A Small Dose of Toxicology Intro Principles of Toxicology A Small Dose of Toxicology Introduction to...

A Small Dose of Toxicology Intro Principles of Toxicology

A Small Dose of Toxicology

Introduction to the Health Effects of

Chemicals

Steven G. Gilbert, PhD, DABT

www.asmalldoseof.orgwww.toxipedia.org

Child Health

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

Human & 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?

“It is not the truth that makes you free. It is your possession of the power to discover the truth. Our dilemma is that we do not know how to provide that power.”

Richard Lewontin (New York Review of Books, Jan 7, 1997)

Power To Discover The Truth

What Is This?

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

A Small Dose of Toxicology Intro Principles of ToxicologySuperman

Neuron

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Withdrawn in 1961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?

(CH3-CH2-OH)

Effects of Prenatal Alcohol

A Small Dose of Toxicology Intro Principles of ToxicologyFAS 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

A Small Dose of Lead

Lead In Homes

Lead History

Greek 2nd BC

Lead Makes the Mind Give Way

Lead - Absorption

Orally Consumed Lead Absorbed In Place of Calcium

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

Increased During Pregnancy

Children Vulnerability

CHILDREN are more vulnerable exposure than ADULTS

Size Consume More Food

Inhale More AirDeveloping Nervous SystemIncreased need for Calcium

Agency Blood Lead Levels

CDC1960

CDC1973

CDC1975

CDC1985

WHO1986

EPA1986

CDC1990

CDC2006?

Agency and Year

Acceptable Childhood Blood Lead Levels

A Small Dose of Mercury

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

Structure of PBDEs

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

PolyBrominated Diphenyl Ether

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

PBDEs In Milk Fat

PBDE in milk fat - Puget Sound mothers

13 13 1326

117126

1 2 3 4 5 6 7 8 9

Sample Number

(adapted from Northwest Environmental Watch, 2004)

Pollution in People

http://www.pollutioninpeople.org/

Key Words

Risk =

Hazard X Exposure

Dose / Response

Individual Sensitivity

Effects of Amount on Response

Effects of Size on Response

Glasses of Wine - Dose Response

0 1 2 3 4 5 6 7 8

Glasses of Wine

All Effected

NO Effect

Amount half are effected

Dose (mg/kg body weight)Increasing dose

Dose Response Function

0 10 20 30 40 50 60 70 80 90 100

NO Effect

All Effected

Half Effected

Ethyl alcohol 10,000Salt (sodium chloride) 4,000Iron (Ferrous sulfate) 1,500Morphine 900Mothballs 500 (paradichlorobenzene)Aspirin 250DDT 250Cyanide 10Nicotine 1Tetrodotoxin (from fish) 0.01Dioxin (TCDD) 0.001Botulinum Toxin 0.00001Bee Venom ??

Agent LD-50 (mg/kg)

1) Skin (dermal)

2) Lung (inhalation)

3) Oral (gut)

Route of exposure

Exposure & Absorption

Number of Times

Time Between

4 Beers in an hour or4 Beers in 4 Days

Frequency Of Exposure

Acute Exposure

Sub-chronic Exposure

Chronic Exposure

Duration Of Exposure

Where It Goes

(body water, fat, bone)

Where It Accumulates

Distribution

How The Body Breaks It Down

What It Turns Into

How Fast It Does It

Metabolism

Caffeine - 1,3,7 Trimethylxanthine

Time (hrs)

How Long It Takes To Go

Half-life

0 1 2 3 4 5 6 7 8 9 10 11

• Young or Old

• Male or Female

• Individual Variability

• Genetics Differences

• Species Differences

Susceptibility & Variability

What Is This?

The Potential of Children

Principles of Toxicology

Additional Information

• A Small Dose of Toxicology• www.asmalldoseof.org

Authorship Information

For Additional Information ContactSteven G. Gilbert, PhD, DABT

E-mail: smdose@asmalldoseof.orgWeb: www.asmalldoseof.org

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

Pesticide Application

Classes Of Pesticides

Insecticides (kill insects)• Organochlorines• Organophosphates• Carbamates• Synthetic Pyrethroids

Herbicides (kill plants) Rodenticides (kill rodents) Fungicides (kill fungus) Fumigants (kill whatever)

Other Exposure

Dietary exposure• Pesticide residues on crops, dust –

hand to mouth

Community exposure• Airborne drift from commercial app

Contaminated drinking water• Leaching from soils to ground water

• Focus – long-term prevention of pest problems

• Reduce or eliminate chemical pest control methods

• Monitor for the presence of pests before treating

• Nonchemical strategies (make habitat less attractive, physical controls)

• Learn about your pests

Integrated Pest Management (IPM)

A Small Dose of Toxicology Intro Principles of Toxicology A Small Dose of Toxicology Introduction to...

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