LDDI Consensus Statement
http://www.iceh.org/LDDI.html
Scientific Consensus Statement on Environmental Agents Associated with
Neurodevelopmental DisordersDeveloped by the Collaborative on
Health and the Environment’s Learning and Developmental Disabilities
InitiativeFebruary 20, 2008(revised July 1, 2008)
ParacelsusParacelsus was so grandiose
And perhaps just a little bit grossManure, blood, and sandand thus you create man
But what makes it a poison is dose!
The Undecided DoseToo much of a thing makes you blue
But not having it can kill you tooToo much or too littleLet's not be so fickle
We'll go Dutch and divide it by two.
Limericks by Toni Hayes
ObjectiveAssess our understanding of how chemicals affect child health.
OverviewGiven established scientific knowledge, protecting children from neurotoxic exposures from the earliest stages of fetal development is clearly an essential public health measure. By reducing environmental factors that may lead to learning and developmental disorders, we will create a healthier environment in which all children can reach and maintain their full potential.
Authors and ReviewersDrafted and edited by:Steven G. Gilbert, PhD, DABT, Institute of Neurotoxicology and
Neurological Disorders
Scientific Review Committee:David C. Bellinger, PhD, MSc, Harvard Medical SchoolLynn R. Goldman, MD, MPH, Johns Hopkins University, Bloomberg School
of Public HealthPhilippe Grandjean, MD, Harvard School of Public HealthMartha Reed Herbert, MD, PhD, Massachusetts General HospitalPhilip J. Landrigan, MD, MSc, Mount Sinai School of MedicineBruce P. Lanphear, MD, MPH, University of CincinnatiBarbara McElgunn, RN, Learning Disabilities Association of CanadaJohn Peterson Myers, PhD, Environmental Health SciencesIsaac Pessah, PhD, University of California, DavisTed Schettler, MD, MPH, Science and Environmental Health NetworkBernard Weiss, PhD, University of Rochester School of Medicine and
Dentistry
AcknowledgementsOther Reviewers, Editors, and Researchers:Aimee Boulanger, Institute for Children’s Environmental
HealthSean Foley, Toxipedia, Institute of Neurotoxicology and
Neurological DisordersElise Miller, MEd, Institute for Children’s Environmental
Health and the Collaborative on Health and the Environment’s Learning and Developmental Disabilities Initiative
Nancy Snow, MS, Institute for Children’s Environmental Health
AudienceThis statement is intended as a
guide to scientists, medical professionals, policymakers, public health advocates, and the general public in advancing their efforts to address the important individual and social issues raised by learning and developmental disabilities.
Learning and developmental disorders broadly as conditions resulting from interference of normal brain development and function that adversely affect an individual’s performance. Learning and developmental disabilities (LDDs) include but are not limited to deficits in learning and memory, reduced IQ, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, conduct disorders and developmental delays.
Define LDDs
“Conditions that ensure that all children have the best opportunity to reach and maintain their full genetic potential.”
Children's Environmental Health
Incidence of LDDS
Affects between 5 and 15 percent of all children under the age of 18 in the United States, or more than 12 million children.
Incidence of ADHD
ADHD is conservatively estimated to occur in 3 to 6 percent, or about 2 million children
What we don’t know about chemicals
More than 80,000
unknown
~1,000 suspected
~200 with good
evidence
~10 we know for sure
High Volume Chemicals Approximately 3,000 chemicals are
produced more than one million pounds per year.
For the majority little information exists about the potential effects on learning and development.
There is good evidence that about 200 of these chemicals are adult neurotoxicants and another 1000 are suspected of affecting the nervous system.
Toxicology Definitions
The study of poisonsor
the adverse effects of chemical and physical agents
on living organisms.
Key Words of Toxicology
Hazard X Exposure = Risk
Individual Susceptibility
Dose / Response
Greater Dose – Greater Response
Dose
Res
pons
e
Threshold (NOAEL)
ED50
LOAEL
Principles of Toxicology
N
N N
N
CH3
CH3
CH3
O
O
1
3
7
Exposure starts early – pre-conception, breast milk
For their body weight, children eat and breathe more than adults, thus a small exposure translates into a big dose.
Brain developing, cells dividing Behavior – hand to mouth
increases exposure to chemicals
Children are not little adults
Environmental Contributors to Disorders
Timing of exposure Bioaccumulation and mixtures Mechanisms of disruption Variable sensitivity Evidence of exposures (body
burden) Persistent chemicals
Timing of exposure
A child’s developing nervous system is more sensitive to
chemical exposures than the adult nervous system.
Other environmental factors
Pharmaceuticals Genetic factors Environmental justice:
socioeconomics, nutrition and stress
Environmental agents that we are confident cause learning and developmental disabilities in humans
Environmental Agents
AlcoholLeadMercury PCBsPBDEsManganese
ArsenicSolventsPAHsPesticidesNicotine & ETS
Fetal Alcohol Spectrum Disorder (FASD), is the most preventable form of behavioral and learning disabilities.
Alcohol
In the US, FASD is estimated to affect 9.1 per 1000 infants with even higher rates in other parts of the world.
Do not consume alcohol during pregnancy.
There is no safe level of lead exposure for children
Even the lowliest of lead exposure cause impairs overall intelligence as measured by IQ, learning and memory
Lead
60
40
3025
2015
102
0
10
20
30
40
50
60
Blo
od L
ead
(ug/
dl)
CDC1960
CDC1973
CDC1975
CDC1985
WHO1986
EPA1986
CDC1990
CDCWhen?
Agency and Year
Acceptable Childhood Blood Lead Levels The CDC should lower the blood lead action level
Rationale for Lowering the Blood Lead Action Level From 10 to 2 µg/dl. Steven G. Gilbert and Bernard Weiss. Neurotoxicology Vol 27/5, September 2006, pp 693-701.
Mercury bioaccumulates in fish Mercury is distributed in the
environment by coal burning electric utility plants
Mercury
Mercury advisories limit fish consumption for women and children
US EPA RfD 0.1 ug/dL
Highly persistent and bioaccumulative. Stored in fat and excreted in women’s
breast milk. Exposure can adversely affect motor
skills, learning and memory as shown in lower full-scale and verbal IQ scores and reading ability
PCBs - Polychlorinated biphenyls
Commonly used as flame-retardant PBDEs, structurally similar to PCBs Bioaccumulates in animals and
humans, and are excreted in human breast milk.
Developmental neurotoxicants
PBDEs - Polybrominated diphenyl ethers
O
Brx Bry
Manganese is a trace element which is necessary in small amounts for growth and development.
High levels of manganese exposure, from inhalation (welding fumes) or through drinking water, can damage the developing nervous system as measured in full-scale IQ and verbal
US EPA water levels of manganese should not exceed 300 μg Mn/L
Manganese
Commonly found in drinking water around the world, sometimes in concentrations high enough to cause cancer
Arsenic
Dose-response relationship between exposure to arsenic and intellectual impairment
Broad array of different compounds including toluene, benzene, alcohol, turpentine, acetone and tetrachloroethylene (TCE)
Solvents
More than 50 million metric tons used in the US and more than 10 million people exposed in the workplace.
Widely distributed air pollutants and well-recognized human mutagens and carcinogens.
PAHs - Polycyclic aromatic hydrocarbons
PAHs are generated during combustion of fuels from motor vehicles, coal-fired power plants, residential heating, cooking, and tobacco smoke
PAHs results in lower birth weight and affects cognitive development
Designed to kill insects, plants, fungi or animals
Agricultural and residential application of pesticides in the US totals more than one billion pounds per year
Pesticides
Childhood exposure enhances the risk for developmental disorders including deficits in memory poorer motor performance
Maternal smoking or exposure to ETS during pregnancy leads to behavioral disorders in children
CDC reported in 2002 that 11.4 percent of all women giving birth in the United States smoked during pregnancy
Nicotine and ETS
Childhood exposure to ETS also results in developmental disorders
1.Endocrine disruptors2.Fluoride3.Food additives
Contributors and emerging evidence
Endocrine disruptors
Phthalates, PCBs and polychlorinated dibenzodioxins, brominated flame retardants, dioxins, DDT, perfluorinated compounds (PFCs), organochlorine pesticides, bisphenol A, and some metals
Fluoride Commonly added to
municipal drinking water across the US based on data that it reduces dental decay.
Multiple routes of exposure, from drinking water, food and dental care products
Emerging science suggests we need to further study the dose at which fluoridation may increase risks of neurodevelopment disorders, cancer and skeletal or dental fluorosis, particularly for sensitive individuals.
Food additives Artificial or synthetic
food colors and additives are ubiquitous in the food supply
Artificial food colorings such as sunset yellow, tartrazine, carmoisine and ponceau, as well as the preservative sodium benzoate, can cause conduct and hyperactivity disorders
1. Better assessment tools and procedures2. In vitro (test-tube) screening of both new and
old compounds3. Chronic effects of hazardous chemicals4. Multiple exposures5. Low-level exposures6. Interactions with socioeconomic factors
(environmental justice)7. Effects of endocrine disruption on cognitive
deficits8. Interactions with genetics and identification of
susceptible subpopulations
Call for Further Research
The consequences of LDDs are most significant for the affected individual but also have profound implications for the family, school system, local community and greater society. Despite some uncertainty, there is sufficient knowledge to take preventive action to reduce fetal and childhood exposures to environmental contaminants. Given the serious consequences of LDDs, a precautionary approach is warranted to protect the most vulnerable of our society.
Conclusion
Precautionary Principle
“When an activity raises threats of harm to human health or the environment, precautionary measures should be take even if some cause and effect relationships are not fully established scientifically.”
Wingspread Conference, 1998.
Central components Setting goals (Health indicators) Taking preventive action in the face of
uncertainty Shifting the burden of responsibility to the
proponents of an activity (Who benefits?) Exploring a wide range of alternatives to
possibly harmful actions (Is it necessary?) Increasing public participation in decision
making (transparency of information & environmental justice)
The Potential of Children
Additional Information
National Research Council, Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC, 1983
World Health Organization - The International Programme on Chemical Safety (IPCS) – Risk Assessment –http://www.who.int/pcs/ra_main.html
U.S. Environmental Protection Agencies - National Center for Environmental Assessment (NCEA) – http://cfpub.epa.gov/ncea/
A Small Dose of Toxicology – Risk Assessment - http://www.asmalldoseof.org/toxicology/risk_assessment.php
Questions / Comments
Small Dose of Toxicology
Milestones of Toxicology
www.toxipedia.orgA free toxicology encyclopedia and resource center that anyone can edit. Toxipedia provides comprehensive, accurate, and scientifically based information on the hazards and risks of chemical and physical agents, with the goal of advancing human and environmental health. Toxipedia
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Coupling art and science to forge a more healthy
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Healthy World Theater
Coupling art and science to forge a more healthy and peaceful world
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Public Health and the Precautionary
PrincipleBy Steven G. Gilbert