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Validation of a tiered approach to aggregate exposure modelling
Project B7-ETHZ
CEFIC LRI 2014 Annual Meeting
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Introduction
Project team and structure
Steering board Bruno Hubesch, CEFIC-LRI Chris Money, ExxonMobil Carlos Rodriguez, P&G
Project Leader/Manager Dr. Natalie von Goetz, ETH
Team 1
(Guidance and modelling)
Team 2
(Questionnaire and biomonitoring)
Team 3 T
(Modelling and validation)
Other stakeholders Cosmetics Europe Dow Corning Corp. Unilever
1 of 9 [email protected] CEFIC LRI 2014 Annual Meeting
WP1 WP2 WP3
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Introduction 2 of 9
Motivation >89 million unique chemicals (CAS registry, 2014) Aggregate exposure – multi-source and multi-route Tier 1 tools are available (ECETOC TRA, A.I.S.E. REACT) Methodologies for realistic assessment are required
Consumer products
Pharmaceuticals
Housing & construction
Energy
Agriculture & Food
Electronics [email protected] CEFIC LRI 2014 Annual Meeting
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Aggregate consumer exposure modelling
HIGHER TIER assessment
! Adequate aggregation strategy § Person-oriented approach – authentic robust input data (e.g. products co-use)
§ Toxicokinetics – aggregation over different routes on an appropriate timescale
! Validation piece is missing
ü Retention
ü Residue transfer
ü Inadvertent ingestion
ü Indoor air conc.
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Universität Zürich | 06 December 2013 | XeRR annual meeting
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Higher Tier exposure model (PACEM)
Introduction
Product database
§ Fraction of a substance that is available for further intake as a result of product application
§ Is either a point value or frequency distribution
Questionnaire database
! intake !
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(Biesterbos et al., 2013)
(Dudzina et al., 2013)
! Aggregation per individual per day !
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Evaluation of tiered approach (WP3)
Introduction
5.5-fold
toothpaste
lipstick/lipbalm
10-fold
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Properties
Molar mass [g/mol] 371
Vapor pressure at 25C [Pa]
33.2
logKow 8.0
Effect on the environment vPvB
LOAEL [mg/kg_bw/day] 100
NOAEL [ppm] 150
D5 case-study
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Validation of tiered approach (WP3)
[email protected] CEFIC LRI 2014 Annual Meeting
(Pieri et al., 2013)
Baseline D5 concentrations in end-exhaled air
from 15 volunteers (Biesterbos et al., 2014)
Baseline D5 concentrations in blood plasma from 94 women
(Hanssen et al., 2013)
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Indoor air concentrations
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Population HBM data
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Validation exercise
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Individual HBM data (WP2)
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 150
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
D4D5Women
Men
Volunteer
Con
cent
ratio
n in
end
-exh
aled
air
(ng/
m3 )
Panel biomonitoring study with 5 men
and 10 women
End-exhaled air analysis (GC-TD-MS)
after normal use of personal care
products (24h product use diaries)
A B C D E F G H I J X K Y L M
?
Validation exercise
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Key findings
! Person-oriented approach allows more realistic aggregate consumer exposure modelling, BUT...
n Need for robust high-quality data n Not necessarily applicable to other sectors of consumer products
! Individual-based HBM data enable robust validation of exposure predictions
! Main challenges for validation:
n Aggregate multi-route exposure n Identify dominant sources n Consider time intervals between single exposure events relative to elimination half-life
(relevant for short-lived biomarkers)
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Universität Zürich | 06 December 2013 | XeRR annual meeting
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Thank you
Dr. Natalie von Götz [email protected]
Christiaan Delmaar Martine Bakker Bas Bokkers Jacqueline van Engelen
Jacqueline Biesterbos Paul Scheepers Nel Roelveld
Universität Zürich | 06 December 2013 | XeRR annual meeting
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PACEM uncertainty analysis
Introduction
Input parameter
use amounts 1.2 14.4
use frequencies 1.1 10.0
D5 concentrations 2.5 24.9
eFs 1.1 12.1
ALL together 4.5 38.9
Input parameter
use amounts 1.2 14.4 use frequencies 1.1 10.0 D5 concentrations 2.5 24.9 eFs 1.1 12.1 ALL together 4.5 38.9
Universität Zürich | 06 December 2013 | XeRR annual meeting
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Perfume_spray
