Transcript LIVING WITH THE EARTH

Fig. 5-1, “Toxic Triangle”,
Epidemiologic Triad
Environmental Factors
Agents
Host
Factors
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Epidemiologic Triad
Agents
• Organisms
• Chemicals
– exogenous
– endogenous
Host Factors
• Immunity
• Immunologic
response
• Host behavior
Environmental
Factors
• Physical
– hot, cold
– altitude
• Nutrients
– diet
• Biologic
• Physical
• Social
forces
– economic
• Psychological
factors
Agents have characteristics such as
infectivity, pathogenicity, virulence
• Genetic
Source: Smith, Theobald, 1934
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Pathogens are also toxic
agents that can cause cancer
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HP - Gastric; Mucosal-associated lymphoid tissue
Schistosoma haematobium - Bladder cancer
HTLV-I - Adult T-cell leukemia/lymphoma
HBV - Liver cancer
HHV-8 - Kaposi’s sarcoma
EBV - Lymphoproliferative disorders;
Nasopharyngeal; Burkitt’s lymphoma
• HPV - Anogenital carcinoma; cervical cancer
•
HP = Helicobacter pylori V.; HTLV = Human T-cell Leukemia/lymphoma V.;
HHV = Hepatitis B V.; EBV = Epstein-Barr V.; HPV = Human papilloma V.
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Classes of Xenobiotics
Pollutants (Air, Water, Soil)
Pesticides
Industrial
Chemicals
Pharmaceuticals
Food
Additives
Cosmetics
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• LD50
Dose - Response
A is more toxic than B
100
A
B
50
Response
0
Dose mg/kg
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• Metabolites
Dose - Response
100
1st Event
A
Intermediate
2nd Product
3rd Product
50
Response
All are Active
Targets may not be the same
0
Dose mg/kg
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• Dose related
Toxicity
Dose - Response
100
Parathion
DDT
50
Response
0
80
500
Dose mg/kg
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• Modes of
Action
Dose - Response
100
A
50
Same LD50
Response
A >> Toxic at Low Dose
0
Dose mg/kg
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Factors Governing Toxicity
• The outcome of exposure to a toxin depends
on a number of factors that may include:
• Age
– very young or old
• Strain
– e.g. skin color & UV
• Gender
• Weight
• Exercise and
Physical Stress
• Health Status
– immune
deficiencies
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Dr. Robson’s Medical Terms
Artery
Barium
Benign
Dilate
Morbid
Nitrate
Tumor
Urine
The study of fine painting
What you do after CPR fails
What you are after you be eight
To live longer
A higher offer
Lower than the day rate
An extra pair
The opposite of you’re out
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The New Risk Assessment Paradigm
Problem
Context
Evaluation
Communication
Throughout
Risks
Most
Important
Step
Engage
Stakeholders
Actions
Options
Decisions
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Benefits of Engaging
Stakeholders
• Supports Democratic
decision-making
• Ensures public values
are considered
• Develops the
understanding needed
for better decisionmaking
• Improves knowledge
base for decisionmaking
• Can reduce time &
expense involved in
decision-making
• May improve
credibility of agencies
managing risk
• Should generate
better accepted, more
readily implemented
risk management
decisions
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Three “Laws” of Toxicology
• Dose makes the Poison
– everything can create toxic effects
• Chemicals have specific effects
– structure relationships, subtle changes
can mediate toxicity
• Human is an animal
– animals can be used as “human”
surrogates, choice is important
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LD50
ToxicityA > ToxicityB
Dose Response
100
A
B
50
Response
0
Dose mg/kg
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ED50
EDA > EDB
Dose Response
100
A
B
50
Response
10
0
Dose mg/kg
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NOAEL
Dose Response
No Observable Adverse Effect Level
10
Response
5
NOAEL
Dose
Response
0
0/10
7
0/10
50
2/10
100
5/10
500
10/10
2
0
7
50
100
500
Dose mg/kg
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LOAEL
Lowest Observable Adverse Effect Level
Dose Response
10
Response
5
Dose
Response
0
0/10
7
0/10
50
2/10
100
5/10
500
10/10
LOAEL
2
0
7
50
100
500
Dose mg/kg
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Reference Dose, RfD
• Allowable daily dose
over a lifetime
• = (NOAEL) / (UF)
• Uncertainty Factors
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–
–
–
10x, Animals to Man
10x, Susceptibility
10x, Only Acute Studies
1-10x, Others
Dose Response
LOAEL
2
• In absence of NOAEL
– = (LOAEL) / (10)
– + UF as above
• Found in EPA’s IRIS
database
NOAEL
0
7
50
Dose mg/kg
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Exposure Studies
• Animal Based (surrogate for human)
– Acute (high dose)
• two weeks
– Subchronic (not as high as acute)
• 30 - 90 days, some less
– Long term or Chronic (lower doses)
• up to two years
– Maximum Tolerated Dose (MTD)
• controversy
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Non Cancer Endpoint
Risk = Exposure/ADI
• Exposure = Average Daily Dose
– = [(C x IR x EF x ED) / (BW x AT)] x factor
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C = Concentration, e.g., soil = mg/kg
IR = Intake rate, e.g., soil = mg/day
EF = Exposure frequency, days/yr
ED = Exposure duration, years (chronic > 7)
BW = Body weight, 70 kg, child = 16 kg
AT = Averaging time, days
• ADI = Acceptable Daily Intake, RfD
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Risk
• If ADD/ADI > 1, Risk of Adverse
Health Effect
• If ADD/ADI < 1, No Adverse Health
Effect Anticipated
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Cancer Endpoints
• A similar approach is used
– Slope Factor is used as the ADI
• = upper 95% CI of dose-response curve
• e.g., for ingestion units of mg/kg-day
• Typically an acceptable risk is
defined as < 1 x 10-6
– However, 10-4 to 10-5 may be acceptable
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Time to accumulate
1 in 1,000,000 Risk
Activity
• MV Accident, 1.5 days
• Fall, 6 days
• Drowning, 10 days
• Fire, 13 days
• Firearms, 36 days
• Tornado, 20 months
• Flood, 20 months
• Lightning, 2 years
• Animal bite, 4 years
Adapted from Moeller, 1997
Occupation
• Mining, 9 hrs
• Firefighting, 11 hrs
• Coal mining, 14 hrs
• Construction, 14 hrs
• Agriculture, 15 hrs
• Transport, 1 day
• Police duty, 1.5 days
• Government, 3.5 days
• Manufacturing, 4.5 days
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Lifestyle activities with
1 in 1,000,000 Risk
Eating & Drinking
• 0.5 liter wine
• 6 # of peanut butter
(aflatoxin)
• 180 pints of milk
(aflatoxin)
• 200 gallons of
drinking water from
Miami, New Orleans
• 90 # of broiled steak
Adapted from Moeller, 1997
Smoking
• 2 cigarettes
Other
• Paddling in canoe for 6
minutes
• Traveling 10 miles by
bicycle
• Traveling 30 miles by
car
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$$ per year of life saved
Program
• Childhood measles
• Lead Phaseout
• Underground safety rules
• Hemodialysis at dialysis ctr.
• Coronary artery bypass
• Front-seat airbags
• Dioxin effluent control - paper
• Control of routine PP radiation
Adapted from Moeller, 1997
Cost
saves $
saves $
52,234
56,076
67,579
108,593
5,566,386
164,875,379
Uncertainty
low
low
low
low
low
medium
high
high
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“Typical” Risk Perceptions
“Acceptable” if:
• Voluntary
• Proximate Benefit
• Known
• Workplace
• Natural
• Self
• Organ Damage
• Distant (time, place)
“Unacceptable” if:
• Involuntary
• No Benefit
• Unknown
• Residential
• Anthropogenic
• Children
• Cancer
• Near
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EPA’s Cardinal Rules of Risk Communication
Problem
Context
Evaluation
Risks
Engage
Stakeholders
Options
Actions
Decisions
• Accept & involve public
as legitimate partner
• Plan carefully and
evaluate your efforts
• Listen to public’s
specific concerns
• Be honest, frank, & open
• Coordinate & collaborate
w/other credible sources
• Meet the media’s needs
• Speak clearly and with
compassion
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10 Key principles of risk assessment,
John Graham, HSPS - CRA
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Use the best science for attributable health risk
Acknowledge scientific disagreements
Acknowledge assumptions, & sensitivity of results
Develop central estimates of risk and CI’s + uncertainty
Acceptable risk is policy that requires public involvement
No universally acceptable level of risk exists; context
Health risk decisions require consideration of values
– quality of life, equity, ecological health, choice, economic welfare
• Risk reduction programs should avoid side effects that  risk
• Programs should consider economic incentives + command c.
• Context of risk may be as significant as the magnitude
– voluntary vs. involuntary risk
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