21St International Neurotoxicology Conference

21St International Neurotoxicology Conference

NTX XXI: Twenty-First International Neurotoxicology Conference

Tuesday Morning - 10 Feb 2004

Session I: Opening Ceremonies, Overview, Goals and Welcome Keynote

Opening of the conference, Overview & Goals: why hawaii?

Conference Chair: Joan M. Cranmer, PhD

Professor, University of Arkansas for Medical Sciences

Conference Co-Chairs:

Lynn R. Goldman, MD, MPH – Professor, Johns Hopkins University

Donald R. Mattison, MD– Senior Advisor to the Directors of NICHD and CRMC, National Institutes of Health

Deborah C. Rice, PhD

Senior Scientist, Maine Department of Environmental Protection


(Hawaii Official: The Governor’s Office, Mayor of Oahu, Health Commissioner, or Dean of the Medical School)

Greetings on Behalf of All Sponsors: Sponsors Expectations

Kenneth Olden, PhD- Director, NIEHS/NIH

Recognition of federal leaders by the governer of hawaii

The Honorable Linda Lingle

Governor, State of Hawaii (invited)

Recognition of the leaders of Federal Agencies for their contributions to Children, Environmental Health, and the special needs of oceanic people!

Duane Alexander, MD

Director, National Institute of Child Health and Human Development/NIH

Jose Cordero, MD

Director, National Center for Birth Defects and Developmental Disabilities/CDC

Henry Falk, MD, MPH

Director, National Center for Environmental Health/CDC and Assist. Administrator, Agency for Toxic Substances and Disease Registry

Paul Gilman, PhD

Assistant Administrator for Research and Development, and Science Advisor to the EPA Administrator

Richard Jackson, MD, MPH

Senior Advisor to the Director, CDC

Kenneth Olden, PhD

Director, National Institute of Environmental Health Sciences/NIH

Introduction of Keynote Speaker

Robert Amler, MD, MPH

Regional Health Administrator, USDHHS/PHS

Welcoming Keynote:

“Children’s Environmental Health:

An International Perspective”

Henry Falk, MD, MPH

Director, NCEH/CDC and Assistant Administrator, ATSDR
Session II: Cross-Cutting Issues

Chair: Donald Mattison

Neurodevelopmental Effects of Persistent Pollutants: Data Gaps and Policy Implications

Lynn Goldman - Johns Hopkins University

Biomonitoring: An Integral Part of Exposure Analysis

Larry L. Needham

Chief, Organic Analytical Toxicology Branch, NCEH/CDC

Open Discussion

Tuesday afternoon - 10 Feb 2004

Session III: Hot New Results from the NIEHS/EPA Children’s Centers

Co-Chairs: Gwen Collman, NIEHS & Chris Saint, EPA

This session will feature the hottest and most exciting new findings from the NIEHS/EPA-funded Children’s Centers that address the issues in this conference including: Pesticides, PCBs, Methylmercury, Mixtures, Autism, Neurodevelopment, Growth and Development, Intervention, Outreach

Centers and Principal Investigators

Friend's Children's Environmental Health Center

Susan L. Schantz - University of Illinois, Urbana-Champaign

Center for Child Environmental Health Risks Research

Elaine Faustman

Univ. of Washington School of Public Health & Community Medicine

Exposures and Health of Farm Worker Children in California

Brenda Eskenazi

University of California at Berkeley, School of Public Health

Center for Childhood Neurotoxicology and Assessment

George H. Lambert

University of Medicine & Dentistry, NJ

The Center for the Study of Environmental Factors in the Etiology of Autism

Isaac N. Pessah

University of California, Davis

Columbia Center for Children's Environmental Health

Frederica Perera

Columbia University School of Public Health

Low-Level Environmental Lead Exposure and Intellectual Impairment in Children

Bruce Lanphear - Children’s Hospital Research Fdn, Cincinnati

Inner City Toxicants and Neurodevelopmental Impairment

Mary Wolff - Mount. Sinai School of Medicine

6:00 –8:00 PM

Welcoming Reception

Hosted Buffet Dinner

Ginger Terrace Poolside

Wednesday Morning - 11 Feb 2004

Session IV: Infant and Child Longitudinal Neurotoxicity Studies – Part I

(Methylmercury, PCBs, Pesticides, Lead, Combinations)

Co-Chairs: Deborah Rice and Sherry Selevan

Persistent Bioaccumulative Toxicants (PBTs) are chemicals that are persistent in the environment, bioaccumulate and bioconcentrate in living organisms, and are toxic to ecosystems and human health. Epidemiological studies in the 1970s and 1980s largely studied the effects of single toxicants on the neuropsychological development of children. However, there is increasing concern regarding the fact that children and exposed simultaneously to multiple chemicals, particularly PBTs, and that studying only a single chemical may result in misleading interpretations. Several cohort studies begun in the 1990s are studying the effects of multiple PBTs, allowing exploration of the pattern of effects of individual chemicals in the same group of children, as well as chemical-chemical interactions. This symposium will present new data from ongoing studies.

Introduction of Keynote Speaker

Lynn Goldman

Johns Hopkins University

Opening Keynote

“Children, Obesity

and Environmental Health”

Richard Jackson, MD, MPH

Director, National Center for Environmental Health/CDC

Interaction of Environmental Risk Factors and Modulation of Developmental Neurotoxicity

Deborah Cory-Slechta

Rutgers, The State University of New Jersey and EOSHI

Strategies for Assessing the Effects of Environmental Toxicant Exposure in Developmental Epidemiological Studies

Deborah Rice

Maine Dept Environmental Protection

New Data from Ongoing Children’s Environmental Health Studies

Effects of Methylmercury and PCBs on Behavior of Children at 14 years: The Faroe Islands Study

Roberta White

Boston University, Boston, MA

Interactions of PCBs, Pesticides, and Nutritional Factors on Early Development in an Inuit Community

Gina Muckle

University of Laval, Montreal, Quebec, Canada

Specificity of the Neuropsychological Effects of Prenatal Exposure to PCBs, Methylmercury, and Lead on Infant Cognitive Development (Effects of PBTs on neuropsychological function in children in circumpolar regions)

Sandra W. Jacobson

Wayne State University, Detroit, Michigan

Effects of Exposure to Chemicals from Industrial Contamination in New Bedford, Mass

Susan Korrick

Harvard University, Boston, MA

Wednesday Afternoon - 11 Feb 2004

Session V: Infant and Child Longitudinal Neurotoxicity Studies – Part II

Co-Chairs: David Bellinger and TBA

This session is a continuation of Session IV, involving presentation of four additional studies of the neuro-developmental effects from prenatal and early postnatal exposures to environmental contaminants

What is an Adverse Effect? Resolution of Clinical and Epidemiological Perspectives on Neurobehavioral Toxicity

David Bellinger

Harvard Medical School, Boston, MA

New Data from Ongoing Long-term Children’s Environmental Health Studies:

Neurodevelopmental Outcomes at Age 9 in the Seychelles Child Development Study

Philip W. Davidson

Univ of Rochester School of Medicine & Dentistry, Rochester, NY

Cognitive Development in Children Exposed Prenatally to PCBs and MeHg: The Oswego Newborn and Infant Study

Paul W. Stewart

State University of New York at Oswego, NY

Organochlorines, Lead and Mercury in Akwesasne Mohawk Youth

Lawrence M. Schell and/or Joan Newman

State University of New York at Albany, NY

Prenatal Exposure to PCBs and Infant Development: The Collaborative Perinatal Project

Matthew P. Longnecker

National Institute of Environmental Health Science, RTP, NC

Methylmercury/PCB Studies with First Nation Populations in Canada: Maximizing Nutritional Value from Traditional Foods and Minimizing Toxic Risks

Donna Mergler - University of Montreal, Quebec

Children Exposed to PCBs in Taiwan: Long-Term Follow-up Studies

Leon Guo, Taiwan and George Lambert, UMDNJ

Panel and Open Discussion:

Interpretation of Child Epidemiological Studies of Subtle Effects“

Moderator: David Bellinger

Panelists: Speakers in Sessions III, IV & V-A

Wednesday Evening - 11 Feb 2004

Session VI:General Poster Session

No Host Bar & Refreshments

The poster session is a highlight of this conference series. It has proven to be an effective venue for informal in-depth discussion and collaboration building as well as an important networking opportunity for all participants. Judging and selection of Pre – and Post-Doctoral Student Awardees will be made during this session. Papers on any aspect of neuroscience, toxicology or children’s environmental health are invited and welcome!

Note: The General Poster Session traditionally is scheduled as an evening session because it is conducive to discussion and getting acquainted in a less formal atmosphere without time constraints. This year it has the added advantage of allowing more Hawaiians to participate without work or school conflicts.

Thursday Early Morning -12 Feb 2004

Methylmercury Risks vs. Fish Benefits

Co-Chairs: Linda Rosen, Hawaii State Health Dept and TBA

Background/Justification: to be supplied

Introduction and Session Overview

Linda Rosen

Hawaii State Health Department

Volcanic Sources of Mercury in Hawaii, Levels of Mercury in Hawaii Fish, and Hawaiian/Pacific Islander Cultural and Social Issues

Bruce Anderson

University of Hawaii School of Medicine (former health commissioner)

Proposition 65 and Methylmercury in Fish

Mark Miller
Environmental Protection Agency, California

Perspectives of the US Food and Drug Administration

Mike Bolger or TBA

Methylmercury in Hawaii Fish: Risk/Benefit issues

Lynn Goldman - Johns Hopkins University

Panel and Open Discussion

SESSION VII–B: Parkinson’s Disease, Environment and Genes
Cellular Mechanisms Involved in Environmental Neurotoxin-Induced Selective Neuronal Damage and Its Relevance to Parkinson’s Disease

Co-Chairs: Anumantha G. Kanthasamy, Cindy Lawler and Syed F. Ali

Environmental neurotoxic chemical exposures are increasingly recognized as dominant risk factors in the etiology of Parkinson’s disease. Exposure to pesticides, PCBs and metals promote selective neuronal damage that is often superimposed with the pathological hallmarks of Parkinson’s disease. However, cellular mechanisms underlying selective neuronal degenerations remain to be established. In recent years, cell death signaling has been investigated extensively. Despite this growing amount of information regarding the cell death process, little effort has been made to integrate this body of knowledge with the field of selective neuronal injury and establish its relevance to neurodegenerative diseases. This symposium is designed to fill this gap by entertaining discussion of key cell death signaling molecules and other cellular targets that may impact the disease process of Parkinson’s disease. Specifically, novel findings obtained from neurotoxicity models using state-of-the-art approaches including toxicogenomics, transgenics, knockouts, and RNA interference (RNAi) will be presented. The symposium presentations are expected to uncover unifying concepts and set the groundwork for translation of key analogies between neurotoxicity research and neurodegenerative disorders. Furthermore, this symposium is likely to accelerate understanding of the role of environmental chemicals in the etiopathogenesis of Parkinson’s disease as well as to foster the development of novel therapeutic strategies.

Introduction to Chemicals-induced Selective Neuronal Injury

Syed Ali

FDA -National Center for Toxicological Research, Jefferson, AR

Role of Oxidative Stress-Sensitive Kinase in Dieldrin-induced Dopaminergic Cell Death: Relevance to Parkinson’s disease

Anumantha Kanthasamy - Iowa State University, Ames, IA

Dopamine Transporters as Mediators of Environmentally-Induced Dopamine Damage

Gary Miller

Center for Neurodegenerative Diseases, Atlanta, GA

Do PCBs Alter Dopamine Mediated Function in Aging Workers?

Richard Seegal

New York State Dept of Health, Albany, NY

Selective Vulnerability of Dopaminergic Neurons to Oxidative Damage: Implications to Parkinson’sDisease

Donato Di Monte - The Parkinson’s Institute, Sunnyvale, CA

Others planning to submit abstracts and present their latest related research results: Deborah Cory-Slechta, Clem Furlong, Web Ross, James O’Callaghan. Other talks to be selected from submitted abstracts

Thursday LATE MORNING - 12 Feb 2004

Session VIII-A: Role ofObesity in Children’s Environmental Health

Co-Chairs: William Slikker and TBA

The prevalence of childhood obesity has nearly doubled during the last two decades and is the most common nutritional disorder, showing an increasing prevalence. Overweight children have a higher risk for being overweight in adulthood and are therefore at risk for disease states associated with obesity, including Type 2 diabetes, cancer, and cardiovascular problems. Although family genetic factors are prime risk factors for childhood obesity, non-genetic factors also show a strong association with obesity. Some of these non-genetic factors include frequent TV viewing/video games and frequent consumption of snacks while watching TV. While a large number and variety of agents are associated with abnormal human development, efforts to identify an association between perinatal exposure to a substance and subsequent childhood obesity are just beginning. Recent studies have demonstrated an increased risk for overweight and obesity in children of mothers who smoked during pregnancy. These data and other clinical observations and animal model studies support the hypothesis that obesity in children of mothers who smoked during pregnancy is the result of long lasting behavioral teratogenic effects of nicotine exposure in utero. The search for environmental explanations of childhood obesity should be expanded because of the detrimental effect on health quality and the impact on our already-stressed health care capabilities. In addition, understanding the risk factors associated childhood obesity may lead to successful strategies for prevention.

Impact of Childhood Obesity on Children's Health

Rear Admiral Ken Moritsugu, Deputy Surgeon General, Washington, DC

or Bern Schwetz, HHS/Office of Human Research Protection Rockville, MD

The Fetal Programming Hypothesis: Possible Role in Childhood Obesity

William Slikker, Jr., NCTR/FDA, Jefferson, AR

or Julia Steinberger, University of Minnesota, Minneapolis, MN

Maternal Smoking During Pregnancy and Association with Childhood Obesity

Michael Toschke or Rüdiger von Kries

Ludwig-Maximilians-University, Munich, Germany

Animal Models of Developmental Nicotine Exposure: Possible Mechanisms of Childhood Obesity

Edward Levin or Theodore Slotkin - Duke University, Durham NC

Obesity Exacerbates Neurotoxicity

James O’Callaghan, NIOSH-CDC, Morgantown, WV

Session VIII–B: The Honolulu-Hawaii-Asia Aging Cohort Study

A Population-Based Longitudinal Study Providing Clues as to how Lifestyle & Workplace Factors Can Contribute to Neurodegenerative Disease

Co-Chairs: James O’Callaghan and Dan Sharp

The Honolulu-Asia Aging Study (HAAS) began in 1991 as a supplement to the Honolulu Heart Program, a longitudinal study of cardiovascular disease in a cohort of Japanese-American men living on Oahu at the time of the baseline examination in 1965. The original cohort consisted of 8006 men born 1900 through 1919. Some members of this cohort were occupationally exposed to persistent pesticides, including Heptachlor.Brain samples from descendentsof the HAAS cohort are being analyzed for levels ofpesticides and an attempt is being made to relate these data to occupational exposures, premortem diagnosis of neurological disease as well as postmortem evidence ofgliosis and neuropathological hallmarksof specific neurological disease states. Participation at NTX-XXI allows CDC-NIOSH scientists to present their most recent data to the neurotoxicological community as part of their visit to Honolulu.

The Design of Population-Based Longitudinal Studies and Their Role in Establishing Etiology of Human Disease

Dan Sharp, Wayne Sanderson

CDC-NIOSH, Morgantown, WV

The Honolulu-Asia Aging Study - Design, Description and Data Resources

Lon White

Pacific Health Research Institute, Honolulu, HI

Neuropathology Assessment in the HAAS

Jim Nelson

Pacific Health Research Institute, Honolulu, HI

Neurodegenerative Diseases in the HAAS

Web Ross

Department of Veteran Affairs, Honolulu, HI

Work Factors and Exposure to Pesticides in the HAAS

Helen Petrovitch,Wayne Sanderson, Michael Kashon, Pacific Health Research Institute, Honolulu, HI, CDC-NIOSH

Brain Tissue Analysis in the HAAS – Persistent Pesticides in the Caudate Putamen, Characterization of the Dopamine System and Parkinson's Disease

Diane Miller, Web Ross, Jim O'Callaghan, Michael Kashon, Edo Pellizaro, CDC-NIOSH, Dept of Veteran's Affairs, Res Triangle Inst

Thursday Early Afternoon - 12 Feb 2004

Session IX-A

Workshop:Mechanisms of Methylmercury Toxicity - The Latent Phase

Co-Chairs: Michael Aschner and Kenneth Reuhl.

Invited Participants: William Atchison, David Bellinger, Philip Davidson, Thomas Clarkson, Toshio Narahashi, Deborah Rice, Linda Rosen, Tore Syversen, Bernard Weiss, Roberta White, Others TBA

Outbreaks of methylmercury (MeHg) exposure in human populations and experimental studies in non-human primates suggest that poisoning symptoms may not occur for weeks or months after exposure, a period commonly referred to as silent or latent-phase. Since most, if not all, toxicological or pharmacological agents exert their maximal effect or efficacy at the time of peak blood concentration, this phenomenon has for decades puzzled the research community. In addition, the pathophysiology of MeHg, specifically in the adult brain, is confined to distinct brain regions, such as the cerebellum and visual cortex. Given the high affinity of MeHg for sulfhydryl groups and their ubiquitous nature, this specificity, has also been a puzzle.

Workshop Goal: The workshop should provide new hypotheses on mechanisms of MeHg neurotoxicity issues.

Workgroup Questions for Discussion: (20 minutes each = 2 hrs)

A series of questions have been developed which should help focus the workshop. These questions are meant to help structure the workshop but not unduly constrain scientific discussion.

1.What potential mechanisms can be invoked for the silent phase of MeHg?

2.Can analogies be drawn from other compounds?

3. What mechanisms guide the distribution of MeHg in the brain?

4. In the absence of differences in regional MeHg concentrations, what mechanisms might be invoked to describe cellular and regional specificity?

5.Does demethylation play a role in the neurotoxicity of MeHg?

6.Is MeHg's effect potentially mediated via extracellular effects?

Session IX-B: Emerging Issues in Children’s Health: International Perspectives

Co-Chairs: William A. Suk and Kalpana Balakrishnan

Indoor Air Pollution and Children’s Health: The Situation in Developing Countries

Kalpana Balakrishnan, Sri Ramachandra Medical College & Research Institute, India

Association Between Drinking Water and Urinary Arsenic Levels and Skin Lesions in Women and Children in Bangladesh

Iftikhar Hussein, National Institute of Preventive and Social Medicine, Bangladesh and H. Ahsan, Columbia Univ, School of Public Health

Critical Periods of Susceptibility in Neurodevelopmental Processes in Infants and Children

P.K. Seth, Industrial Toxicology Research Centre, Lucknow, India

Potential Mechanisms of Causes in Developmental and Learning Disabilities: Reflections from Developing Countries

David Carpenter, School of Public Health, University at Albany