 years of federal service, and Environmental Health Perspectives (EHP) will need a new editor-in-chief. It has been a real privilege to lead this important scientific journal since 2008. I believe in EHP, the science it supports, and the communities it serves, and I am proud to have had a part in the journal’s continued success and growing impact.In my inaugural editorial as editor-in-chief (Tilson 2008), I wrote that EHP must adhere to the principles of independence, transparency, and balance and be prepared to recognize emerging themes in order to attract a wider audience and have an impact on the field. Adherence to these standards has served the journal well. In 6 years, the journal’s impact factor increased from 5.86 to 7.26. EHP is one of the top-ranked journals in Public, Environmental, and Occupational Health and in Environmental Sciences. The journal receives nearly 1,500 research manuscripts each year and has an acceptance rate of 15%. We have more than 40 internationally recognized members of the Board of Associate Editors and more than 100 active members of the Editorial Review Board. The journal routinely publishes highly recognized news articles on a variety of emerging topics in environmental health research. In collaboration with the Shanghai Center for Disease Control and Prevention, we also publish news and other articles in a bimonthly issue of EHP Chinese Edition. The journal established and cultivated a thriving social media presence on Facebook and Twitter, and updated its format to provide easy access on personal communication devices. In 2013, EHP was one of the first environmental health journals to publish exclusively online, with the entire journal available electronically and free of charge.I thank the leadership of the National Institute of Environmental Health Sciences (NIEHS) for providing continuous and enthusiastic support and for making good on its commitment to editorial independence and unfettered scientific peer review. The EHP staff members also deserve my gratitude and thanks. They are of some of the most dedicated and passionate individuals I have ever known. I believe that the articles and news we published have made a significant contribution to improving human health and have provided the best available information for decision makers and policy makers worldwide. I am confident that my successor will find the NIEHS and the EHP staff eager to carry on this tradition of excellence.The NIEHS is organizing a search committee to recruit my replacement. I have agreed to assist with the transition and, if necessary, will happily work as a volunteer until a new editor-in-chief is named. In the meantime, EHP will continue to receive manuscripts and publish research and news stories each month. Keep sending us your science, and by all means, keep reading EHP !The author declares he has no actual or potential competing financial interests.ReferenceTilson HA. 2008. Building on a firm foundation. [Editorial]Environ Health Perspect 116:A12; doi:10.1289/ehp.1113118197275. Link, Google ScholarFiguresReferencesRelatedDetailsCited by Feng Q, Liu S, Mao Z, Xu J, Wang Z and Le X (2016) Highlights and new Editorial Advisory Board members of the Journal of Environmental Sciences, Journal of Environmental Sciences, 10.1016/j.jes.2016.08.003, 47, (1-6), Online publication date: 1-Sep-2016. van der Kamp J and Bachmann T (2015) Health-Related External Cost Assessment in Europe: Methodological Developments from ExternE to the 2013 Clean Air Policy Package, Environmental Science & Technology, 10.1021/es5054607, 49:5, (2929-2938), Online publication date: 3-Mar-2015. Birnbaum L and Woychik R (2014) Retirement of Hugh A. Tilson, Environmental Health Perspectives, 122:8, (A202-A202), Online publication date: 1-Aug-2014. Vol. 122, No. 4 April 2014Metrics About Article Metrics Publication History Originally published1 April 2014Published in print1 April 2014 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Study the effect of drug resident time on in vivo efficacy (844.6)

When developing a new drug, it is difficult to predict from in vitro parameters to in vivo efficacy. It is generally accepted that drugs with the strong interactions with their target are more likely to show better efficacy. Therefore, thermodynamic parameter: dissociation constant or inhibition constant (Ki) are often considered as the most important factor to be determined as the first screening to prioritize the drug candidates. However, the kinetic parameter: the dissociation rate constant (koff) of the drugs is often neglected although several reports suggested that koff is as important as or more than Ki to estimate in vivo efficacy.Soluble epoxide hydrolase (sEH) has been proven to play an important role on regulating important lipid mediators, epoxy‐polyunsaturated fatty acid. Inhibition of sEH has been showed to be beneficial to human health in several aspects, anti‐inflammatory, analgesic and promoting tissue regeneration. We recently synthesized a series of new sEH inhibitors with different Kis and koffs. These inhibitors will be used as tools to test if koff can predict in vivo efficacy as equal as or better than the Ki.Here, a series of inhibitors with improved in vitro efficacy will be reported. Our in vivo results suggested that koff is crucial parameters to affect drug efficacy in an alternate way.Grant Funding Source: National Institute of Environ‐ mental Health Sciences (NIEHS) grant ES002710

PFCs and Early Menopause: Association Raises Questions about Causality

Polyfluoroalkyl chemicals (PFCs)—chemicals used in the manufacture of stain- and water-repellant products—are suspected endocrine disrupters.1 Animal studies have suggested an association between exposure to two of the most commonly encountered PFCs (perfluorooctanoate, or PFOA, and perfluorooctane sulfonate, or PFOS) and altered hormonal function,1,2 although evidence in humans remains inconsistent. A small number of cross-sectional epidemiological studies have reported an association between PFOA/PFOS exposure and timing of puberty,3 menopause,4 and thyroid function,5 while others have reported no association.6 In this issue of EHP, researchers report an association between PFC concentrations in circulating blood and rate of hysterectomy as well as earlier age at natural menopause.7 The findings, say the researchers, raise the question of whether high PFC exposure may lead to early menopause or, conversely, whether early menopause may lead PFCs to build up in women’s bodies. Either way, the results are of interest because women who reach menopause by their late 40s are at increased risk for various forms of heart disease.8,9,10 “If PFC levels are predictors of earlier menopause,” the investigators write, “exposure may also increase the risk of other serious health outcomes (e.g., cardiovascular disease and stroke).”7 According to the North American Menopause Society, menopause occurs, on average, at age 51 in U.S. women. Women characterized as having early or premature menopause will have had their last menstrual period before age 40.11 In the current study, researchers from the National Institute of Environmental Health Sciences (NIEHS) and the University of North Carolina at Chapel Hill analyzed data for 2,732 women, more than two-thirds of whom were premenopausal. The investigators compared blood concentrations of four PFCs—PFOA, PFOS, perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS)—and, for postmenopausal women, age at natural or surgically induced menopause. The data were collected as part of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. NHANES data are intended to be nationally representative, and past analyses have indicated ubiquitous exposure to PFOS, PFOA, and other PFCs. One 2007 NHANES analysis showed that 98% of adults sampled had measurable levels of at least two PFCs in their blood.12 In the current study, women with the highest blood levels of PFOA, PFNA, and PFHxS were, respectively, 36%, 47%, and 70% more likely to have experienced menopause than women with the lowest concentrations of these compounds. Premenopausal women had the lowest levels of all four PFCs, whereas women who had undergone hysterectomy had the highest levels.7 PFHxS was most strongly associated with rate of hysterectomy. Women with the highest blood levels were 3.5 times more likely to have had a hysterectomy than women with the lowest levels. PFOA, PFNA, and PFOS were also significantly associated with having had a hysterectomy.7 Hysterectomy was associated with the highest blood levels of all four PFCs studied, possibly a result of unusually early menopause— although longitudinal studies are necessary to test that hypothesis. Women in the study reached natural menopause at a median age of 49, while women who had hysterectomies reported their last period at a median age of 38. The cross-sectional nature of the study makes it impossible to distinguish whether higher PFC levels may have led to earlier menopause or vice versa. “PFCs circulate in blood, so menstruating women may lose PFCs through blood loss, which would not be the case for postmenopausal women,” says lead author Kyla Taylor, a health scientist at the NIEHS. Whereas many persistent organic pollutants are stored primarily in fat tissue, PFCs form bonds with blood proteins. That means they tend to accumulate in serum rather than in fat. “While this study suggests the potential for reverse causation in the association between PFCs and earlier menopause, we don’t know what that means or whether it’s the sole explanation [for the association],” says Sarah Knox, an epidemiologist at West Virginia University who studies PFCs but was not involved in this research. Only a longitudinal study can provide the insight to determine causality. “This is an area of concern and an area clearly in need of further research,” Knox says.

Editorial: Does RCR Education Make Students More Ethical, and Is This the Right Question to Ask?

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTS This article is the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS) and National Institutes of Health (NIH). However, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the United States government. Notes 1. I use will the term “education” in this essay because it has more of an academic connotation than other terms that are sometimes used in the literature, such as “instruction,” and “training.” Training seems to imply mastery of a pre-determined set of materials or skills by rote memorization or practice, whereas “education” seems to imply active participation in an open-ended, evolving learning process. Education includes formal courses, seminars, lectures, online modules, and mentoring.

Nanotoxicology and nanotechnology: new findings from the NIEHS and Superfund Research Program scientific community

Nanomaterials are characterized by their small size (i.e., nanometer scale) and can be engineered from nearly any chemical substance, creating materials that differ in composition, particle size, shape, and surface coatings. These materials are often seen as a "double-edged sword" by having properties that make them potentially beneficial in product development, drug delivery, and remediation of hazardous substances, but these same properties may result in interaction with biological systems and potential effects in the environment. The National Institute of Environmental Health Sciences (NIEHS) is interested in both the potential risks associated with exposure to these materials, while harnessing the power of engineered nanomaterials to improve public health. This presentation will consist of discussion of nanoparticle studies by NIEHS researchers and the extramural community and its efforts to develop cross-agency initiatives to solve the many vexing issues associated with nanomaterials. For example, researchers from the NIEHS National Toxicology Program (NTP) are evaluating a number of nanomaterial classes in comprehensive toxicology studies. NIEHS also has an extensive extramural research grant portfolio consisting of the Nano Grand Opportunities (Nano GO) Program and NIEHS Centers for Nanotechnology Health Implications Research (NCNHIR) Consortium consisting of U19 and U01 Cooperative Centers. Furthermore, the NIEHS Superfund Research Program (SRP), which supports a network of university (P42, R01), small business (SBIR/STTR), and training grants (R25), provides funding to grantees evaluating the toxicology of nanomaterials, developing new or improved nanotechnologies to monitor and remediate hazardous substances, and training professionals in the use of these of materials. The NIEHS's Worker Education Branch also offers educational materials for training workers on risks of nanotechnology in laboratories, manufacturing facilities, at hazardous waste cleanup sites, and during emergency responses. In conclusion, this presentation will stimulate dialogue regarding the need for more research on these complex materials and serve as a resource about the wide variety of ongoing studies on nanomaterials at NIEHS that will contribute to the determination of risk associated with this class of compounds.

Florida red tide knowledge and risk perception: Is there a need for tailored messaging

Harmful algal blooms of the toxic dinoflagellate, Karenia brevis, occur throughout the Gulf of Mexico. Recent research efforts sponsored by the National Institute of Environmental Health Sciences (NIEHS) and others found that Florida red tide causes both acute and possibly chronic health effects from the toxic aerosols. Florida red tide also demonstrated significant social and economic impacts to both coastal residents and visitors. In conjunction with the research, persistent outreach efforts were conducted over the 11-year period. The goal of this project was to assess potential needs for tailored messaging needed among different red tide information user groups. Survey participants included 303 local residents, both with asthma and without, and ‘snowbirds (seasonal residents that reside in the Sarasota area for more than 3 months but less than 6 months/year), also both with asthma and without. The questionnaire assessed Florida red tide knowledge and risk perception regarding Florida red tide using items drawn from two previously published surveys to allow comparison. Our results reveal that overall knowledge of Florida red tide has not changed. We found that knowledge was consistent across our selected groups and also did not vary by age, gender and education level. However, knowledge regarding consumption of seafood during Florida red tide has declined. Risk perception increased significantly for people who have asthma. Individuals responsible for public health communication regarding Florida red tide and human health concerns need to continue to pursue more effective outreach messages and delivery methods.

Editorial introductions

Editorial introductions

What Are Reasonably Foreseeable Risks?

Click to increase image sizeClick to decrease image size Acknowledgments This article is not subject to US copyright law. This article is the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). However, the statements, opinions, or conclusions contained herein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the U.S. government.

Greatest 'HITS': A new tool for tracking impacts at the National Institute of Environmental Health Sciences

Evaluators of scientific research programs have several tools to document and analyze products of scientific research, but few tools exist for exploring and capturing the impacts of such research. Understanding impacts is beneficial because it fosters a greater sense of accountability and stewardship for federal research dollars. This article presents the High Impacts Tracking System (HITS), a new approach to documenting research impacts that is in development at the National Institute of Environmental Health Sciences (NIEHS). HITS is designed to help identify scientific advances in the NIEHS research portfolio as they emerge, and provide a robust data structure to capture those advances. We have downloaded previously un-searchable data from the central NIH grants database and developed a robust coding schema to help us track research products (going beyond publication counts to the content of publications) as well as research impacts. We describe the coding schema and key system features as well as several development challenges, including data integration, development of a final data structure from three separate ontologies, and ways to develop consensus about codes among program staff.

Molecular Competition: Flame Retardants Interact with Key Metabolism Enzyme

Using X-ray crystallography to visualize the three-dimensional structure of an enzyme associated with regulating levels of estrogen, a team of National Institutes of Health scientists have discovered new information on how flame retardants may alter estrogen metabolism.1 Their results suggest one way in which these chemicals may disrupt the body’s endocrine system. Flame retardants are added to foam, textiles, electronics, building materials, and other items to reduce flammability.2 The new research focuses on tetrabromobisphenol A (TBBPA), currently the most heavily produced flame retardant in the world, and 3-OH-BDE-47, a metabolite of the Penta bromodiphenyl ethers (PentaBDEs), which were widely used prior to 2004 and remain in many long-lived consumer goods. Flame retardants come in two types: reactive agents, which are chemically bound to base materials during manufacturing, and additive agents, which are incorporated into products but not chemically bound, allowing them to escape into the surrounding environment.3 People are exposed mainly to additive flame retardants that have migrated into house dust,4 with children potentially more exposed than adults because of their more frequent hand-to-mouth activity and contact with floors.5,6 PentaBDEs were used as additive flame retardants, and although TBBPA is mainly used as a reactive agent, it can also be used as an additive retardant. The new research shows how both TBBPA and 3-OH-BDE-47 can bind to an enzyme known as estrogen sulfotransferase (SULT1E1). This enzyme’s job is to bind the major endogenous estrogen 17β-estradiol and add a sulfate molecule to it; the sulfated estradiol is more readily eliminated from the body. “Basically, the flame retardants are going to compete with estradiol for binding to the sulfotransferase,” says coauthor Linda Birnbaum, director of the National Institute of Environmental Health Sciences (NIEHS). The result may be to raise levels of estradiol in the body, explains corresponding author, Lars Pedersen of the NIEHS Laboratory of Structural Biology. Figure 1 TBBPA (pink) binds to same active site of the estrogen-metabolizing enzyme SULT1E1 (blue) as the body’s major natural estrogen (transparent grey). Endocrine disruption can take several forms—transport disruption, receptor binding, and metabolism are all processes that will affect the endocrine system, Pedersen says. This research demonstrates a potential metabolic impact on the endocrine system and shows that xenobiotic compounds don’t have to bind to the hormone receptor in order to perturb the system, Birnbaum points out. Pedersen adds that these structures only show how these chemicals inhibit the enzyme in the lab. “We need to figure out if this is what is going on in the body,” he says. Given the structural differences between 17β-estradiol and the flame retardants, Pedersen says he was surprised the exogenous molecules were able to bind SULT1E1. Craig Butt, a postdoctoral environmental chemist at Duke University’s Nicholas School of the Environment, observes, “It shows that there is a little bit of flexibility in terms of what molecules can fit into the enzyme, which explains why these foreign chemicals can inhibit the action of the enzyme.” The new research raises concerns because hormones are designed to regulate key mechanisms in our bodies, and they do this at very low levels in our bloodstream and tissues, says Heather Stapleton, an associate professor of environmental chemistry at Duke and Butt’s advisor. “Having continuous exposure to man-made chemicals that can bind with the same affinity as endogenous hormones may have very significant consequences on development and overall health,” Stapleton says. Birnbaum agrees: “We know that hormones are important in many, many aspects of our lives. … One of the important things is, it’s not a single hormone that may be critical. Often it’s the balance of multiple hormones. We all have our own balance. It’s possible you can throw one person out of balance by perturbing one system while in another person you would not.”

Uncertain Inheritance: Transgenerational Effects of Environmental Exposures

Andrea Cupp made a serendipitous discovery when she was a postdoctoral fellow at Washington State University: While investigating how chemicals affect sex determination in embryonic animals, she bred the offspring of pregnant rats that had been dosed with an insecticide called methoxyclor. When the males from that litter grew into adults, they had decreased sperm counts and higher rates of infertility. Cupp had seen these same abnormalities in the animals’ fathers, which had been exposed to methoxyclor in the womb. But this latest generation hadn’t been exposed that way, which suggested that methoxyclor’s toxic effects had carried over generations. “At first I couldn’t believe it,” says Cupp’s advisor, Michael Skinner, a biochemist and Washington State professor. “But then we repeated the breeding experiments and found that the results held up.” Skinner and Cupp, who is now a professor at the University of Nebraska–Lincoln, published their findings in 2005.1 Since that paper—which showed that reproductive effects not just from methoxyclor but also from the fungicide vinclozolin persisted for at least four generations—the number of published articles reporting similar transgenerational findings has increased steadily. “In the last year and half there’s been an explosion in studies showing transgenerational effects from exposure to a wide array of environmental stressors,” says Lisa Chadwick, a program administrator at the National Institute of Environmental Health Sciences (NIEHS). “This is a field that’s really starting to take off.” According to Chadwick, the new findings compel a reevaluation of how scientists perceive environmental health threats. “We have to think more long-term about the effects of chemicals that we’re exposed to every day,” she says. “This new research suggests they could have consequences not just for our own health and for that of our children, but also for the health of generations to come.” Figure 1 Glossary The NIEHS recently issued requests for applications totaling $3 million for research on transgenerational effects in mammals.2 Chadwick says funded studies will address two fundamental data needs, one pertaining to potential transgenerational mechanisms and another to the number of chemicals thought to exert these effects. These studies will extend to what’s known as the F3 generation—the great-grandchildren of the originally exposed animal. That’s because chemicals given to pregnant females (the F0 generation) interact not only with the fetal offspring (the F1 generation) but also the germ cells developing within those offspring, which mature into the sperm and eggs that give rise to the F2 generation. Thus, the F3 animals are the first generation to be totally unexposed to the original agent. Effects that extend to the F2 generation are known as “multigenerational,” whereas those that extend to the F3 generation are known as “transgenerational.”3 Transgenerational effects have now been reported for chemicals including permethrin, DEET, bisphenol A, certain phthalates, dioxin, jet fuel mixtures, nicotine, and tributyltin, among others. Most of these findings come from rodent studies.4,5,6,7 But preliminary evidence that chemical effects can carry over generations in humans is also emerging, although no F3 data have been published yet. Given the challenges of tracking effects over multiple human lifespans, the evidence is more difficult to interpret, particularly with respect to potential mechanisms, says Tessa Roseboom, a professor of early development and health at the Academic Medical Center in Amsterdam, the Netherlands. Still, some reports have linked nutritional deficiencies from famine and exposure to diethylstilbestrol (DES)—a nonsteroidal estrogen used to protect against miscarriage from the 1940s to the 1970s—to effects that persist among the grandchildren of exposed women.8,9,10,11,12,13

Measuring Impacts from Public Health Research

BACKGROUND: The importance of measuring progress towards goals was recently highlighted in the Gates Foundation Annual Letter[1]. Public health researchers sometimes struggle to make direct connections between their activities and interventions with longer term public health impact. The Evaluation Metrics Manual[2], a resource developed by the National Institute of Environmental Health Sciences (NIEHS), can help researchers articulate their goals and develop tangible metrics of progress toward their achievement. This paper will review the Manual, which promotes the use of logic models to demonstrate linkages among research project activities, outputs, and impacts. Particular attention will be given to using logic models to develop specific metrics of public health impact that go beyond typical measures such as counts of peer reviewed publications and journal impact factors. AIMS and METHODS: NIEHS grantees asked for help in understanding and documenting the impacts and outcomes of their work. In response, we developed the Manual based on environmental public health literature, interviews with grantees and reviews of their projects. CONCLUSION: Good measurement is critical for documenting impact. Researchers and science managers benefit from better measurement and evaluation approaches in that they are better able to: identify and publicize program achievements; determine whether a project worked and why (or why not); identify areas for improvement; describe expenditures; justify a need for additional funding; and inform policy and other decision making. [1] Gates, Bill. (2013). Annual Letter from the Bill & Melinda Gates Foundation. http://annualletter.gatesfoundation.org/ [2] NIEHS (2012). Partnerships for Environmental Public Health Evaluation Metrics Manual. http://www.niehs.nih.gov/pephmetrics

The Environment Within: Exploring the Role of the Gut Microbiome in Health and Disease

The human genome codes for approximately 23,000 genes,1 yet some experts have suggested that the total information coded by the human genome alone is not enough to carry out all of the body’s biological functions.2 A growing number of studies suggest that part of what determines how the human body functions may be not only our own genes, but also the genes of the trillions of microorganisms that reside on and in our bodies. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million genes.3 “The genetic richness and complexity of the bugs we carry is much richer than our own,” says Jayne Danska, an immunologist at the Hospital for Sick Children Research Institute in Ontario, Canada. “They serve as a buffer and interpreter of our environment. We are chimeric organisms.” Figure 1 False-color scanning electron micrograph shows the surface of the colon mucosa with pink clusters of rod-shaped bacteria, possibly Escherichia coli, attached. The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million ... A role for gut microbes in gastrointestinal function has been well documented since researchers first described differences in the fecal bacteria of people with inflammatory bowel disease.4 The molecular mechanisms responsible for the gut microbiome’s impact on metabolism and diseases throughout the body remain largely unknown. However, researchers are beginning to decipher how the microorganisms of the human intestinal tract influence biological functions beyond the gut and play a role in immunological, metabolic, and neurological diseases.

Embryo-fetal development study of the hedgehog pathway inhibitor vismodegib

Recently, medical research has seen a strong push toward translational research, or “bench to bedside” collaborations, that strive to enhance the utility of laboratory science for improving medical treatment. The success of that paradigm supports the potential application of the process to other fields, such as risk assessment. Close collaboration among academic, government, and industry scientists may enhance the translation of scientific findings to regulatory decision making. The National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively academic and guideline-compliant research. An initial proof-of-concept collaboration, the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), uses bisphenol A (BPA) as a test chemical. The CLARITY-BPA program combines a core perinatal guideline-compliant 2-year chronic toxicity study with mechanistic studies/endpoints conducted by academic investigators. Twelve extramural grantees were selected by NIEHS through an RFA-based initiative to participate in the overall study design and conduct disease-relevant investigations using tissues and animals from the core study. While the study is expected to contribute to our understanding of potential effects of BPA, it also has ramifications beyond this specific focus. Through CLARITY-BPA, NIEHS has established an unprecedented level of collaboration among extramural grantees and regulatory researchers. By drawing upon the strengths of academic and regulatory expertise and research approaches, CLARITY-BPA represents a potential new model for filling knowledge gaps, enhancing quality control, informing chemical risk assessment, and identifying new methods or endpoints for regulatory hazard assessments.