Ethical, Legal, and Social Issues Related to DART

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Ethical, Legal, and Social Issues Related to DART
ELSI Children Toxicology
Reproductive Developmental Toxicology
Pharmaceutical, Environmental, and Legal
Considerations Northern and Southern California
Chapters of the Society of Toxicology - Fall 2004
Meeting Sept 30 Oct 1, 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 Reproductive and Developmental
  Toxicology
• Policy Approach within an ethical framework
• Social responsibilities
• No technical solutions
• Restriction of freedoms
• Precautionary Principle

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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?id0900f3ec8000e044
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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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American Academy of Pediatrics
The APA goes on to state To this purpose, the
AAP and its members dedicate their efforts and
resources. The vision 1) to advocate for
infants, children, adolescents, and young adults
and provide for their care 2) to collaborate
with others to assure child health and .
http//www.aap.org/member/memcore.htm
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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

• Dose Response Issues
• Higher metabolic rate
• Different nutritional requirements
• Rapidly dividing migrating cells
• Immature organs

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Sequence of Human Development
Red - most sensitive, Gray - Less
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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
• 1830s - Etienne Geoffroy Saint-Hilaire
  experimented with chicken eggs
• 1900s began acceptance of malformations related
  to genetics
• 1940s - Josef Warkany environmental factors
  affect rat development

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Historical Events

• 1941 Human malformations linked to rubella
  virus
• 1960s Thalidomide (a sedative and anti-nausea
  drug) found to cause human malformations
• 1950s Methylmercury recognized as
  developmental toxicant
• 1970s Alcohol related to developmental effects
  Fetal Alcohol Syndrome (FAS)

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Case Studies

• Thalidomide
• Methylmercury
• Lead
• Ethanol (Alcohol)
• PBDEs

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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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Fetal Effects of MeHg
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The Mercury Cycle
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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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San Francisco Hg TMDL
San Francisco Bay Regional Water Quality Control
Board. San Francisco Bay Mercury Total Maximum
Daily Load (TMDL) Numeric targets for mercury
concentrations in suspended sediment fish tissue,
and berg eggs
http//www.swrcb.ca.gov/rwqcb2/sfbaymercurytmdl.ht
m
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Lead In Homes
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Lead History

• 6500 BC. - Lead discovered in Turkey, first mine.
  
• 500 BC-300 AD.- Roman lead smelting produces
  dangerous emissions.
• 100 BC. - Greek physicians give clinical
  description of lead poisoning. Lead makes the
  mind give way.
• 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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Workplace Lead
Health of lead exposure on workers in London -
Steel dust, stone dust, clay dust, alkali dust,
fluff dust, fiber dust- all these things kill,
and they are more deadly than machine-guns and
pom-poms. Worst of all is the lead dust in the
white lead trades. 1903 book The People of
the Abyss Jack London
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Agency Blood Lead Levels
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Alcohol
(CH3-CH2-OH)
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FAS Child
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FAS FAE
Most common preventable cause of adverse CNS
development Fetal Alcohol Syndrome
(FAS) 4,000-12,000 infants per year in US Fetal
Alcohol Effect (FAE) 7,000-36,000 infants per
year in US 1 to 3 infants per 1,000 world wide??
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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.
• 1990 - U.S. Dietary Guidelines state that women
  who are pregnant or planning to become pregnant
  should not drink alcohol.
• 1998 - 19 states require the posting of alcohol
  health warning signs where alcoholic beverages
  are sold

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Structure of PBDEs
PolyBrominated Diphenyl Ether
X Y are number of Bromine atoms Common Penta,
Octa, and Deca
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PBDEs in House Dust (ppb)
From EWG - Toxic Fire Retardants Contaminate
American Homes - http//www.ewg.org/reports/inthed
ust/summary.php
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PBDEs in Breast Milk (ppb)
From EWG - Toxic Fire Retardants in Breast Milk
from American Mothers - http//www.ewg.org/reports
/mothersmilk/es.php
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PBDEs California Status

• Legislation to ban - Penta and Octa-PBDE
• Did not ban Deca-PBDE
• Must report amount of electronic waste and toxic
  chemicals in waste such as PBDEs, metals

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Scientific Process
Variability Uncertainty
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Types of Uncertainty

• Statistical
• Model
• Fundamental

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Statistical Uncertainty
Reducing Variability

• Easiest to examine reduce
• Not knowing the exact value of a variable (inter
  and intra subject variance)
• Sample size

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Model or System Uncertainty

• Not fully understanding the relations between
  variables (mechanism of action)
• Which variables are most important (high dose vs
  low dose)

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Fundamental Uncertainty

• Not knowing the right questions to ask
• Most sensitive end point
• we dont know what we dont know

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Sir Austin Bradford Hill
"All scientific work is incomplete - whether it
be observational or experimental. All scientific
work is liable to be upset or modified by
advancing knowledge. That does not confer upon us
a freedom to ignore the knowledge we already have
or postpone the action that it appears to demand
at a given time. " Sir Austin Bradford Hill
(1965)
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Determining Causation

• Strength of association
• Consistency of findings
• Biological gradient
• Temporal sequence
• Biologic or theoretical plausibility
• Coherence with established knowledge
• Specificity of association
• Sir Austin Bradford Hill (1965)

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Socially responsible white guys?
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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?

• Lead and kids
• Fetal alcohol syndrome
• Nuclear disarmament
• Bioterrorism
• Ocean Fisheries
• Persistent chemicals
• The Commons

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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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Central components

• Taking preventive action in the face of
  uncertainty
• Shifting the burden of proof/responsibility 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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Values of the precautionary principle
1) Respect - for the needs and rights of this and
future generations as well as others who cannot
speak for themselves 2) Humility - towards the
natural world and our ability to understand it
through science 3) Democracy - giving people a
voice in matters that affect their lives 4)
Responsibility - governments public trust
responsibility to manage the commonwealth for
this and future generations. - Individuals
including industry, obligation to take
responsibility for their actions in the world.
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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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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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Citizen Toxicologist
Socially Responsible Toxicologist
The citizen toxicologist is a thoughtful advocate
for human and environmental health, who strives
to share their scientific knowledge with the
public, speaking to public interests rather than
private or special interests.
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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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SOT - ESLI Specialty Section

• Forum in which to discuss the ethical
  implications of results from our science as well
  as the resulting legal and social implications.
• 2005 SOT meeting workshop on Conflict of
  Interest

http//www.toxicology.org/memberservices/specsecti
on/specsection.html
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The Potential of Children
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ELSI - Children Toxicology
Questions or Comments?
Download Presentation from www.asmalldoseof.org
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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_issu
  e_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_at_innd.org www.asmalld
oseof.org