ILSI Health and Environmental Sciences Institute HESI'S RISK21 Program Roadmap and Matrix
Paradigm Shift in Risk Assessment
Uncertainty
factor
Hazard ID
Hazard characterisation
Exposure assessment
Risk characterisationR
esp
on
se
Dose
Risk Assessment in the 21st Century (RISK21)
• MISSION: Bring applicable, accurate, and resource
appropriate approaches to the evolving world of human
health risk assessment
• Convened experts from academia, industry, government
and other stakeholders
• RISK21 involved > 120 scientists from Europe and USA
• Developed a risk assessment approach that embraces
advances in scientific knowledge and methods
• Revised current thinking about how to approach the
science and art of risk assessment
How is RISK21 Different?
• Think about the problem that needs to be addressed; then select
sources of information which will have the most value
• RISK21 Principles:
– Problem-formulation based
– Exposure-driven
– Prior knowledge
– “Enough precision to make the decision”
• Provide a framework that is…
– Flexible
– Transparent
– Visual
Problem
Formulation ConcludeExposure?
Toxicity?
Risk? Safety?Mode of Action
In vivo
In vitro
QSAR/
TTC
1
4
Biomonitoring
Probabilistic
Deterministic
Minimal
Info
2
3
Problem
Formulation ConcludeExposure?
Toxicity?
Risk? Safety?Mode of Action
In vivo
In vitro
QSAR/
TTC
1
4
Biomonitoring
Probabilistic
Deterministic
Minimal
Info
2
Exposure
range
Toxicity range
3
Problem Formulation: The Starting Point
• Sets out:
– Objectives
– Scope
– Hypotheses
• Asks:
– what do you know?
– what do you need to know?
– How do you know when you’re done?
Enough precision to make a decision
Enough Precision for Exposure EstimateIn
cre
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Estimate based on
samples from exposed
individuals
Detailed use
knowledge. Use
measurements
specifically relevant to
use
Use exposure
model(s) with
population,
exposure route,
environmental
fate, volume,
release, and
specific-use
information
Minimal information, such as
physical-chemical properties and
use knowledge. Estimate may
include :
Environmental background
Consumer Uses
Industrial Uses
Tier 3:
Biomonitoring
Tier 2:
Probabilistic
Tier 1:
Deterministic
Tier 0: Minimal
Info
Exposure Assessment
• Evaluation of the concentration of a particular agent that reaches a target – Nature
– Magnitude
– Frequency
– Duration
– Route
– Extent
• Describes the ways people come into contact with an agent
• Describes the relevant media and exposure routes
• Provides metrics of exposure to characterize health risks
• Determines if guidance value of an exposure concentration indicates need to perform a risk characterization
10
Sources of Information for Exposure Tiers
Tier DescriptionExamples of
tools/models/data
Tier 0 Limited substance and/or specific use knowledge.
Use of physical-chemical properties.
EPI Suite, look-up tables
from various models,
monitoring databases,
physical-chemical
properties, etc.
Tier 1
Limited use knowledge. Models with population,
exposure route, environmental fate, volume, release,
and specific-use information; geometric mean
monitoring values.
ECETOC TRA, USETox,
ConsExpo, EUSES, etc.
Tier 2
Detailed use knowledge. Specific contaminant
monitoring and measurement data for use in
probabilistic modeling.
PRZM-EXAMS, SHEDS, full
distribution of monitoring
data, etc.
Tier 3
Extensive use knowledge. Internal dose,
biomonitoring information, specific contaminant
monitoring and measurement data.
National Report on Human
Exposure to Environmental
Chemicals, NHANES, etc.11
Enough Precision for Toxicity Estimate
Structure & activity relationships
plus existing databases such as
Threshold of Toxicological
Concern (TTC)
Predictive assays plus in
vitro to in vivo
extrapolation (IVIVE)
Apical
endpoints
Dose-response for mode
of action, Key Events
Dose-Response
Framework (KEDRF)
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Tier 3:
Mode of Action
Tier 2:
In vivo
Tier 1:
In vitro
Tier 0:
QSAR/
TTC
Benefits of the RISK21 Framework
• Optimizes use of existing data and integration of new data,
using conventional or emerging methods, when relevant
• Gives appropriate weight to exposure and hazard
• Highly visual, flexible and very transparent
• Effective risk communications tool
• Multiple applications, e.g:
– Priority setting
– Evaluation of data needs
– Evaluation of new use or release scenario
– Comparison of different risk mitigation options
– Value of information analysis
• Can inform study design & resource allocation