Environment

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Environment Health Risk Assessment

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Outline

• Fate of chemicals in the body
• Risk assessment
• Risk management
• Risk perception
• Conclusion

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Fate of Chemicals in the body

• Chemicals can enter the body through
• Skin
• Gastrointestinal tract
• Respiratory tract

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• Absorption of toxicants through the skin
• lipid soluble cpds appear to dissolve in and
  diffuse through the lipid matrix and the rate of
  diffusion is related to lipid solubility
• Water soluble molecule hardly penetrates the
  skin unless the molecule is minute

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• Absorption of toxicants through the GI tract
• The less polar, unionized forms will diffuse
  rapidly across a lipoid membrane

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• Absorption of toxicants through the lungs
• Exposure to toxicants by inhalation will be
  absorbed through lung
• Carbon monoxide
• Nitrogen dioxide
• Sulfur dioxide
• Vapour of volatile liquids such as benzene
• Aerosol

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Distribution

• The rate of diffusion to the tissue of each organ
  is determined by the blood flow through the organ
• Distribution of any substances can be affected by
  accumulation at various tissues in the body
• - plasma protein
• - body fat
• - bone
• - liver and kidney

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Storage

• Body fat A number of insecticides such as DDT,
  Chlordane, are highly lipid soluble and can be
  stored by simple physical dissolution in the
  neutral fats
• Bone Lead, fluoride
• Liver and Kidney High capacity for binding and
  concentrating chemicals including metals
  (cadmium, zinc)

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Metabolism

• The biochemical process involving enz catalysed
  reactions that transform any chemical to another
  form with different chemical structures
• The new form can be more or less active than the
  parent compound

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Elimination

• Most toxicants are eliminated from the target
  tissues, blood and body at rates dependent upon
  blood concentration
• Biliary excretion
• Renal excretion

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• The toxicity of a chemical depends on the target
  dose exposure and ADME
• Intervidual differences in response could be due
  to genetic factors controlling, e.g. ADME
• Molecular toxicology can be used to characterize
  mechanism of action

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Environment
Super hydrophobic
Hydrophobic
Polar
Hydrophilic
Accumulate in fatty tissues
Oxidation, reduction, hydrolysis
Bioactivation or detoxification Conjugation
Hydrophilic
Excretion
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Risk assessment

• Standard setting of environmental exposures to
  chemical in various media
• Prioritizing risk management
• Risk hazard (toxicity) x exposure

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Risk assessment

• Hazard identification
• Dose response relationship
• Exposure assessment
• Risk characterization

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Hazard Identification

• Collect and analyse toxicity data (human,
  animals)
• Identify types of toxicity (acute, chronic,
  teratogenic, reproductive toxicity)
• Evaluate whether toxicity that occurs in one
  setting (lab) will occur in another setting
  (environment)

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Dose response curve
Maximum response
Response
Threshold
LOEL
NOEL
Dose (mg/kg BW/day)
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Exposure assessment

• Measurements have to be made of chemical
  concentrations in the environment (soil, water,
  air)
• Mathematical / computer models are generated to
  predict patterns of exposure
• Analysis of chemical residues on food can be used
  to make an estimation of exposure

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Risk characterization

• Integrating toxicity exposure data to determine
  risk

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Reference dose (RfD)

• Also known as acceptable daily intake ADI an
  estimate (with some certainty) of a daily
  exposure to the human population
• RfD (ADI) NOAEL / Uncertainty factor
• U.F. extrapolation from animals to human,
  various in general population/sensitive subgroups

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Theoretical Daily Intake

• TDI S (MRL x F)
• MRL maximum residue limit for a given food
• F Regional consumption of that food commodity
  per person
• Units of mg/kg BW per day

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Risk characterization

• Compare RfD (ADI measure of toxicity) and TDI-
  measure/estimation of exposure)
• If ADI TDI, use is acceptable

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Example

• Chlorpyrifos is an organophosphorus insecticide
  used for control of various crop pests in soil
  and on foilage, household pests.
• Exposure information
• - residue limits have been set by the WHO/FAO
  (Codex) for several food products including beef,
  eggs, milk
• - The MRLs for beef, eggs and milk are 2.0, 0.05
  and 0.01 mg/kg respectively
• - The FAO has reported that the average daily
  consumption of beef, eggs and milk are 0.005,
  0.0017 and 0.025 kg/person/day

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Chlopyrifos

• A concentration of 0.1 mg/kg BW/day of
  Chlopyrifos was considered a NOAEL
• Assuming an uncertainty factor of 10
• Assuming an average body weight of 60 kg.
• ADI NOAEL/U.F.
• 0.1/10 0.01

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TMDI S (MRL x F) 2 x 0.005 0.05 x 0.0017
0.01 x 0.025 60 60
60 1.67x10-4 0.0142x10-4
0.0417x10-6 1.72x10-4 mg/day Compare ADI
and TMDI ADI gt TMDI
safe to use
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Risk management

• The process of identifying, evaluating, selecting
  and implementing actions to reduce risk to human
  health and to ecosystem

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Risk Assessment/Risk Management
Dose Response Assessment
Technical
Socioeconomic
Hazard identification
Risk Characterization
Regulatory Decision
Political
Other
Exposure Assessment
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Risk management

• Prevention
• Control
• Mitigation/Remedy
• Risk reduction

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Risk reduction

• Controls on manufacture
• Restrictions on use
• Redesign of process, change of materials
• GMPs
• Labelling
• Personal protection
• Emission control

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Risk perception

• A person with a knowledge / work experience has
  more choice when faced with a situation where
  there is risk to health, the choice may be one of
  a few jobs choose the one with greatest
  safety/least risk
• A person with fewer choices may have to choose
  either risk to health or hunger for
  himself/herself and/or family

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Conclusion

• Dose Response
• Tumors or systemic toxicity

• Hazard Identification
• Epidemiology
• Animal toxicity
• In Vitro Studies

Risk Characterization

• Exposure Assessment
• Magnitude
• Frequency/Duration
• Pathways

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