Dose and Response Relationships

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Dose and Response Relationships
Stephen Corbett Centre for Public Health Western
Sydney Area Health Service
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Dose and Response Relationships
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Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

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What is a Standard

• A description of a set of conditions that define
  occupational and environmental quality and which
  are intended to protect human health and safety

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Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

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Approaches to Environmental and Occupational
Standards Setting

• Levels of exposure
• if not exceeded will protect the health of the
  average, or even the whole population
• will take account of economic factors and provide
  a compromise between benefits and costs
  associated with the risks to those exposed
• is a number used in relation to engineering
  design considerations.

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Setting Environmental Standards 1

• 2 approaches
• 1. Threshold
• 2. Non Threshold - usually cancer as the health
  endpoint

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Setting Environmental Standards

• 1. Threshold
• Obtain a No Observed Adverse Effect Level (NOAEL)
  from animal (most sensitive species) or human
  epidemiological studies
• Divide this number by safety factors for
• inter/intra species variability
• severity of effect
• NOAEL/ Safety Factor Tolerable Intake (ADI,
  PTWI, RfD)

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Setting Environmental Standards 3

• 2. Non Threshold
• Obtain a Cancer slope factor from animal (most
  sensitive species) or human epidemiological
  studies
• Assume a shape of the DR curve between NOAEL and
  zero
• Calculate dose corresponding to predetermined
  acceptable level of risk (usually 1x 106)
• Lifetime Dose not causing increase gt 1x 106
  Guidance Dose

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Setting Environmental Standards4

• Obtain Guidance Dose or TI
• Assess Bioavailability
• Apportion Guidance Dose or TI to source of
  exposure
• Background
• Soil
• Water
• Air
• Dermal exposure

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Setting Environmental Standards4

• Obtain Guidance Dose or Tolerable Intake
• Assess Bioavailability
• Apportion Guidance Dose or TI to source of
  exposure
• Background
• Soil
• Water
• Air
• Dermal exposure

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Toxicity and Dose

• The toxicity (poisonous nature) of any substance
  is inversely related to the amount (dose)
  required to cause harm
• Substances which can cause harm following
  exposure to very small amounts, sometimes no more
  than a few molecules, are said to be extremely
  toxic
• Substances which require exposure to many grams
  before harm results are said to have low toxicity
• Even essential nutrients become toxic if the
  amount ingested is above a certain acceptable
  dose

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Dose-Response Curve

• A dose response curve records the percentage of a
  population showing a given response such as death
  when each individual member of the population is
  subjected to the same dose of toxicant
  (reflecting a given exposure)
• The LD50 is the median dose associated
• with the death of 50 of the population

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Dose-Response Curve
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Dose-Effect Curves

• The relationship between dose and effect
  illustrates what happens in an individual as
  dose increases
• The curves are similar to dose-response curves
• For essential nutrients there is an optimum
  range
• of dose required for good health
• For toxicants, there may or may not be
  thresholds of effect

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Dose-Effect Curves
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Tolerable Daily Intake

• The Tolerable Daily Intake is an estimate of the
  daily intake of a chemical contaminant which can
  occur over a lifetime without appreciable health
  risk. The concept of a TDI generally applies to
  unavoidable and undesirable contaminants of food
  or water which have no useful purpose. The term
  tolerable is intended to signify permissibility
  rather than acceptability

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Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

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Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

23
Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

24
Environmental Standards

• What are standards
• How are standards developed
• Standards play a vital role in public health
  development.
• Standards are seldom a matter of technical
  specification alone.
• Design and manufacturing standards are often
  overlooked
• How are standards used

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Environmental Standards HealthSummary

• Standards play a vital role in public health
  development.
• Need transparency in methods used to develop
  standards
• Public Health role in the development of Design
  and manufacturing standards
• Wide variation in the interpretation of
  Environmental Health Standards by communities,
  regulators and public health scientists