Risk Assessment

Lecture 10

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 What is the Risk?
• Risk - possibility or
probability of suffering
harm from a hazard ????

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 Introduction to Risk Assessment,
a Regulatory Science
• Why risk assessment?
– Must sometimes take action without full scientific
understanding of hazard

– Risk assessment sets default procedures for

bridging gaps in scientific understanding

– Basic framework: evaluate exposure and toxicity;

bring this information together to characterize a
health risk →

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Environmental Sites Assessment
What is Risk Assessment?
PHASE PHASE PHASE PHASE

I II III IV
Assessment Characterization Remediation/ Verification
Management
Document Review Intrusive Sampling Contaminant Verification Sampling
Interviews Investigation Destruction or to Confirm Estimates
Removal Management Plan
Site Inspection Physical Testing
Risk Assessment
Contact
Authorities
“… technical, scientific assessment of
Risk assessment – scientific process the nature and magnitude of risks”
in estimating how much harm a (from MOE Guidance document)
particular hazard can cause
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 Benefits of Risk Assessment
(extracted from Natural Research Council)

• When agent suspected of causing diseases

• Testing new chemical
• Help rank contribution to overall risk
• Help identify risks that are easily reduced or
eliminated
• Help clarified what is known and not known about
situation
• Can provide quantitative information for decision
making

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 Applications
• Health Canada – regulations for foods and drugs
• Canada Council of Ministers of the Environment
◦ National Contaminated Sites Program
◦ Canada-Wide Environmental Standards (CWES)

• Ontario Ministry of Environment

◦ Site-specific clean-up guidelines for contaminated soils

• CEPA (Canadian Environmental Protection Agency)

◦ 23 000 substances currently in use
◦ Persistent, bioaccumulation, toxic ????

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 Stages of Risk Assessment
1.Problem Definition
2. Identify Contaminant
3. Receptor Analysis
4. Pathways Analyses
5. Exposure Assessment
6. Toxicity Assessment
7. Risk Characterisation
8.Uncertainties
9. Critique In the past

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Risk Assessment Framework
Problem Definition

Qualitative Contaminant Receptor Pathway

Stage Screening Screening Analysis

Conceptual Exposure Model

Exposure Toxicity
Assessment Assessment
Quantitative
Stage

Risk
Characterization

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 1. Problem Definition
• Purpose
• Management goals
• Policy context
• Audience?
• Hazard definition
• Receptors ?
• Level of funding

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 2. Identify Contaminant
• Single compounds or
• Complex mixture with a few compounds
driving toxicity
• Contaminated soil, and/or air pollution
and/or …?

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 3. Receptor Analysis
• Organism, species or groups of species exposed to stressor
• Define scenario:
– Length of exposure (life time, 20 years – latency for cancer)
– Incremental or total exposure
– Define routes of exposure (ingestion, inhalation, dermal)
– Determine rate of exposure from each route
– Characterized activity pattern that results in exposure
– Human: who? average person, age, gender
– Average & worst case
– Sensitive subpopulation (recent interest in children)

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 4. Pathways Analyses
• Determine environmental fate that results in
exposure to receptor
• Evaluate routes of exposure
• Quantify amount of exposure (DOSE)
• Methods
– Measurements (how representative ??)
– Modeling

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 5. Exposure Assessment (1)
• Multiple routes of exposure

• Quantify exposure from:

– Air (indoor/outdoor)
– Water (drinking, showering, …)
– Soil
– Sediments
– Diet (many varieties)
– Other
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 5. Exposure Assessment (2)
• Exposure (g of chemical / day) is :

CONCENTRATION x INTAKE RATE

OR
Cf X IRf = exposure from ingestion (food)
Ca X IRa = exposure from inhalation (air)
Cd X IRd = exposure from dermal contact
Where
Cf,a,d is concentration (e.g. g of chemical / kg of food)
IR is intake rate (e.g. kg of food / day)

Total exposure = exposure 1 (food) + exposure 2

(air) + exposure 3 (dermal ) + …… 14
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EESA10 Dr. Silvija Stefanovic
 5. Exposure Assessment (3)
• EDI - Estimated Daily Intake (estimate dose, for each
exposure medium) Exposure factor
EDI = IR x C x B X EF x ED
BW AT
Exposure
EDI is estimated daily intake , mg/kg body weight /day
IR is intake rate, m3 air /day or kg food/day
C is chemical concentration, mg/m3 air or mg/kg food
B is bioavailability factor, dimensionless, fraction of chemical
available for uptake in organism
EF is exposure frequency, d/y ED
is exposure duration, d
BW is body weight, kg Considers biologically
AT is averaging time, d effective dose

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 Example
• A child is exposed to contaminated soil at her
nursery school. She attends the school 3 days
a week over 4 years

• Exposure factor : 3 d/week x 52 weeks/y x 4 y

4y x 365 d /y

EF x ED Exposure factor
AT

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 Total EDI
EDI - Estimated Daily Intake (estimate dose, for each
exposure medium)

Total EDI = EDI (food) + EDI (air) + EDI (dermal)

+ ……

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 6,7. Toxicity and Risk Assessment
• A fundamental assumption in chemical risk
assessment:
– Noncancer effects have thresholds
– Carcinogenicity has no threshold
• Therefore, key steps in risk assessment play
out differently for cancer (no threshold) and
non cancer (threshold) effects

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Assessment of non-carcinogenic
Hazard

1.Exposure assessment—measure or
estimate dose in mg/(kg*day)

2.Hazard identification—establish range of

noncancer effects; select one as basis

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 Assessment of non-carcinogenic
Hazard
3. Dose-response assessment
– Determine dose-response relationship (Chronic rodent
bioassay)
– Determine NOAEL and LOAEL from the graph
– Derive reference dose (RfD) in mg/(kg*day)—dose expected to
have no adverse effects in sensitive people with lifelong
exposure
– How??? Derive RfD from rodent NOAEL or LOAEL, by dividing it
by uncertainty factors (to make RfD lower and thus more
protective)

4. Risk characterization:
– Hazard quotient (unitless) = actual or EDI (estimated dose) /
reference dose
– Hazard quotient >1.0 indicates potential for harm at actual or
estimated dose EESA10 Dr. Silvija Stefanovic 20
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 Assessment of Carcinogenic Hazard
• No safe dose
• Theoretically 1 molecule could induce 1 tumour

1. Exposure assessment—measure or estimate

dose in mg/(kg*day)

2. Hazard identification—assess toxicant’s

potential to cause cancer in humans. How???

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 Assessment of Carcinogenic Hazard

Weight-of-the-evidence categories for

carcinogenicity, as defined by IARC: IARC- International
Agency for Research on
– Group 1: Carcinogenic to humans Cancer
– Group 2A: Probably carcinogenic to humans
– Group 2B: Possibly carcinogenic to humans
– Group 3: Not classifiable as to carcinogenicity to
humans
– Group 4: Probably not carcinogenic to humans

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Assessment of Carcinogenic Hazard
3. Dose-response assessment
• Determine dose-response relationship (Chronic rodent
bioassay)
• Derive cancer slope factor —estimate of potency
(cancer risk per mg/(kg*day)

4. Risk characterization
• Incremental lifetime risk (probability) = actual or EDI
(estimated dose) * slope factor
• Hazard quotient >1.0 indicates potential for cancer at
actual or estimated dose
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 Assessment of Carcinogenic
Hazard
RMOS -Calculate exposure that will result in acceptable risk

RMOS (Relative margin of safety)= EDI

RsD

RsD (Risk specific Dose) = Acceptable risk

Slope factor

Decision Point:
OK if RMOS < 1
Not OK if RMOS >1

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 8. Uncertainties
• Pathways analyses
– Insufficient data
– Measurement errors
– Capturing natural variability
– Future predictions (assume conditions same as today)

• Exposure analysis EDI

– Difficult to estimate for children
– Bioavailability

• Toxicity Assessment
– RsD, RMOS, establish relevant dose-response relationship

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 9. Critique
• Best developed for human carcinogens

• What about others????

• Based on numerous assumptions and large

uncertainties

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 Risk Analyses
• Comparative risk analyses - Ranking risk
• Risk management – options and decisions about
reducing or eliminating risk
• Risk communication –informing decision makers and
public

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 Risk Management
• Actions taken, often by government agencies,
to control or reduce environmental risks to
human health

• Considers magnitude of the health risk,

regulatory framework, technical options for
controlling the hazard, costs, and social
context including environmental justice

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 Risk Management
• Individual chemicals (e.g., in drinking water or
workplace air)
– Decisions about goals for standards
– Decisions about feasible standards

• Contaminated sites
– Complex: multiple chemicals, multiple media
– Consider: toxicity, future uses of site,
effectiveness of cleanup options, costs

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 Other Examples of
Risk Management
• Limits on emissions, requirements to treat wastes

• Changes to industrial processes, isolation of a

hazardous process in the workplace

• Incentives for compliance, penalties for noncompliance

• Publicly available information as incentive

• Work of local health departments

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 Risk Communication
• Risk communication = exchange of
information about a hazard between experts
and those affected

• Public perception of environmental health

risks as “hazard plus outrage”

• Specific features of environmental hazards

often generate outrage

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 The Precautionary Principle
• The 1998 Wingspread Statement on the Precautionary Principle
summarizes the principle this way:
"When an activity raises threats of harm to human health or the
environment, precautionary measures should be taken even if some cause
and effect relationships are not fully established scientifically."

• The February 2, 2000 European Commission Communication on the

Precautionary Principle notes:
"The precautionary principle applies where scientific evidence is insufficient,
inconclusive or uncertain and preliminary scientific evaluation indicates
that there are reasonable grounds for concern that the potentially
dangerous effects on the environment, human, animal or plant health
may be inconsistent with the high level of protection chosen by the EU".

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 The Precautionary Principle
• Examples of precautionary approach
– International agreements
• Kyoto Protocol on global climate change
• Montreal Protocol on ozone-depleting chemicals
– US Toxic Substances Control Act
– European Union’s REACH program for new
chemicals
– CCA wood preservative

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 The Precautionary Principle
• Some lost opportunities for precaution
– Widespread, long-term use of asbestos
– Large-scale development and use of synthetic
organic chemicals
• eg.DDT
– Depletion of global fisheries
– Food industry practices that amplified “mad cow
disease” and caused human illness

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