Renske de Veer (rdeveer)
Q7 Research – Uncertainty factors in Risk assessment
HC 1. Introduction uncertainty factors in risk assessment
Fields/factors that determine individual health:
- Human biology (genetics)
- Health care organization
- Lifestyle
- Environment
Toxicology: study of the adverse effects of xenobiotics (compounds foreign to the body) in living
systems
- Toxicology applies safety evaluation and risk assessment.
- Important questions:
o Is the compound toxic?
o What are the harmful effects? What is the exposure?
o How large is the risk for man, animals and environment?
o Why is the compound toxic? What is the mechanism of action?
Pesticides, water, and mercury are toxic → paradigm of toxicity: Paracelsus. “It is the dose that
makes the poison”.
Most deadly poison in the world: Botox. → intrinsic toxicity is huge.
Why is benzene more toxic than toluene?: Formation of toxic metabolites
Risk assessment/Risk management
Exposition phase: Behaviour of a substance in the environment, changes in the application form,
available for uptake.
Toxicokinetic phase: Absorption, distribution, biotransformation (toxification, detoxification),
excretion.
Toxicodynamic phase: Interactions with receptors or other (macro)molecules at the site of operation.
➔ Phases together determine effect.
Risk = Hazards x Exposures
,Renske de Veer (rdeveer)
- NOAEL: No observed adverse effect level
- TDI is the same as ADI (Acceptable daily intake).
Dose response relationships
Important routes of exposure
Toxicokinetics – Dose frequency (how much of the compound gets in) and elimination rate
,Renske de Veer (rdeveer)
- Compound A gets really slowly eliminated: shaded area → toxic.
- Repeated exposure: compounds can build up in the body.
ConsExpo
- ConsExpo is a computer program that enables the estimation and assessment of exposure to
substances from consumer products such as paint, cleaning agents and personal care
products
- Exposure routes for all consumer product:
o Inhalation:
▪ Gas/vapour
▪ Aerosols (sprays)
o Dermal absorption
o Ingestion
- Deterministic model: algorithm-based
o Calculation-generated output
- Some predefined exposure scenarios:
o Inhalation exposure: evaporation, paint and spray scenarios
o Oral exposure: hand-mouth contact, residue-on-plate scenario
o Dermal exposure: fixed volume scenario
- Exposure situation:
o Use amount (g)/source strength (g/s)
o Use frequency (per year)
o Use duration (hours)
o Exposure duration (hours)
- Environmental factors
o Temperature (C)
o Ventilation rate (1/h)
- Physicochemical substance properties
o Molecular weight
o Vapour pressue (mbar)
- Input
o Biometric data of exposed individuals
▪ Body weight (kg)
▪ Inhalation frequency (m3/24h)
• Rest
, Renske de Veer (rdeveer)
• Light exercise
• Heavy exercise
- Output
o Point value
o Distribution
▪ Median
▪ Mean
▪ 90-percentile
▪ 99-percentile
Advantages of modelling
Modelling
- Distributional or probabilistic calculations account for:
o Uncertainty: variation due to imperfect/incomplete knowledge
o Variability: natural variation in a parameter
- Modelling can be effective and efficient especially in the preparation phase
- Modelling can increase insight in the contribution of personal and environmental factors that
determine exposure exposure (sensitivity analysis)
- The uncertainty and variability in these factors can be calculated and visualized using Monte
Carlo simulation (distributional or probabilistic calculations
Sensitivity analysis
- Model sensitivity depends on:
o Model structure
o Range of parameter values
- Study the effect of changing one parameter at a time on the output
Q7 Research – Uncertainty factors in Risk assessment
HC 1. Introduction uncertainty factors in risk assessment
Fields/factors that determine individual health:
- Human biology (genetics)
- Health care organization
- Lifestyle
- Environment
Toxicology: study of the adverse effects of xenobiotics (compounds foreign to the body) in living
systems
- Toxicology applies safety evaluation and risk assessment.
- Important questions:
o Is the compound toxic?
o What are the harmful effects? What is the exposure?
o How large is the risk for man, animals and environment?
o Why is the compound toxic? What is the mechanism of action?
Pesticides, water, and mercury are toxic → paradigm of toxicity: Paracelsus. “It is the dose that
makes the poison”.
Most deadly poison in the world: Botox. → intrinsic toxicity is huge.
Why is benzene more toxic than toluene?: Formation of toxic metabolites
Risk assessment/Risk management
Exposition phase: Behaviour of a substance in the environment, changes in the application form,
available for uptake.
Toxicokinetic phase: Absorption, distribution, biotransformation (toxification, detoxification),
excretion.
Toxicodynamic phase: Interactions with receptors or other (macro)molecules at the site of operation.
➔ Phases together determine effect.
Risk = Hazards x Exposures
,Renske de Veer (rdeveer)
- NOAEL: No observed adverse effect level
- TDI is the same as ADI (Acceptable daily intake).
Dose response relationships
Important routes of exposure
Toxicokinetics – Dose frequency (how much of the compound gets in) and elimination rate
,Renske de Veer (rdeveer)
- Compound A gets really slowly eliminated: shaded area → toxic.
- Repeated exposure: compounds can build up in the body.
ConsExpo
- ConsExpo is a computer program that enables the estimation and assessment of exposure to
substances from consumer products such as paint, cleaning agents and personal care
products
- Exposure routes for all consumer product:
o Inhalation:
▪ Gas/vapour
▪ Aerosols (sprays)
o Dermal absorption
o Ingestion
- Deterministic model: algorithm-based
o Calculation-generated output
- Some predefined exposure scenarios:
o Inhalation exposure: evaporation, paint and spray scenarios
o Oral exposure: hand-mouth contact, residue-on-plate scenario
o Dermal exposure: fixed volume scenario
- Exposure situation:
o Use amount (g)/source strength (g/s)
o Use frequency (per year)
o Use duration (hours)
o Exposure duration (hours)
- Environmental factors
o Temperature (C)
o Ventilation rate (1/h)
- Physicochemical substance properties
o Molecular weight
o Vapour pressue (mbar)
- Input
o Biometric data of exposed individuals
▪ Body weight (kg)
▪ Inhalation frequency (m3/24h)
• Rest
, Renske de Veer (rdeveer)
• Light exercise
• Heavy exercise
- Output
o Point value
o Distribution
▪ Median
▪ Mean
▪ 90-percentile
▪ 99-percentile
Advantages of modelling
Modelling
- Distributional or probabilistic calculations account for:
o Uncertainty: variation due to imperfect/incomplete knowledge
o Variability: natural variation in a parameter
- Modelling can be effective and efficient especially in the preparation phase
- Modelling can increase insight in the contribution of personal and environmental factors that
determine exposure exposure (sensitivity analysis)
- The uncertainty and variability in these factors can be calculated and visualized using Monte
Carlo simulation (distributional or probabilistic calculations
Sensitivity analysis
- Model sensitivity depends on:
o Model structure
o Range of parameter values
- Study the effect of changing one parameter at a time on the output
