Environmental Effects Research Laboratory Research Articles

Epigenetics: The Science of Change

For nearly a century after the term “epigenetics” first surfaced on the printed page, researchers, physicians, and others poked around in the dark crevices of the gene, trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence. Today, a wide variety of illnesses, behaviors, and other health indicators already have some level of evidence linking them with epigenetic mechanisms, including cancers of almost all types, cognitive dysfunction, and respiratory, cardiovascular, reproductive, autoimmune, and neurobehavioral illnesses. Known or suspected drivers behind epigenetic processes include many agents, including heavy metals, pesticides, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria, and basic nutrients. In the past five years, and especially in the past year or two, several groundbreaking studies have focused fresh attention on epigenetics. Interest has been enhanced as it has become clear that understanding epigenetics and epigenomics—the genomewide distribution of epigenetic changes—will be essential in work related to many other topics requiring a thorough understanding of all aspects of genetics, such as stem cells, cloning, aging, synthetic biology, species conservation, evolution, and agriculture.

Arsenic: In Search of an Antidote to a Global Poison

Arsenic. No other element has such a complex and variegated past. As early as 500 B.C. the ancients knew about arsenic, whose name comes from the Greek word for potent. Through the centuries, this “king of poisons” was a common means of homicide. And yet, arsenic’s image has not always been so morbid. People in the Middle Ages wore arsenic amulets around their necks to ward off the bubonic plague, and women in Victorian times applied arsenic compounds to their faces to whiten their complexions. Hippocrates, the father of western medicine, recorded arsenic’s usefulness as a topical remedy for skin ulcers.

An Approach to Predict Risks to Wildlife Populations from Mercury and Other Stressors

Ecological risk assessments for mercury (Hg) require measured and modeled information on exposure and effects. While most of this special issue focuses on the former, i.e., distribution and fate of Hg within aquatic food webs, this paper describes an approach to predict the effects of dietary methylmercury (CH3Hg) on populations of piscivorous birds. To demonstrate this approach, the U.S. Environmental Protection Agency's National Health and Environmental Effects Research Laboratory (U.S. EPA NHEERL) is working cooperatively with environmental and conservation organizations to develop models to predict CH3Hg effects on populations of the common loon, Gavia immer. Specifically, a biologically-based toxicokinetic model is being used to extrapolate CH3Hg effects on the reproduction of a tested bird species, the American kestrel (Falco sparverius), to the loon. Population models are being used to incorporate stressor effects on survival and reproduction into projections of loon population effects. Finally, habitat and spatially-explicit population models are being used to project results spatially, assess the relative importance of CH3Hg and non-chemical stressors, and produce testable predictions of the effects of biologically-available Hg on loon populations. This stepwise process provides an integrated approach to estimate the impact on wildlife populations of regulations that limit atmospherically-distributed Hg, and to develop risk-based population-level regulatory criteria.

Deposition of Inhaled Particulate Matter in the Human Upper Respiratory Tract

*Author to whom correspondence should be addressed. Tel: +1-919-541-7875; fax: +1-919-541-4284; e-mail: martonen.ted@epa.gov 1National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599; 3Department of Mechanical Engineering, University of Rhode Island, Kingston, RI 02881; 4Los Alamos National Laboratory, Los Alamos, NM 87545, USA

Development of a research strategy for integrated technology-based toxicological and chemical evaluation of complex mixtures of drinking water disinfection byproducts.

Chemical disinfection of water is a major public health triumph of the 20th century. Dramatic decreases in both morbidity and mortality of waterborne diseases are a direct result of water disinfection. With these important public health benefits comes low-level, chronic exposure to a very large number of disinfection byproducts (DBPs), chemicals formed through reaction of the chemical disinfectant with naturally occurring inorganic and organic material in the source water. This article provides an overview of joint research planning by scientists residing within the various organizations of the U.S. Environmental Protection Agency Office of Research and Development. The purpose is to address concerns related to potential health effects from exposure to DBPs that cannot be addressed directly from toxicological studies of individual DBPs or simple DBP mixtures. Two factors motivate the need for such an investigation of complex mixtures of DBPs: a) a significant amount of the material that makes up the total organic halide and total organic carbon portions of the DBPs has not been identified; and b) epidemiologic data, although not conclusive, are suggestive of potential developmental, reproductive, or carcinogenic health effects in humans exposed to DBPs. The plan is being developed and the experiments necessary to determine the feasibility of its implementation are being conducted by scientists from the National Health and Environmental Effects Research Laboratory, the National Risk Management Research Laboratory, the National Exposure Research Laboratory, and the National Center for Environmental Assessment.

Airway Identification Within Planar Gamma Camera Images

*Author to whom correspondence should be addressed. Tel: +1-919-541-7875; fax: +1-919-541-4284; e-mail: martonen.ted@epa.gov 1Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA; 2National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA; 3GlaxoSmithKline Research and Development, Stockley Park, Uxbridge, Middlesex, UK; 4IBM Corporation, Research Triangle Park, NC 27709, USA

Defining the population of spermatozoal RNAs in normal fertile men

Objective: Idiopathic male infertility will affect at least 6% of all couples. Often, this is not diagnosed until several IVF cycles have been completed. This places couples at unnecessary risk. The recent demonstration that mature ejaculate spermatozoa contain RNAs may provide a window that is indicative of the past events of spermatogenesis. If true, ejaculate spermatozoa could be used as a non-invasive marker of fertility status. Design: Verify that spermatozoal transcripts encapsulate spermatogenic gene expression and assess the variation using high density human microarrays. Materials/Methods: A set of 27,016 unique expressed sequence tags (ESTs) was interrogated using cDNAs from a pool of testes from 19 trauma victims’, a pool of 9 individuals’ ejaculate spermatozoal mRNAs and RNA of a single individual’s ejaculate spermatozoa. Subsets of these ESTs were then probed using RNA populations isolated from ejaculate spermatozoa of individual normal fertile men. Results: Of the 27,016 ESTs surveyed, testes cDNAs hybridized to 7,157 ESTs. All of the 3,281 ESTs identified by the pooled-ejaculate probe were contained within this population. The veracity of this observation was assessed by cross-examining the same set of ESTs with cDNAs derived from the spermatozoa of an individuals’ ejaculate. All 2,784 of the ESTs identified were contained within the pooled testes cDNA and 2,780 of these were present within the pooled ejaculate probe. Further comparison of spermatozoal transcript profiles among normal fertile men revealed a universal core and range of gene transcripts within ejaculate spermatozoa. Conclusions: Microarray analysis supports the view that spermatozoal mRNAs encapsulate spermatogenic gene expression. Some variation among the populations of spermatozoal transcripts was observed. We expect that the invariant RNAs represent messages necessary for the production of normal fertile spermatozoa. Thus, we are now establishing the range of variation in the normal fertile male. It is fully anticipated that this information will provide the means to clinically diagnose male factor infertility using a “Male Factor fertility gene chip.” Supported by: This work was funded in part by NIH grant HD36512 and WSU grant 95200 to SAK and NIH grant HD39005 to MPD. GCO is supported in part by a Wayne State University’s School of Medicine Dean’s Post-Doctoral Fellowship award and the NICHD CIR-LRP. Special thanks to RJ Goodrich and K Collins for their technical assistance. The information in this document has been funded in part by the U.S. Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Inhibition of tobacco smoke-induced lung inflammation by a catalytic antioxidant.

Cigarette smokers experience airway inflammation and epithelial damage, the mechanisms of which are unknown. One potential cause may be free radicals either in tobacco smoke or produced during persistent inflammation. Inflammation may also be a driving force to cause airway epithelium to undergo changes leading to squamous cell metaplasia. To test whether tobacco smoke-induced inflammation could be reduced by a catalytic antioxidant, manganese(III)meso-tetrakis(N,N'-diethyl-1,3-imidazolium-2-yl) porphyrin (AEOL 10150) was given by intratracheal instillation to rats exposed to filtered air or tobacco smoke. Exposure to tobacco smoke for 2 d or 8 weeks (6 h/d, 3 d/week) significantly increased the number of cells recovered by bronchoalveolar lavage (BAL). AEOL 10150 significantly decreased BAL cell number in tobacco smoke-treated rats. Significant reductions in neutrophils were noted at 2 d and macrophages at 8 weeks. Lymphocytes were significantly reduced by AEOL 10150 at both time points. Squamous cell metaplasia following 8 weeks of tobacco smoke exposure was 12% of the total airway epithelial area in animals exposed to tobacco smoke without AEOL 10150, compared with 2% in animals exposed to tobacco smoke, but treated with AEOL 10150 (p <.05). We conclude that a synthetic catalytic antioxidant decreased the adverse effects of exposure to tobacco smoke.

Extrapolation in Human Health and Ecological Risk Assessments: Proceedings of a Symposium

A symposium was conducted in April 1998 by the U.S. Environmental Protection Agency's National Health and Environmental Effects Research Laboratory (NHEERL) to explore issues of extrapolation in human health and ecological risk assessments. Over the course of three and one half days, leading health and ecology experts presented and discussed research methods and approaches for extrapolating data among taxa and across levels of biological organization, through time, and across spatial scales. The intended result of this symposium was enhanced interaction among a diverse array of scientists, policymakers, and risk assessors to promote identification of approaches for reducing the uncertainties of extrapolation in risk assessment.

Extrapolation in Human Health and Ecological Risk Assessments: Fourth Symposium of U.S. EPA's National Health and Environmental Effects Research Laboratory

Extrapolation in Human Health and Ecological Risk Assessments: Fourth Symposium of U.S. EPA's National Health and Environmental Effects Research Laboratory

Indicators in Health and Ecological Risk Assessment: Fifth Symposium of U.S. EPA's National Health and Environmental Effects Research Laboratory

"Indicators in Health and Ecological Risk Assessment: Fifth Symposium of U.S. EPA's National Health and Environmental Effects Research Laboratory." Human and Ecological Risk Assessment: An International Journal, 7(5), pp. 959–960

Under What Conditions Is Trichloroethylene Likely To Be a Carcinogen in Humans?

This manuscript has been reviewed in accordance with the policy of the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or use recommendation.Exposures to trichloroethylene (TCE) induce several types of cancer in experimental animals. TCE is metabolized in the body to multiple compounds, several of which are carcinogenic at relatively high doses in rodents. Risk assessments can be pursued with any one of the animal cancer endpoints after consideration of their relevance for humans exposed at low environmental concentrations. Among the TCE metabolites, dichloroacetic acid (DCA), trichloroacetic acid (TCA), chloral hydrate (CHL), and 1,2-dichlorovinylcysteine (DCVC) are each considered carcinogenic in rodents. Two of these, DCA and CHL, are used therapeutically in humans, while a third, TCA, has metabolic effects similar to compounds used therapeutically in humans to reduce lipid concentrations in blood. Each of these three compounds produces biological responses that are expected in humans. However, these biological responses, although they serve as precursors for tumor formation in rodents, are not expected to lead to tumors in humans at any environmentally relevant exposure situations. 1,2-DCVC, formed by a minor pathway of TCE metabolism, is further metabolized in kidney to a reactive thioketene. Of the observed animal carcinogenic responses, only the kidney tumors from the DCVC pathway are considered relevant as predictors of human cancer. Factors that increase TCE metabolism to glutathione conjugates or predispose humans to kidney damage should increase risks posed to workers from high-concentration exposures to TCE. Based on our knowledge of the cytotoxic and mutagenic modes of action expected for these active metabolite (s), a nonlinear cancer risk assessment approach is recommended to be used with the kidney tumor data to assess the human risks of TCE.

Effects of food availability on survival, growth, and reproduction of the grass shrimp Palaemonetes pugio: a laboratory study

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 220:231-239 (2001) - doi:10.3354/meps220231 Effects of food availability on survival, growth, and reproduction of the grass shrimp Palaemonetes pugio: a laboratory study Kathleen A. Reinsel1,*, Patricia S. Glas2, James R. Rayburn3, M. Karen Pritchard4, William S. Fisher5 1Department of Biology, Wittenberg University, PO Box 720, Springfield, Ohio 45504, USA 2Department of Biology, The Citadel, 171 Moultrie Street, Charleston, South Carolina 29409, USA 3Department of Biology, Jacksonville State University, 700 Pelham Road. N., Jacksonville, Alabama 36265-1602, USA 4Biology Department, Pensacola Junior College, Pensacola, Florida 32504, USA 5Gulf Ecology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Gulf Breeze, Florida 32561, USA *E-mail: kreinsel@wittenberg.edu ABSTRACT: Grass shrimp are abundant, ecologically important inhabitants of estuarine ecosystems that have been used extensively in laboratory experiments. However, optimal laboratory feeding conditions have not been determined. We used a laboratory experiment to determine the effects of food availability on survival, growth and reproduction in adult Palaemonetes pugio Holthuis and hatching success of their offspring. Fifteen groups of 50 shrimp were fed 1 of 5 rations of TetraMin® flake food, a standard laboratory diet, for 12 wk; supplementary amounts of newly hatched Artemia sp. nauplii were also given twice weekly. Adult survival, female reproductive condition, and embryo hatching success were determined every 2 wk. Growth was determined from measurements at the beginning and end of the study. Limited food availability caused severe mortality and reduced growth of female shrimp, whereas male shrimp were not affected. Reproduction, as measured by percent gravid females and individual clutch size, was not affected by food availability. However, estimated population-level embryo production was reduced indirectly for the lower rations through mortality and smaller size of females. Hatching success was low in all treatments. Further studies are needed to determine optimal laboratory feeding conditions for grass shrimp so they may be better utilized as predictors of responses in the field. KEY WORDS: Feeding · Reproduction · Grass shrimp · Palaemonetes · Food limitation · Nutrition · Hatching success Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 220. Online publication date: September 27, 2001 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2001 Inter-Research.

Values, Policy, and Ecosystem Health

Robert T. Lackey (email: lackey.robert@epa.gov) is a natural resource ecologist at the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Corvallis, Oregon 97333. He is also courtesy professor of fisheries science and adjunct professor of political science at Oregon State University. The views and opinions expressed do not necessarily reflect those of any organization. Citation: Lackey, Robert T. 2001. Values, policy, and ecosystem health. BioScience. 51(6): 437-443.

The 1999 Fresno Particulate Matter Exposure Studies: Comparison of Community, Outdoor, and Residential PM Mass Measurements

ABSTRACT Two collaborative studies have been conducted by the U.S. Environmental Protection Agency (EPA) National Exposure Research Laboratory (NERL) and National Health and Environmental Effects Research Laboratory to determine personal exposures and physiological responses to par-ticulate matter (PM) of elderly persons living in a retirement facility in Fresno, CA. Measurements of PM and other criteria air pollutants were made inside selected individual residences within the retirement facility and at a central outdoor site on the premises. In addition, personal PM exposure monitoring was conducted for a subset of the participants, and ambient PM monitoring data were available for comparison from the NERL PM research monitoring platform in central Fresno. Both a winter (February 1-28, 1999) and a spring (April 19-May 16, 1999) study were completed so that seasonal effects could be

RESEARCH INTEGRITY: A GOVERNMENT PERSPECTIVE

What is research integrity? At the United States Environmental Protection Agency (U.S. EPA) research integrity can be defined as conducting and fostering research to define, anticipate, and understand environmental problems; and generating sound, appropriate, credible, and effective solutions to those problems. Whether in government, academia, or industry, integrity is required at all stages of research--from data generation to data analysis. What constitutes research integrity? Simply put, Did we do the right thing? Did we do it the right way? Did we honestly document what we did? This is especially important if the research is used as a basis for public policy. The extensive and intensive use of the results of science in EPA's standard setting, regulatory, and enforcement responsibilities means that scientific misconduct can lead to costly and inappropriate actions through unnecessary expenditure or inadequate protection. The soundness, effectiveness, and credibility of EPA's regulations ultimately rest on the scientific and technical bases for these actions. Careful attention to research record keeping can help ensure data quality and integrity. The U.S. Environmental Protection Agency, its research requirements, and the work of the National Health and Environmental Effects Research Laboratory are discussed below.

Data quality objectives in environmental research planning.

This paper presents highlights of a Data Quality Objectives course relating the Environmental Protection Agency's (EPA) seven step research planning process to research efforts at the U.S. EPA National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, in Duluth, Minnesota. Introductory materials were derived from "Guidance for the Data Quality Objectives Process, EPA QA/G-4." Case studies illustrate decisions that were made during the systematic planning process and subsequent experimentation. This paper demonstrates how the Data Quality Objectives Process clearly links research goals and objectives with the final product. Application of the process to environmental research ensures that environmental research data are of known, credible, defensible and usable quality.

Behavioral assessments of learning and attention in rats exposed perinatally to 3,3',4,4',5-pentachlorobiphenyl (PCB 126)

Evidence from humans suggests that cognitive dysfunction may result from perinatal exposure to polychlorinated biphenyls (PCBs), and the results of some animal research with PCBs have been interpreted in terms of possible impairment of attention. Long-Evans rats were fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a coplanar congener, at doses of 0.25 or 1 microgram/kg/day [corrected] throughout gestation and nursing. Male offspring of these rats were trained as adults to perform 2 tests of attention for food reward. First, a cued target-detection task, modeled after Posner's covert orienting method for humans, was used to assess visuospatial attention. In this task, a visual target stimulus was presented in 1 visual hemifield on each trial, preceded either by a valid cue, an invalid cue, or no cue. A valid cue appeared in the same hemifield as the target, and an invalid cue appeared in the opposite hemifield. As expected, valid cues increased accuracy and speed of target detection and invalid cues decreased accuracy and speed; moreover, these effects were systematically related to changes in cue intensity and target duration. However, perinatal exposure to PCB 126 did not affect acquisition or performance of this task. The second task assessed sustained attention by means of a signal detection method in which a brief, spatially-constant but temporally unpredictable, visual signal indicated which of 2 responses would yield food. Varying the intensity of the signal greatly affected the probability of correctly reporting the signal. Perinatal exposure to PCB 126 did not affect acquisition of the response rule or performance of the task. Finally, all rats were challenged with chlordiazepoxide (CDP) at doses of 0, 3, 5, 8, or 12 mg/kg SC, 20 min before testing in the sustained attention task. In control rats, low doses (3, 5, and 8 mg/kg) of CDP reduced accuracy at low signal intensities only, suggesting an increase in visual threshold. The high dose of CDP reduced accuracy at all signal intensities and increased the false-alarm rate as well, suggesting an impairment of attention. The rats exposed perinatally to PCB 126 at 0.25 micrograms/kg [corrected] were unaffected by CDP, and those exposed to PCB 126 at 1 microgram/kg [corrected] showed a smaller decrement in performance after CDP than did the controls. Taken together, these data provide little support for the possibility that perinatal exposure to PCB 126 causes deficits in attention, but suggest that PCB 126 may alter GABA-mediated pathways in the CNS during development.

Polycyclic aromatic hydrocarbons in carcinogenesis.

A symposium on "Polycyclic Aromatic Hydrocarbons (PAHs) in Carcinogenesis" was presented at the third International Congress of Pathophysiology held in Lathi, Finland, 28 June-3 July 1998. The congress was also sponsored by the International Union of Biological Sciences and the International Society of Free Radical Research. Institutional support for the symposium included the Electric Power Research Institute, National Center for Toxicological Research, and EPA/National Health and Environmental Effects Research Laboratory and the Office of Solid Waste and Emergency Response. The symposium focused on the sources, carcinogenicity, genotoxicity, and risk assessment of individual and mixtures of PAHs that are found in solid wastes, Superfund sites, and other hazardous waste sites. Based on the occurrence of PAHs at numerous Superfund sites and the significant data gaps on the toxic potential of certain PAHs, the information developed during this symposium would be of value in assessing health risks of these chemicals at Superfund and other hazardous waste sites.

Polycyclic Aromatic Hydrocarbons in Carcinogenesis

Polycyclic Aromatic Hydrocarbons in Carcinogenesis