A Small Dose of Toxicology Children & Environment – 6/25/05 Children: The Health Effects of A Small Dose of Chemicals A Small Dose of Toxicology Steven

A Small Dose of Toxicology Children & Environment – 6/25/05

Children: The Health Effects of A Small Dose of Chemicals

A Small Dose of Toxicology

Steven G. Gilbert, PhD, DABTwww.asmalldoseof.org

Children and Their EnvironmentJune 25, 2005


A Small Dose of Toxicology

See: www.asmalldoseof.org -- smdose


Child Health


"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

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 & Human Health


• Hong Kong

• Princess Diana

• Ambassador to Mexico

• Coeur d’Alene, Silver Valley, ID

• Tacoma

• Seattle Schools

• $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


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 Children & Environment – 6/25/05FAS Child


Fetal Effects of MeHg


The Mercury Cycle


A Small Dose of Lead


Lead In Homes


Lead History

Greek 2nd BC

Lead Makes the Mind Give Way


Lead in Families


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


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


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


“Conclusions: Blood lead concentrations, even those below 10 mgc/dL, are inversely

associated with children’s IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than

at higher concentrations. These findings suggest that more U.S. children may be

adversely affected by environmental lead than previously estimated.”

Canfield et al. 2003, NEJM, 384

Canfield et al…, 2003


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

Half-life Of Lead


Lead Based Paint

1887 - US medical authorities diagnose childhood lead poisoning

1904 - Child lead poisoning linked to lead-based paints

1909 - France, Belgium and Austria ban white-lead interior paint

1914- Pediatric lead-paint poisoning death from eating crib paint is described

1921 - National Lead Company admits lead is a poison

1922 - League of Nations bans white-lead interior paint; US declines to adopt

1943- Report concludes eating lead paint chips causes physical and neurological disorders, behavior, learning and intelligence problems in children

1971- Lead-Based Paint Poisoning Prevention Act passed


Lead Industry Advertisements

http://www.cincinnatichildrens.org/research/project/enviro/hazard/lead/lead-advertising/default.htm

History of Lead Industry Advertisements (LINK)

http://www.cincinnatichildrens.org/research/project/enviro/hazard/lead/lead-advertising/default.htm


Lead-associated Reading Deficits in U.S. Children

75

80

85

90

95

100

105

<2.5 2.5 5 7.5 10

Blood lead levels (g/dl)

Rea

ding

Sco

re

Lanphear BP, et al. Public Health Reports 2000;115:521-529. (BL’s slide)


Canfield R, et al. NEJM 2003;348:1517-1526

IQ and Blood Lead

Life time overall• Increase in 1 mcg/dl = 0.87 IQ drop• Covariates - 1 mcg/dl = 0.46 IQ drop

1 to 10 mcg/dl (bigger drop)• Increase in 1 mcg/dl = 1.37 IQ drop• Non-linear - 1 mcg/dl = 7.4 IQ drop


Environmental Pollutants and Disease in American Children: Estimates of

Morbidity, and Costs for Lead Poisoning, Asthma, Cancer, and Developmental

Disabilities, by Landrigan, P. et al. EHP, 110, July 2002, 721-728.

Cost of Childhood Lead

Assumptions in calculating costs

• All lead is harmful and from environment

• Blood lead of children age 5 – 2.7 ug/dl (CDC)

• 5-year old boys (1,960,200) and girls (1,869,800)

• 1 ug/dl of lead = 0.25 IQ point reduction

• Cost – boys $27.8 and girls $15.6 Billion

Total Costs $43.4 Billion


Current CDC Policy

Blood lead level µg/dL)b

ActionsTime frame for beginning intervention

10-14 Provide caregiver lead education. Provide follow-up testing. Refer the child for social services if necessary.

Within 30 days

15-19 Above actions, plus:If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs 20-44.

Within 2 weeks

20-44 Above actions, plus:Provide coordination of care (case management).Provide clinical evaluation and care.c

Provide environmental investigation and control currentlead hazards.

Within 1 week

45-70 Above actions. Within 48 hours

70 or higher Above actions, plus hospitalize child for chelation therapy immediately.

Within 24 hours


Proposed CDC PolicyBlood lead level (µg/dL)

Actions Time frame for beginning intervention

<2 No action

2-5 Provide caregiver lead education. Provide follow-up testing. Refer the child for social services to investigate possible sources of lead exposure.

Within 30 days

5-10 Above actions, plus:If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs 10-20.

Within 2 weeks

10-20 Above actions, plus: Provide coordination of care (case management). Provide clinical evaluation and care. Provide environmental investigation and control current lead hazards.

Within 1 week

20-70 Above actions. Within 24 hours

70 or higher Above actions, plus hospitalize child for chelation therapy immediately.

Within 24 hours


Recycling Lead


Precautionary Principle

“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.


• 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 Potential of Children


Principles of Toxicology

www.asmalldoseof.org


Additional Information

• A Small Dose of Toxicology www.asmalldoseof.org

• Inst. Children’s Env Health (ICEH) –www.iceh.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”


An Introduction To The Health Effects of

Arsenic (As)

A Small Dose of ™ Arsenic


A Therapeutic Agent and A Poison

2400 Years Ago

In Greece and Rome

Ancient Awareness


For many years used to treat syphilis and amebic dysentery

But caused skin cancer in patients treated with arsenicals

Historical Awareness


• By product of smelting for cooper, lead, zinc• Last smelter in Tacoma Washington closed

in 1985 – still dealing with pollution issues • Annual use 20,000 tons imported

Production


Chronic exposure (drinking water)• Skin cancer (recognized 100 years ago)• Garlic odor on breath• Excessive perspiration • Muscle tenderness and weakness• Changes in skin pigmentation• Paresthesia in hands and feet • Peripheral vascular disease• Gangrene of feet – Blackfoot disease

Chronic - Toxicity


Exposure

Drinking water Burning arsenic treated

wood Handling treated wood


US Arsenic Map


Arsenic in drinking water is a worldwide human health hazard

Avoid the use of arsenic treated wood

Reduce or avoid arsenic exposure

Summary


Children with >10 mcg/dL

In 1999 and 2000, 2.2% of children 1-5 year age had lead levels that were above 10 mcg/dL.

Approximately 20 million children under age 5, thus about 440,000 children in the US have blood lead levels above 10 mcg/dL.

From CDC

Documents

A Small Dose of Toxicology Children & Environment – 6/25/05 Children: The Health Effects of A Small Dose of Chemicals A Small Dose of Toxicology Steven