Human Health Risk Assessment

Classes Of Human Health Hazards:

1) infectious and degenerative diseases ( e.g. AIDS; cancers)

2) "natural" catastrophes (e.g. hurricanes, floods)

3) failure of large technological systems (e.g. dams failing, airplane)

4) discrete, small-scale accidents (e.g. highway accidents)

5) low-level delayed effect hazards (e.g. asbestos, radiation, stress)

6) sociopolitical disruptions (e.g. terrorism)

LOW-LEVEL DELAYED-EFFECT HAZARDS

• Most frustrating to assess
• Requires
  1. assessing exposure
  2. proving exposure is harmful
  3. gauging extent of the effect across society

ANALYZING THE DAILY RISKS OF LIFE

Risks That Increase Chance of Death by 0.000001^* (1/10⁶)

Smoking 1.4 cigarettes	Cancer, heart disease
Drinking 1/2 liter of wine	Cirrhosis of the liver
Spending 1 hour in a coal mine	Black lung disease
Spending 3 hours in a coal mine	Accident
Living 2 days in New York or Boston	Air pollution
Travelling 6 minutes by canoe	Accident
Travelling 10 miles by bicycle	Accident
Travelling 300 miles by car	Accident
Flying 1000 miles by jet	Accident
Flying 6000 miles by jet	Cancer caused by cosmic radiation
Living 2 months in Denver on vacation from N.Y.	Cancer caused by cosmic radiation
Living 2 months in average stone or brick building	Cancer caused by natural radioactivity
One chest x-ray taken in a good hospital	Cancer caused by radiation
Living 2 months with a cigarette smoker	Cancer, heart disease
Eating 40 tablespoons of peanut butter	Liver cancer caused by aflatoxin B
Drinking Miami drinking water for 1 year	Cancer caused by chloroform
Drinking 30 12 oz. cans of diet soda	Cancer caused by saccharin
Living 5 years at site boundary of a typical nuclear power plant in the open	Cancer caused by radiation
Drinking 1000 24 oz. soft drinks from recently banned plastic bottles	Cancer from acrylonitrile monomer
Living 20 years near PVC plant	Cancer caused by vinyl chloride (1976 standard)
Living 150 years within 20 miles of a nuclear power plant	Cancer caused by radiation
Eating 100 charcoal broiled steaks	Cancer from benzopyrene
Risk of accident by living within 5 miles of a nuclear reactor for 50 years	Cancer caused by radiation
*(1 part in 1 million)	Wilson (1990) Readings in Risk

Human Health Risk Assessment Paradigm

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Common Human Health Risk Assessment Problems

Using animal experiments to assess human health risks

1. conduct animal experiment
2. model (administered?) dose - (tumor) response [estimate tumor response at low doses]
3. interspecies conversion
4. overall human risk estimate is obtained from iii and any other relevant information

Low Dose Extrapolation

• model dependent
• questions of thresholds for noncarcinogenic outcomes (e.g.neurological effects, hearing loss)
• linear model often used for low doses
  • belief that this may be an upper bound on risk
  • linearity may result if substance augments existing carcinogenic processes
  • DNA adduct formation obs. to be linear for very low doses

Species Extrapolation

Species dose-response is similar if dose examined in terms of amount of "substance" that reaches a critical target site. (i.e. common dose -->same risk)

If no "internal" dose available, often allometric scaling factors are used, (e.g. metabolism a*(BW)^0.75

Route Extrapolation

dose modified by physiological processing and various assumptions

EXAMPLE: occupational exposure is by inhalation -> toxicity experiments used gavage or injections

Pharmacokinetic Models

• reflect anatomical, physiological, clearance, metabolism, thermodynamics; and transport components of a physiological system.
• if adequately characterized, the concentration (dose) at a target tissue can be derived regardless of the route of dosing.