Is a mixture assessment factor (MAF) the right way forward? Thomas Backhaus University of Gothenburg

AreaSizeReference Environment100 Janssen, 2004; van Vlaardingen, 2007 Environment100Tørsløv, 2013 Human health100Muilerman, 2011 Human health10Tørsløv, 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 AssessmentHazard AssessmentRisk Assessment

Assessment of Mixtures Exposure AssessmentHazard AssessmentRisk 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 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

Distribution of Risk Quotients 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 16.0

Maximum Cumulative Ratio Equitoxic Mixture:

4 different scenarios Mixture Typen Prior adjustment After risk mitigation for single compounds Risk quotient MCR Risk quotient MCR Pesticides Pharmaceuticals Anti-androgens Organic air pollutants

Maximum exceedance of a safe level in various situations ‘n’ known Individual RQ’s < 1 RQ’s quantified Info. on interactions? MAF nounknownno arbitrary value yesunknownno arbitrary value yes no number of mixture components*IF yes no interactions unlikely number of mixture components yes noMCR*IF yes interactions unlikely MCR yes case-by-case based on weight of evidence

Maximum exceedance of a safe level in various situations ‘n’ known Individual RQ’s < 1 RQ’s quantified Info. on interactions? MAF nounknownno arbitrary value yesunknownno arbitrary value yes no number of mixture components*IF yes no interactions unlikely number of mixture components yes noMCR*IF yes interactions unlikely MCR yes case-by-case based on weight of evidence

Maximum exceedance of a safe level in various situations ‘n’ known Individual RQ’s < 1 RQ’s quantified Info. on interactions? MAF nounknownno arbitrary value yesunknownno arbitrary value yes no number of mixture components*IF yes no interactions unlikely number of mixture components yes noMCR*IF yes interactions unlikely MCR yes case-by-case based on weight of evidence

Maximum exceedance of a safe level in various situations ‘n’ known Individual RQ’s < 1 RQ’s quantified Info. on interactions? MAF nounknownno arbitrary value yesunknownno arbitrary value yes no number of mixture components*IF yes no interactions unlikely number of mixture components yes noMCR*IF yes interactions unlikely MCR yes case-by-case based on weight of evidence

Maximum exceedance of a safe level in various situations ‘n’ known Individual RQ’s < 1 RQ’s quantified Info. on interactions? MAF nounknownno arbitrary value yesunknownno arbitrary value yes no number of mixture components*IF yes no interactions unlikely number of mixture components yes noMCR*IF yes interactions unlikely MCR 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 Backhaus University of Gothenburg 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