Lecture 5 - Hazard and Risk Assessment Flashcards
(26 cards)
Hazard
The intrinsic potential of a chemical or drug to cause adverse health effects (or unwanted environmental changes)
Risk
The likelihood that a hazard will induce adverse health effects under particular conditions of exposure
Risk = intrinsic hazard of substance x exposure
Hazard identification, hazard assessment, and risk assessment
- The identification of an intrinsic hazard
- Characterisation of the hazard (particular potency)
- The likelihood that an adverse health effect will be induced under particular conditions of exposure
Potency
What amount/level of exposure is required to elicit an adverse health effect
Measured by a dose response
Contact sensitisation: what is it also known as, what is it used for, and what is the underlying mechanisms?
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Allergic contact dermatitis
Hazard identification and risk assessment
Monitoring allergic reactions caused by low molecular weight reactive chemicals
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Murine local lymph node assay
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EC3
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Application concentration of test - chemical required to provoke a 3-fold increase in LN proliferative activity compared with concurrent vehicle treated controls.
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Risk assessment: how variable is it between different chemicals, what are the typical steps, and what do these steps allow calculation of?
Risk assessment process is fundamentally the same regardless of product/ingredient
Step 1: Hazard identification
Step 2: Dose-response assessment
Step 3: Exposure assessment
Step 4: Risk characterization
Acceptable Exposure Level (RfD)
RfD: what is it, what does it mean, and how is it calculated?
Acceptable Exposure Level
Estimate of daily exposure to an agent that is assumed to be without a health impact on the human population
NOEL/UF - no-observable effect level divided by uncertainty factor
NOEL: what is it, what is it based on, and how conservative are its values?
No observed effect level of a substance
Based on robust hazard identification data
Assigned a conservative default value if hazard identification data is less robust
SAF: what is it and how is it measured?
Sensitisation assessment factors - uncertainty factors (Uf)
Extrapolate data from the NOEL (experimental) to consumer exposure (real life)
Hazard identification: what is it determined from and what does it allow to be gathered?
- Pre-clinical studies e.g. Guinea-Pig Test, local Lymph Node Assay (LLNA)
- Human data (historical)
- Structure-based predictive approach
Weight of evidence approach
Skin sensitisation risk assessment dose response: what does it measure?
- Allergen potency
- Uncertainty factors
Skin sensitisation risk assessment dose response: what are the three areas for consideration?
- Inter-individual susceptibility - age, gender, ethnicity, genetic effects
- Vehicle or product matrix (delivery) effects - composition of the consumer product versus the experimental NOEL vehicle and presence of irritants and penetration enhancers (mixed chemicals with the substance have what kind of effect)
- Use considerations - site of contact, dermal integrity, occlusion
Occlusion
The blockage of an opening - typically a plaster blocking an open wound
Typically may result in increased absorption to the blocked location
Uncertainty factors: what are some examples, what are their issues, and by what degree do they increase the SAF?
- Inter-individual variation - large differences, difficult to assess - 10
- Product - role of vehicle/matrix - 0.3 (inert objects), 1 (most products), or 3 (containing penetration enhancers)
- Frequency/duration of use -0 extended periods of use may result in bioaccumulation - 1 (intermittent/limited use) or 3 (extended use)
- Occlusion - skin could be occluded - 1 (all body parts could be covered by clothing)
- Skin condition/site - pre-existing inflammation or a site prone to irritation - 1 (no inflammation), 3 (pre-existing inflammation or site), or 10 (sensitive sites (ie axilla))
Inter-individual variation: why and to what degree may it affect SAF?
Large differences, difficult to assess
- 10
Uncertainty fctors: what are some examples, what are their issues, and by whar defree do they increase the SAF?
- Inter-individual variation - large differences, difficult to assess - 10
- Product - rold of vehicle/matrix - 0.3 (inert objects), 1 (most products), or 3 (containning penetration enhancers)
- Frequency/duration of use -0 extended periods of use may result in bioaccumulation - 1 (intermittent/limited use) or 3 (extended use)
- Occlusion - skin could be occluded - 1 (all body parts could be covered by clothing)
- Skin condition/site - pre-existing inflammation or site prone to irriliattion - 1 (no inflammation), 3 (pree existing inflammaruin or site), or 10 (sensitive sites (ie axilla))
Product variation: why and to what degree may it affect SAF?
Role of vehicle/matrix
- 0.3 (inert objects)
- 1 (most products)
- 3 (containing penetration enhancers)
Frequency/duration of use: why and to what degree may it affect SAF?
Extended periods of use may result in bioaccumulation
- 1 (intermittent/limited use)
- 3 (extended use)
Occlusion: why and to what degree may it affect SAF?
Skin could be occluded
- 1 (all body parts could be covered by clothing)
Skin condition/site: why and to what degree may it affect SAF?
Pre-existing inflammation or a site prone to irritation
- 1 (no inflammation)
- 3 (pre-existing inflammation or site)
- 10 (sensitive sites (ie axilla))
Skin sensitisation risk assessment risk characterisation: what stage of risk assessment is this, what does it do, and why is it so important?
Step 4
Calculate the maximum acceptable exposure level using NOEL and uncertainty factors, and comparing this value to the calculated consumer exposure (RfD/CE)
The amount per xg/xm² that is in the acceptable level should be accepted for use, but the amount per xg/xm² that is in the uncertainty factor zone or NOEL zone is unlikely to be accepted for use
axilla
armpit
