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1,4-Dioxane: Occurrence, Toxicity and Population Risk

October 30, 2020

1,4-Dioxane (1,4-DX), is a cyclic ether that is used as a solvent in the manufacture of other chemicals, and for decades it was extensively used as a stabilizer for chlorinated solvents, most notably 1,1,1,-trichloroethane. This has led to extensive environmental release and groundwater contamination. 1,4-DX is also found as a contaminant in cosmetics, detergents, and shampoos. It has been classified as a class 2B carcinogen by IARC, and the US-EPA considers it to be a likely human carcinogen.

1,4-DX is an emerging contaminant of growing concern based on its common occurrence in drinking water supplies worldwide. Its high polarity and low biodegradability hamper its retardation or removal from aquifer systems. 1,4-DX is carcinogenic in both mice and rats. While the mechanism by which this occurs remains unknown, it appears to be distinct from other well-known liver carcinogens. A lack of biomarkers of exposure to or the effects of this compound hampers epidemiological studies. Given that liver cancer incidence rates have more than tripled since 1980, there is an urgent need to evaluate emerging water contaminants that may be contributing to this increase, such as 1,4-DX.

In this daylong symposium hosted by the Department of Environmental Health Sciences of Yale School of Public Health, experts from Yale University, the International Agency on Research on Cancer (IARC), the National Institute of Environmental Health Sciences and National Toxicology Program, Universities of California Los Angeles, Michigan, North Carolina State, State and Federal government agencies (CT DPH, CT DEEP, US EPA), and public and private sectors will review the current state of the science on 1,4-DX, and highlight the challenges associated with understanding health risks and setting regulatory policy, while exploring promising opportunities for addressing them.

Speakers

  • Vasilis Vasiliou (Organizer), Chair, Department of Environmental Health Science
  • Linda Birnbaum
  • Mary Schubauer-Berigan
  • Gary Ginsberg
  • Michaela A. Cashman
  • Detlef Knappe
  • Ashley Dummer
  • Shannon Pociu
  • Patricia Bisacky
  • Shaily Mahendra
  • Michael Hyman
  • David T. Adamson
  • Nicole Deziel
  • Adrienne Esposito
  • Ronald Hines

Program

11:00-11:10: Vasilis Vasiliou, Yale School of Public Health, “Welcome and Introduction”
11:10-11:30: Linda Birnbaum, Former Director of National Institute for Environmental Health Sciences, “Emerging Contaminants in Drinking Water: Progress and Challenges”
11:30-11:50: Mary Schubauer-Berigan, International Agency for Research on Cancer, “Evaluation of the Carcinogenicity to Humans of 1,4-Dioxane by the Monographs Programme of the International Agency for Research on Cancer”
11:50-12:10: Gary Ginsberg, New York State DOH, Center for Environmental Health, “Process for Setting a Maximum Contaminant Level (MCL) for 1,4-Dioxane in New York State”
12:10-12:30: Michaela A. Cashman, US EPA, Narragansett, RI, “The Fate of 1,4-Dioxane in Groundwater Systems”
12:30-12:50: Detlef Knappe, North Carolina State University, “Occurrence of 1,4-Dioxane in Drinking Water – National and North Carolina Perspectives”
12:50-1:10: Ashley Dummer, California State Water Resources Control Board, “Water California Division of Drinking Water: Actions on 1,4 Dioxane”
1:10-1:30: Shannon Pociu, CT Department of Energy and Environmental Protection, Patricia Bisacky, CT Department of Public Health, “1,4-Dioxane Occurrence in Drinking Water – Connecticut Case Studies”
1:30-1:50: Shaily Mahendra, University of California Los Angeles, “1,4-Dioxane Biodegradation: Microbes, Enzymes, Pathways, Co-contaminant Effects and Monitoring Tools”
1:50-2:10: Michael Hyman, North Carolina State University, “Bacterial Co-metabolism of 1,4-Dioxane: Omic Insights and Practical Applications”
2:10-2:30: David T. Adamson, GSI Environmental Inc, “Trends in 1,4-Dioxane Analyses: Implications for Identification and Characterization of Contaminated Groundwater Sites”
2:30-2:50: Vasilis Vasiliou, Yale School of Public Health, “Current Status on 1,4-Dioxane Mode and Molecular Mechanism of Action”
2:50-3:10: Nicole Deziel, Yale School of Public Health, “Human Epidemiological Studies on 1,4-Dioxane: Challenges and Opportunities”
3:10-3:30: Adrienne Esposito, Citizen Campaign for the Environment “Banning 1,4-Dioxane in New York State”
3:30-4:00: Round Table Discussion moderated by Ronald Hines

Abstracts

1,4 Dioxane: Occurrence, Toxicity and Population Risk

Vasilis Vasiliou, Yale School of Public Health
1,4-Dioxane (1,4-DX), is a cyclic ether that is used as a solvent in the manufacture of other chemicals and, for decades, was extensively used as a stabilizer for chlorinated solvents, most notably 1,1,1,-trichloroethane. This had led to extensive environmental release and groundwater contamination. 1,4-DX is also found as a contaminant in cosmetics, detergents, and shampoos. It has been classified as a class 2B carcinogen by IARC and the US-EPA considers it to be a likely human carcinogen. 1,4-DX is an emerging contaminant of growing concern based on its common occurrence in drinking water supplies worldwide. Its high polarity and low biodegradability hamper its retardation or removal from aquifer systems. 1,4-DX is carcinogenic in both mice and rats. While the mechanism by which this occurs remains unknown, it appears to be distinct from other well-known liver carcinogens. A lack of biomarkers of exposure to or the effects of this compound hampers epidemiological studies. Given that liver cancer incidence rates have more than tripled since 1980, there is an urgent need to evaluate emerging water contaminants that may be contributing to this increase, such as 1,4-DX.

Emerging Contaminants in Drinking Water: Progress and Challenges

Linda Birnbaum, Former Director of National Institute for Environmental Health Sciences
Public drinking water supplies can be affected by emerging contaminants from a number of sources including pharmaceuticals, industrial chemicals, products of disinfection, contaminants stemming from consumer products, and contaminants of natural origin. Prime examples include hormones and their byproducts, poly- and perfluoroalkyl substances (PFAS), algal toxins, and the chemical which this workshop is focusing upon, 1,4-dioxane. These chemicals are considered to be emerging because they are unregulated at the federal level and in most states, they have emerging exposure and toxicology profiles, and they raise important risk assessment and policy questions. These questions include the role of chemical management policy in preventing uses that lead to drinking water contamination, the role of traditional and emerging toxicology methods to assess risks to public health, and improved detection of these contaminants through unregulated contaminant monitoring (UCMR testing) and other research initiatives. The increasing tendency to use recycled water for potable uses and the potential effects of climate change on drinking water supplies (drought, algal blooms) further emphasizes the public health implications of such unregulated and sparsely tested contaminants. The federal process for setting Maximum Contaminant Levels (MCLs) is slow and has not met the needs for evaluation and mitigation of these contaminants. This is evident for the important emerging contaminant, 1,4-dioxane, in that it is widespread in public supplies from industrial and consumer sources, its toxicology profile shows carcinogenic effects, and yet the contaminant is largely unregulated. The research needs and regulatory challenges related to drinking water emerging contaminants will be discussed.

Evaluation of the Carcinogenicity to Humans of 1,4-Dioxane by the Monographs Programme of the International Agency for Research on Cancer

Mary Schubauer-Berigan, Acting Group Head and Senior Epidemiologist, Monographs Programme, International Agency for Research on Cancer, WHO
Since 1971, the Monographs programme of the International Agency for Research on Cancer (IARC) has convened international expert Working Groups to evaluate the carcinogenic hazards to humans posed by more than 1000 chemical, physical, and biological agents, as well as complex mixtures and exposure circumstances. In 1998, as described in vol. 71 of the IARC Monographs, the chemical 1,4-dioxane was classified as “possibly carcinogenic to humans” on the basis of “sufficient” evidence of carcinogenicity in experimental animals and “inadequate” evidence of carcinogenicity in humans. The basis of the IARC Monographs evaluation will be described in this presentation.

Process for Setting a Maximum Contaminant Level (MCL) for 1,4-Dioxane in New York State

Gary Ginsberg, New York State DOH, Center for Environmental Health
The New York State promulgated new emerging contaminant Maximum Contaminant Levels (MCLs) on August 26, 2020. This presentation will focus on the background and process for the setting of the NYS MCL for 1,4-dioxane of 1 ug/L (part per billion), including toxicology and risk assessment, Drinking Water Quality Council and implementation going forward.

The Fate of 1,4-Dioxane in Groundwater Systems

Michaela A. Cashman, US EPA, Office of Research and Development (ORD), Atlantic Coastal Environmental Sciences Division (ACESD), Narragansett, RI
1,4-Dioxane (1,4-DX) is a heterocyclic ether found in groundwater plumes at industrial sites worldwide. 1,4-DX was historically used as a dispersing agent for textile processing and printing, as well as a stabilizer for chlorinated solvents such as 1,1,1-Trichloroethane (TCA). Incidences of poor handling, storage, and disposal of industrial waste have contributed to significant 1,4-DX pollution in the environment. Physical characteristics of 1,4-DX have resulted in large groundwater contaminant plumes that are recalcitrant to most conventional remediation technologies. This presentation will focus on the fate of 1,4-DX in the environment and highlight several sites in New England currently facing 1,4-DX contaminated groundwater.

Occurrence of 1,4-Dioxane in Drinking Water – National and North Carolina Perspectives

Detlef Knappe, North Carolina State University
The cyclic diether 1,4-dioxane is a likely human carcinogen, and an excess one-in-a-million cancer risk is associated with a lifetime consumption of drinking water containing 0.35 µg/L 1,4-dioxane. Although no federal drinking water standard exists for 1,4-dioxane, several states have developed local standards and guidelines. Goals of this presentation are to (1) provide an overview of 1,4-dioxane occurrence in US drinking water, (2) highlight 1,4-dioxane occurrence in North Carolina (NC), and (3) describe factors controlling 1,4-dioxane concentrations in NC surface water. In data collected for US EPA’s third unregulated contaminant monitoring rule (UCMR3), 1,4-dioxane was found above the reporting limit of 0.07 µg/L in finished drinking water of 21% of public water systems (PWSs) and above the health-based reference concentration of 0.35 µg/L in 6.9% of PWSs that serve a total of ~29.4 million people. While 1,4-dioxane was more frequently associated with groundwater sources, it was also an important contaminant in surface water sources. For example, seven of the 20 highest 1,4-dioxane concentrations in the UCMR3 data occurred in NC drinking water that was derived from surface water in the Cape Fear River basin. For one small NC surface water system that was not included in the UCMR3 effort, our data showed that concentrations of 1,4-dioxane in weekly composited samples have exceeded 100 µg/L. At least three-point sources in the headwater region of the watershed have impacted the drinking water quality of this small community and of more than 1 million North Carolinians living further downstream. Efforts by a stakeholder group involving downstream drinking water providers, upstream wastewater dischargers, river keepers, regulators, and academic researchers are beginning to show signs of success as 1,4-dioxane concentrations have started to decrease.

Water California Division of Drinking Water: Actions on 1,4 Dioxane

Ashley Dummer, California State Water Resources Control Board - Division of Drinking
1,4-dioxane is a solvent and mainly a stabilizer for chlorinated solvents. It is used in a variety of industrial and commercial applications. The chemical causes cancer in laboratory animals, is reasonably anticipated to be a human carcinogen, and was first listed in the Annual Report on Carcinogens in 1981. In 1988, 1,4-dioxane was added to the list of chemicals known to the State of California to cause cancer. To date the State Water Resource Control Board’s Division of Drinking Water has taken a number of actions to address 1,4-dioxane including developing a notification level and a response level. Additionally, the State Water Resource Control Board’s Division of Drinking Water requested the Office of Environmental Health Hazard and Assessment develop a public health goal, which is needed prior to developing a maximum contaminant level. While drinking water systems are not currently required to routinely monitor for 1,4-dioxane, some systems have either voluntarily sampled, or have been directed to sample pursuant to Health and Safety Code section 116400. Based on occurrence data gathered since January 1, 2014, there are 204 sources impacted by 1,4-dioxane. These sources supply 58 public water systems and serve a population of approximately 8.2 million people. Each of these sources has reported at least one result with a detection above the current reporting limit of 1 µg/L. The total number of persons impacted by 1,4-dioxane is likely underestimated.

1,4-Dioxane Occurrence in Drinking Water – Connecticut Case Studies

Shannon Pociu, CT Department of Energy and Environmental Protection, Remediation Division, and Patricia Bisacky, CT Department of Public Health, Drinking Water Section
The environmental issues and potential risks surrounding 1,4-dioxane were first brought to light in Thomas Mohr’s White Paper on solvent stabilizers published in 2001. Soon thereafter, the Connecticut Department of Energy and Environmental Protection (DEEP) began requiring sampling for this contaminant at solvent release and other remediation sites with the primary concern focusing on potential impacts to drinking water. In addition to known chlorinated solvent pollution at some private wells in Connecticut, subsequent testing of the same wells for 1,4-dioxane in the early 2000s identified exceedances of the Connecticut Department of Public Health’s (DPH’s) Drinking Water Action Level (DWAL), which have proved difficult to treat. More recently, nationwide sampling of large public water systems for 1,4-dioxane between 2013 and 2015 under EPA’s Unregulated Contaminant Monitoring Rule 3 (UCMR3) led to the discovery of one well source at a public water system in Connecticut with 1,4-dioxane levels exceeding the state’s non-enforceable DWAL and detections in several other public water systems. This presentation will provide an overview of select case studies involving the presence of 1,4-dioxane in both private wells and public water supplies in Connecticut and the approaches taken to minimize human exposure to the affected drinking water.

Biodegradation of 1,4-Dioxane: Microbes, Enzymes, Pathways, Co-contaminant Effects and Monitoring Tools

Shaily Mahendra, Environmental Engineering, University of California Los Angeles.
The cyclic ether structure of 1,4-dioxane confers recalcitrance towards chemical and biological degradation processes. Fortunately, biodegradation of 1,4-dioxane is being reported in a growing number of laboratory and field studies. We have characterized a 1,4-dioxane-metabolizing bacterium Pseudonocardia dioxanivorans CB1190, sequenced its genome, and determined the complete 1,4-dioxane biodegradation pathway. In strain CB1190 and other bacteria capable of co-metabolizing dioxane, monooxygenases were established as primary enzymes responsible for catalyzing the initial oxidation of 1,4-dioxane. My group designed the first sets of primers targeting biomarker genes for 1,4-dioxane degradation, and stable carbon and hydrogen isotopic signatures for environmental monitoring applications. While evidence for natural attenuation is growing, cleanup is likely to be challenging because 1,4-dioxane is often commingled with chlorinated volatile organic compounds (CVOCs), and many technologies that target CVOCs are not effective for 1,4-dioxane. The inhibitory effects of CVOCs such as TCE, 1,1-DCE, cis-1,2-DCE, as well as Cr6+ on 1,4-dioxane biodegradation were characterized in our research. I will summarize and synthesize mechanistic and quantitative data available for understanding 1,4-dioxane biodegradation mechanisms, especially in contaminant mixtures, and molecular tools for validating natural or enhanced bioremediation effectiveness.

Bacterial Co-metabolism of 1,4-Dioxane: Omic Insights and Practical Applications

Michael Hyman, North Carolina State University
1,4-dioxane (14D), like other important ether pollutants such as methyl tertiary butyl ether (MTBE), is highly water soluble, is poorly biodegradable under anaerobic conditions, and requires treatment at low µg/L concentrations. Although several aerobic bacteria and fungi have been identified that can grow on 14D as a sole source of carbon and energy, these organisms are typically rare, inefficient and slow-growing, and have half saturation constants for 14D that are many orders of magnitude greater than either typical environmental concentrations of 14D (=100 µg/L) or common treatment goals (=1 µg/L). In contrast, many widely distributed aerobic bacteria have been identified that can fortuitously degrade 14D after growth on benign compounds such as gaseous alkanes. This process is called cometabolism and it can be used to rapidly degrade 14D over a wide range of concentrations (mg/L to ng/L). In this presentation I will summarize what is currently known about the cometabolic degradation of 14D and highlight recent insights into this process obtained from genomic and proteomic approaches. I will also summarize how different cometabolic degradation processes are being used and developed for the treatment of environmentally relevant concentrations of 14D.

Trends in 1,4-Dioxane Analyses: Implications for Identification and Characterization of Contaminated Groundwater Sites

David T Adamson, GSI Environmental Inc
There is significant uncertainty about how the environmental occurrence is being assessed given the variety of analytical methods available. This study compiled public sampling records from 2000 to 2019 that included > 106,000 analyses of 1,4-dioxane from 822 different sites in the U.S. The 1,4-dioxane detection frequency in the entire dataset (including all methods) was 45%, and the median concentration among detections was 10 ug/L, highlighting the dilute nature of 1,4-dioxane and the importance of selecting a method with adequate sensitivity. The annual distribution of samples analyses was used to confirm a shift towards methods designed for semi-volatile compounds (Method 8270/Method 8270 SIM) that exhibited consistently lower reporting limits (typically = 1 ug/L). In contrast, methods designed for volatile compounds (Method 8260) exhibited less sensitivity for 1,4-dioxane (median reporting limit per year between 40 and 100 mg/L) and its use declined significantly over time with increasing use of the moderately-sensitive Method 8260 SIM. This shift contributed to an increase in the 1,4-dioxane detection frequency over time, with a strong correlation between the annual detection frequency and the median reporting limit. Sites where 1,4-dioxane was analyzed but not detected overwhelmingly used less-sensitive methods that may not have been adequate for the expected concentration levels. This indicates that a significant number of 1,4-dioxane contaminated sites have not been properly identified due to method limitations, although estimates based on co-occurrence data suggest that this false negative rate is only approximately 10%. The trends in method selection suggest that future efforts are likely to rely on more sensitive methods, and there are additional modifications that can further lower reporting limits and improve accuracy. Given the sub-ppb groundwater criteria issued for 1,4-dioxane by some state regulatory agencies, more sensitive methods will be increasingly needed to assess compliance.

Current Status on 1,4-Dioxane Mode and Molecular Mechanism of Action

Vasilis Vasiliou, Yale School of Public Health
Although 1,4-Dioxane (1,4-DX) is carcinogenic in animals, very little is known about the mechanisms by which it elicits liver carcinogenicity. Previous studies have shown that the pattern of gene modulation induced by 1,4-DX is unique relative to the patterns of other liver carcinogens which are well-known genotoxic initiators or a PPARa agonist promoters. Since the mechanism of 1,4-DX promotional and genotoxic effects are currently unknown, additional mechanistic studies are urgently needed to understand how it may contribute to liver carcinogenesis. To explore possible mechanisms of the mode of action, we have performed several dosing studies in mice administering various concentrations of 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one, four, and twelve weeks. Immunohistochemical analysis of the liver revealed 1,4-DX-induced increase in the number of H2AX?-positive (a marker of DNA double strand breaks) hepatocytes. Pathway analysis of the transcriptomic data revealed 1,4-DX-induced perturbations in multiple signaling pathways in the liver, including those involved in xenobiotic metabolism, nicotine degradation and glutathione-mediated detoxification. In particular, high dose 1,4-DX induced transient NRF2 antioxidant response, persistent inductions of xenobiotic metabolizing enzymes CYP2E1 and NQO1, increased production of lipid peroxidation by-product 4-HNE, and elevation in DNA damage marker. Interestingly, aforementioned 1,4-DX-elicited molecular changes were amplified in a mouse model deficient in glutathione (GSH; namely Gclm knockout mice). Overall, our studies indicate that 1,4-DX in the drinking water disrupts hepatic redox homeostasis leading to genotoxicity, the process of which is modulated by the ubiquitous antioxidant GSH. These changes as a result of 1,4-DX exposures would be predicted to impact the oxidative stress response, xenobiotic detoxification, and DNA damage repair.

Human Epidemiological Studies on 1,4-Dioxane: Challenges and Opportunities

Nicole Deziel, Yale School of Public Health
1,4-Dioxane (1,4-DX) has been classified as a probable human carcinogen by the United States Environmental Protection Agency (USEPA) and a possible human carcinogen by the International Agency for Research on Cancer (IARC) based on evidence from experimental animal studies. Information from human studies to confirm that 1,4-DX is a human carcinogen is incomplete. Over one-fifth of the US public drinking water supply contains detectable levels of 1,4-DX and approximately 7% of water samples tested across the US exceed 0.35 µg/L, the concentration associated with a 10-6 cancer risk. There are no established federal or state minimum concentration levels and drinking water guidelines range widely from 0.3-70 µg/L across the US. This is in part because cancer mechanisms of 1,4-DX are unknown, which has resulted in different interpretations of its potential risk at low doses. In addition, the exposure potential in humans is not well understood due to the limitations of traditional analytical techniques which cannot detect low level concentrations of 1,4-DX in biological samples. Given the widespread occurrence of 1,4-DX in drinking water and its potential heath impacts based on experimental animal studies, there is an urgent need for population-based studies to characterize human exposure to 1,4-DX and the potential harmful impact on human health. Using a novel and sensitive approach for measurements (high resolution GC-Orbitrap mass spectrometry), we propose a cross-sectional study on Long Island (an area with many Superfund sites potentially contributing to contamination of drinking water with 1,4-DX) to i) assess human exposure to 1,4-DX and evaluate the relationship between environmental and biological exposure indicators, and ii) determine the relationship between 1,4-DX exposure and biomarkers of effect. The results from such a study would provide scientific evidence for policy makers who need to set guidelines for for 1,4-DX, and provide researchers with data to better design future epidemiologic studies of 1,4-DX and human health.

Banning 1,4-Dioxane in New York State

Adrienne Esposito, Citizen Campaign for the Environment
1,4-dioxane is considered a “likely human carcinogen” which has been found in drinking water wells throughout the nation. Out of 4,400 wells tested by the EPA, Long Island was home to the highest levels in the country. To better understand 1,4-dioxane contamination in local wells, Citizens Campaign for the Environment (CCE) compiled drinking water quality reports from the EPA and local water suppliers and created an interactive map of 1,4-dioxane contamination (or lack of contamination) at each water district on Long Island. Thirty nine water districts had 1,4-dioxane detections and wells in both Nassau and Suffolk Counties contained contamination levels over 100 times higher than the EPA’s cancer risk guideline for the chemical. While many of these high detections were likely legacy contamination, there were also 1,4-dioxane detections in areas with no history of heavy industry or manufacturing. CCE theorized some of this contamination was likely from household products, which can contain 1,4-dioxane as a bi-product of manufacturing but do not list the chemical on the label. We conducted first-of-its-kind testing on 80 popular household products, including shampoo, body washes and soaps, laundry detergent, and even baby products, and found that 80% of these products contained detectable levels of 1,4-dioxane. From this data, we created a consumer guide to help residents to avoid products with high levels of 1,4-dioxane, conducted an extensive community outreach program, and lobbied for a 1,4-dioxane ban in New York State. In 2019, NY became the first state to pass legislation mandating the removal of 1,4-dioxane in products. In 2020, NY approved the strongest drinking water standard for 1,4-dioxane in the nation. We believe that the extensive work done to combat 1,4-dioxane contamination in NY can serve as a guide for other states and federal regulators looking to tackle this emerging contaminant.

Discussion moderated by Ronald Hines

Vasilis Vasiliou, Yale School of Public Health
Vasilis Vasiliou, is the Susan Dwight Bliss Professor of Epidemiology and the Chair of the Department of Environmental Health Sciences at Yale School of Public Health. He received his BSc in Chemistry (1983) and PhD in Biochemical Pharmacology (1988) from the University of Ioannina, Greece. He then trained as Fogarty Fellow in gene-environment interactions, molecular toxicology and pharmacogenetics at the Department of Environmental Health in the College of Medicine at the University of Cincinnati (1991-1995). In 1996, he joined the faculty of the University of Colorado School of Pharmacy where he rose through the ranks to become Professor and Director of the Toxicology Graduate Program. Since 2008, he was also Professor of Ophthalmology at the University of Colorado School of Medicine. In July 2014, he joined the faculty of Yale University in his new position. Professor Vasiliou has established an internationally recognized research program that has been continuously funded by several federal agencies such as NEI/NIH and NIAAA/NIH since 1997, and recently NIEHS. Dr. Vasiliou’s research interests include the etiology and molecular mechanisms of environmentally-induced human disease, such as liver disease, obesity & diabetes, cancer, and neurodegenerative diseases. His research focuses on the means by which the exposome (total exposures throughout life), metabolism (specifically aldehyde dehydrogenases and cytochrome P-450s) and antioxidants (glutathione and catalase) contribute to human health and disease. His laboratory utilizes state-of-the-art integrated system approaches that include metabolomics, lipidomics, exposomics, tissue imaging mass spectrometry, deep-learning, as well as human cohorts and genetically-engineered mouse models in order to elucidate mechanisms, and to discover biomarkers and novel interventions for human disease. Dr. Vasiliou has trained over twenty five doctoral and post-doctoral students and mentored several junior faculty. He has published over 200 papers and edited three books on Alcohol and Cancer. Dr. Vasiliou is the editor of Human Genomics and serves on the editorial boards of several toxicology and visual sciences journals.

Linda Birnbaum, Former Director of National Institute for Environmental Health Sciences
Linda Silber Birnbaum is an American toxicologist, microbiologist and the former director of the National Institute for Environmental Health Sciences, as well as the National Toxicology Program, positions she held from January 18, 2009 until she retired after 40 years of federal service on October 3, 2019. She currently serves as a Scientist Emeritus at NIEHS, an adjunct professor at the University of North Carolina at Chapel Hill School of Public Health and Duke University, and as a member of the editorial board of Environment International.

Mary Schubauer-Berigan, International Agency for Research on Cancer
Mary Schubauer-Berigan, PhD, MS, is a senior epidemiologist and acting Group Head in the Monographs Programme of the International Agency for Research on Cancer (IARC). Since joining IARC in 2018, she has provided senior-level leadership in epidemiologic evaluations of the evidence base regarding potentially carcinogenic agents in Monographsevaluations. As acting Group Head, she manages the Programme, including the prioritization of agents for future Monographs evaluations, and communicates internally and externally about the Programme. From 1999-2018, she was a research epidemiologist at the National Institute for Occupational Safety and Health (NIOSH), where she led multidisciplinary teams conducting etiologic epidemiology studies to evaluate the health effects (mainly cancer) of exposure to occupational chemical and physical agents (including ionizing radiation, beryllium, and carbon nanotubes and nanofibers) and working conditions (circadian disruption). She also led strategic planning for epidemiology and health surveillance at NIOSH and contributed to its development in the U.S. National Nanotechnology Initiative. She contributed to the development of methods to analyze cohort studies, as well as risk-based analytic tools for the compensation of radiogenic cancers among U.S. nuclear workers. She helped to develop global guidance on compensation programs for nuclear workers. She was named a Fellow of the American College of Epidemiology in 2012.

Gary Ginsberg, New York State DOH, Center for Environmental Health
Dr. Gary Ginsberg directs the NYS DOH Center for Environmental Health (CEH), a Center which administers and coordinates water supply protection, radiation protection, food protection, contaminated site investigations, environmental epidemiological investigations, toxic substance risk assessments, and occupational health and injury prevention across NYS. He has served on a number of national committees including US EPA’s Science Advisory Board, USEPA’s Children’s Health Protection Advisory Committee and a variety of National Academy of Sciences panels (Biomonitoring, 2004-2006; USEPA Risk Methods, 2006-2008; Inorganic Arsenic, 2012-2015, Adult Lead Modeling, 2018-present, Emerging Science in Public Health 2016-present). Dr. Ginsberg has published risk evaluations in the peer reviewed literature on fish contaminants, synthetic turf fields, children’s vulnerabilities, genetic polymorphisms, and on a wide range of chemical exposures. Dr. Ginsberg’s current research interests focus upon the intersection between environmental exposures and the burden of chronic disease, combined effects of chemical and non-chemical stressors, and incorporating advanced toxicology test methods into public health decisions. As director of CEH, Dr. Ginsberg is involved with many environmental health issues that require the integration of research, policy and implementation. Dr. Ginsberg is also on the faculty of Yale University School of Public Health.

Michaela Cashman, US EPA, Narragansett, RI
Michaela Cashman is a Biologist with the US Environmental Protection Agency’s Office of Research and Development in Narragansett, Rhode Island. While completing her Master of Science at the University of Rhode Island, Michaela researched in-situ chemical oxidation of 1,4-Dioxane in groundwater systems. These findings contributed to the Department of Defense Strategic Environmental Research and Development Program (SERDP) Project Report ER-2302: Facilitated Transport Enabled In-Situ Chemical Oxidation of 1,4-Dioxane-Contaminated Groundwater, as well as the peer reviewed publication, Identification of hydroxyl and sulfate free radicals involved in the reaction of 1,4-Dioxane with peroxone activated persulfate oxidant in the Journal of Hazardous Materials. Michaela’s current research with the EPA focuses on identifying contaminants of emerging concern from marine and freshwater matrices.

Detlef Knappe, North Carolina State University
Detlef Knappe is the S. James Ellen Distinguished Professor of Civil, Construction, and Environmental Engineering at NC State University. Detlef received his BS, MS, and PhD degrees from the Department of Civil and Environmental Engineering at the University of Illinois at Urbana-Champaign. He joined the NC State faculty in 1996, where he is also a member of Center for Human Health and the Environment and Deputy Director of the Superfund Research Program Center “Human and Environmental Health Effects of Per- and Polyfluoroalkyl Substances (PFAS).” Detlef serves on the North Carolina Secretaries’ Science Advisory Board (convened by the Secretaries of the North Carolina Departments of Environmental Quality and Health and Human Services) and as Trustee of the Water Science and Research Division of the American Water Works Association.

Ashley Dummer, California State Water Resources Control Board
Ashley Dummer is a licensed civil engineer in California. She works for the California State Water Resources Control Board in the Division of Drinking Water as a Senior Water Resource Control Engineer in the Technical Operations Section. She has been with the Division of Drinking Water for over 11 years. Currently she is working on writing regulations for the Division of Drinking Water. Prior to joining the Technical Operations Section she worked for the for the Riverside District Office, San Diego District Office, Santa Barbara District Office as a staff engineer and for the Santa Ana District Office as the District Engineer.

Shannon Pociu, CT Department of Energy and Environmental Protection
Shannon Pociu is an Environmental Analyst 3 at the Department of Energy and Environmental Protection (DEEP) where she has worked in the Remediation Division within the Bureau of Water Protection and Land Reuse for 20 years. She is the Remediation Division’s lead on PFAS and emerging contaminants and was appointed the Agency’s lead on PFAS in 2019. An active participant in the Governor’s Interagency PFAS Task Force, Shannon provides technical advice on PFAS to colleagues within the Remediation Division and throughout DEEP. Shannon has presented on 1,4-dioxane at the AEHS conference and for training workshops given by the Northeast Waste Management Officials’ Association (NEWMOA). In addition, she has considerable experience managing the investigation and cleanup of State and Federal Superfund sites, potable water projects, and other remediation sites. Prior to joining DEEP, Shannon worked in environmental consulting for 4 years. Shannon holds a BS in Renewable Natural Resources and a BA in Geography from the University of Connecticut and a Master’s of Science Degree in Environmental Science from the University of New Haven. She is also lecturer at the Department of Environmental Health Sciences at the Yale School of Public Health.

Patricia Bisacky, CT Department of Public Health
Patricia Bisacky an Environmental Analyst 3 with the Department of Public Health Drinking Water Section Source Assessment and Protection Unit. She is the lead staff for the SA&P Unit and the CTDPH Environmental Health and Drinking Water Branch’s PFAS Team Lead. Pat has over ten years of experience in the regulatory and policy aspects of public drinking water supply source protection. Regulatory aspects include the review of permit applications for the sale and change in use of water company land, recreational activities on water company land and development of new sources of public drinking water supply. Policy aspects include review of state agency actions proposed in public drinking water supply source water areas and development of broad strategies for addressing contaminants of emerging concern in public drinking water supplies. She is the state representative on the Source Water Protection Committees of the Association of State Drinking Water Administrators and the Ground Water Protection Council and is the Drinking Water Section champion for the CT Source Water Collaborative.

Shaily Mahendra, Department of Civil and Environmental Engineering, UCLA.
Dr. Shaily Mahendra is a Professor in the UCLA Department of Civil and Environmental Engineering, and a member of the California NanoSystems Institute, Institute of the Environment and Sustainability, and the Molecular Toxicology Program. She received Ph.D. from University of California, Berkeley, and postdoctoral training at Rice University. The overarching theme of her research is characterization of microbial interactions with environmental contaminants such as 1,4-dioxane, chlorinated solvents, per- and polyfluoroalkyl substances, nanoparticles, pesticides, munitions, antibiotics, and bisphenol analogs. Her laboratory is equipped for studying biogeochemical processes in natural and engineered systems, biodegradation of water contaminants, applications of molecular and isotopic tools in environmental microbiology, energy positive wastewater treatment, design of antimicrobial and antifouling coatings for medical and environmental applications, and application of enzymes packaged in vault nanoparticles for water treatment and bioremediation. Shaily serves as the Secretary of AEESP Board and Associate Editor of Journal of Hazardous Materials and Journal of Hazardous Materials Letters. She received the NSF CAREER Award, DuPont Young Professor Award, Northrop Grumman Excellence in Teaching Award, Samueli Fellowship, Hellman Fellowship, Poptech Science and Public Leadership Fellowship, Walter Huber Civil Engineering Research Prize, and Paul Busch Award from the Water Research Foundation."

Michael Hyman, North Carolina State University
Dr. Hyman is a Professor of Microbiology at NC State University and has 30 years’ experience in the characterization of microbial degradation processes. His research focuses on the cometabolic biodegradation of ethers and chlorinated hydrocarbons by aerobic hydrocarbon-oxidizing bacteria and fungi. His laboratory uses physiological, genome-enabled proteomic, and stable-isotope-based approaches to characterize the enzymes, pathways, intermediates and physiological consequences of microbial co-metabolism.

David T Adamson, GSI Environmental Inc
Dr. Adamson is a Principal Engineer with GSI Environmental Inc. and has more than 20 years of experience in academic research and as an environmental consultant. He has provided consulting expertise on a broad range of projects including chemical fate and transport, site investigation, remedy screening, risk assessment, remedial design, and litigation matters. He has managed projects that focus on monitored natural attenuation (MNA), source zone characterization, emerging contaminants, matrix diffusion, and the development and testing of innovative treatment technologies. Dr. Adamson’s professional experience includes site investigation, characterization, and remediation, with projects in the U.S., Europe, Latin America, and the Middle East, including the design, implementation, and management of full-scale remediation projects. He has served as a PI or co-PI on over a dozen federally-funded R&D projects and has authored or co-authored over 40 published technical articles on topics such as 1,4-dioxane fate and transport, matrix diffusion of contaminants, source zone characterization and attenuation, in situ bioremediation, remediation performance, improved treatment methods. He is a coauthor of the DoD-sponsored guidance document “Frequently-Asked Questions About MNA” and was one of three co-instructors for the DoD sponsored “Massive Open Online Course” (MOOC) on MNA. Prior to joining GSI, he worked as a post-doctoral research associate at Cornell University and Rice University. Dr. Adamson has served an Adjunct Assistant Professor(s) at Rice University in the Civil and Environmental Engineering Department, where he has taught several courses and currently serves as a Lecturer.

Nicole Deziel, Yale School of Public Health
Nicole Deziel, PhD, MHS, is an Associate Professor in Environmental Health Sciences at the Yale School of Public Health with expertise in exposure science and interdisciplinary training in epidemiology and biostatistics. Her research is focused on applying existing and advanced statistical models, biomonitoring techniques, and environmental measurements to provide comprehensive and quantitative assessments of exposure to combinations of legacy and emerging environmental contaminants. Her exposure assessment strategies aim to reduce exposure misclassification for epidemiologic studies, advancing understanding of relationships between of exposure to environmental chemicals and risk of adverse health outcomes. I conduct detailed community-based field studies and larger exposure studies leveraging administrative datasets. A major focus of her work is directed towards evaluating potential drinking-water related exposures and health impacts from unconventional oil and gas development.

Adrienne Esposito, Citizen Campaign for the Environment.
Adrienne holds a degree in Geology and Environmental Science from CW Post University. She is a co-founder of Citizens Campaign for the Environment (CCE) which started in 1985. CCE is a non-profit organization working in NY and CT to protect our natural resources and public health. Adrienne and her staff conduct research, lobbying and public education on diverse environmental campaigns including advocating for state funding and upgrading failing sewage treatment systems, protection of drinking and surface water, remediation of toxic plumes, stewardship of land and water, support for large scale renewable energy projects, reduced pesticide application, fighting plastic pollution and more. Esposito is widely considered an expert on environmental protection issues. She recently received a national award recognizing her as one of the Top Ten Women of Water in the United States.

Ronald N. Hines, Ph.D., ATS
Dr. Hines earned his Ph.D. in biochemistry from the University of Texas Southwestern Medical School in 1980. Following his postdoctoral fellowship at the University of Vermont College of Medicine (1980-1983), he became Assistant Professor (1983-1988) and, later (1988-1989), Associate Professor at the Eppley Institute for Research in Cancer and Allied Diseases and the Department of Biochemistry at the University of Nebraska Medical Center. In 1989, Dr. Hines was recruited to the Wayne State University School of Medicine as Associate Professor of Pharmacology and Pediatrics Associate and in 1995, was promoted to Professor of Pharmacology. In 1999, he assumed a position as Professor of Pediatrics and Pharmacology and Toxicology at the Medical College of Wisconsin where he also served as Associate Director of the Children’s Research Institute of the Children’s Hospital and Health Systems (2005-2012) and Co-Section Chief of Clinical Pharmacology, Pharmacogenetics, and Teratology in the Department of Pediatrics. In addition, Dr. Hines was Adjunct Professor of Biological Sciences at the University of Wisconsin-Milwaukee (2006-2012). In 2012, Dr. Hines accepted the position of Associate Director for Health at the National Health and Environmental Effects Research Laboratory (NHEERL) in the Office of Research and Development of the U.S. Environmental Protection Agency. In this position, he managed the three NHEERL health divisions and their diverse research portfolio, as well as the Research Core Unit. He retired from the US Environmental Protection Agency in 2020. Throughout his academic career, Dr. Hines’ research was supported by various organizations, including state health departments, private foundations, industry contracts and the National Institutes of Health. He is a member of the Society of Toxicology where he was elected to the Presidential Chain, serving as President from May 1, 2019 through April 30, 2021. He has served on numerous Federal and State science advisory panels and as an Associate Editor or Editorial Board Member for nine peer-reviewed journals. He currently is a member of the Drug Metabolism and Disposition Editorial Board. During his career, Dr. Hines approached research questions using a transdisciplinary tactic, assembling and leading research teams with expertise spanning from molecular biology and analytical chemistry to clinical cohort studies. Dr. Hines has over 150 publications focused on mechanisms whereby exposures to environmental toxicants or drugs alter gene regulation and the genetic/epigenetic basis for interindividual differences in response to exposures. Over the last 13 years of his academic career, his research turned to elucidating how and through what mechanisms the enzymes involved in toxicant and drug disposition change during early life stages and the interaction of genetic/epigenetic variation with this normal developmental process. The impact of this body of work has resulted in an h-index of 47 and numerous invitations to present his research at both national and international meetings.