a small dose of toxicology children & environment – 6/25/05 children: the health effects of a...
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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 Children & Environment – 6/25/05
A Small Dose of Toxicology
See: www.asmalldoseof.org -- smdose
A Small Dose of Toxicology Children & Environment – 6/25/05
Child Health
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"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
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“An ethic, ecologically, is a limitation on freedom of action in the struggle for
existence”Aldo Leopold
Limits on Freedom
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“The Commons”
The Tragedy of the CommonsBy Garrett Hardin, Science, 1968
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Technical Solutions
“It is our considered professional judgment that
this dilemma has no technical solution.”
The Tragedy of the CommonsBy Garrett Hardin, Science, 1968
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Problems – Solutions?
Lead and kids Fetal alcohol syndrome Nuclear disarmament Bioterrorism Ocean Fisheries Persistent chemicals The Commons
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The study of poisonsor
the adverse effects of chemical and physical agents on living
organisms.
Toxicology Definitions
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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 Children & Environment – 6/25/05
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
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“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
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• 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?
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Who are these white guys?
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What Is This?
N
NN
N
CH3
CH3
CH3
O
O
1
3
7
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Key Words
Risk =
Hazard X Exposure
Dose / Response
Individual Sensitivity
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“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
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“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
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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
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What Is This?
CH
H
H
OHC
H
H
(CH3-CH2-OH)
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Effects of Prenatal Alcohol
A Small Dose of Toxicology Children & Environment – 6/25/05FAS Child
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Fetal Effects of MeHg
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The Mercury Cycle
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A Small Dose of Lead
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Lead In Homes
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Lead History
Greek 2nd BC
Lead Makes the Mind Give Way
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Lead in Families
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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
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Structure of PBDEs
X & Y are number of Bromine atomsCommon Penta, Octa, and Deca
PolyBrominated Diphenyl Ether
O
BrxBry
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PBDEs in House Dust (ppb)
From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php
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PBDEs in Breast Milk (ppb)
From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php
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Key Words
Risk =
Hazard X Exposure
Dose / Response
Individual Sensitivity
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Effects of Amount on Response
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Effects of Size on Response
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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
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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
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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)
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1) Skin (dermal)
2) Lung (inhalation)
3) Oral (gut)
Route of exposure
Exposure & Absorption
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Number of Times
Time Between
4 Beers in an hour or4 Beers in 4 Days
Frequency Of Exposure
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Acute Exposure
Sub-chronic Exposure
Chronic Exposure
Duration Of Exposure
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Where It Goes
(body water, fat, bone)
Where It Accumulates
Distribution
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How The Body Breaks It Down
What It Turns Into
How Fast It Does It
Metabolism
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N
NN
N
CH3
CH3
CH3
O
O
1
3
7
Caffeine - 1,3,7 Trimethylxanthine
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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
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“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
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• 25 DAYS -- BLOOD• 40 DAYS -- SOFT TISSUE • 20 YEARS -- BONE
Half-life Of Lead
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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
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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
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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)
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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
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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
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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
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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
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Recycling Lead
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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.
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• 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
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The Potential of Children
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Principles of Toxicology
www.asmalldoseof.org
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Additional Information
• A Small Dose of Toxicology www.asmalldoseof.org
• Inst. Children’s Env Health (ICEH) –www.iceh.org
A Small Dose of Toxicology Children & Environment – 6/25/05
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”
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An Introduction To The Health Effects of
Arsenic (As)
A Small Dose of ™ Arsenic
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A Therapeutic Agent and A Poison
2400 Years Ago
In Greece and Rome
Ancient Awareness
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For many years used to treat syphilis and amebic dysentery
But caused skin cancer in patients treated with arsenicals
Historical Awareness
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• 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
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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
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Exposure
Drinking water Burning arsenic treated
wood Handling treated wood
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US Arsenic Map
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Arsenic in drinking water is a worldwide human health hazard
Avoid the use of arsenic treated wood
Reduce or avoid arsenic exposure
Summary
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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