A Small Dose of Toxicology
Child Development and Social
Responsibility
ENVH 517a – Children’s Environmental Health
Department of Environmental and
Occupational Health Sciences, University of
Washington
April 19, 2004
Steven G.Gilbert, PhD,DABT
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Child Health
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Convergence of Issues
• Vision of Child Health
• Knowledge of toxicology
• Policy Approach within an
ethical framework
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Social responsibilities
No technical solutions
Restriction of freedoms
Precautionary approach
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WHO Vision for Child Health
A World Fit for Children
• Promoting healthy lives
• Providing quality education
• Protecting against abuse,
exploitation and violence
• Combating HIV/AIDS.
http://www.unicef.org/why/why_worldgoals.html
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CDC Vision for Child Health
“Environmental Health at CDC
strives to promote health and
quality of life by preventing or
controlling those diseases or
deaths that result from
interactions between people
and their environment.”
http://www.cdc.gov/node.do?id=0900f3ec8000e044
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American Academy of Pediatrics
Mission and vision
To attain optimal physical,
mental and social health and
well-being for all infants,
children, adolescents and young
adults.
http://www.aap.org/member/memcore.htm
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University of Washington
• The Child Health Institute (CHI)
– promotes interdisciplinary
collaboration
• Center for Child Environmental
Health Risks Research (CHC) –
focus on susceptibility to
pesticides
http://depts.washington.edu/chc/index.html
http://depts.washington.edu/chiorg/
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Vision for Child Health
“Children can develop
and mature in an
environment that allows
them to reach and
maintain their full
potential.”
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Vision of Environmental Health
“Conditions that ensure that all
living things have the best
opportunity to reach and maintain
their full genetic potential.”
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Susceptibility of Children
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Dose Response Issues
Higher metabolic rate
Different nutritional requirements
Rapidly dividing & migrating cells
Immature organs
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Vision of Child Health
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Life – Potential & Harm
All life depends on
reproduction and
development.
What effects this process
and harms a child's
potential?
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Terms
 Monster – abnormal or strange
animal or plant. From Latin monstrum
omen, from monere to warn (abnormal
infants reflect the future).
 Teratology – The study of
malformations. From the Greek word
for monster – teras.
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Three Areas
 Reproduction – issues associated
with the egg and sperm
 Pregnancy – the critical
environment of early development
 Development of the infant.
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Ancient Awareness
 Many ancient cultures had fertility goddess
 Many ancient documentation of
malformations
 Malformations rich aspect of mythology
 6500 BC – Turkey - figurine of conjoined
twins
 4000-5000 BC – Australia drawings of twins
 2000 BC - Tablet of Nineveh – describes 62
malformations and predicts the future
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Historical Awareness
 15th-16th centuries malformations caused
by the devil, mother and child killed
 1830’s - Etienne Geoffroy Saint-Hilaire
experimented with chicken eggs
 1900’s began acceptance of
malformations related to genetics
 1940’s - Josef Warkany – environmental
factors affect rat development
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Historical Events
 1941 – Human malformations linked
to rubella virus
 1960’s – Thalidomide (a sedative and
anti-nausea drug) found to cause
human malformations
 1950’s – Methylmercury recognized as
developmental toxicant
 1970’s – Alcohol related to
developmental effects – Fetal Alcohol
Syndrome (FAS)
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Human Reproductive Facts
• 50% of pregnancies end in
miscarriage or spontaneous
abortion often before pregnancy
is recognized
• 15% of couples of reproductive
age are infertile
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Reproductive Endpoints
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Fertility
Menstrual cycle
Sperm count and viability
Sexual behavior
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Reproductive Toxicants
 Endocrine disruptors
• DDT, Dioxin
 Heavy metals
• Lead (decreased sperm)
 Organic Solvents
• Toluene, benzene
 Drugs
• Alcohol
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Pregnancy Effects the Women
• Cardiovascular
•
Increased - cardiac output heart rate, blood
pressure, blood volume expands
• Oxygen consumption increases by 15-20%
• Urine volume increases
• Gut absorption changes
•
Increases in iron and calcium (toxic lead
substitutes for calcium)
• Liver metabolism decreases for some
drugs or chemicals (caffeine)
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Developmental Endpoints
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Teratology (physical malformations)
Birth weight
Growth
Neurobehavioral
 Decreased intelligence
 Decreases learning and memory
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Chemicals/Radiation
 Chlorobiphenyls
 Solvents (Toluene)
 Endocrine disruptors
 DDT, PCBs
 TCDD
 X-rays (therapeutic)
 Atomic fallout
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Infections/Medical Conditions
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Rubella virus
Herpes simplex virus
Toxoplasmosis
Syphilis
 Diabetes
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Plants
 Skunk cabbage
(Veratrum californicum)
– sheep & cattle
 Parasites (frogs)
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Medical Drugs
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Antibiotics (tetracylines)
Anticancer drugs
Anticonvulsants (Valproic Acid)
Lithium
Retinoids (Vitamin A)
Thalidomide
Diethylstilbestrol (DES)
Anticoagulants (Warfarin)
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Recreational Drugs
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Alcohol (ethanol)
Tobacco
Cocaine
Solvent abuse
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Case Studies
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Thalidomide
Ethanol (Alcohol)
Methylmercury
Lead
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Thalidomide
 Introduced in 1956 as
sedative (sleeping pill) and to
reduce nausea and vomiting
during pregnancy
 Withdrawn in 1961
 Discovered to be a human teratogen
causing absence of limbs or limb
malformations in newborns
 5000 to 7000 infants effected
 Resulted in new drug testing rules
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Discharge into Minamata Bay
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with HG
Fetal Effects of MeHg
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Life-Long Effects of MeHg
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Hg - Inorganic & Organic
Hg
Inorganic – Quick Silver
Hg
CH3
Organic – Methyl Mercury
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The Mercury Cycle
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Mercury & Toxicology
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Atmospheric Hg
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WA State Advisory
Limit the amount of canned tuna you
eat, based on your bodyweight.
Guidelines are: Women of childbearing age should limit the amount
of canned tuna they eat to about one can per week (six ounces.) A
woman who weighs less than 135 pounds should eat less than one
can of tuna per week. Children under six should eat less than one
half a can of tuna (three ounces) per week. Specific weekly limits for
children under six range from one ounce for a twenty pound child,
to three ounces for a child weighing about sixty pounds.
http://www.doh.wa.gov/fish/FishAdvMercury.htm
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WA State Advisory
Washington State Mercury Chemical
Action Plan
http://www.ecy.wa.gov/biblio/0203016.html
Legislature saves effort to tackle toxic flame
retardants
http://www.ecy.wa.gov/../news/2004news/../2004news/200
4-051.html
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Alcohol
H
H
H
C
C
H
H
(CH3-CH2OH)
OH
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FAS Child
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Ethanol (Alcohol)
 The common preventable cause of
adverse fetal development
 Fetal Alcohol Syndrome (FAS) first
described in 1970’s
 Symptoms included facial deformities,
growth retardation, sever nervous
system effects and reduced intelligence
 4,000-12,000 infants per year in US
 Fetal Alcohol Effect (FAE) – milder form
but still serious nervous system effects
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Fetal Alcohol Syndrome (FAS)
Most common preventable cause of
adverse CNS development
4,000-12,000 infants per year in US
Characteristics
Growth retardation
Facial malformations
Small head
Greatly reduce intelligence
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Fetal Alcohol Effect (FAE)
Milder form of FAS
7,000-36,000 infants per year in US
1 to 3 infants per 1,000 world wide??
Characteristics
Growth deficiency
Learning dysfunction
Nervous systems disabilities
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Policy Approaches
•
1981 - U.S. Surgeon General first advised that
women should not drink alcoholic beverages
during pregnancy.
•
1988 - U.S. requires warning labels on all
alcoholic beverages sold in the United States.
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1990 - U.S. Dietary Guidelines state that women
who are pregnant or planning to become
pregnant should not drink alcohol.
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1998 - 19 states require the posting of alcohol
health warning signs where alcoholic beverages
are sold
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Lead History
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6500 BC. - Lead discovered in Turkey, first mine.
100 BC. - Greek physicians give clinical description of
lead poisoning.
1904 - Child lead poisoning linked to lead-based paints.
1922 - League of Nations bans white-lead interior paint;
U.S. declines to adopt
1923 - Leaded gasoline goes on sale in selected markets
1971- U.S. Lead-Based Paint Poisoning Prevention Act
passed
1923 - Leaded gasoline goes on sale in selected markets
1986 - Primary phase out of leaded gas in US completed
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Ancient Awareness
"Lead makes the
mind give way."
Greek
Dioscerides - 2nd BC
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Lead In Homes
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Lead in Families
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Agency Blood Lead Levels
Blood Lead (ug/dl)
Acceptable Childhood Blood Lead Levels
40
35
40
30
30
25
25
20
15
20
15
10
10
5
0
CDC
1973
CDC
1975
CDC
1985
WHO
1986
EPA
1986
CDC
1990
Agency and Year
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Lead Health Effects
 Children more vulnerable than adults
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Orally consumed lead absorbed in place of calcium
CHILDREN absorb 30-50% of oral lead
ADULTS absorb 5-10% of oral lead
Increased absorption during pregnancy
 Childhood effects
• Decreased intelligence (lower grades)
• Hyperactivity (higher school dropout rate)
• Growth retardation
• Effects at blood lead levels of 10 µq/dl
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Recycling Lead
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Risk Assessment
Process of estimating
association between an
exposure to a chemical or
physical agent and the
incidence of some adverse
outcome.
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Risk of What?
Obvious
Death, Cancer, Acid burn, Birth defect,
asthma,
Subtle
Decreases in learning and memory (lead),
Sensitivity of the individual (child)
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Risk Management
Policy developed to deal with
hazards identified through risk
assessment
Process of evaluating alternative
regulatory options and selecting
among them
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“The Commons”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
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Technical Solutions
“It is our considered
professional judgment that
this dilemma has no
technical solution.”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
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Problems – Solutions?
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Lead and kids
Fetal alcohol syndrome
Nuclear disarmament
Bioterrorism
Ocean Fisheries
Persistent chemicals
The Commons
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Freedom?
Hegel –
“Freedom is the
recognition of necessity”
Restriction of Freedom?
The Managed Commons?
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Business Goals
1.Grow
2.Reduce Costs
3.Increase Revenue
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Adam Smith
The Wealth of Nations - 1776
“the invisible hand”
“an individual who intends
only his own gain is led by an
invisible hand to promote …
the public interest”
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Socially responsible white guys?
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Scientific Process
Variability
Uncertainty
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Human Epidemiological
Human Studies
Does the chemical or agent causes
adverse effect in human
populations?
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Pros and Cons - Humans
Advantages
 Yields information in humans
 Yields associations relevant to “real
world” exposures
Disadvantages
 Can be very expensive (large N, many
years)
 Lack control relative to lab
 Many confounding variables
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Human Variability
Human Subject Variability
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Lifestyle – risk of exposure to ….
Occupation – risk of exposure to ….
Breathing & digestion – uptake of chemicals
Metabolism & kidney function – elimination
Age, gender & disease – susceptibility to
toxicity
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Examples of Variability
• Occupational – exposure to multiple
chemicals
• Lung function and susceptibility are altered
by smoking or asthma
• Disease effects liver function
The overall dose-response behavior is subject
to both intra-individual and inter-individual
variability.
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Uncertainty
• Measurements error in experiments
• Extrapolation from animal studies to
human
• Sample sizes for animal and human
studies
• Selection of endpoint
• Intra and inter subject variability
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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.
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Safety & Efficacy vs Harm
 FDA regulations of Drugs (1938)
 FDA regulations of Dietary
Supplements (Dietary Supplement
Health and Education Act of 1994
(DSHEA))
 Ephedra present an unreasonable risk
of illness or injury (Dec, 2003)
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A Tool
 Precautionary Principle is a tool to
assist in an integrated assessment
of the human health,
environmental issues, scientific
facts, uncertainty, and alternatives
as well as the ethical, legal and
social implications of any
decisions.
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Central components
• Taking preventive action in the face of
uncertainty
• Shifting the burden of proof to the
proponents of an activity
• Exploring a wide range of alternatives to
possibly harmful actions
• Increasing public participation in decision
making
Wingspread Conference, 1998.
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Purpose/Objectives
 Improve decision making
 Promote integrated assessments
 Promote transparency
 Promote sharing of information
 Examine alternatives
 Examine uncertainties
 Encourage discussion among
stake holders
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Seattle Initiative
City Comprehensive Plans
• Every citizen of Seattle has an
equal right to a healthy and safe
environment.
• Seattle sees the Precautionary
Principle approach as its policy
framework to develop laws for a
healthier and more just Seattle.
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Advantages of Initiative
• Broad philosophical statement
• Provides common decision
making platform across
government departments
• Something many groups can
unite behind – Collaborative on
Health and the Environment –
(CHE-NW)
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Knowledge - Responsibility
• Children have a right to a safe, fair
and healthy environment
• Ethical Responsibility to share
and use of knowledge
• Duty to promote health and well
being of children
• Thoughtful public health advocate
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Socially Responsible Actions
• Testifying
• Writing review papers
• K-12 class room
teaching
• Adding expertise to
community groups
• Education
• Mentoring
• Speakers Bureau
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The Potential of Children
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Socially Responsible
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ELSI of Toxicology and Kids
Questions or Comments?
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Additional Information
 The Science and Environmental Health
Network (SEHN) (www.sehn.org)
 Late lessons from early warnings: the
precautionary principle 1896-2000 –
European Environment Agency (free)
(http://reports.eea.eu.int/environmental_issue_report_2001_22/en)
 Garrett Hardin - The Tragedy of the
Commons (Science, 1968)
 Ethics and Environmental Health – Mini
Monograph - Environmental Health
Perspectives (November 2003)
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Authorship Information
Steven G. Gilbert, PhD, DABT
Director, INND
8232 14th Ave NE Seattle, WA
Ph: 206.527.0926
Fx: 206.525.5102
E-mail: sgilbert@innd.org
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Biomedical Ethics
• Respect for Autonomy
• Nonmaleficence
• Beneficence
• Justice
Beauchamp and Childress, 1994
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