Based on USEPA (1986) Table 2 for mixtures risk assessment, please select the best classification for data quality for PFAS exposure information

Answer Explanations

• Exposure estimates for some components are lacking, uncertain, or variable. Information on health effects of environmental chemistry suggests that this limitation is not likely to substantially affect the risk assessment

  Expert 3

  Again these are old classifications that don't completely apply to the state of the science in 2021. Note that many authoritative bodies, including USEPA have published useful information on making appropriate use of incomplete data sets.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 6

  In this case, I was torn between dot points 1 and 4. There are good exposure monitoring data for most of the more important PFAS (those with good toxicological information as well), but these data are lacking for some PFAS likely to be found in mixed exposures. Furthermore, levels of exposure are likely to be highly variable. Where exposure data are better defined for a specific environmental scenario, the choice could default to dot point 1.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 9

  While there are abundant data on numbers of certain PFAS and their levels in environmental media and in living organisms, these data are limited only to a relatively small number of individual PFAS for which there are methods or standards available for targeted analysis. Fewer than 80-100 PFAS have been included in targeted analysis (due to the availability of standards) and USEPA methods for assessing PFAS in drinking water include fewer than 50 PFAS. Therefore, not all components of PFAS mixtures in the environment have been identified due to the lack of methods and/or standards for targeted identification.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 10

  As I mentioned above, one must first decide on the critical effect that is the basis of the risk assessment for multiple PFAS. Here, there is a lack of consensus as shown by the differences in critical effect used as the basis for risk assessments among international authorities. The recent EFSA opinion was based on immunotoxicity and for this effect there is a lack of information on mode and mechanism of action for the four PFAS (sum of PFOS, PFOA, PFNA and PFHxS) for which the tolerable weekly intake was based.
  Some would say that if there is a lack of information on the mode and mechanism of action then there is insufficient information for conducting a risk assessment (Goodrum et al., 2021). Whereas many authorities are prepared to apply simple additive mixture toxicity approaches for drinking water thresholds (e.g. 100 ng/L for sum of 20 PFAS in the EU) on the basis of the precautionary principle, while at the same time realizing that individual PFAS will vary in their toxic potencies, modes of action and human elimination half-lives.

  Goodrum, P.E.; Anderson, J.K.; Luz, A.L.; Ansell, G.K. (2021) Application of a Framework for Grouping and Mixtures Toxicity Assessment of PFAS: A Closer Examination of Dose-Additivity Approaches. Tox. Sci., 179, 2, 262–278.

• Expert 11

  I am not an expert on the current data on PFAS exposures, but like the prior question on adequacy of exposure data the answer to this question varies with the substance. Some substances have reasonable levels of exposure data others are just peaks on an output of a GC-MS.

• Expert 7

  Cannot comment on this question since the database is unknown to me as well as the data generators.
  There are differences between official surveillance data and research data when referring to long-term monitoring and comparability of data. See comments above to 2.5.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 4

  Same sort of response as for previous question: The limited data does not "INSUFFICIENT" for conducting a quantitative risk assessment. However, it affects the degree of confidence in risk estimates (both accuracy and precision). Uncertainty should be discussed in detail within the uncertainty analysis section of every QRA.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 1

  Few studies have looked into the fraction of total organofluorine in drinking water attributed to targeted/known PFAS, but the data suggests that a significant portion of the organofluorine load is unknown (e.g., https://pubs.acs.org/doi/10.1021/acs.est.7b03994#). In terms of exposure, PFAS levels definitely vary in drinking water, with hotspots having higher levels of certain compounds (the fingerprint also varies from one hotspot to another). With regards to health effects, there is increasing toxicological data (especially in vitro) on emerging PFAS (e.g., ToxCast, Yauk/Atlas lab), but there are still plenty of PFAS with no information on toxicity.

• Exposure estimates for some components are lacking, uncertain, or variable. Information on health effects of environmental chemistry suggests that this limitation is not likely to substantially affect the risk assessment

  Expert 2

  For some PFAS, such as PFOS and PFOA, there is adequate exposure information. For example, PFOS and PFOA in drinking water. However, exposure from dietary sources, even for these two compounds is not well known. Inhalation related exposure to precursor PFAS is not known.
  My suggestion is to create subgroups of PFAS - identify sources of use/application of each subgroup and predict potential exposure sources/pathways for those subgroups.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 8

  It is not clear what the context for this question is. The problem formulation statement provided is not sufficiently detailed to provide the actual PFAS to be considered. If one is only considering the 6 PFAS included in the UCMR3 (PFOA, PFOS, PFNA, PFHxS, PFHpA and PFBS) then the first criteria applies - Monitoring information either alone or in combination with modeling is sufficient to accurately characterize human exposure to the mixture or its components.
  If one is considering other PFAS, then in the absence of drinking water monitoring data, the fourth or fifth criteria would apply – 4. Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment. 5. The available exposure information is insufficient for conducting a risk assessment.

• Not all components of the mixture have been identified, or levels of exposure are highly uncertain or variable. Information on health effects of environmental chemistry is not sufficient to assess the effect of this limitation on the risk assessment

  Expert 5

  Given the absence of a definition of the PFAS acronym, identification of the components of the mixture cannot be determined. With definition, components of a mixture can be identified through environmental sampling with adequate (TBD) limits of detection/quantitation. It may be anticipated that there will be variability of the mixture, dependent perhaps on the siting of potential emitters. Information (dose response information) on health effects is certainly a limitation. For the animal dose response data that are available for health effects, we experience the limitations of unknown human relevance of the mode of action, and of the lack of toxicokinetic information sufficient to serve as a basis for quantitative extrapolation across species.