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Your Environment. Your Health.

Goal 4 – Combined Environmental Exposures

Implementation Highlights and Accomplishments

Woman wearing protective mask

Understand how combined environmental exposures affect disease pathogenesis.

  1. Assess the joint action of multiple environmental insults, including chemicals, nonchemical stressors, and nutritional components, on toxicity and disease, and identify interactions resulting from combined exposures.
  2. Study the role of the human microbiome and its influence on environmental health, and explore the role of the microbiome in responses to environmental exposures.
  3. Study the interactions of infectious agents with environmental exposures.
  4. Understand how nonchemical stressors, including socioeconomic, behavioral factors, etc., interact with other environmental exposures to impact human health outcomes, and identify preventive measures that could be taken.

Research Funding

Powering Research through Innovative Methods for mixtures in Epidemiology (PRIME)(R01)
Developed to stimulate the development of innovative statistical, data science, or other quantitative approaches to studying the health effects of complex chemical mixtures in environmental epidemiology. RFA-ES-17-001

Worker Training Program (WTP) Ebola Biosafety and Infectious Disease Response Training (UH4)
The NIEHS WTP Ebola Biosafety Training and Infectious Disease Response Initiative – developed in partnership with CDC, HHS, ASPR, OSHA, and NIOSH – invites applications for cooperative agreements to support the development and implementation of occupational safety and health and infection control training programs for workers who may be at risk during infectious disease outbreaks.  The major objective of this funding opportunity is to assist in the training and education of workers within the US in understanding how infectious diseases with varying transmissibility, incubation periods and clinical outcome are spread in an occupational environment and what measures can be taken to shield workers from potential exposure.  RFA-ES-15-018

Children's Health Exposure Analysis Resource (CHEAR)
NIEHS is establishing an infrastructure, the Children's Health Exposure Analysis Resource (CHEAR), to provide the extramural research community access to laboratory and statistical analyses to add or expand the inclusion of environmental exposures in their research.  The National Institute of Environmental Health Sciences (NIEHS) intends to promote the characterization of the exposome ( as originally defined by Christopher Wild in his 2005 Cancer Epidemiology, Biomarkers, and Prevention paper as the totality of environmental exposures from conception through development, including chemical, physical and biological stressors as well as lifestyle and social environments) in studies of children’s health through the establishment of an infrastructure to enable the measurement and integration of environmental exposures.  NIEHS is publishing three distinct but integrated Funding Opportunity Announcements (FOAs) that solicit a coordinated network of laboratories and statistical and data science resources to provide access to comprehensive exposure analysis that can be performed using biological samples collected in studies of children’s health.  This resource will be known as the Children's Health Exposure Analysis Resource (CHEAR). ES-15-009, ES-15-010, ES-15-011

Centers of Excellence on Environmental Health Disparities Research (P50)
This Funding Opportunity Announcement (FOA) encourages grant applications to support Centers of Excellence on Environmental Health Disparities Research to stimulate basic and applied research on environmental health disparities. The proposed research is expected to develop innovative approaches to understand environmentally-driven health disparities and improve access to healthy environments for vulnerable populations and communities. The proposed Centers are expected to support research efforts, mentoring, research translation and information dissemination. RFA-ES-14-010

Children's Environmental Health and Disease Prevention Research Centers (P50)
NIEHS and EPA will continue to support and facilitate integrated fundamental, clinical, laboratory, and public health science to: (1) identify the harmful influences of environmental exposures and changing environments as well as the protective and nurturing impact of healthy environments on normal physiological function of organs and systems of the fetus/child during gestation/childhood/adolescence; (2) determine the mechanisms of vulnerability to environmental stressors of the fetus and young child at all stages of early development; and (3) consider children’s health from a holistic perspective where the impact of complex environmental exposures may be exacerbated by non-chemical stressors encountered in community settings.

Chemical stressors may be considered as single chemicals, or as mixtures and aggregates as may be found in consumer products used by children and environments and microenvironments frequented by children. Non-chemical stressors include mediating and modifying factors such as economic deprivation, discrimination, poverty, lack of health care, fear of crime, diet and nutrition, physical activity, psychosocial factors, and the design of the built environment (e.g., settings: home, school, play areas) from birth through young adulthood. Non-chemical stressors, social and cultural factors, and settings cannot be considered alone, but they may be included as modifier variables to the primary environmental stressor(s).  RFA-ES-14-002

Selected Programs and Awards

2017 Outstanding New Environmental Scientist (ONES) Awardees Mohit Jain, Ph.D., M.D., from the University of California, San Diego, will use high-throughput mass spectrometry to measure exposure-related small molecules in human blood. He hopes to map the non-genetic underpinnings of human cardiovascular disease.

Zheng Sun, Ph.D., from Baylor College of Medicine, will address how metabolic change differs in males and females in response to inorganic arsenic. He will examine the role of sex hormones and their receptors using animal models.

David Volz, Ph.D., from the University of California, Riverside, hopes to uncover the mechanisms of developmental toxicity for two organophosphate flame retardants that are commonly detected indoors.

2016 Outstanding New Environmental Scientist (ONES) Awardees Daniel Gorelick, Ph.D., from the University of Alabama at Birmingham, will study how pollutants, such as dioxins, use the aryl hydrocarbon receptor protein to cause toxic effects on the heart.

Cheryl Rockwell, Ph.D., of Michigan State University, will study how the food additive tert-butylhydroquinone, or TBHQ, promotes allergies, in order to identify similar environmental chemicals that may affect the immune system.

New Centers
On May 25, the National Institutes of Health announced a partnership with the U.S. Environmental Protection Agency (EPA) to fund five new research centers to improve health in communities overburdened by pollution and other environmental factors that contribute to health disparities. The Centers of Excellence on Environmental Health Disparities Research are jointly funded by NIEHS, the National Institute on Minority Health and Health Disparities (NIMHD), and the National Center for Environmental Research at EPA. The new centers, funded by five-year grants, are an expansion of a successful pilot program originally started by NIMHD and EPA.

  • The Harvard T.H. Chan School of Public Health and Boston University School of Public Health, Boston, Massachusetts, led by Francine Laden, Sc.D., and Jonathan Levy, Sc.D., will study how housing conditions may affect birth weight, childhood growth trajectories, and risk of death from cardiovascular disease, and whether improved urban housing may benefit health. New NIH-EPA research centers to study environmental health disparities.
  • Johns Hopkins University, Baltimore, Maryland, led by Nadia Hansel, M.D., will compare urban and rural effects of poverty on chronic obstructive pulmonary disease, and the impact of improved dietary intake on preventing or mitigating disease progression. New NIH-EPA research centers to study environmental health disparities.
  • The University of Arizona, Tucson, led by Jeff Burgess, M.D., and Stephanie Rainie, Dr.P.H., will work with indigenous populations to examine chemical contamination of traditional foods, water, air, and household environments, and increase environmental health literacy. New NIH-EPA research centers to study environmental health disparities.
  • The University of New Mexico, Albuquerque, led by Johnnye Lewis, Ph.D., and Melissa Gonzales, Ph.D., will examine how contact with metal mixtures from abandoned mines affects rural Native American populations through exposures related to inadequate drinking water infrastructure, reliance on local foods, and other uses of local resources to maintain their traditional lifestyle and culture. New NIH-EPA research centers to study environmental health disparities.
  • The University of Southern California, Los Angeles, led by Frank Gilliland, M.D., Ph.D., and Carrie Breton, Sc.D., will study how environmental factors may contribute to childhood obesity and excessive weight gain during pregnancy in Hispanic and Latino communities. New NIH-EPA research centers to study environmental health disparities.

Center for Urban Responses to Environmental Stressors (CURES)

A new grant from NIEHS will allow researchers to study how exposures to stressors that are prevalent in the urban industrialized environment impact human health in Detroit and beyond. The grant, awarded to Wayne State University, is one of 21 Environmental Health Sciences Core Centers funded by NIEHS. The new Center for Urban Responses to Environmental Stressors (CURES) includes collaborators at Henry Ford Health System, the University of Michigan, and Michigan State University, as well as community organizations. CURES places special emphasis on understanding how environmental exposures, during life windows of heightened susceptibility, can adversely affect health, particularly in vulnerable persons, such as children and adults of low socioeconomic status, older adults, first responders, and refugees. The center emphasizes broad interactions with the public, as well as leaders of advocacy, community, and government organizations dealing with the environment and health. New NIEHS-funded center focuses on urban environmental stressors.

Selected Scientific Advances

2017

  • Gao L, Mutlu E (DNTP), Collins LB, Walker NJ (DNTP), Hartwell HJ, Olson JR, Sun W, Gold A, Ball LM, Swenberg JA. 2017. DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure. Chem Res Toxicol 30(3):794-803. [Abstract]
    In this study, researchers evaluated the toxic equivalency factor (TEF) from the standpoint of induced DNA oxidation products and their relationship to toxicity and carcinogenicity.
  • O' Lenick CR, Chang HH, Kramer MR, Winquist A, Mulholland JA, Friberg MD, Sarnat SE. 2017. Ozone and childhood respiratory disease in three US cities: evaluation of effect measure modification by neighborhood socioeconomic status using a Bayesian hierarchical approach. Environ Health 16(1):36. [Abstract]
    Researchers evaluated individual and area-level factors as modifiers of the association between warm-season (May-Sept.) temperature and pediatric respiratory morbidity in Atlanta.
  • Zhong J, Trevisi L, Urch B, Lin X, Speck M, Coull BA, Liss G, Thompson A, Wu S, Wilson A, Koutrakis P, Silverman F, Gold DR, Baccarelli AA. 2017. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial. Sci Rep 7:45322. [Abstract]
    Researchers determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial.

2016

  • Ferrucio B, M Tiago, RD Fannin (DIR), L Liu (DIR), K Gerrish (DIR), SS Maria-Engler, RS Paules (NTP) and SB de Moraes Barros. 2016. Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes. Toxicol In Vitro 38:67-76. [Abstract]
    This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100 μM) and solar radiation (375 mJ/cm2).
  • Andreotti G, Freedman ND, Silverman DT, Lerro CC, Koutros S, Hartge P, Alavanja MC, Sandler DP (DIR), Beane Freeman L. 2016. Tobacco use and cancer risk in the Agricultural Health Study. Cancer Epidemiol Biomarkers Prev 26(5):769-778. [Abstract]
    Using data from the Agricultural Health Study, researchers examined the cancer incidience in relation to exclusive use of six tobacco products as well as the added cancer risks associated with use of cigarettes and other tobacco products.
  • Eckel SP, Cockburn M, Shu YH, Deng H, Lurmann FW, Liu L, Gilliland FD. 2016. Air pollution affects lung cancer survival. Thorax 71(10):891-898. [Abstract]
    This study aimed to determine whether ambient air pollutant exposures are associated with the survival of patients with lung cancer.
  • Dunaway KW, Islam MS, Coulson RL, Lopez SJ, Vogel Ciernia A, Chu RG, Yasui DH, Pessah IN, Lott P, Mordaunt C, Meguro-Horike M, Horike SI, Korf I, LaSalle JM. 2016. Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes. Cell Rep 17(11):3035-3048. [Abstract]
    Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, this study describes how significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression.
  • Davé V, Street K, Francis S, Bradman A, Riley L, Eskenazi B, Holland N. 2016. Bacterial microbiome of breast milk and child saliva from low-income Mexican-American women and children. Pediatr Res 79(6):846-54. [Abstract]
  • Hicks KD, Sullivan AW, Cao J, Sluzas E, Rebuli M, Patisaul HB. 2016. Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats. Horm Behav 84:121-126. [Abstract]
  • Gassman NR (DIR), E Coskun, P Jaruga, M Dizdaroglu and SH Wilson (DIR). 2016. Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts. Environ Health Perspect 124(8):1241-1252. [Abstract]
  • Stingone JA, McVeigh KH, Claudio L. 2016. Association between prenatal exposure to ambient diesel particulate matter and perchloroethylene with children's 3rd grade standardized test scores. Environ Res 148:144-153. [Abstract]
  • Zota AR, Phillips CA, Mitro SD. 2016. Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010. Environ Health Perspect 124(10):1521-1528. [Abstract]

2015

  • Thorne PS, Mendy A, Metwali N, Salo P, Co C, Jaramillo R, Rose KM, Zeldin DC. 2015. Endotoxin Exposure: Predictors and Prevalence of Associated Asthma Outcomes in the United States. J Respir Crit Care Med 192(11):1287-97. [Abstract]
  • Sen A, Heredia N, Senut MC, Land S, Hollocher K, Lu X, Dereski MO, Ruden DM. 2015. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren. Sci Rep 5:14466. [Abstract]
  • Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. 2015. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect 124(6):733-9. [Abstract]
  • Fang M, Webster TF, Stapleton HM. 2015. Activation of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) by Semi-Volatile Compounds (SVOCs) and Chemical Mixtures in Indoor Dust. Environ Sci Technol 49(16):10057-64. [Abstract]
    This work examined chemical mixtures present in house dust as well as 30 common semi-volatile compounds and assessed their effects on a signaling pathway suspected to play a role in obesity. This work found the majority of compounds assessed and over half of the house dust samples activated the signaling pathway.
  • Hernández-Cadena L, Zeldin DC (DIR), Barraza-Villarreal A, Sever ML (DIR), Sly PD, London SJ (DIR), Escamilla-Nuñez MC, Romieu I. 2015. Indoor determinants of dustborne allergens in Mexican homes. Allergy Asthma Proc 36(2):130-7. [Abstract]
    Scientists studied a birth cohort from Mexico City to examine exposure to allergens using cord blood samples, dust samples from the mother’s bed and bedroom floor, and information on environmental home exposures. The study identified the main predictors of high exposure and discovered each allergen appeared to have a distinct set of predictors. This is important information given increased levels of allergens are strongly associated with asthma and asthma and allergic diseases are an important public health burden in Mexico.
  • Whitworth KW, Baird DD (DIR), Steiner AZ, Bornman RM, Travlos GS (DIR), Wilson RE (DIR), Longnecker MP (DIR). 2015. Anti-müllerian hormone and lifestyle, reproductive, and environmental factors among women in rural South Africa. Epidemiology 26(3):429-35. [Abstract]
    This research found decreased ovarian health was associated with exposure to pyrethroid pesticides in rural South African women, while exposure to indoor air pollution was not associated with decreased ovarian health.
  • Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, Godleski JJ, Coull BA. 2015. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16(3):493-508. [Abstract]
    Here, scientists present a novel modeling approach to study mixtures and estimate the exposure-response as well as pinpoint components of the mixture that result in adverse health outcomes.
  • Goodson WH et al., 2015. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis 36(Suppl 1):S254-296. [Abstract]
    A team of scientists discuss the lack of research surrounding chemical mixtures, their combined effects, and how current risk assessment methods fail to capture cumulative effects of chemicals acting on cancer pathways.

2014

  • Furlong MA, Engel SM, Barr DB, Wolff MS. 2014. Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood. Environ Int 70:125-31. [Abstract]
    Adding to the literature that supports potential adverse neurobehavioral outcomes result from prenatal organophosphate pesticide exposure, this work also highlights a potential health disparity in blacks and boys exposed to specific pesticides.
  • Chen A, Yolton K, Rauch SA, Webster GM, Hornung R, Sjödin A, Dietrich KN, Lanphear BP. 2014. Prenatal Polybrominated Diphenyl Ether Exposures and Neurodevelopment in U.S. Children through 5 Years of Age: The HOME Study. Environ Health Perspect 122(8):856-62. [Abstract]
    Research in the Health Outcomes and Measures of the Environment (HOME) Study between March 2003 and February 2006 in Cincinnati suggests prenatal exposures to PBDE flame retardants leads to lower IQs and increased hyperactivity in children.
  • Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, Hansen RL, Hertz-Picciotto I. 2014. Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study. Environ Health Perspect 122(10):1103-9. [Abstract]
    The Childhood Autism Risk from Genetics and the Environment (CHARGE) Study provided additional evidence that autism spectrum disorders are linked to prenatal pesticide exposures and highlights a risk of autism spectrum with pyrethroid exposure, a chemical that is supposed to be a safe alternative to organophosphates that were shown to increase risk of autism spectrum disorder by 60%.
  • Chrysovergis K (DIR), X Wang (DIR), J Kosak (DIR), SH Lee, J Sik Kim (DIR), JF Foley (NTP), G Travlos (NTP), S Singh (DIR), S Joon Baek and TE Eling(DIR). 2014. NAG-1/GDF15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism. Int J Obes (Lond) 38(12):1555-64. [Abstract]
    This work suggests the human gene NAG1 protects against obesity and colon cancer, in part, via epigenetic regulation.
  • Lu K, Mahbub R, Cable PH, Ru HY, Parry NMA, Bodnar WM, Wishnok JS, Styblo M, Swenberg JA, Fox JG and Tannenbaum SR. 2014. Gut Microbiome Phenotypes Driven by Host Genetics Affect Arsenic Metabolism. Chem. Res. Toxicol 27(2):172-174. [Abstract]
    Scientists examined the interaction between genetics and the gut microbiome in the biotransformation of arsenic and found genetic susceptibility to arsenic exposure with changes in the gut microbiome resulting in altered arsenic metabolism.

Other Implementation Activities

A Community Conversation on Toxics, Climate Change & Health On May 21, Dr. Linda Birnbaum, participated in a Community Forum in Brooklyn, NY. The industrial waterfront is one of the city’s last working waterfronts. It is known for its port facilities, maritime commerce, and vibrant industrial sectors. The waterfront is home to several manufacturers ranging from apparel to woodwork. Due to the industrial and manufacturing nature of the waterfront the community has faced a number of disproportionate environment and health burdens such as a bus depot, numerous truck routes, including the overtaxed Gowanus Expressway, two New York Power Authority electrical turbine engines with 100 tons of yearly emissions, three antiquated power plants, a sludge transfer facility and dozens of brownfield sites. Birnbaum joins community leaders at forum in Brooklyn.

One Bioregion/One Health This new framework provides an approach to transboundary regional planning that considers relationships between people and nature in the quest for healthier living spaces. The One Health concept acknowledges that human health is interconnected and dependent on the health of animals and the environment. A bioregion is a territory that is socially and culturally defined by its people rather than borders on a map. Bioregions are shaped by global trends, including climate change, food and water issues, economic crisis, large-scale natural disasters, and widespread increases in preventable diseases. The framework, funded in part by NIEHS and developed by researchers at the University of California-San Diego Superfund Research Center, merges regional planning and ecosystem management as a way to improve public and environmental health. Bioregional planning to improve public and environmental health.