22/11/2012 Aggregate exposure assessment: tiered...
Transcript of 22/11/2012 Aggregate exposure assessment: tiered...
22/11/2012
Aggregate exposure assessment: tiered approaches and illustration for indoor environments Rudi Torfs, VITO
22/11/2012 2 © 2012, VITO NV
CEFIC-LRI projects B4-CERTH & B5-THL (2010-2012)
22/11/2012 3 © 2012, VITO NV
AEA: an assessment of exposure to a single agent from all potential sources and pathways (the physical course taken by an agent as it moves from a source to a point of contact with a person) and the related exposure routes
22/11/2012 4 © 2012, VITO NV
Context
» ECETOC: Contribute to the development of a pragmatic, realistic, and science-based framework for the risk assessment of chemical mixtures.
» CEFIC-LRI: 21st Century Approaches to Risk Sciences
» Health impact of complex environments
» Exposure to mixtures, from multiple sources, indoor…
» Why? the need to have a better representation of exposure
» REACH (Biocides, food safety…)
» Moving towards integrated exposure science
(‘the exposome’)
22/11/2012 5 © 2012, VITO NV
Challenges
» Quantifying all possible sources, pathways and routes of exposure can become a very complex task in terms of data collection, data assessment, exposure modelling and – not least – verification.
» TAGS to provide a ‘decision structure’
» When to go to higher tiers
» Partial or incomplete tools to evaluate a full AEA
» ECETOC-TRA
» Full chain modelling tools (INTERA)
» Inconsistent ways to evaluate adequacy of models and data
» Verification strategy in TAGS
22/11/2012 6 © 2012, VITO NV
The Tiered Aggregate Approach (TAGs) - within Exposure Scenario
6
Tier 0
Tier 1
Tier 2
Define exposure scenario (single source)
Basis for
aggregation across
routes /
pathways?
dominant route /
pathway?
SEA – within exposure scenario
(Tier 1)
SEA – within exposure scenario
(Tier 2)
AEA – within exposure Scenario
(Tier 1)
AEA – within exposure Scenario
(Tier 2)
No
Yes
Yes
No
22/11/2012 7 © 2012, VITO NV
The Tiered Aggregate Approach (TAGs) - within Exposure Scenario
7
Tier 0
Tier 1
Tier 2
Define exposure scenario (single source)
Basis for
aggregation across
routes /
pathways?
dominant route /
pathway?
SEA – within exposure scenario
(Tier 1)
SEA – within exposure scenario
(Tier 2)
AEA – within exposure Scenario
(Tier 1)
AEA – within exposure Scenario
(Tier 2)
No
Yes
Yes
No
Identify all relevant routes of exposure (inhalation, dermal, ingestion) and the pathways for each exposure route.
Identify toxicological and/or health endpoints associated with each route and assess these for commonality.
22/11/2012 8 © 2012, VITO NV
The Tiered Aggregate Approach (TAGs) - within Exposure Scenario
8
Tier 0
Tier 1
Tier 2
Define exposure scenario (single source)
Basis for
aggregation across
routes /
pathways?
dominant route /
pathway?
SEA – within exposure scenario
(Tier 1)
SEA – within exposure scenario
(Tier 2)
AEA – within exposure Scenario
(Tier 1)
AEA – within exposure Scenario
(Tier 2)
No
Yes
Yes
No
Identify if there is one dominant route and/or pathway of exposure compared to all other routes/pathways combined
22/11/2012 9 © 2012, VITO NV
Define relevant exposure scenario
(multiple source)
Basis for
aggregation across
exposure scenarios
(plausible)?
dominant plausible
exposure
scenarios?
No AEA across exposure scenarios AEA – across exposure scenario (Tier 1)
AEA – across exposure scenario (Tier 2)
No
Yes
No Yes
The Tiered Aggregate Approach (TAGs) - across Exposure Scenarios
22/11/2012 10 © 2012, VITO NV
Define relevant exposure scenario
(multiple source)
Basis for
aggregation across
exposure scenarios
(plausible)?
dominant plausible
exposure
scenarios?
No AEA across exposure scenarios AEA – across exposure scenario (Tier 1)
AEA – across exposure scenario (Tier 2)
No
Yes
No Yes
The Tiered Aggregate Approach (TAGs) - across Exposure Scenarios
define the population groups of interest (e.g. consumers, workers, susceptible groups, geographical area, socio-economic status)
can the exposure from different scenarios lead to the same health endpoint or not
22/11/2012 11 © 2012, VITO NV
Define relevant exposure scenario
(multiple source)
Basis for
aggregation across
exposure scenarios
(plausible)?
dominant plausible
exposure
scenarios?
No AEA across exposure scenarios AEA – across exposure scenario (Tier 1)
AEA – across exposure scenario (Tier 2)
No
Yes
No Yes
The Tiered Aggregate Approach (TAGs) - across Exposure Scenarios
For each combination of plausible exposure scenarios, determine if there are any scenarios that completely dominate the exposure from all other scenarios combined
22/11/2012 12 © 2012, VITO NV
Tiered approach : next steps
» Steps to go from TIER 0, via pre-TIER 1 to TIER 1 and further
TIER 1 – stage 1
TIER 1 INFORMATION
Default tier 1 model
- optional -
Module for input of
exposure estimates
from other tier 1
models
TIER 0 OUTPUT
· Quantification of uses/sources
· Toxicological criteria (by route, age,
duration)
· Physicochemical properties
· Levels in compartments
· Generates exposure (dose/concentration) for the
selected use/source and routes
· Generates exposure by predefined subpopulations
· Aggregates exposure across relevant routes for each
scenario
· RCR by route for each scenario
· Aggregate RCR across routes for each scenario
· Relative contribution of routes for each scenario
TIER 1 INFORMATION
· Plausible combinations of
scenarios
TIER 1 – stage 2
· Combines plausible combinations of scenarios to
describe hypothetical (sub)populations
· Aggregates exposure within (sub)populations (across
scenarios, across routes if relevant)
· RCR by route within (sub)population
· RCR by pathway, use/source within (sub)population
· Relative contribution of routes, pathways, uses, sources
TIER 1 – measured data
- optional -
Module for dose
calculations from levels
in compartments
· Default exposure
parameters
· Exposure by routes
and pathways
· Exposure by
predefined sub-
populations
· RCR by route
within
(sub)population
· RCR by pathway
within
(sub)population
· Relative
contribution of
routes, pathways
TIER 1 OUTPUT· Integrated evaluation
· Need for higher tier AEA
· Delineation of higher tier
Optional
pre-Tier 1
Select appropriate exposure scenario
Perform Tier 1 – stage 1 for every identified use/source
22/11/2012 13 © 2012, VITO NV
Tiered approach : next steps
TIER 1 – stage 1
TIER 1 INFORMATION
Default tier 1 model
- optional -
Module for input of
exposure estimates
from other tier 1
models
TIER 0 OUTPUT
· Quantification of uses/sources
· Toxicological criteria (by route, age,
duration)
· Physicochemical properties
· Levels in compartments
· Generates exposure (dose/concentration) for the
selected use/source and routes
· Generates exposure by predefined subpopulations
· Aggregates exposure across relevant routes for each
scenario
· RCR by route for each scenario
· Aggregate RCR across routes for each scenario
· Relative contribution of routes for each scenario
TIER 1 INFORMATION
· Plausible combinations of
scenarios
TIER 1 – stage 2
· Combines plausible combinations of scenarios to
describe hypothetical (sub)populations
· Aggregates exposure within (sub)populations (across
scenarios, across routes if relevant)
· RCR by route within (sub)population
· RCR by pathway, use/source within (sub)population
· Relative contribution of routes, pathways, uses, sources
TIER 1 – measured data
- optional -
Module for dose
calculations from levels
in compartments
· Default exposure
parameters
· Exposure by routes
and pathways
· Exposure by
predefined sub-
populations
· RCR by route
within
(sub)population
· RCR by pathway
within
(sub)population
· Relative
contribution of
routes, pathways
TIER 1 OUTPUT· Integrated evaluation
· Need for higher tier AEA
· Delineation of higher tier
Optional
pre-Tier 1
Select appropriate exposure scenario
Perform Tier 1 – stage 1 for every identified use/source
TIER 0 OUTPUT
Adequate biomonitoring
and associated health
criteria available?
Compare exposure
and heath criteria
Go to tier 1
assessment
Potential human
health risk?
No
Yes
StopNo
Yes
Go to tier 1 or
higher tier
assessment
Risk reduction
strategies
22/11/2012 14 © 2012, VITO NV
Tools for AEA
» The current, non-aggregated version of the ECETOC TRA tool forms a good basis for the further development of a Tier 1 tool for AEA.
» The structure and the current formulas and spreadsheets of the ECETOC TRA tool allow fairly easily the modifications to turn the tool into a more complete AEA tool.
» In TAGS we suggest modifications to account for:
» adult and children exposure separately in the consumer module ;
» adult and children exposure separately in the environment module ;
» aggregate exposure across routes (within scenario);
» aggregate exposure across scenarios (and across routes).
22/11/2012 15 © 2012, VITO NV
Verification strategy » To strengthen the plausibility of the assessment.
A. verification of the applicability domain of substances and spatial and temporal resolution;
B. verification of the conceptual model;
C. verification of the applicability domain of databases and parameters;
D. verification of model software implementation;
E. verification of model predictions (assessment verification):
» E1. verification of intermediate steps along the source to receptor chain, and
» E2. verification of by means of biomonitoring data.
validity of conceptual
model
validity of
implementation
availability of existing
data for verification
verification data supporting
asssessment
assessment A major source missing
assessment B OK not OK - -
assessment C OK OK - -
assessment D OK OK limited data
data inappropriate for
verification
assessment E OK OK OK
limited support due to
inappriate data
assessment E OK OK OK
verification data support
assessment
22/11/2012 16 © 2012, VITO NV
Illustration of Tiered Aggregate exposure: TAGS BDE 209 case study
» TIER 0 : need for aggregation? » Yes : systemic health effects: neurodevelopmental, liver, thyroid and possible contribution
from different pathways and routes
» Pre-TIER 1: Indication of low risk, however: » data for children; lower brominated congeners
» TIER 1: » ECETOC TRA v2 overconservative
» Assessment based on measured levels:
» Highly exposed subpopulations
» Lacks direct contact with articles
» Generation of lower brominated congeners
not accounted for
» TIER 2: » Low to no health risk
» Need to account for children in all tiers
» Evaluate EFSA dietary methodology and data versus ECETOC TRA dietary data
0
5
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45
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1975 1980 1985 1990 1995 2000 2005 2010 2015
ng
/g li
pid
Austria Belgium Denmark Faroer France Greece
Luxemburg Norway Spain Sweden the Netherlands United Kingdom
0
50
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150
200
250
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2002 2003 2004 2005 2006
ng
/g li
pid
Luxemburg the Netherlands United Kingdom
Adult serum levels
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Summary
» The TAGS project developed a tiered approach to (non-occupational) aggregate exposure assessment, distinguishing three tiers with increasing levels of data needs and complexity.
» A methodology and process for verification of aggregate exposure assessments is available.
» A tiered approach guiding the user towards the relevant aspects of aggregation helps to optimize and reduce efforts.
» Suggestions to improve the ECETOC TRA with TAGS findings
» Full chain modelling tool has been developed for indoor exposures =INTERA
22/11/2012 18 © 2012, VITO NV
Integrated Exposure for Risk Assessment in Indoor Environments (INTERA)
» The INTERA project (http://www.intera-home.eu/) developed and applied a full chain mechanistic modelling approach that includes:
» The relations among the sources of contamination (outdoor and indoor), and the levels of indoor contamination.
» The modelling of actual exposure to indoor contamination, from source to dose, including internal dose modelling (Physiology Based ToxicoKinetic (PBTK) modeling)
» Available at http://www.intera.cperi.certh.gr
» As part of INTERA a Knowledge Management System has been developed: » Incorporating appropriate databases of quality assured source data;
» Making available and applying suitable models and statistical methodologies for the characterization and treatment of such data;
» With the ability to display exposure predictions in a number of formats.
» Available at http://en.opasnet.org/w/Intera
22/11/2012 19 © 2012, VITO NV
Client side (browser)
Server side
Computational platform
Visualization platform
(PHP data processing) 1 2
3
Results database
22/11/2012 20 © 2012, VITO NV
To conclude and continue
» Better and more integrated tools for tiered aggregate exposure assessment are needed to overcome the current difficulties when using different models for part of the aggregate exposure modelling.
» More data is needed in many cases, for instance for model parameterization and verifying the aggregate exposure assessment.
» Try developing research to differentiate the exposure assessment between children and adults.
» In the longer term all knowledge and tools, including aggregate exposure tools, should be integrated in an overall framework to characterize the exposome.
22/11/2012 21 © 2012, VITO NV
Thank you
Arja Asikainen, Katleen DeBrouwere, Emma Doust, Karen Galea, Alberto Gotti, Einari Happonen, Araceli Sanchez Jimenez, Anastasios Karabelas, Spyros Karakitsios, Periklis Kontoroupis, Eelco Kuipers, Elias
Mplatsis, Spyridoula Nikolaki, Denis Sarigiannis, Sean Semple, Arnout Standaert, Rudi Torfs, Matti Jantunen, Martie van Tongeren, John Cherrie, Christa Cornelis, Carole Garden, Sally Spankie
created for Cool Risk.com by Michael Mittag