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?

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

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Withdrawn in 1961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?

CH

H

H

OHC

H

H

(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

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 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

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


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)


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

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


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


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


N

NN

N

CH3

CH3

CH3

O

O

1

3

7

Caffeine - 1,3,7 Trimethylxanthine


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


• Young or Old

• Male or Female

• Individual Variability

• Genetics Differences

• Species Differences

Susceptibility & Variability


N

CH3N

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: [email protected]: 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...

Documents

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