Transcript Document

A Small Dose of Toxicology
Beyond Risk Assessment to Precautionary
Precautionary Assessment
Getting Out of the Risk Assessment Box:
Precautionary Approaches for Public Health
(Critical Analysis of Risk Assessment &
Alternative Approaches)
How Chemicals Affect Your Health
Steven G. Gilbert, PhD, DABT
A Small Dose of Toxicology
www.asmalldoseof.org
www.toxipedia.org
Beyond Risk Assessment to Precautionary
Risk Assessment
"We should remember that
risk assessment data can
be like the captured spy: If
you torture it long enough,
it will tell you anything you
want to know."
(William Ruckelshaus -1st administrator of
U.S. EPA 1984.)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Outline
Risk Assessment –
Arbitrary and Capricious
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Vision and Ethics
Principles of Risk Assessment
Risk Assessment - examples
Weaknesses of Risk Assessment
Beyond Risk Assessment to
Precautionary Assessment
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Vision for Child Health
“Children can develop
and mature in an
environment that allows
them to reach and
maintain their full
potential.”
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Human & Environmental Health
“Conditions that ensure that all
living things have the best
opportunity to reach and maintain
their full genetic potential.”
S. Gilbert (1999)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Socially responsible white guys?
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
The First Bioethicist
Aldo Leopold
"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
---------- 1887 - 1948 ---------A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Limits on Freedom
“An ethic, ecologically, is
a limitation on freedom of
action in the struggle for
existence”
Aldo Leopold
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
“The Commons”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Technical Solutions
“It is our considered
professional judgment that
this dilemma has no
technical solution.”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Problems – Solutions?
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A Small Dose of Toxicology
Lead and kids
Fetal alcohol syndrome
Nuclear disarmament
Bioterrorism
Ocean Fisheries
Persistent chemicals
The Commons
Beyond Risk Assessment to Prec – 09/19/07
Sir Austin Bradford Hill
"All scientific work is incomplete - whether it
be observational or experimental. All
scientific work is liable to be upset or
modified by advancing knowledge. That
does not confer upon us a freedom to
ignore the knowledge we already have or
postpone the action that it appears to
demand at a given time. "
Sir Austin Bradford Hill (1965)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Determining Causation
1.
2.
3.
4.
5.
6.
7.
Strength of association
Consistency of findings
Biological gradient
Temporal sequence
Biologic or theoretical plausibility
Coherence with established knowledge
Specificity of association
Sir Austin Bradford Hill (1965)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
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.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Central components
• Setting goals (Health indicators)
• Taking preventive action in the face of
uncertainty
• Shifting the burden of responsibility to the
proponents of an activity (Who benefits?)
• Exploring a wide range of alternatives to
possibly harmful actions (Is it necessary?)
• Increasing public participation in decision
making (transparency of information &
environmental justice)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Key Words of Toxicology
Dose / Response
Hazard X Exposure = Risk
Individual Susceptibility
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Modern Risk Assessment
Developed in 1960-1970s
Concern over increased cancer rates
Expanded to non-cancer effects
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Perspective
"If someone had evaluated the risk of fire right
after it was invented, they may well have
decided to eat their food raw."
Julian Morris of the Institute of Economic
Affairs in London
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Quantitative Risk Assessment
Process of estimating
association between an
exposure to a chemical or
physical agent and the
incidence of some adverse
outcome.
National Research Council, Risk Assessment in the Federal
Government: Managing the Process. National Academy Press,
Washington, DC, 1983
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Steps in Risk Assessment
 Hazard Identification
 Exposure Assessment
 Dose-Response Assessment
 Risk Characterization
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
What Hazard?
Obvious
Death, Cancer, Acid burn, Birth defect,
asthma …..
Subtle
Decreases in learning and memory (lead)
Loss of potential
Sensitivity of the individual (child)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Hazard Identification
Review human and animal data
to determine if a chemical or
agent has biological effects.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Toxicity Endpoints
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Carcinogenicity
Mutations
Altered immune function
Teratogenicity
Altered reproductive function
Neuro-behavioral toxicity
Organ-specific effects
Ecological effects (wildlife,
environmental persistence)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Exposure Assessment
 Route of exposure (skin, oral,
inhalation)
 Amount of exposure (dose)
 Duration of exposure
 To whom (animals, humans,
environment)
 Children, other sensitive individuals
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Exposure Issues
•
•
•
•
•
•
Home environment
Workplace (occupational)
School
Food
Consumer products
Global and local environment
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Dose-Response Assessment
How much exposure to a chemical
or agent will cause what effect?
Dose – Response
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Some Jargon
LOAEL – Lowest Observed
Adverse Effect Level (mg/kg)
NOAEL – No Observed Adverse
Effect Level (mg/kg)
RfD – Reference Dose (mg/kg-day)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Response
Greater Dose – Greater Response
ED50
Threshold (NOAEL)
LOAEL
Dose
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Risk Characterization
Risk = Hazard X Exposure
Hazard (including sensitive
populations)
–Low dose extrapolation
Exposure
– Route of exposure, amount, duration
• dermal, oral, inhalation, injection
– To Whom? Sensitive Individuals?
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Use of Uncertainty Factors
Divide Dose by Power of 10
• Human variability
• Interspecies extrapolation
• Children
• Subchronic to chronic extrapolation
• Absence of a NOAEL
• Database uncertainty
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Human Variability
Human Subject Variability
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Lifestyle – risk of exposure to ….
Occupation – risk of exposure to ….
Breathing & digestion – uptake of chemicals
Metabolism & kidney function – elimination
Age, gender & disease – susceptibility to
toxicity
• Socio/economic facts
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Doubt / Uncertainty
"Doubt is our product since it is the best
means of competing with the 'body of fact' that
exists in the mind of the general public.“
1969 an executive at Brown & Williamson
owned by R. J. Reynolds Tobacco Company
(Doubt Is Their Product by David Michaels in
Scientific American, June 15, 2005)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Use of Uncertainty Factors
Animal Dose Response Data
NOAEL (No Observed Adverse Effect Level) or LOAEL
Divide by 10
(Account for inadequate animal data)
Divide by 10
(Animal to Human Extrapolation)
Divide by 10
(Human Variability or Individual Sensitivity)
Reference Dose (RfD) Or Acceptable Daily Intake (ADI)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Mercury & Toxicology
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
The Mercury Cycle
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Atmospheric Hg
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Neurobehavioral Effects
• Blindness - Deafness
• Cerebral Palsy - Seizures
• Abnormal reflexes & muscle tone
• Retarded motor development
• Visual and Auditory Deficits
• Delayed motor development
• Human and animal data
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Effects On The Brain
 Decrease in Brain Size
 Cell loss
 Disorganization of cells
 Cell migration failures
 Behavioral effects –
learning and memory
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Fetal Effects of MeHg
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Animal - Risk Assessment
 MONKEY - 25 µg/kg - LOAEL
 RAT - 10 µg/kg - LOAEL
 RAT - 50 µg/kg - replicated
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Animal - Risk Assessment
 2.5 µg/kg - NOAEL (animals)
 0.25 µg/kg - Human
 0.025 µg/kg - Sensitive populations
(the rule of dividing by 10)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Human - Risk Assessment
• 10-20 ppm hair - LOAEL •
• 40-80 ppb blood - LOAEL •
• 0.645 µg/kg •
• 0.06 µg/kg - RfD •
Gilbert, S.G., and Grant-Webster, K.S. Neurobehavioral effects of developmental
methylmercury exposure. Env. Health Persep. 103(Suppl 6), 135-142, 1995.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
MeHg Consumption Limits
US EPA – 0.1 ug/kg-day
US FDA – 1 ppm (mg/kg)
in tuna
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Ancient Awareness
"Lead makes the
mind give way."
Greek
Dioscerides - 2nd BC
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Agency Blood Lead Levels
Acceptable Childhood Blood Lead Levels
Blood Lead (ug/dl)
60
60
50
40
40
30
30
25
20
20
15
10
10
2
0
CDC CDC
1960 1973
CDC CDC WHO EPA
1975 1985 1986 1986
CDC CDC
1990 2006?
Agency and Year
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Recycling Lead
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Limitations of Risk Assessment
 Lack of adequate data
 Most sensitive endpoint
 Low dose extrapolation
 Exposure information
 Multiple chemical exposures
 Complex – expert driven –
undemocratic
 Individual sensitivity
 Narrow perspective – Ethical??
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
An approach to evaluating the
scientific, safety, community, ethical,
and social issues related to a
compound or procedure.
 Community / Social Issues
 Exposure Issues
 Hazard / Toxicity
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
 Community / Social Issues
 G = Goal
 N = Need
 F = Future Generations
 D = Democratic, community
based process
 A = Alternatives
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
Initial
G
N
F
D
A
Parameter
Score
Comment
Community /
Social Issues
Evaluate effects on the community and related
social issues.
G=Goal
1-3
1-a lot, 2-some, 3-little. Does this move forward
the goal of human and environmental health?
1-3
1-a lot, 2-some, 3-little or not sure. Ask the
question: Is it necessary? Do we really need this?
1-3
1-little, 2-some, 3-high impact. Is there a potential
impact on future generations of humans and other
species?
1-3
1-a lot of community involvement and consultation,
2-some, 3-little. Was the community consulted
early and often in the process? Was the process
democratic and inclusive.
1-3
1-alternatives were carefully considered, 2-some
consideration, 3-no consideration. Where
alternatives considered?
5-15
5-good, supportive of health and community
15-poor, not supportive of health or community
N=Need
F=Future
Generations
D=Democratic,
community
based process
A=Alternatives
Total
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
 Exposure Issues
 E = Exposure
 M = Multiple exposures
 Ch = Children exposed
 CP = Consumer products
 O = Occupational exposure
 F = Food exposure
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
Exposure
Issues
Evaluate potential exposure issues.
E
E=Exposure
0-3
0-none, 1-little, 2-some, 3-high. Do we have control
over the exposure?
M
M=Multiple
exposures
0-3
0-none, 1-little, 2-some, 3-high. Is there exposure to
other chemicals with similar hazard?
Ch
Ch=Children
exposed
CP
CP=Consumer
products
O
O=Occupationa
l exposure
F
F=Food
exposure
Total
A Small Dose of Toxicology
0,3,5
0-none, 3-little, 5-some or high or don't know.
Children are often more vulnerable. Are children
being exposed.
0-3
0-not in consumer products, 1-little, 2-some, 3- a lot
or do not know. Is this compound in consumer
products?
0-3
0-no occupational exposure, 1-little, 2-some, 3- a lot
or do not know. Is there occupational exposure?
0-3
0-not in food supply, 1-little, 2-some, 3- a lot or do not
know. Is the compound present in the food supply.
0-20
0-no exposure, no problems
20-significant exposure, serious concern
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
 Hazard / Toxicity
 H = Hazard
 IS = Individual Sensitivity
 EC = Ecological hazard
 UC = Uncertainty
 V = Volume
 P = Persistent
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
Hazard /
Toxicity
Evaluate potential hazards.
H
H=Hazard
1-low, 5-some, 10-high. Follow classical hazard evaluation, pick
endpoint, exam relevant quality studies (cancer, reproductive,
neurotoxicity, irreversible)
IS
IS=Individual
Sensitivity
EC
EC=Ecological
hazard
V
V=Volume
1,5,10
1-3
1-little 2-some, 3-a lot. Determine if any individuals are more
sensitive than health adult such as the very young or old.
1-3
1-little 2-some, 3-a lot. Is it a hazard to other species or the
environment?
1-5
how much is produced (1=research only, 2=<1000 lbs,
3=<10,000, 4=<100,000, 5=>100,000 or do not know)
1-3
1-little persistence 2-some, 3-a lot of persistence or do not know.
Is the compound presistent in the environment?
P
P=Persistent
B
B=Bioaccumul
ate
1-3
1-little 2-some, 3-a lot. Does it bioaccumulative in humans or
animals or move up the food chain?
UC
UC=Uncertaint
y
1-3
1-little 2-some, 3-a lot. How certain is the information?
7-30
7-low hazard
30-significant hazards or unknowns, serious concern
Total
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Precautionary Assessment
Lead
 Community / Social Issues - 12/15
 Exposure Issues – 16/20
 Hazard / Toxicity – 27/30
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Rights and Policy
• We have a right to an environment
in which we can reach and
maintain our potential
• A matter of POLICY not Risk
Assessment
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
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.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Central components
• Setting goals (Health indicators)
• Taking preventive action in the face of
uncertainty
• Shifting the burden of responsibility to the
proponents of an activity (Who benefits?)
• Exploring a wide range of alternatives to
possibly harmful actions (Is it necessary?)
• Increasing public participation in decision
making (transparency of information &
environmental justice)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
WSPHA 2006 Resolutions
The Washington State Public Health Association
(WSPHA at www.wspha.org) unanimously adopted two
important resolutions at the 13th Annual Washington
State Joint Conference on Health that addressed
human health and the environment.
“Endorsing the Precautionary Principle as a Public
Health Tool for Preventing Harm from Persistent
Bioaccumulative Toxic Chemicals (PBTs)”
Resolved that - “The WSPHA endorses the precautionary principle as a
vital component of our preventive approach to public health in
Washington State, advancing the goal that all people have an opportunity
to reach and maintain their full potential.”
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
WSPHA 2006 Resolutions
“Supporting Safer Chemicals Policies to
Benefit Human and Environmental
Health”.
This resolution addressed the need to 1) reduce
exposure to PBTs, 2) encourages development and
use of safer, cost-effective alternative products,
materials, and processes, 3) development of ‘green
chemistry’, and 4) provide full information on the
health effects of all chemicals placed into the
marketplace.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Seattle Initiative
City Comprehensive Plans
• Every citizen of Seattle has an equal
right to a healthy and safe environment.
• Seattle sees the Precautionary Principle
approach as its policy framework to
develop laws for a healthier and more
just Seattle.
• Seattle Precautionary Principle White
Paper (www.asmalldoseof.org)
Seattle PP working group – CHE-WA
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Asthma & Diabetes
Survey Measures of Percent Ever Having Had Asthma and Diabetes Diagnoses, Seattle, 19942002
14.0
asthma
weighted percent of survey respondents
12.0
10.0
8.0
6.0
diabetes (excluding during pregnancy)
4.0
2.0
Data Source: Behavioral Risk Factor Surveillance System, Washington
State Department of Health and Centers for Disease Control
Prepared by: Public Health- Seattle & King County, EPE, 5/04
0.0
1994
1995
A Small Dose of Toxicology
1996
1997
1998
1999
2000
2001
2002
Beyond Risk Assessment to Precautionary
Overweight & Obese
Survey Measures of Percent Overweight and Obese, Seattle, 1994-2002
70.0
60.0
weighted percent of survey respondents
overweight
50.0
40.0
30.0
20.0
obese
10.0
Data Source: Behavioral Risk Factor Surveillance System, Washington
State Department of Health and Centers for Disease Control
Prepared by: Public Health- Seattle & King County, EPE, 5/04
0.0
1994
1995
1996
1997
1998
1999
2000
2001
2002
year
A Small Dose of Toxicology
Beyond Risk Assessment to Precautionary
Conclusion
The Precautionary Principle is
part of the evolution in our
thinking and decision making
toward ensuring human and
environmental health.
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Estimated Costs - National
Estimated Costs of Pediatric Disease of
Environmental Origin, United States,1997 (billions)
Lead Poisoning
Asthma
Cancer
Neurobehavioral
Disorders
TOTAL
Best
Estimate
Low Estimate
High
Estimate
$43.4
$43.4
$43.4
$2.0
$0.3
$9.2
$0.7
$0.2
$4.6
$2.3
$0.7
$18.4
$54.9
$48.8
$64.8
(From “Environmental Pollutants and Disease in American Children,” Landrigan, Schechter, et.al., 2002)
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Estimated Costs - Washington
Diseases and disabilities (asthma, cancer, lead exposure,
birth defects, and neurobehavioral effects) attributable to
environmental contaminants.
Disease/Disability (2004 $ million)
Best
Direct Indirect Range
Estimate Costs
Costs
$1,600Childhood $1,875 $310.6 $1,565 $2,200
Adult &
$2,800child
$2,734 $782.1 $1,953 $3,500
Kate Davies Economic costs of diseases and disabilities attributable to environmental
contaminants in Washington State. Antioch University Seattle 2005.
http://washington.chenw.org/pdfs/EnvironmentalCosts.pdf
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Characteristics of Risk
Characteristic
Knowledge
Newness
Voluntariness
Control
Dreadedness
Catastrophic
potential
Equity
Level
Little known
Much known
Old
New
Not voluntary
Voluntary
Not controllable
Controllable
Little dread
Great dread
Not likely
Likely
Distributed
Undistributed
Adapted from Kraus and Slovic (1988), Risk Anal., 8: 435.
A Small Dose of Toxicology
Examples
Food additives
Alcoholic drinks
Guns
Space travel
Crime
Rock climbing
Natural disasters
Smoking
Vaccination
Nerve gas
Sunbathing
War
Skiing
Hazardous dump
Beyond Risk Assessment to Prec – 09/19/07
Risk Perceptions
Unknown
w DNA Research
Nuclear Power w
w
Herbicides
Pesticides w
Little Dread
w Anesthetics
w Power Tools
Alcohol
w
w
Motor vehicles
A Small Dose of Toxicology
Asbestos
Known
Knowable
Newness
Lack of scientific knowledge
Exposure is unknown/unknowable
w
w Food coloring
Saccharin w
Microwave ovens w
w Aspirin
Dreaded
w Smoking
Dread
Catastrophic potential
Involuntariness
Personal risk
Inequity
w Dynamite
w Warfare
w Handguns
Beyond Risk Assessment to Prec – 09/19/07
The Potential of Children
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Additional Information
 National Research Council, Risk Assessment in
the Federal Government: Managing the
Process. National Academy Press, Washington,
DC, 1983
 World Health Organization - The International
Programme on Chemical Safety (IPCS) – Risk
Assessment –http://www.who.int/pcs/ra_main.html
 U.S. Environmental Protection Agencies National Center for Environmental Assessment
(NCEA) – http://cfpub.epa.gov/ncea/
 A Small Dose of Toxicology – Risk Assessment
- http://www.asmalldoseof.org/toxicology/risk_assessment.php
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07
Risk Assessment
A Small Dose of Toxicology
Beyond Risk Assessment to Prec – 09/19/07