Risk Assessment

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Risk Assessment

• Chemicals, Risk Cancer 9
• David R. Bell
• Risk analysis, perception management ISBN
  0-85403-467-6

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Why Risk Assess ?

• Unsatisfactory to wait for epidemiology
• HAZARD
• The ability to cause cancer
• RISK
• What is the chance of it doing so ?
• Paracelsus
• All substances are poisons there is none which
  is not a poison. The right dose differentiates a
  poison and a remedy

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Hazard Assessment

• Use of Maximal Tolerated Dose (MTD) in two-animal
  bioassay
• High dose required to obtain a significant result
• Human exposure at low dose
• How to extrapolate from high dose to low dose ?

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Extrapolation
Data
Extrapolation
5
Extrapolation
US/ Europe 1 cancer in 106 is tolerable UK
guidelines more flexible
Extrapolation
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Extrapolation 3
No Observed Effect Level
NOEL
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Linear extrapolation

• Mechanism associated with genotoxicity
• 1 DNA adduct may lead to a single mutation may
  lead to cancer
• No safe dose
• Any amount of chemical will cause cancer
• Conservative

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Linear extrapolation

• Carcinogens may require metabolic activation
• Enzyme kinetics are non-linear
• Trichloroethylene produces lung tumours in mouse,
  but not rat
• TCE metabolised to chloral in mouse
• P450 mediated species differences (TCE.pdf)

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Linear extrapolation

• Non-genotoxic carcinogens activate receptors
• Receptor activation follows non-linear kinetics

V
Substrate
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Is linear extrapolation correct ?

• Linearity has been tested for acetyl-aminofluorene
  , which produces liver and bladder cancers- down
  to 1
• Linear for liver cancer 30-150 ppm
• Non-linear for bladder cancer
• NOEL of 60 ppm
• Increased bladder DNA synthesis above 60 ppm AAF

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Linear extrapolation

• For a chemical which causes cancer
• Extrapolate linearly to a level which causes
  cancer at 1 in 106
• i.e. MTD/ 1 000 000
• Applies to pesticides/ fungicides/ industrial
  chemicals/ etc
• Pharmaceuticals risk/ benefit balance
• UK regulation less clear

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Carcinogen exposure

• gt60 of all chemicals are carcinogens
• Food is composed of chemicals
• Plants produce a variety of secondary products
• Pesticides
• Of a selection of plant pesticides, 27/52 were
  carcinogenic

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Carcinogen exposure

• Estimate that people eat 1.5 g of natural
  pesticides per day
• 2g of burnt food products
• 50 carcinogens
• 1 cup of coffee contains 32mgs of known
  carcinogenic chemicals ( gt1000 untested)

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Carcinogen exposure

• Epidemiology fruit veg are beneficial
• It is not clear that there is evidence that low
  dose effects are significant for human cancer
• Compare lt0.1mg of synthetic pesticides
• Why regulate synthetic pesticides when 99.99 of
  pesticides are natural chemicals ?

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Risk

• Deaths per 109 km
• 1 Railways
• 4 Car
• 50 Bicycle
• 70 Pedestrian
• 100 Motorbike

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Risks

• Deaths per 106 participant hours
• 0.5 boxing
• 10 canoeing
• 45 cave exploring
• 220 scuba
• 1500 hang-gliding

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Acceptability of risk
Disease
Motor crash
Cancer
Pregnancy
Botulism
Flood
smallpox vaccine
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Consequences of perception

• Government health campaigns to stop people
  smoking
• Educate the public about the risks of smoking
• The public believe the risk is worse than it is
• ???

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Factors influencing perception

• Involuntary exposure
• No personal control
• Uncertainty about probabilities/ consequences
• Lack of experience
• Effects of exposure delayed in time
• Genetic effects

• Infrequent but catastrophic events (Kill size)
• Benefits not highly visible
• Benefits go to others
• Accidents caused by human failure

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The public and risk regulation

• The public has a view on risk
• This is an unknown, and can change dramatically
• Is the public view a basis for regulation ?
• Risk assessment is performed on behalf of the
  public, and must have public confidence

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Cost/ benefit analysis

• How much is the cost of regulation ?
• How much benefit accrues from this ?
• The cost of reducing chemical discharges can be
  enormous
• Reducing dioxin emissions during burning/
  bleaching
• Requirement for expensive incinerators

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Cost/ benefit analysis

• Use of Chlorination for bleaching/ sterilising
  water supplies
• Production of chloromethanes, which may be
  carcinogenic
• Greater risks with no chlorination
• EPA estimates a cost of 140 billion (1997)
• Highly inefficient method of saving life

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Food standards

• Major food killers
• Obesity, heart disease, colon cancer
• Small contribution from exposure to synthetic
  chemicals
• Public expectation that chemicals cause cancer,
  cf organic food