A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Toxicology An Introduction to the Health Effects of Common Chemicals and A Bit of Ethics

A Small Dose of Toxicology Texas A&M – 2/21/05

A Small Dose of Toxicology

An Introduction to the Health Effects of Common Chemicals

and A Bit of Ethics

Steven G. Gilbert, PhD, DABT“A Small Dose of Toxicology”

www.asmalldoseof.org

College of Veterinary MedicineTexas A&M, College Station

February 21, 2005


A Small Dose of Toxicology

See: www.asmalldoseof.org -- smdose


Child Health


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


• 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

Convergence of Issues


Socially Responsibility

What is social responsibility?

What are our responsibilities to society?


"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

The First Bioethicist

---------- 1887 - 1948 ----------

Aldo Leopold


“An ethic, ecologically, is a limitation on freedom of action in the struggle for

existence”Aldo Leopold

Limits on Freedom


“The Commons”

The Tragedy of the CommonsBy Garrett Hardin, Science, 1968


Technical Solutions

“It is our considered professional judgment that

this dilemma has no technical solution.”

The Tragedy of the CommonsBy Garrett Hardin, Science, 1968


Problems – Solutions?

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


The study of poisonsor

the adverse effects of chemical and physical agents on living

organisms.

Toxicology Definitions


399 BC Death of Socrates by HemlockSocrates 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.

Ancient Awareness


From Romeo and Juliet - act 5Come bitter pilot, now at once run on

The dashing rocks thy seasick weary bark!

Here’s to my love! O true apothecary!

Thy drugs are quick. Thus with a kiss I die.

Shakespeare (1564-1616)

Historical Awareness


“Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.”

Steven G. Gilbert, 1999

Environmental Health


• Hong Kong

• Princess Diana

• Ambassador to Mexico

• Coeur d’Alene, Silver Valley, ID

• Tacoma

• $100 Billion, $65 Billion

• Food, noise, dust

• 11,000 to 689,000 Children

What do these have in common?


Who are these white guys?


What Is This?

N

NN

N

CH3

CH3

CH3

O

O

1

3

7


Key Words

Risk =

Hazard X Exposure

Dose / Response

Individual Sensitivity


“All substances are poisons; there is none which is not a

poison. The right dose differentiates

a poison from a remedy.”

Paracelsus (1493-1541)

Paracelsus


“The sensitivity of the individual differentiates a poison from a remedy.

The fundamental principle of toxicology is the individual’s response to a dose.”

S. G. Gilbert (1997)

An Individual View


Case Studies

Thalidomide Ethanol (Alcohol) Methylmercury Lead PBDEs


Effects of Amount on Response


Effects of Size on Response


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


What Is This?

CH

H

H

OHC

H

H

(CH3-CH2-OH)


Effects of Prenatal Alcohol

A Small Dose of Toxicology Texas A&M – 2/21/05FAS Child


Mouse – Scanning EM


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??


• 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

Policy Approaches


Are we doing enough?

Given what we know about the fetal effects of alcohol are we doing enough?


A Small Dose of Lead


Lead In Homes


Lead History

Greek 2nd BC

Lead Makes the Mind Give Way


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


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

Lead Out of Gasoline


Lead - Absorption

Orally Consumed Lead Absorbed In Place of Calcium

CHILDREN – 30-50% OF LEADADULTS – 5-10% OF LEAD

Increased During Pregnancy


• 25 DAYS -- BLOOD• 40 DAYS -- SOFT TISSUE • 20 YEARS -- BONE

Half-life Of Lead


Lead in Families


40

30

25

20

15

10

0

5

10

15

20

25

30

35

40

Blo

od

Lea

d (

ug

/dl)

CDC1973

CDC1975

CDC1985

WHO1986

EPA1986

CDC1990

Agency and Year

Acceptable Childhood Blood Lead Levels

CDC Blood Lead Levels



CDC Lead level 10 to 2 Mcg/dL?

Lead in the drinking water of Seattle schools!

SB 5189 Reducing childhood lead exposure


A Small Dose of Mercury

A Small Dose of Toxicology Texas A&M – 2/21/05Polluting with HG

Discharge in Minamata Bay


Fetal Effects of MeHg


Life-Long Effects of MeHg


The Mercury Cycle


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.

WA State Advisory

http://www.doh.wa.gov/fish/FishAdvMercury.htm



Mercury in our fish

Restrictions on eating fish


Structure of PBDEs

X & Y are number of Bromine atomsCommon Penta, Octa, and Deca

PolyBrominated Diphenyl Ether

O

BrxBry


PBDEs in House Dust (ppb)

From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php


PBDEs in Breast Milk (ppb)

From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php


Legislation to ban - Penta and Octa-PBDE

Did not ban Deca-PBDEMust report amount of electronic

waste and toxic chemicals in waste such as PBDEs, metals

PBDEs – California Status


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

PBDEs – WA State Status


Socially responsible white guys?


“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.

Precautionary Principle


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)

Safety & Efficacy vs Harm


• 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.

Central components


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 - government’s 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.

Values of the precautionary principle


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.

Seattle Initiative


• 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

Knowledge - Responsibility


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.

Citizen Toxicologist

Socially Responsible Toxicologist


• Testifying

• Writing review papers

• K-12 class room teaching

• Adding expertise to community groups

• Education

• Mentoring

• Speakers Bureau

Socially Responsible Actions


• 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

SOT - ESLI Specialty Section

http://www.toxicology.org/memberservices/specsection/specsection.html


The Potential of Children


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


Principles of Toxicology


Additional Information

A Small Dose of Toxicologywww.asmalldoseof.org


Authorship Information

For Additional Information ContactSteven G. Gilbert, PhD, DABT

E-mail: [email protected]: www.asmalldoseof.org

This presentation is supplement to “A Small Dose of Toxicology”


• Dose Response Issues

• Higher metabolic rate

• Different nutritional requirements

• Rapidly dividing & migrating cells

• Immature organs

Susceptibility of Children


“Children can develop and mature in an

environment that allows them to reach and maintain their full

potential.”

Vision for Child Health

Documents

A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Toxicology An Introduction to the Health Effects of Common Chemicals and A Bit of Ethics