A Small Dose of Toxicology

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A Small Dose of Toxicology
An Introduction to the Health Effects of Common
Chemicals and A Bit of Ethics
College of Veterinary Medicine Texas AM, College
Station February 21, 2005
Steven G. Gilbert, PhD, DABT A Small Dose of
Toxicology www.asmalldoseof.org
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A Small Dose of Toxicology
See www.asmalldoseof.org -- smdose
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Child Health
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Current Bioethical Issues

• Check the local news paper
• Stem cells (state, national, international)
• Genetically Engineered Organisms
• Knowing your genes
• In vetro fertilization choosing your child's
  genes and characteristics
• Global warming
• Nanotechnology
• Chemicals exposures human health
• Environmental health

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Convergence of Issues

• Expanding Knowledge of Biological sciences
  genomics, stem cells
• Ability to engineer life
• Vulnerability of Children
• Global issues warming, famine, war
• Policy Approach within an ethical framework
• Social responsibilities
• No technical solutions
• Restriction of freedoms

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Socially Responsibility
What is social responsibility? What are our
responsibilities to society?
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The First Bioethicist
Aldo Leopold
"A thing is right when it tends to preserve the
integrity, stability, and beauty of the biotic
community. It is wrong when it tends otherwise."
- Aldo Leopold, 1949, A Sand County Almanac
---------- 1887 - 1948 ----------
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Limits on Freedom
An ethic, ecologically, is a limitation on
freedom of action in the struggle for
existence Aldo Leopold
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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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Toxicology Definitions
The study of poisons or the adverse effects of
chemical and physical agents on living organisms.
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Ancient Awareness
399 BC Death of Socrates by Hemlock Socrates was
charged with religious heresy and corrupting the
morals of local youth. The active chemical used
was the alkaloid coniine which, when ingested
causes paralysis, convulsions and potentially
death.
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Historical Awareness
From Romeo and Juliet - act 5 Come bitter pilot,
now at once run on The dashing rocks thy seasick
weary bark! Heres to my love! O true
apothecary! Thy drugs are quick. Thus with a
kiss I die. Shakespeare (1564-1616)
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Environmental Health
Conditions that ensure that all living things
have the best opportunity to reach and maintain
their full genetic potential. Steven G.
Gilbert, 1999
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What do these have in common?

• Hong Kong
• Princess Diana
• Ambassador to Mexico
• Coeur dAlene, Silver Valley, ID
• Tacoma
• 100 Billion, 65 Billion
• Food, noise, dust
• 11,000 to 689,000 Children

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Who are these white guys?
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What Is This?
O
CH3
CH3
N
N
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1
3
N
O
N
CH3
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Key Words
Dose / Response

• Risk
• Hazard X Exposure

Individual Sensitivity
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Paracelsus
All substances are poisons there is none which
is not a poison. The right dose differentiates a
poison from a remedy. Paracelsus (1493-1541)
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An Individual View
The sensitivity of the individual differentiates
a poison from a remedy. The fundamental principle
of toxicology is the individuals response to a
dose. S. G. Gilbert (1997)
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Case Studies

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

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Effects of Amount on Response
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Effects of Size on Response
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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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What Is This?
(CH3-CH2-OH)
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Effects of Prenatal Alcohol
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FAS Child
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Mouse Scanning EM
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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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Are we doing enough?
Given what we know about the fetal effects of
alcohol are we doing enough?
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A Small Dose of Lead
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Lead In Homes
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Lead History
Lead Makes the Mind Give Way

• Greek 2nd BC

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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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Lead Out of Gasoline
1990 lead removed from Gasoline Between 1976
and 1994, the mean blood lead concentration in
children dropped from 13.7 mcg/dL to 3.2
mcg/dL One of the major public health triumphs
of the 20th century
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Lead - Absorption
Orally Consumed Lead Absorbed In Place of
Calcium CHILDREN 30-50 OF LEAD ADULTS 5-10
OF LEAD Increased During Pregnancy
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Half-life Of Lead
25 DAYS -- BLOOD 40 DAYS -- SOFT TISSUE 20
YEARS -- BONE
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Lead in Families
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CDC Blood Lead Levels
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Are we doing enough?
CDC Lead level 10 to 2 Mcg/dL? Lead in the
drinking water of Seattle schools! SB 5189
Reducing childhood lead exposure
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A Small Dose of Mercury
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Polluting with HG
Discharge in Minamata Bay
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Fetal Effects of MeHg
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Life-Long 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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Are we doing enough?
Mercury in our fish Restrictions on eating fish
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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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PBDEs WA State Status

• HB 1488 SB 5515 Prohibiting the sale of
  products that contain polybrominated diphenyl
  ethers.

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Socially responsible white guys?
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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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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)
• Garrett Hardin - The Tragedy of the Commons
  (Science, 1968)
• Ethics and Environmental Health Mini Monograph
  - Environmental Health Perspectives (November
  2003)
• Ethical, legal, and social issues our children's
  future. Steven G. Gilbert. Neurotoxicology, in
  press, 2005

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Principles of Toxicology
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Additional Information
A Small Dose of Toxicology www.asmalldoseof.org
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Authorship Information
This presentation is supplement to A Small
Dose of Toxicology
For Additional Information Contact Steven G.
Gilbert, PhD, DABT E-mail smdose_at_asmalldoseof.org
Web www.asmalldoseof.org
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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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Vision for Child Health
Children can develop and mature in an
environment that allows them to reach and
maintain their full potential.