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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
A Small Dose of Toxicology Intro Principles of Toxicology
Child Health
A Small Dose of Toxicology Intro Principles of Toxicology
The study of poisonsor
the adverse effects of chemical and physical agents on living
organisms.
Toxicology Definitions
A Small Dose of Toxicology Intro Principles of Toxicology
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
A Small Dose of Toxicology Intro Principles of Toxicology
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
A Small Dose of Toxicology Intro Principles of Toxicology
“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
A Small Dose of Toxicology Intro Principles of Toxicology
• 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?
A Small Dose of Toxicology Intro Principles of Toxicology
Who are these white guys?
A Small Dose of Toxicology Intro Principles of Toxicology
“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
A Small Dose of Toxicology Intro Principles of Toxicology
What Is This?
N
NN
N
CH3
CH3
CH3
O
O
1
3
7
A Small Dose of Toxicology Intro Principles of Toxicology
Key Words
Risk =
Hazard X Exposure
Dose / Response
Individual Sensitivity
A Small Dose of Toxicology Intro Principles of Toxicology
“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
A Small Dose of Toxicology Intro Principles of Toxicology
“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
A Small Dose of Toxicology Intro Principles of Toxicology
Neuron
A Small Dose of Toxicology Intro Principles of Toxicology
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
A Small Dose of Toxicology Intro Principles of Toxicology
What Is This?
CH
H
H
OHC
H
H
(CH3-CH2-OH)
A Small Dose of Toxicology Intro Principles of Toxicology
Effects of Prenatal Alcohol
A Small Dose of Toxicology Intro Principles of ToxicologyFAS Child
A Small Dose of Toxicology Intro Principles of Toxicology
Mouse – Scanning EM
A Small Dose of Toxicology Intro Principles of Toxicology
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??
A Small Dose of Toxicology Intro Principles of Toxicology
• 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 Toxicology Intro Principles of Toxicology
A Small Dose of Lead
A Small Dose of Toxicology Intro Principles of Toxicology
Lead In Homes
A Small Dose of Toxicology Intro Principles of Toxicology
Lead History
Greek 2nd BC
Lead Makes the Mind Give Way
A Small Dose of Toxicology Intro Principles of Toxicology
Lead - Absorption
Orally Consumed Lead Absorbed In Place of Calcium
CHILDREN – 30-50% OF LEADADULTS – 5-10% OF LEAD
Increased During Pregnancy
A Small Dose of Toxicology Intro Principles of Toxicology
Children Vulnerability
CHILDREN are more vulnerable exposure than ADULTS
Size Consume More Food
Inhale More AirDeveloping Nervous SystemIncreased need for Calcium
A Small Dose of Toxicology Intro Principles of Toxicology
Agency Blood Lead Levels
60
40
3025
2015
10
20
10
20
30
40
50
60
Blo
od
Lea
d (
ug
/dl)
CDC1960
CDC1973
CDC1975
CDC1985
WHO1986
EPA1986
CDC1990
CDC2006?
Agency and Year
Acceptable Childhood Blood Lead Levels
A Small Dose of Toxicology Intro Principles of Toxicology
A Small Dose of Mercury
A Small Dose of Toxicology Intro Principles of Toxicology
The Mercury Cycle
A Small Dose of Toxicology Intro Principles of Toxicology
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
A Small Dose of Toxicology Intro Principles of Toxicology
Structure of PBDEs
X & Y are number of Bromine atomsCommon Penta, Octa, and Deca
PolyBrominated Diphenyl Ether
O
BrxBry
A Small Dose of Toxicology Intro Principles of Toxicology
PBDEs in House Dust (ppb)
From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php
A Small Dose of Toxicology Intro Principles of Toxicology
PBDEs in Breast Milk (ppb)
From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php
A Small Dose of Toxicology Intro Principles of Toxicology
PBDEs In Milk Fat
PBDE in milk fat - Puget Sound mothers
13 13 1326
50 56
117126
156
0
25
50
75
100
125
150
175
1 2 3 4 5 6 7 8 9
Sample Number
pp
b in
Milk
Fat
(adapted from Northwest Environmental Watch, 2004)
A Small Dose of Toxicology Intro Principles of Toxicology
Pollution in People
http://www.pollutioninpeople.org/
A Small Dose of Toxicology Intro Principles of Toxicology
Key Words
Risk =
Hazard X Exposure
Dose / Response
Individual Sensitivity
A Small Dose of Toxicology Intro Principles of Toxicology
Effects of Amount on Response
A Small Dose of Toxicology Intro Principles of Toxicology
Effects of Size on Response
A Small Dose of Toxicology Intro Principles of Toxicology
Glasses of Wine - Dose Response
0
25
50
75
100
0 1 2 3 4 5 6 7 8
Glasses of Wine
% D
iffi
cult
y W
alki
ng
All Effected
NO Effect
Amount half are effected
A Small Dose of Toxicology Intro Principles of Toxicology
Dose (mg/kg body weight)Increasing dose
Dose Response Function
0
25
50
75
100
0 10 20 30 40 50 60 70 80 90 100
% R
esp
on
se
NO Effect
All Effected
Half Effected
A Small Dose of Toxicology Intro Principles of Toxicology
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)
A Small Dose of Toxicology Intro Principles of Toxicology
1) Skin (dermal)
2) Lung (inhalation)
3) Oral (gut)
Route of exposure
Exposure & Absorption
A Small Dose of Toxicology Intro Principles of Toxicology
Number of Times
Time Between
4 Beers in an hour or4 Beers in 4 Days
Frequency Of Exposure
A Small Dose of Toxicology Intro Principles of Toxicology
Acute Exposure
Sub-chronic Exposure
Chronic Exposure
Duration Of Exposure
A Small Dose of Toxicology Intro Principles of Toxicology
Where It Goes
(body water, fat, bone)
Where It Accumulates
Distribution
A Small Dose of Toxicology Intro Principles of Toxicology
How The Body Breaks It Down
What It Turns Into
How Fast It Does It
Metabolism
A Small Dose of Toxicology Intro Principles of Toxicology
N
NN
N
CH3
CH3
CH3
O
O
1
3
7
Caffeine - 1,3,7 Trimethylxanthine
A Small Dose of Toxicology Intro Principles of Toxicology
Co
nce
ntr
atio
n (
µg
/ml)
Time (hrs)
How Long It Takes To Go
Half-life
02
46
810
1214
0 1 2 3 4 5 6 7 8 9 10 11
A Small Dose of Toxicology Intro Principles of Toxicology
• Young or Old
• Male or Female
• Individual Variability
• Genetics Differences
• Species Differences
Susceptibility & Variability
A Small Dose of Toxicology Intro Principles of Toxicology
N
CH3N
What Is This?
A Small Dose of Toxicology Intro Principles of Toxicology
The Potential of Children
A Small Dose of Toxicology Intro Principles of Toxicology
Principles of Toxicology
A Small Dose of Toxicology Intro Principles of Toxicology
Additional Information
• A Small Dose of Toxicology• www.asmalldoseof.org
A Small Dose of Toxicology Intro Principles of Toxicology
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”
A Small Dose of Toxicology Intro Principles of Toxicology
Pesticide Application
A Small Dose of Toxicology Intro Principles of Toxicology
Classes Of Pesticides
Insecticides (kill insects)• Organochlorines• Organophosphates• Carbamates• Synthetic Pyrethroids
Herbicides (kill plants) Rodenticides (kill rodents) Fungicides (kill fungus) Fumigants (kill whatever)
A Small Dose of Toxicology Intro Principles of Toxicology
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
A Small Dose of Toxicology Intro Principles of Toxicology
• 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)