Intoduction Toxicology

Limericks by Toni Hayes
Paracelsus
Paracelsus was so grandiose And perhaps just a little bit gross Manure, blood, and sand and thus you create man But what makes it a poison is dose! The Undecided Dose Too much of a thing makes you blue But not having it can kill you too Too much or too little Let's not be so fickle We'll go Dutch and divide it by two.
A Small Dose of Toxicology Intro Principles of Toxicology
A Small Dose of Toxicology
Intro Principles of Toxicology
Welcome !!

Introduction to the Health Effects of Chemicals
Steven G. Gilbert, PhD, DABT
www.asmalldoseof.org www.toxipedia.org
Objective
Increase our understanding of how chemicals affect human health.
Logistics
Course evaluation Very important Other stuff!!! Ask questions Talk to me!!!
Thanks to Organizers
Special Thank you to:
Those that really make this happen

9:00 9:10 10:30 10:45 11:45 12:00 1:00 2:00 2:45 3:00 3:30 4:15 4:30 Welcome to A Small Dose of Toxicology An Introduction to Principles of Toxicology Break Non-Cancer and Neurotoxicology Q&A Basic toxic Lunch on your own Case Study: Health Effects of Lead An Intro to Reproductive and Developmental Toxicology Break Pollution in People - Biomonitoring Precautionary Assessment Beyond Risk Assessment Questions and Answers Adjourn
All
All
An Introduction to the Principles of Toxicology

How Chemicals Affect Your Health
Steven G. Gilbert, PhD, DABT
www.asmalldoseof.org www.toxipedia.org
See: www.asmalldoseof.org -- smdose

Small Dose of Toxicology
Milestones of Toxicology
www.toxipedia.org
A free toxicology encyclopedia and resource center that anyone can edit. Toxipedia provides comprehensive, accurate, and scientifically based information on the hazards and risks of chemical and physical agents, with the goal of advancing human and environmental health. Toxipedia
Healthy World Theater

Coupling art and science to forge a more healthy and peaceful world
Healthy World Theater reaches to the heart to promote awareness and understanding through the arts to create a more healthy and peaceful world so that all creatures may reach, maintain, and enjoy their potential.
www.healthyworldtheater.org
Healthy World Theater

HWT Lyceum Sept. 29th Seattle, WA www.healthyworldtheater.org
Coupling art and science to forge a more healthy and peaceful world
NW Public Health Public Health and the Precautionary Principle

By Steven G. Gilbert
See: http://healthlinks.washington.edu/nwcphp/nph/ nwph
Child Health
So Many Chemicals so Little Data
2863 above 1 Million pounds

12 or 0.4% good data 21.4% some data
78.2% no data
www.preventingharm.org
The Consequences
Nearly 12 million children (17%) under age 18 in the US suffer from one or more developmental disabilities Learning disabilities 5-10% of kids in public school ADHD 3-6% of all school kids, maybe higher
Toxicology Definitions
The study of poisons or the adverse effects of chemical and physical agents on living organisms.
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.
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)
Human & 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
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
Who are these white guys?
Power To Discover The Truth

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)
What Is This?
O CH3 N
1 3
CH3 N
7
N CH3
Key Words
Dose / Response Risk = Hazard X Exposure Individual Sensitivity

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)
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)
Superman
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?
H H C H
H C H OH
(CH3-CH2OH)
A Small Dose of Toxicology FAS 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??
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
A Small Dose of Lead
Lead In Homes
Lead History
Lead Makes the Mind Give Way Greek

nd 2
BC
Lead - Absorption
Orally Consumed Lead Absorbed In Place of Calcium
CHILDREN 30-50% OF LEAD ADULTS 5-10% OF LEAD Increased During Pregnancy

Children Vulnerability
CHILDREN are more vulnerable exposure than ADULTS Size Consume More Food Inhale More Air Developing Nervous System Increased need for Calcium
Agency Blood Lead Levels

Acceptable Childhood Blood Lead Levels
60 60
Blood Lead (ug/dl)
50 40 30 20 10 0 CDC CDC 1960 1973 CDC CDC WHO EPA 1975 1985 1986 1986 Agency and Year CDC CDC 1990 2006? 40 30 25 20 15 10 2
A Small Dose of Mercury
The Mercury Cycle
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
Structure of PBDEs
PolyBrominated Diphenyl Ether
O
Brx
Br
y
X & Y are number of Bromine atoms Common Penta, Octa, and Deca
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
175 150 156 117 126
ppb in Milk Fat
125 100 75 50 25 0 1 2 3 4 5 6 13 13 13 26 50 56
Sample Number
A (adapted Toxicology Small Dose of from Northwest
Environmental Watch, 2004)
Pollution in People
http://www.pollutioninpeople.org/
Key Words
Dose / Response Risk = Hazard X Exposure Individual Sensitivity

Effects of Amount on Response
Effects of Size on Response
Glasses of Wine - Dose Response

All Effected
% Difficulty Walking
100 75 50 25 0 0 1 2 3 4 5 6 7 8
Amount half are effected NO Effect
Glasses of Wine
Dose Response Function

All Effected
100
% Response
75 50 25 0 0 10 20 30 40 50 60 70 80 90 100
NO Effect Half Effected
Dose (mg/kg body weight) Increasing dose

Agent
Ethyl alcohol Salt (sodium chloride) Iron (Ferrous sulfate) Morphine Mothballs (paradichlorobenzene) Aspirin DDT Cyanide Nicotine Tetrodotoxin (from fish) Dioxin (TCDD) Botulinum Toxin Bee Venom
LD-50 (mg/kg)
10,000 4,000 1,500 900 500 250 250 10 1 0.01 0.001 0.00001 ??
Exposure & Absorption

Route of exposure 1) Skin (dermal) 2) Lung (inhalation) 3) Oral (gut)
Frequency Of Exposure
Number of Times Time Between
4 Beers in an hour or 4 Beers in 4 Days
Duration Of Exposure
Acute Exposure Sub-chronic Exposure Chronic Exposure
Distribution
Where It Goes
(body water, fat, bone)
Where It Accumulates
Metabolism
How The Body Breaks It Down What It Turns Into How Fast It Does It
Caffeine - 1,3,7 Trimethylxanthine

O CH3 N
1
CH3 N
7
N CH3
Half-life
How Long It Takes To Go
Concentration (g/ml)
14 12 10 8 6 4 2 0 0 1 2 3 4 5 6 7 8 9 10 11
Time (hrs)
Susceptibility & Variability

Young or Old Male or Female Individual Variability Genetics Differences Species Differences
What Is This?
N
CH3
N
The Potential of Children
Principles of Toxicology
Additional Information
A Small Dose of Toxicology www.asmalldoseof.org
Authorship Information
This presentation is supplement to A Small Dose of Toxicology
For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org
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
Intro Principles of Toxicology A Small Dose of Toxicology
Integrated Pest Management (IPM)

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

Intoduction Toxicology

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Limericks by Toni Hayes

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

Those that really make this happen

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

A Small Dose of Toxicology

A Small Dose of Toxicology

An Introduction to the Principles of Toxicology

Steven G. Gilbert, PhD, DABT

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

See: www.asmalldoseof.org -- smdose

Small Dose of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

Healthy World Theater

Healthy World Theater

NW Public Health Public Health and the Precautionary Principle

A Small Dose of Toxicology

Intro Principles of Toxicology

So Many Chemicals so Little Data

2863 above 1 Million pounds

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

From Romeo and Juliet - act 5

A Small Dose of Toxicology

Intro Principles of Toxicology

Human & Environmental Health

A Small Dose of Toxicology

Intro Principles of Toxicology

What do these have in common?

A Small Dose of Toxicology

Who are these white guys?

A Small Dose of Toxicology

Intro Principles of Toxicology

Power To Discover The Truth

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

Dose / Response Risk = Hazard X Exposure Individual Sensitivity

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology

Intro Principles of Toxicology

A Small Dose of Toxicology