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Abstract Introduction Disaster research response (DR2) is necessary to answer scientific questions about the environmental health impacts of disasters and the effectiveness of response and recovery strategies. This research explores the preparedness and capacity of National Institute of Environmental Health Sciences (NIEHS) P30 Core Centers (CCs) to conduct DR2 and engage with communities in the context of disasters. Methods In early 2018, we conducted an online survey of CC Directors (n = 16, 69.5% response rate) to identify their DR2 relevant scientific assets, capabilities, and activities. Summary statistics were calculated. We also conducted in-depth, semi-structured interviews with 16 (69.5%) CC Community Engagement Core directors to identify facilitators and barriers of DR2 community engagement. Interview notes were coded and thematically analyzed. Results Survey: While 56% of responding CCs reported prior participation in DR2 and preparedness to repurpose funding to support DR2, less than one third reported development of a disaster-specific data collection protocol, deployment plan, or concept of operations plan, participation in an exercise to test DR2 capacity, development of academic partnerships to conduct DR2, development of a process for fast-tracking institutional review board approvals for DR2, or maintenance of formal agreements with state, local, or community-based partner(s). A number of CCs reported developing or considering developing capacity in these areas. Barriers to, and tools and resources to enhance, CC engagement in DR2 were identified. Interviews: Four key components for community engaged DR2 were identified: pre-existing community relationships, responsive research that benefits communities, coordination among researchers, and coordination with community response partners. Several roles for, benefits of, and barriers to Community Engagement Rapid Response Teams (CERRT) were described. Conclusions CCs have significant scientific assets and community partnerships that can be leveraged for DR2; however, additional planning is necessary to ensure that these scientific assets and community partnerships are leveraged when disasters strike.

National Toxicology Program (NTP) pathologists are engaged in important initiatives that have significant global impact. These initiatives build on its leadership in pathology peer review and publications in the areas of toxicologic pathology, clinical pathology, and laboratory animal medicine. Over the past decade, NTP/National Institute of Environmental Health Sciences research initiatives have focused on cancer and noncancer hazard identification, with the goal of understanding cellular and molecular mechanisms of disease. New initiatives of significant global impact include the web-based nonneoplastic lesion atlas and an NTP partnership with international scientists to investigate molecular mechanisms at the whole genome level, which will be used to inform potential mechanisms of environmental exposures in human cancers. Also, we are dedicated to contributing to pathology and toxicology organizations through service on executive committees and editorial boards, participating in international projects and symposiums, and providing training for future leaders in toxicologic pathology. Herein, we provide highlights of our global contributions. [ABSTRACT FROM AUTHOR]

On the occasion of the 50th anniversary of the National Institutes of Environmental Health Sciences we reflect on how environmental research incorporating community members as active partners has evolved, benefited communities and advanced environmental health research. We highlight the commitment to community partnerships in the aftermath of the 2010 Deep Water Horizon Oil Spill, and how that commitment helped improve science. We provide examples of community-academic partnerships across the engagement spectrum. Finally, we offer suggestions to improve the community engagement in order to cultivate more long partnerships and better scientific research. [ABSTRACT FROM AUTHOR]

In response to the human health threats stemming from Hurricanes Katrina and Rita, inter-disciplinary working groups representing P30-funded Centers of the National Institute Environmental Health Sciences were created to assess threats posed by mold, harmful alga blooms, chemical toxicants, and various infectious agents at selected sites throughout the hurricane impact zone. Because of proximity to impacted areas, UTMB NIEHS Center in Environmental Toxicology was charged with coordinating direct community outreach efforts, primarily in south Louisiana. In early October 2005, UTMB/NIEHS Center Community Outreach and Education Core, in collaboration with outreach counterparts at The University of Texas MD Anderson Cancer Center @ Smithville TX/Center for Research in Environmental Disease sent two groups into southern Louisiana. One group used Lafourche Parish as a base to deliver humanitarian aid and assess local needs for additional supplies during local recovery/reclamation. A second group, ranging through New Iberia, New Orleans, Chalmette, rural Terrebonne, Lafourche and Jefferson Parishes and Baton Rouge met with community environmental leaders, emergency personnel and local citizens to 1) sample public risk perceptions, 2) evaluate the scope and reach of ongoing risk communication efforts, and 3) determine how the NIEHS could best collaborate with local groups in environmental health research and local capacity building efforts. This scoping survey identified specific information gaps limiting efficacy of risk communication, produced a community “wish list” of potential collaborative research projects. The project provided useful heuristics for disaster response and management planning and a platform for future collaborative efforts in environmental health assessment and risk communication with local advocacy groups in south Terrebonne-Lafourche parishes.

I would certainly never have predicted that I would become the director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP) when I was a Jewish girl growing up in Teaneck, New Jersey. My family stressed the importance of education. Yet for a girl there were many not-so-subtle suggestions that the appropriate careers were in teaching or nursing, and the most important thing was to be a wife and mother. Well, I can't disagree with the latter, although I would have to add grandmother to that list of achievements. My parents were both college graduates, but my mom only taught high school English for one year before leaving the field to start our family. My dad returned from World War II and joined his brother in accounting. After my first sister was born, my father joined my mother's family jewelry business and helped to open a second retail store. My mother helped my dad out during the busy times-Christmas and wedding season-but otherwise focused on our growing family of three girls and one boy. This became increasingly challenging when it became clear that my little brother was severely retarded and would require extra care. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, 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 a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical used to make polycarbonate plastic and is found in many consumer products. Some studies using animal models have suggested that BPA exposures may have adverse health effects. However, research gaps have precluded a full understanding of the effects of BPA in humans and engendered controversies surrounding the chemical's potential toxicity. OBJECTIVES: The National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program (NTP) have developed an integrated, multipronged, consortium-based approach to optimize BPA-focused research investments to more effectively address data gaps and inform decision making. DISCUSSION: NIEHS/NTP BPA research investments made over the past 4 years include extramural research grants, establishment of a BPA Grantee Consortium, intramural research activities on BPA's mechanisms of action, the launch of two clinical studies and an occupational study, development of a round-robin experiment to validate BPA measurements in human serum, and, in collaboration with the Food and Drug Administration (FDA), formation of a consortium to design and execute a chronic toxicity study of BPA in rats. The NIEHS's new consortium-based approach has led to more integrated, collaborative efforts and should improve our ability to resolve controversies over the potential human health effects of exposures to low levels of endocrine-active agents. [ABSTRACT FROM AUTHOR]

oBjective: In this review we highlight the need to expand the scope of environmental health research, which now focuses largely on the study of toxicants, to incorporate infectious agents. We provide evidence that environmental health research would be strengthened through finding com­mon ground with the tools and approaches of infectious disease research. data sources and extraction: We conducted a literature review for examples of interactions between toxic agents and infectious diseases, as well as the role of these interactions as risk factors in classic "environmental" diseases. We investigated existing funding sources and research mandates in the United States from the National Science Foundation and the National Institutes of Health, particularly the National Institute of Environmental Health Sciences. data synthesis: We adapted the toxicological paradigm to guide reintegration of infectious disease into environmental health research and to identify common ground between these two fields as well as opportunities for improving public health through interdisciplinary research. conclusions: Environmental health encompasses complex disease processes, many of which involve interactions among multiple risk factors, including toxicant exposures, pathogens, and susceptibil­ity. Funding and program mandates for environmental health studies should be expanded to include pathogens in order to capture the true scope of these overlapping risks, thus creating more effective research investments with greater relevance to the complexity of real-world exposures and multifactorial health outcomes. We propose a new model that integrates the toxicology and infectious disease paradigms to facilitate improved collaboration and communication by providing a framework for interdisciplinary research. Pathogens should be part of environmental health research planning and funding allocation, as well as applications such as surveillance and policy development. [ABSTRACT FROM AUTHOR]

In response to the human health threats stemming from Hurricanes Katrina and Rita, inter-disciplinary working groups representing P30-funded Centers of the National Institute Environmental Health Sciences were created to assess threats posed by mold, harmful alga blooms, chemical toxicants, and various infectious agents at selected sites throughout the hurricane impact zone. Because of proximity to impacted areas, UTMB NIEHS Center in Environmental Toxicology was charged with coordinating direct community outreach efforts, primarily in south Louisiana. In early October 2005, UTMB/NIEHS Center Community Outreach and Education Core, in collaboration with outreach counterparts at The University of Texas MD Anderson Cancer Center @ Smithville TX/Center for Research in Environmental Disease sent two groups into southern Louisiana. One group used Lafourche Parish as a base to deliver humanitarian aid and assess local needs for additional supplies during local recovery/reclamation. A second group, ranging through New Iberia, New Orleans, Chalmette, rural Terrebonne, Lafourche and Jefferson Parishes and Baton Rouge met with community environmental leaders, emergency personnel and local citizens to 1) sample public risk perceptions, 2) evaluate the scope and reach of ongoing risk communication efforts, and 3) determine how the NIEHS could best collaborate with local groups in environmental health research and local capacity building efforts. This scoping survey identified specific information gaps limiting efficacy of risk communication, produced a community "wish list" of potential collaborative research projects. The project provided useful heuristics for disaster response and management planning and a platform for future collaborative efforts in environmental health assessment and risk communication with local advocacy groups in south Terrebonne-Lafourche parishes. [ABSTRACT FROM AUTHOR]

P53 is probably the most important tumor suppressor known. Over the years, information about this gene has increased dramatically. We have built a comprehensive knowledgebase of p53, which aims to facilitate wet-lab biologists to formulate their experiments and new-comers to learn whatever they need about the gene and bioinformaticians to make new discoveries through data analysis. Using the information curated, including mutation information, transcription factors, transcriptional targets, and single nucleotide polymorphisms, we have performed extensive bioinformatics analysis, and made several new discoveries about P53. We have identified point missense mutations that are over-represented in cancers, but lack of functional studies. By assessing the capability of six p53 transcriptional targets' tag SNPs selected from HapMap to capture SNPs obtained from National Institute of Environmental Health Sciences (NIEHS) Environmental Genome project and vice versa, we conclude that NIEHS data is a better source for tagSNP selections of these genes in future association studies. Analysis of microRNA regulation in the transcriptional network of the p53 gene reveals potentially important regulatory relationships between oncogenic microRNAs and transcription factors of p53. By mapping transcription factors of p53 to pathways involved in cell cycle and apoptosis, we have identified distinctive transcriptional controls of p53 in these two physiological states. [ABSTRACT FROM AUTHOR]

In response to significant environmental health challenges in Southeast Texas, a National Institute for Environmental Health Sciences Center at the University of Texas Medical Branch at Galveston was created to promote and conduct inter-disciplinary research in the areas of: (1) the molecular biology of DNA repair, replication and mutagenesis, (2) asthma pathogenesis in response to oxidative stress and viral exposures, and (3) environmental toxicant biotransformation. In addition, the NIEHS Center maintains close ties with neighboring communities through an active Community Outreach & Education Program (COEP) that develops and disseminates translational materials for use in environmental health awareness outreach, toxicology consultation, K-12 curriculum enrichment and in developing site-specific Community Partnership projects. The COEP core service divisions include: Environmental Arts & Sciences, Asthma Outreach & Education, Theater Outreach & Education, and Public Forum & Toxics Assistance. Public Forums focus on the use of Augusto Boal’s Forum Theater dramaturgy to include the voices and local knowledge of communities within the process of Participatory Research. Forums create the preconditions for significant partnerships that link the hazardous risk perceptions and environmental health needs of communities with the expertise of NIEHS Center investigators and translational services provided through COEP outreach programs. The Forum process also creates leadership cores within environmentally challenged communities that facilitate the ongoing translational process and maintain the vital linkage between the health needs of communities and the analytic tools and the field and clinical technologies of the environmental sciences. [Copyright &y& Elsevier]

Abstract: On September 28–29, 2006, the National Institute of Environmental Health Sciences led a team from the National Institutes of Health in hosting a Working Group on Integrated Translational Research in DNA Repair, in Berkeley, CA. In recognition of the far-reaching goals for this area of investigation, the Working Group was charged with conceiving a vision to facilitate projects that would apply the lessons of DNA Repair research to clinical application and public health. The participants included basic and physician scientists working in the various areas of DNA Repair and genome stability, as well as agency representatives of the National Cancer Institute and the National Institute of General Medical Sciences. In constructing this vision of practical research recommendations, the Working Group was asked to identify roadblocks to progress, suggest enabling technologies, and to consider areas that are ripe for translation. This report summarizes the rationale for this initiative and the recommendations that emerged. [Copyright &y& Elsevier]

Environmental health research is at a promising stage for more precisely identifying gene-environment components of disease. Simplistic models and reductionist approaches that have been the norm both in toxicology and in clinical medicine are beginning to be replaced with a more holistic or systems biology approach. We are slowly moving to an understanding that the time between an exposure and its consequence as a diagnosed disease is a time during which many different biochemical changes are occurring and a time during which many biomarkers of disease progression could be identified and used. With such information in hand, clinicians would be able to intervene early in disease progression. With such information, environmental health researchers and policy makers could more reliably identify which elements in our environment need to be controlled or reduced and which populations need the most protection. With such information, the incidence of many human diseases could be dramatically reduced., (Copyright © 2021. Published by Elsevier B.V.)

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Depression in women is a public health problem. Studies have reported positive associations between pesticides and depression, but few studies were prospective or presented results for women separately., Objectives: We evaluated associations between pesticide exposure and incident depression among farmers' wives in the Agricultural Health Study, a prospective cohort study in Iowa and North Carolina., Methods: We used data on 16,893 wives who did not report physician-diagnosed depression at enrollment (1993-1997) and who completed a follow-up telephone interview (2005-2010). Among these wives, 1054 reported physician diagnoses of depression at follow-up. We collected information on potential confounders and on ever use of any pesticide, 11 functional and chemical classes of pesticides, and 50 specific pesticides by wives and their husbands via self-administered questionnaires at enrollment. We used inverse probability weighting to adjust for potential confounders and to account for possible selection bias induced by the death or loss of 10,639 wives during follow-up. We used log-binomial regression models to estimate risk ratios and 95% confidence intervals., Results: After weighting for age at enrollment, state of residence, education level, diabetes diagnosis, and drop out, wives' incident depression was positively associated with diagnosed pesticide poisoning, but was not associated with ever using any pesticide. Use of individual pesticides or functional or chemical classes of pesticides was generally not associated with wives' depression. Among wives who never used pesticides, husbands' ever use of individual pesticides or functional or chemical classes of pesticides was generally not associated with wives' incident depression., Conclusions: Our study adds further evidence that high level pesticide exposure, such as pesticide poisoning, is associated with increased risk of depression and sets a lower bound on the level of exposure related to depression, thereby providing reassurance that the moderate levels of pesticide exposure experienced by farmers' wives likely do not increase risk., (Published by Elsevier Inc.)

An evaluation of the toxicogenomic data set for dibutyl phthalate (DBP) and male reproductive developmental effects was performed as part of a larger case study to test an approach for incorporating genomic data in risk assessment. The DBP toxicogenomic data set is composed of nine in vivo studies from the published literature that exposed rats to DBP during gestation and evaluated gene expression changes in testes or Wolffian ducts of male fetuses. The exercise focused on qualitative evaluation, based on a lack of available dose-response data, of the DBP toxicogenomic data set to postulate modes and mechanisms of action for the male reproductive developmental outcomes, which occur in the lower dose range. A weight-of-evidence evaluation was performed on the eight DBP toxicogenomic studies of the rat testis at the gene and pathway levels. The results showed relatively strong evidence of DBP-induced downregulation of genes in the steroidogenesis pathway and lipid/sterol/cholesterol transport pathway as well as effects on immediate early gene/growth/differentiation, transcription, peroxisome proliferator-activated receptor signaling and apoptosis pathways in the testis. Since two established modes of action (MOAs), reduced fetal testicular testosterone production and Insl3 gene expression, explain some but not all of the testis effects observed in rats after in utero DBP exposure, other MOAs are likely to be operative. A reanalysis of one DBP microarray study identified additional pathways within cell signaling, metabolism, hormone, disease, and cell adhesion biological processes. These putative new pathways may be associated with DBP effects on the testes that are currently unexplained. This case study on DBP identified data gaps and research needs for the use of toxicogenomic data in risk assessment. Furthermore, this study demonstrated an approach for evaluating toxicogenomic data in human health risk assessment that could be applied to future chemicals., (Published by Elsevier Inc.)

Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment., (Copyright © 2011. Published by Elsevier Inc.)

An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate (DBP) was selected for the case study exercise. The scoping phase of the dibutyl phthalate case study was conducted by considering the available DBP genomic data, taken together with the entire data set, for whether they could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose-response. A description of weighing the available dibutyl phthalate data set for utility in risk assessment provides an example for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions--Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics?--were selected to focus the case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various qualitative and/or quantitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on experience from the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment., (Published by Elsevier Inc.)