Does the above draft Problem Formulation statement provide appropriate information to identify a path forward for grouping PFAS? Yes or No? If no, what modifications or edits would you proposed to improve the specificity and clarity around this specific problem formulation?

Answer Explanations

• Yes

  Expert 1

  It is clearer now that the main aim is to derive a drinking water guideline for PFAS mixtures. It may be good to indicate if the guideline should be protective for breastfed infants (e.g., the Minnesota Departement of Health based their guideline level on dosimetry in the breastfed infant).

• No (please explain)

  Expert 11

  First off, this question is very different from the first set of questions. I felt very comfortable in responding to technical questions about the best strategy for assessing PFAS, but this first question is much more about supporting/developing a specific draft problem formulation statement. This a task that I am not comfortable addressing since it involves regulatory and program issues that are not technical. I would have preferred it if SciPinion has asked us to focus on the technical aspects of the problem formulation statement.
  That said, the following are my comments on the technical aspects of the proposal and specific wordings that are more policy then science.
  Point 1 “Purpose: Establish scientifically-defensible human-health protective drinking water threshold(s) (e.g., Maximum Contaminant Level (MCL) per the US Safe Drinking Water Act) for PFAS that may be present in the general population’s drinking water”
  o I support the idea of a clear statement of purpose at the beginning of a problem formulation statement. The specific wording involves nontechnical considerations that I am not an expert in. As a result, I do not have any opinions or suggestions. I can say that certain phrases used here are a concern. Terms like “health-protective”, “that may be present”, and “general population” are terms that 1) refer to the specific levels of confidence of decisionmakers on particular topics that trigger decisions, and 2) decisions on the types of information to be considered (the general population). These are not scientific issues - they are social/political decisions and are not appropriate for a technical panel.
  o I did not regard the technical issues raised in round 1 as being limited to setting drinking water standards. If this was truly the scope of the panel, then it should have been much more clearly stated in the first round and in the description of the panel. Since the topic of the scope was discussed by panel members in the discussion section on the first round of questions, SciPinion should have stepped in and clarified this point.

  Point 2 of the draft problem formulation statement “Overall risk management goals and options: Goal is to protect public health in a manner that is efficient, scientifically defensible, technically achievable, and economically responsible for all stakeholders.” is not an unreasonable goal. But it is not the only possible goal nor is it necessarily the most appropriate goal. Some of the elements are not controversial (i.e., they are scientifically defensible), but some are:
  o Efficient – by what criteria?
  o Technically achievable – some goals (like the old MCLGs) need not be technically feasible. If a chemical is posing a risk and there is no cost-effective technology for its control, then it could be very reasonable to have a goal of forcing the development of such a technology. In this case, the goal would not need to be technically achievable.
  o I have no idea what is meant by the phrase “economically responsible for all stakeholders” but it does not sound like a technical issue.

  Point 3 of the draft statement, “Scope and depth of the analysis: Determine which subgroups of PFAS may be assessed via cumulative risk assessment methods and define a method for establishing a single concentration threshold limit for each PFAS subgroup and/or chemical.” Is again not an unreasonable scope and set of results for the assessment. But again, it is not the only possible scope. The text is a bit confusing. It seems to suggest that the subgroups would be the basis for Cumulative Assessment Groups (CAGs) for dose additive models. Inside of such groups individual compounds would have different PODs and RfDs. I was not assuming that a single concentration threshold limit would be applied to all substances in a subgroup. I am not sure that this is an appropriate approach. It also appears to be inconsistent with the idea of a CAG. In addition, it is not clear to me what is meant by “single concentration threshold limit for each PFAS subgroup”. Do you mean the same point of departure for all chemicals in a group, or the same RfD, or the sum of the doses of all PFAS in a group are compared to a single standard? Can you clarify?

  Point 4 of the draft statement, “Analytical approach: Rely upon well-established cumulative or mixtures risk assessment principles and practices”
  o This would only apply to the technical aspects of the grouping, not the legal, engineering, or economic aspects.
  o Do you really want to limit the science to “well-established cumulative or mixtures risk assessment principles and practices”? The field of mixture risk assessment is changing and new concepts like MIEs, AEPs, and AOPs are likely to be very useful for PFAS combined risk assessments. But such techniques are “not well established”. Do you want to exclude them?

  Point 5
  o 5-1 Doesn’t seem to belong in a problem formulation statement. Unless there was a huge technical study of PFAS that was being released in the immediate future and you wanted to clarify whether or not you were going to wait until the results were available, the decision makers have no choice but to use what is available.
  o 5-2 Are you trying to exclude PFAS substances that have not been identified analytically but could be reasonable expected to occur based on known releases and physical/chemical properties? This might not be appropriate.
  o 5-3 looks like it is contradicting 5-2. Were you trying to say:
  “the currently available understanding of occurrence of relevant PFAS in drinking water sources based on either analytical detection or information on physical-chemical properties and patterns of environmental release that suggests a high potential for a given PFAS to be present in a public drinking water supply.”

• Yes

  Expert 2

  As long as the scope is specified on which subgroups of PFAS are included in the risk assessment, it is fine. It is because, for most subgroups of PFAS, we do not have toxicological database or mixture effect related assessments. Considering PFAS as a single group for risk assessment is a daunting task. For example, we cannot group "organochlorines" as one group for risk assessment. Within organochlorines, there were PCBs, chlorinated pesticides and other chlorinated aliphatics and aromatics and they are all treated individually in risk assessments. A similar approach is needed for PFAS. We need to identify subgroups such as sulfonates, carboxylates, ethers, alcohols etc.

• Yes

  Expert 10

  The above draft provides a way forward for grouping PFAS for the specific purpose of establishing scientifically-defensible human-health protective drinking water threshold(s). There are, however, other purposes for grouping PFAS that would require different grouping strategies.

  Additional resources would be the current publicly available human elimination half-life database for the PFAS in each PFAS subgroup.

• No (please explain)

  Expert 9

  For item #3, it is suggested that the following change be made: "...Determine which subgroups of PFAS or if PFAS as a whole may be assessed..." and"...concentration threshold limit for each PFAS subgroup and/or chemical and/or PFAS as a whole." Although from a traditional toxicologically-based risk assessment perspective it may be challenging to evaluate PFAS as a whole, it still may be useful to consider this option and broadening the types of data that are used in establishing human-health protective drinking water threshold(s).

• No (please explain)

  Expert 8

  This is a preliminary or first cut generic problem formulation statement. It tells the assessor that drinking water is the media of concern. However, it does not tell the assessor which PFAS are to be addressed or whether any given PFAS must reach a “threshold” in terms of how many public water systems are affected or how many are above the minimum reporting level. Information is available for 6 PFAS (PFOA, PFOS, PFNA, PFHxS, PFHpA and PFBS) through the UCMR3 survey. The iterative process of problem formulation between the assessor, the risk manager, and perhaps the public would need to address these issues before the assessment formally begins.
  In addition, in the current problem formulation statement it states that the PFAS under consideration includes “3. the assumed physical-chemical properties of some PFAS such as is necessary to make basic assumptions about the potential for a given PFAS to be present in the general population’s drinking water supply”. Simply looking at the pchem properties of all PFAS and determining which could be present in water is not sufficient criteria to assume that the specific PFAS is actually present in the drinking water supply. One would also have to consider the use of the PFAS, the potential pathway to the drinking water, and more importantly whether the specific PFAS is actually present in drinking water.
  In summary, this problem formulation statement is a first step, but requires much refinement.

• No (please explain)

  Expert 5

  Perhaps, yes; but more likely, No. The PF does say to use a subgrouping approach, intimating that it is recognized that PFAS are not to be lumped into a single group. The PF (appropriately) does not go into how the assignment into subgroups should be accomplished.

• No (please explain)

  Expert 7

  The question addresses only one problem: drinking water to protect human health. A MCL may be protective for this goal but would not resolve any problem or be protective to aquatic organisms (fish, shellfish). Water as an environmental matrix would need other goals, approaches and values. this applies not only to PFAS but to all chemicals.
  This is a purely chemical question and for this one example, only chemicals should be included that can be robustly controlled by analytical chemical laboratories. From a practical point of view, chemicals - including certain PFAS - should be in a range around this MCL. It does not make sense to monitor substances that are never quantified (for financial reasons but also fear would be transmitted to the general population for unjustified reasons).
  Since there are more chemicals and other parameters of concern in drinking water, only a few individual PFAS of relevance should be included.

  Note: "level" is the wrong expression since refers to a value to limit an amount. There would result two levels: "safe" for human consumption or "not safe" for...

• No (please explain)

  Expert 6

  It appears that the target for the cumulative risk assessment processes is now to establish drinking water guidance values (drinking water was only listed as an example in Round 1). To me, this is disappointing because I had hoped the development of such grouping/mixtures risk assessment methodologies could be used more broadly (e.g. for contaminated sites or to assist with assessment of human exposure data involving multiple PFAS). This would require a re-write of dot point 1 to something like "Establish scientifically-defensible human-health protective guidance for assessing exposures involving multiple individual chemicals (or groups) identified as PFAS." The remaining four dot points in the draft Problem Formulation would still fit with such a broader purpose.

• No (please explain)

  Expert 3

  It is certainly useful that the scope of the assessment has been limited to drinking water exposure. But where is the Conceptual Model? (I emphasize utility of an appropriate Conceptual Model below). The goals are OK. But if the ultimate purpose is the establishment of MCLs under SDWA 96, the Problem Formulation should mention that one is looking for a regulatory determination. I'm not convinced that this is the real goal of the Problem Formulation or that the proposed Problem Formulation will achieve that goal. It seems to me that the major focus of the rest of the questions (and a lot of Round 1) is how to group PFAS found (or likely to be found) in drinking water in the US.

  The resources described in the Problem Formulation is described as restricted to current availability in terms of exposure data, health effects data, mechanistic data, etc. The cut off of Fall 2021 suggests further limitations to the conceptual model below. Thus, it appears that the analysts could come up with lists of PFAS that meet the criteria of "analyzable now", "detected now", "sufficiently similar to expect detection now", "adverse outcome measured now", and so on. If this is the intent of the assessors who wrote the Problem Formulation draft, then it obviates several of the charge questions below.

  It is appropriate to revise (and publish) the Problem Formulation as needed to ensure fit-for-purpose of the resulting assessment. This is usually done after review and comment on the draft, and certainly can be done as the assessment proceeds and /or the purpose for doing the assessment evolves.