Based on a consideration of feasibilityt, please rate the following grouping strategies on a scale of 1-10 (1=lowest, 10=highest)

Answer Explanations

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  Expert 10

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	1	0	0	0	0	0	0	0
  Potential exposure route	0	0	1	0	0	0	0	0	0	0
  Biological half-life	0	0	0	0	1	0	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	1	0	0	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	1	0	0
  Toxicological endpoints	1	0	0	0	0	0	0	0	0	0
  Mode of action	1	0	0	0	0	0	0	0	0	0
  Other (please explain below)

  The answers depend on the end purpose of grouping and how many PFAS are grouped. If you would group all PFAS together then all the above categories would score 1 due to lack of information of the thousands of PFAS in use. If you take the PFAAs and perfluoroalkyl ether acids only, we know much more than for all PFAS, but are lacking toxicological data for some PFAAs and perfluoroalkyl ether acids. We also know little about production/use, properties and exposure for some perfluoroalkyl ether acids. Lack of information is often the reason for making precuationary simplifications in grouping approaches.

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  Expert 7

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use
  Potential exposure route
  Biological half-life
  Physical-chemical properties
  Carbon chain length/chemical structure
  Toxicological endpoints
  Mode of action
  Other (please explain below)	0	0	0	0	0	0	0	0	0	1

  They are all relevant but priorization needs to be undertaken and communicated before to proceed. And an organizational principle established for the report.

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  Expert 2

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	1	0	0	0	0	0	0
  Potential exposure route	0	0	0	0	1	0	0	0	0	0
  Biological half-life	0	0	0	0	0	1	0	0	0	0
  Physical-chemical properties	0	0	0	0	1	0	0	0	0	0
  Carbon chain length/chemical structure	0	0	0	0	1	0	0	0	0	0
  Toxicological endpoints	0	0	0	0	0	1	0	0	0	0
  Mode of action	0	0	0	0	0	0	0	1	0	0
  Other (please explain below)

  Still we do not know much about physicochemical properties and it is not possible to group based on that.

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  Expert 8

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	0	0	1
  Potential exposure route	0	0	0	0	0	0	0	0	0	1
  Biological half-life	0	0	0	0	0	0	0	0	0	1
  Physical-chemical properties	0	0	0	0	0	0	0	0	0	1
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	0	1
  Toxicological endpoints	0	0	0	0	0	0	0	0	0	1
  Mode of action	0	0	0	0	0	0	0	0	0	1
  Other (please explain below)

  Again, there is no context to this question, and all are equally feasible depending on the specific scenario.

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  Expert 6

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	1	0	0
  Potential exposure route	0	0	0	0	0	0	1	0	0	0
  Biological half-life	0	0	0	1	0	0	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	1	0	0	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	1	0
  Toxicological endpoints	0	0	1	0	0	0	0	0	0	0
  Mode of action	0	1	0	0	0	0	0	0	0	0
  Other (please explain below)

  See also answer to 1.3; the issue of "feasibility" changes the order of merit; with possibly insufficient information on toxicological profile and/or MoA across the spectrum of PFAS, a more pragmatic approach to grouping may be necessary

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  Expert 3

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	1	0	0
  Potential exposure route	0	0	0	0	0	0	1	0	0	0
  Biological half-life	0	0	0	0	0	1	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	0	0	1	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	1	0	0
  Toxicological endpoints	0	0	0	0	1	0	0	0	0	0
  Mode of action	0	0	0	0	1	0	0	0	0	0
  Other (please explain below)

  Data are most abundant for those groups I ranked higher. Assuming that risk assessment strategies and research design are outcomes of this exercise, feasibility does not equal current availability of data. One can design (and in some cases require) studies that most contribute value to the information base.

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  Expert 9

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	1	0	0	0	0	0	0	0	0
  Potential exposure route	0	1	0	0	0	0	0	0	0	0
  Biological half-life	0	1	0	0	0	0	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	0	0	0	1	0
  Carbon chain length/chemical structure	0	0	1	0	0	0	0	0	0	0
  Toxicological endpoints	0	0	1	0	0	0	0	0	0	0
  Mode of action	0	1	0	0	0	0	0	0	0	0
  Other (please explain below)	0	0	0	0	0	0	0	0	1	0

  Persistence. It is known that the vast majority of PFAS are persistent. Even those that are not, i.e., precursors, degrade to stable PFAS end products.

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  Expert 11

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	1	0	0
  Potential exposure route	0	0	0	0	0	0	0	1	0	0
  Biological half-life	0	0	0	0	0	0	0	1	0	0
  Physical-chemical properties	0	0	0	0	0	0	0	1	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	0	1
  Toxicological endpoints	0	0	1	0	0	0	0	0	0	0
  Mode of action	1	0	0	0	0	0	0	0	0	0
  Other (please explain below)

  The above numbers reflect my limited understanding of the availability of data for PFAS compounds that could be used for a grouping strategy and not the effectiveness of such a strategy.

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  Expert 4

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	0	0	1
  Potential exposure route	0	0	0	0	0	1	0	0	0	0
  Biological half-life	0	0	1	0	0	0	0	0	0	0
  Physical-chemical properties	0	0	0	0	1	0	0	0	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	0	1
  Toxicological endpoints	0	0	1	0	0	0	0	0	0	0
  Mode of action	0	0	1	0	0	0	0	0	0	0
  Other (please explain below)

  For most PFAS, there is scant information that would allow grouping by most of these criteria. That is why I gave low feasibility scores to half-life, toxicological endpoints and mode of action. There is a little more data on phys/chem properties. Potential exposure routes could be inferred based on production and use. Grouping by production and use or carbon chain length is the most feasible, since this information is most available.

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  Expert 1

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	1	0	0	0	0	0	0
  Potential exposure route	0	0	0	1	0	0	0	0	0	0
  Biological half-life	0	0	0	0	1	0	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	0	0	1	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	1	0
  Toxicological endpoints	0	0	0	0	0	1	0	0	0	0
  Mode of action	0	0	0	0	0	1	0	0	0	0
  Other (please explain below)

  Given the number of past- and current-use PFAS and the lack of toxicological data on most of them, it seems like using chemical descriptors is the most realistic approach. However, as stated in other sections, grouping all the PFAS together would simplify and accelerate the process.

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  Expert 5

  Grouped by:	1	2	3	4	5	6	7	8	9	10
  Production/Use	0	0	0	0	0	0	0	0	1	0
  Potential exposure route	0	0	0	0	0	0	1	0	0	0
  Biological half-life	0	0	0	0	0	1	0	0	0	0
  Physical-chemical properties	0	0	0	0	0	0	0	1	0	0
  Carbon chain length/chemical structure	0	0	0	0	0	0	0	0	0	1
  Toxicological endpoints	0	0	0	0	1	0	0	0	0	0
  Mode of action	0	1	0	0	0	0	0	0	0	0
  Other (please explain below)

  Feasibility might be interpreted to mean the development of confidence in the determination, or it may mean strictly the ability to apply the specified data/characteristics to successfully group chemicals. Feasibility is here considered to represent “Can we group by “X”?”

  The data most certain to be available might be chemical structure data; these data will be largely independent of chemical production, use, or biological endpoints. Next most available data might be production and use data. The numerical ratings applied here reflect this reviewer’s estimate of the likelihood of having or developing reliable data for each characteristic sufficient to serve as the basis for a credible grouping strategy. So, the toxicological endpoints and mode of action data may be the most reliable basis for chemical grouping to conduct a mixtures risk assessment for PFAS chemicals, but those data sets may also be the least likely to be available (for more than a few PFAS chemicals at present).