is a mixture assessment factor (maf) the right way forward? thomas backhaus university of gothenburg...
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Is a mixture assessment factor (MAF) the right way forward?
Thomas BackhausUniversity of Gothenburg [email protected]
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Area Size Reference
Environment 100 Janssen, 2004; van Vlaardingen, 2007
Environment 100 Tørsløv, 2013
Human health 100 Muilerman, 2011
Human health 10 Tørsløv, 2013, Petersen, 2014
Suggested MAFs
No explicit justification given
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easy to implement
no additional data needed
increased level of protection
CONSPROS
blanket type of approach
hard to justify size
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Conservatism in Hazard Assessment
REACH Guidance Document, Chapter R10, 2008
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No biotransformation
No abiotic transformation
High production volumes, resp. market share
High emission rates
Emission takes place in a confined space
Emission happens suddenly (peak concentrations)
Conservatism in Exposure Assessments
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Hazard Assessment Assessment Factors
Exposure Assessment Conservative Assumptions
Consideration of Uncertainties
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Assessment of Single Substances
Exposure Assessment Hazard Assessment
Risk Assessment
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Assessment of Mixtures
Exposure Assessment
Hazard Assessment
Risk Assessment
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A Mixture Assessment Factor needs to cover exposure and hazard assessment
Assessment of Mixtures
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The simultaneous presence of compounds as mixtures is ignored
Not all components included
Insufficient (eco)toxicological knowledge on the mixture components
Sole use of CA
Interactions (synergistic, antagonistic)
Mixture-specific uncertainties
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Equals the number of expected compounds in a mixture
MAF based on Concentration Addition
n
ECxc i
i
xMixE CA )(
if
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Equals the number of expected compounds in a mixture
E.g.: the CA-expected effect of a mixture is lower than 10%, if all components of a 100-compound mixture are below a concentration of EC10/100
MAF based on Concentration Addition
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Pesticide Mixture
Result from the Swedish pesticide monitoring program
n = 42
.
Example
andardQuality St talEnvironmen
ionConcentrat MonitoredQuotient Risk
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Distribution of Risk Quotients
0
20
40
60
80
100
120
140
Cum
ulati
ve H
azar
d In
dex
136
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Several individual compounds are present at concentrations above their EQS.
Need for regulatory action already on the single substance level
Assumption: successful risk mitigation, i.e. all compounds are present at a concentration below their respective EQS.
Environmental Risk of the pesticide mixture
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Distribution of Risk Quotients after risk mitigation
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
Cum
ulati
ve H
azar
d In
dex
16.0
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Maximum Cumulative Ratio
Units Toxic of Maximum
Units Toxic of SumMCR
nMCR Equitoxic Mixture:
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4 different scenariosMixture Type n Prior
adjustment After risk
mitigation for single compounds
Risk quotient MCR Risk
quotient MCR
Pesticides 42 136 3.6 16.80 17
Pharmaceuticals 18 48 1.2 4.65 4.7
Anti-androgens 15 2.01 2.01 2.00 2.00
Organic air pollutants 29 4.33 2.9 3.78 3.9
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Maximum exceedance of a safe levelin various situations
‘n’ known Individual RQ’s < 1
RQ’s quantified
Info. on interactions?
MAF
no unknown no no arbitrary valueyes unknown no no arbitrary valueyes yes no no number of mixture
components*IFyes yes no interactions
unlikelynumber of mixture components
yes yes yes no MCR*IFyes yes yes interactions
unlikelyMCR
yes yes yes yes case-by-case based on weight of evidence
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Maximum exceedance of a safe levelin various situations
‘n’ known Individual RQ’s < 1
RQ’s quantified
Info. on interactions?
MAF
no unknown no no arbitrary valueyes unknown no no arbitrary valueyes yes no no number of mixture
components*IFyes yes no interactions
unlikelynumber of mixture components
yes yes yes no MCR*IFyes yes yes interactions
unlikelyMCR
yes yes yes yes case-by-case based on weight of evidence
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Maximum exceedance of a safe levelin various situations
‘n’ known Individual RQ’s < 1
RQ’s quantified
Info. on interactions?
MAF
no unknown no no arbitrary valueyes unknown no no arbitrary valueyes yes no no number of mixture
components*IFyes yes no interactions
unlikelynumber of mixture components
yes yes yes no MCR*IFyes yes yes interactions
unlikelyMCR
yes yes yes yes case-by-case based on weight of evidence
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Maximum exceedance of a safe levelin various situations
‘n’ known Individual RQ’s < 1
RQ’s quantified
Info. on interactions?
MAF
no unknown no no arbitrary valueyes unknown no no arbitrary valueyes yes no no number of mixture
components*IFyes yes no interactions
unlikelynumber of mixture components
yes yes yes no MCR*IFyes yes yes interactions
unlikelyMCR
yes yes yes yes case-by-case based on weight of evidence
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Maximum exceedance of a safe levelin various situations
‘n’ known Individual RQ’s < 1
RQ’s quantified
Info. on interactions?
MAF
no unknown no no arbitrary valueyes unknown no no arbitrary valueyes yes no no number of mixture
components*IFyes yes no interactions
unlikelynumber of mixture components
yes yes yes no MCR*IFyes yes yes interactions
unlikelyMCR
yes yes yes yes case-by-case based on weight of evidence
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Mixture hazard assessment not possible without prior /parallel exposure assessment
Transparent use of AF’s: which uncertainty is covered?
Uncertainties in mixture assessment– incomplete exposure data
– incomplete hazard data
– synergism, antagonism
Summary & Conclusions
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n is a sufficiently protective MAF under the assumption of CA
MCR / STU seems a good descriptor for a MAF for coincidental mixtures, if no single compound has a RQ>1.
Only applicable to well characterized mixtures
Summary & Conclusions
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The specific uncertainty of coincidental mixtures cannot be lowered by “the actor” (chemical producer, importer, down-stream user)
Task for regulatory authorities!
Summary & Conclusions
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A MAF basically lowers the critical threshold for regulatory action from a risk quotient of 1 to a lower value.
Needed, because a risk quotient below 1 implies a ‘safe situation’ (no need for action).
Wrong conclusion.
A step in a different direction…
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We need to overcome the notion that a risk quotient below one indicates ‘no risk’ and no need for action.
A risk quotient should not be taken as an indication of risk per se, but as the contribution of a compound to the total risk in a given scenario.
A step in a different direction…
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Is a mixture assessment factor (MAF) the right way forward?
Thomas BackhausUniversity of Gothenburg [email protected] @Twitter
Thomas Backhaus, Mikael Gustavsson, Anke Hartmann, University of Gothenburg, Sweden
Michael Faust, F&B Environmental Consulting, Germany
Markus Klar, Henrik Sundberg, Stefan Gabring, Gunilla Ericson, Sten Flodström, Swedish Chemicals Agency, Sweden