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Is a mixture assessment factor (MAF) the right way forward? Thomas Backhaus University of Gothenburg [email protected]
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Is a mixture assessment factor (MAF) the right way forward?
Thomas BackhausUniversity of Gothenburg [email protected]
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
easy to implement
no additional data needed
increased level of protection
CONSPROS
blanket type of approach
hard to justify size
Conservatism in Hazard Assessment
REACH Guidance Document, Chapter R10, 2008
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
Hazard Assessment Assessment Factors
Exposure Assessment Conservative Assumptions
Consideration of Uncertainties
Assessment of Single Substances
Exposure Assessment Hazard Assessment
Risk Assessment
Assessment of Mixtures
Exposure Assessment
Hazard Assessment
Risk Assessment
A Mixture Assessment Factor needs to cover exposure and hazard assessment
Assessment of Mixtures
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
Equals the number of expected compounds in a mixture
MAF based on Concentration Addition
n
ECxc i
i
xMixE CA )(
if
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
Pesticide Mixture
Result from the Swedish pesticide monitoring program
n = 42
.
Example
andardQuality St talEnvironmen
ionConcentrat MonitoredQuotient Risk
Distribution of Risk Quotients
0
20
40
60
80
100
120
140
Cum
ulati
ve H
azar
d In
dex
136
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
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
Maximum Cumulative Ratio
Units Toxic of Maximum
Units Toxic of SumMCR
nMCR Equitoxic Mixture:
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
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
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
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
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
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
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
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
The specific uncertainty of coincidental mixtures cannot be lowered by “the actor” (chemical producer, importer, down-stream user)
Task for regulatory authorities!
Summary & Conclusions
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…
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…
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
