COMMENTS ON AN ANNEX XV DOSSIER FOR IDENTIFICATION OF A SUBSTANCE AS SVHC AND RESPONSES TO THESE COMMENTS

Substance name: 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof)
CAS number: -
EC number: -

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Equivalent level of concern having probable serious effects on the environment (Article 57f) Equivalent level of concern having probable serious effects on human health (Article 57f)

Disclaimer: Comments provided during public consultation are made available as submitted by the commenting parties. It was the commenting parties own responsibility to ensure that their comments do not contain confidential information. The Response to Comments table has been prepared by the competent authority of the Member State preparing the proposal for identification of a substance of very high concern. RCOM has not been agreed by the Member State Committee nor has the document been modified as result of the MSC discussions. The table does not contain any confidential information.

PART I: Comments and responses to comments on the SVHC proposal and its justification

General comments on the SVHC proposal
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5275
2019/04/18	Health and Environment Alliance (HEAL),
International NGO,
Belgium	-	Thank you for your comments in support of the Annex XV dossier. 

Thank you also for the information provided regarding use, exposure, alternatives and risks. When relevant, these will be considered at later stages of the risk management process.

We have updated the Support Document with the information you provided on new insights in effects on human health (Conley et al. 2019). 	
		Attachment: 5275_HEAL-Comments-GenX.pdf
		
5280
2019/04/25	Germany,
Member State	

-Environmental fate properties:
Field data (3.2.5) Mobility
HFPO-DA is very mobile in the aquatic environment, is widely distributed via waterways far from the point of emission and therefore reaches areas far away from direct emissions. This is clearly demonstrated by monitoring data. The German CA suggests to further summarize the monitoring data in a table to achieve a better overview.
The maps illustrate well the spreading of HFPO-DA in the environment in North America, China and Europe. We suggest using geographical or political maps instead of maps based on satellite pictures in order to have a better orientation. This would improve the demonstration of the wide spread occurrence of HFPO-DA. Additionally we suggest to add a scale as the close ups of the maps differ.

3.5 Enrichments in plants
Currently the section addresses three issues: 1. monitoring in plants, 2. enrichment in plants and 3. mobility in soil in comparison to PFOA. All these issues intertwine. Nevertheless it may help to add subheadings. This could specifically highlight the third issue. These findings are also important for mobility and should be referenced in the mobility section. We suggest to further summarize the monitoring data in a table to achieve a better overview.

-Human health hazard assessment:
Chapter 4 – HH hazard assessment
As stated in the general comments the German CA notes that data are available for several endpoints, including repeated dose toxicity and carcinogenicity. However, for neither of the endpoints discussed in the dossier a harmonized classification and labelling exists. Therefore, the German CA suggests merely using the presented data as additional argument in the equivalent level of concern assessment but not basing the SVHC identification on these properties in first place.

p. 87 ff 4.7 Carcinogenicity.
A combined chronic and carcinogenicity study in rats was presented by the DS. However, it was stated (p. 88) that data are currently insufficient to conclude on the substance its full carcinogenic potential. During substance evaluation a lack of data has been identified and a request was issued on a carcinogenicity study in mice. This study is ongoing.
At the moment, it is difficult to judge, if the concern on carcinogenicity is sufficiently substantiated to base the SVHC identification on these effects.

Therefore, the German CA is of the opinion that it would be more appropriate to wait for the outcome of the study and then initiate the CLH process if the data support this option. Nevertheless, as mentioned above, the available information can be used as supporting evidence to underpin the equivalent level of concern assessment.

Results of the recent evaluation by US EPA (https://www.epa.gov/sites/production/files/2018-11/documents/genx_public_comment_draft_toxicity_assessment_nov2018-508.pdf) could also be added.

-PBT/vPvB and equivalent level of concern assessment:
p. 102 Section 6.3
The German CA suggests that the bullet point “adverse effects on human health” is removed from the first list as in our view the described effects could only be used as supporting evidence for the ELoC assessment due to the missing harmonized classification and labelling for the HH endpoints.

p. 108 6.3.1.10 Effects on human health – carcinogenicity
The DS concludes that the substance possibly meets the CLP criteria for a category 2 carcinogen. Even if the substance would meet the criteria for a category 2 carcinogen, a harmonized classification and labelling should be the basis for SVHC identification according to Article 57 f based on human health effects.

p 111-112 6.3.2.2 ELOC assessment
The German CA does not agree that the human health concern is sufficiently substantiated to identify the substances as SVHC based on adverse effects for human health.
However, as the substances are very persistent and very mobile the human health data can be used as supporting evidence for demonstration of the equivalent level of concern.	Thank you for your comments and further information.

Regarding your comment on 3.2.5: The maps were made new  with labels as you suggested. We tried the use of other maps than the satellite pictures, but this was definitely not an improvement. We were not able to include the summary tables at this moment.

Regarding your comment on 3.5: We thank you for this suggestion but did not further subdivide the section on enrichments in plants, because the section is relatively short and it would be difficult to describe the results study by study. Our concern for uptake in plants is especially exposure based. HFPO-DA uptake in plants may leads to the possibility that both wildlife and humans can be exposed through their food intake. Therefore, we prefer to keep the two topics mobility and uptake in plants separate.

Regarding your comment on chapter 4: We have taken note of your comment (see also later in this response) and have adjusted the text in section 6 to make clear that the ELoC is a weight of evidence assessment on the basis of all concerns we have for the substances.

Regarding your comment on p.87: We see your point and agree that the Substance Evaluation may result in additional insight in adverse effects of HFPO-DA. However, the studies as requested under Substance Evaluation on carcinogenicity and bioaccumulation in humans have not yet started. The earliest, further insight in the carcinogenic potential and the human half-life of the substance via the route of Substance Evaluation may be expected in 2022 and 2021 respectively. Against the background of the very high concern we already have for this substance to day, which includes the concern for adverse effects as described in the Support Document, we are of the opinion that it is disproportionate to await these study results. We have indicated in section 6 that we have serious concern for the carcinogenicity, but that we do not bring it forward as one of the main effects of the substance because substance evaluation on this endpoint is still ongoing. We do bring in this concern as supportive information.

Regarding your comment on the recent evaluation by the US EPA on the toxicity of GenX. We agree that this report gives an extensive overview of possible effects of HFPO-DA and may be of added value to the Support Document. However, this report is currently under public consultation and hence should be considered a preliminary report not representing US-EPA policy. The conclusions of the US-EPA report are in line with those of the Support Document and we have added this to chapter 4. 

Regarding your comment on the bullet point list in 6.3, we have seriously redrafted this section and there is no bullet point list anymore. Instead, we included a table with an overview of components relevant for the assessment of the level of concern (see table 35 of the Support Document) at the end of the section.

Regarding your comments on Chapter 4. p. 87, p. 102, and p. 108 related to the absence of any harmonized classification for HFPO-DA in Annex I of the Regulation No 1272/2008 we, have included a short reflection in Section 6.3.2.6 on different opinions expressed by various Member States on the possibility to classify effects during this RCOM, by the Netherlands in their RMOA, and by the registrant in their registration dossier under REACH. 

We note the following:
1.	In par. 28 of C-323/15P the Court specifies that Classification in Annex I of 1272/2008 is a relevant but not a decisive element to address a probable serious effect for HH or the ENV, and further specifies that Classification in Annex I of 1272/2008 is also not a sufficient element on its own to argue ELoC according to art. 57(f) of the Regulation 1907/2006.

Furthermore we note that effects on humans and the environment should be probable and should be of ELoC:
2.	Art. 57(f) states that “substances… which do not fulfil the criteria of points (d) or (e) — for which there is scientific evidence of probable serious effects to human health or the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) and which are identified on a case-by-case…”. In C-323/15P (par.26) the Court rules that this implies that serious effects on HH or the ENV shall be probable and that these effects should be shown to be of ELoC.

With regard to ELoC, the following is noted:
3.	Whilst a range of arguments are presented for ELoC for each substace, as they are used in a weight of evidence – none of the arguments alone are decisive for the decision and not all of them are necessarily needed to conclude on the equivalent level of concern for a particular substance.  
4.	In par. 37 of the Court ruling C-323/15P reference is made to CMR substances cat 1 and 2 stating that it is justified to identify these substances as SVHC solely on the basis of their hazard properties because these effects on humans are generally  so serious and cannot normally be reversed such that effects have to be prevented rather than remedied.

Given the above, we argue that the very high persistence together with its very high mobility and the adverse effects on human health in combination are of equivalent level of concern to art 57(a) – (e), and that none of these elements should be “put first”. We are highly concerned that HFPO-DA will remain in the environment for much longer times than substances meeting the P or vP criteria for PBT/vPvB due to its very high persistency being much higher than the vP criterion. Once the substance is emitted into the environment, this emission is extremely difficult to reverse. We are highly concerned that this will lead to long term exposure of both humans and wildlife around the globe because the substance is so highly mobile that it will freely migrate through water and, with time (because of its very high persistency) will be able to reach remote and pristine areas giving rise to a continuous environmental exposure. We are also highly concerned that the substance will reach drinking water sources around the world for which we already have some indications that it will lead to the continuous and long term exposure of humans. The current difficulties faced to remove HFPO-DA from the water give rise to a very high concern that once HFPO-A concentrations in drinking water have risen to lead to adverse effects in humans, it will be very difficult, energy intensive and costly to reduce exposures.  Furthermore, we have high concern for this substance because its exposure will not readily reduce when use of the substance is being terminated (because concentrations in the environment will remain constant as the substance is so highly persistent) and hence possible effects cannot normally be reversed due to continuous exposure. As we regard the effects observed from animal studies as serious and adverse for human health, we are of the opinion that emissions, resulting in a gradual increase of exposure with time, that will eventually lead to effects, are rather prevented than remedied and hence conclude this substance is of equivalent level of concern to art 57(a) – (e). 

Regarding your comment on p.112: we note your opinion that the concern that HFPO-DA is very persistent and very mobile is already sufficient to argue an equivalent level of concern with adverse effects as supporting evidence. We have further elaborated on why we are of the opinion that the adverse effects are sufficiently serious to add to the weight-of-evidence for ELoC.	
		-		
5281
2019/04/25	KWR Watercycle Research Institute,
Other contributor,
Netherlands	3 Comments on the decision on substance evaluation of GenX as SVHC (Milou M.L. Dingemans and Thomas ter Laak, KWR Watercycle Research Institute, Nieuwegein, the Netherlands).

It has been proposed to classify substances used in GenX technology (2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides; covering any of their individual isomers and combinations thereof) as a substance of very high concern (SVHC) via the REACH article 57f route. This proposal (in the form of a annex XV report) has been submitted in March 2019 by the EU memberstate the Netherlands. In response, ECHA has decided that the registrants are obliged to supply addition hazard and biomonitoring information to maintain the REACH registration for use of these substances. We have reviewed the decision on substance evaluation and would like to share the following comments:

1) Human relevant mechanisms may not be excluded based on the requested carcinogenicity study in mice.
• The registrants argue that the effects observed in the submitted rat study are not relevant for humans. The registrants are to submit the results of a carcinogenicity study in a second species (mice) with the aim to be able to exclude human relevant mechanisms. It is important to design an adequate experimental plan (Testing Proposal) that is fit to obtain the needed information. ECHA has included guidance on the test methods that should be used in the decision on substance evaluation document. We strongly suggest to also include studies on cellular and molecular mechanisms using New Approach Methods (in vitro models). These methods have the potential to compare the activity of these substances on the PPAR-receptor and other, more human relevant, receptors potentially associated with carcinogenicity (the current knowledge gap for which the additional mouse study is requested).

2) The REACH status of these substances is unclear
• The registrants should submit the additional hazard and biomonitoring information in March 2021 and November 2022. Until then, it is unclear whether this substance will remain on the list of chemicals that are proposed Substances of Very High concern, or whether they will be transferred to the Candidate List of Substances of Very High Concern. ECHA requests additional information on hazards and bioaccumulation of this substance to be able to exclude that these substances are unsafe (based on toxicology and bioaccumulation). In view of the precautionary principle the uncertainty on the absence of health effects and accumulation of internal exposure to these substances already urges risk management measures that need to be addressed by ECHA before the final outcomes of these studies are available. We suggest, based on the presented material and the precautionary principle, to transfer this substance on the Candidate List of Substances of Very High Concern until the additional research has proven that it is not a SvHC.

3) Persistence and mobility in the aquatic environment is not taken into account
• As these substances are persistent, pass natural barriers, are poorly removed in wastewater treatment and are mobile in the aqueous environment, their permitted emission into surface water is a threat to drinking water sources. It is therefore recommended to include criteria for fate and behavior in the water cycle in the REACH registration process. These criteria have been developed in the scientific field of environmental chemistry and researchers stress the relevance of these polar and very polar persistant substances for the environment and human exposure (Reemtsma et al. Environ Sci Technol. 2016; RIVM [Versteegh and de Voogt] 2017).	Thank you for your comments and information provided. We note that the current Support Document solely deals with the SVHC identification of the substance and stands apart from the ongoing substance evaluation. As such, we take it as support that you conclude under 2) that “We suggest, based on the presented material and the precautionary principle, to transfer this substance on the Candidate List of Substances of Very High Concern until the additional research has proven that it is not a SVHC.”

1) We would like to refer to the minutes of MSC-62, where the substance evaluation of HFPO-DA was discussed and agreed upon by all MSC members. The following was concluded:

“The possibility of a carcinogenicity study in mice leading to a Carc. 1B classification of the substance was discussed by MSC. It was acknowledged that sufficient evidence that the effects seen were not relevant to humans was needed in order to make this conclusion for classification. In this case, apart from liver tumors there were also pancreatic tumors and tumors in leydig cells. Hence, a study in mice, could be helpful to confirm or remove the concern for pancreatic tumors. It was also recognized that any mechanistic studies to understand other possible modes of action of Gen-X would be useful.” 

Derived from: https://echa.europa.eu/documents/10162/23843530/msc-62_minutes_en.pdf/e15afa65-f298-783f-4d21-0d62692a4bf4

Hence, we fully acknowledge that mechanistic studies would be helpful to further study the mode of action of the substance, in vitro and in vivo. In this respect, we also would like to refer to a recent study conducted by Li et al. (2019), who noted that HFPO-DA, HFPO-TA, and PFOA were able to activate the murine and human nuclear receptor PPARγ in vitro. This study is also sumarised in the Support Document in Chapter 4. 

2)We thank you for your support

3) We furthermore note your recommendation that further criteria for fate and behavior in the water cycle could be included in the REACH registration process. Though the thought is interesting to further elaborate on, discussing this is not within the scope of the current Support Document. 

Thank you for providing additional information (Reemtsma et al. 2016; Versteegh and de Voogt, 2017). This information, if not already present in the Support Document, has been taken into consideration and has been used as supporting information for ELoC. 
	
		-		
5282
2019/04/25	Advisary Board Water Quality (AW) of the Dutch drinking water companies,
Other contributor,
Netherlands	3 Comments on the decision on substance evaluation of GenX as SVHC (Milou M.L. Dingemans and Thomas ter Laak, KWR Watercycle Research Institute, Nieuwegein, the Netherlands).

It has been proposed to classify substances used in GenX technology (2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides; covering any of their individual isomers and combinations thereof) as a substance of very high concern (SVHC) via the REACH article 57f route. This proposal (in the form of a annex XV report) has been submitted in March 2019 by the EU memberstate the Netherlands. In response, ECHA has decided that the registrants are obliged to supply addition hazard and biomonitoring information to maintain the REACH registration for use of these substances. We have reviewed the decision on substance evaluation and would like to share the following comments:

1) Human relevant mechanisms may not be excluded based on the requested carcinogenicity study in mice.
• The registrants argue that the effects observed in the submitted rat study are not relevant for humans. The registrants are to submit the results of a carcinogenicity study in a second species (mice) with the aim to be able to exclude human relevant mechanisms. It is important to design an adequate experimental plan (Testing Proposal) that is fit to obtain the needed information. ECHA has included guidance on the test methods that should be used in the decision on substance evaluation document. We strongly suggest to also include studies on cellular and molecular mechanisms using New Approach Methods (in vitro models). These methods have the potential to compare the activity of these substances on the PPAR-receptor and other, more human relevant, receptors potentially associated with carcinogenicity (the current knowledge gap for which the additional mouse study is requested).

2) The REACH status of these substances is unclear
• The registrants should submit the additional hazard and biomonitoring information in March 2021 and November 2022. Until then, it is unclear whether this substance will remain on the list of chemicals that are proposed Substances of Very High concern, or whether they will be transferred to the Candidate List of Substances of Very High Concern. ECHA requests additional information on hazards and bioaccumulation of this substance to be able to exclude that these substances are unsafe (based on toxicology and bioaccumulation). In view of the precautionary principle the uncertainty on the absence of health effects and accumulation of internal exposure to these substances already urges risk management measures that need to be addressed by ECHA before the final outcomes of these studies are available. We suggest, based on the presented material and the precautionary principle, to transfer this substance on the Candidate List of Substances of Very High Concern until the additional research has proven that it is not a SvHC.

3) Persistence and mobility in the aquatic environment is not taken into account
• As these substances are persistent, pass natural barriers, are poorly removed in wastewater treatment and are mobile in the aqueous environment, their permitted emission into surface water is a threat to drinking water sources. It is therefore recommended to include criteria for fate and behavior in the water cycle in the REACH registration process. These criteria have been developed in the scientific field of environmental chemistry and researchers stress the relevance of these polar and very polar persistant substances for the environment and human exposure (Reemtsma et al. Environ Sci Technol. 2016; RIVM [Versteegh and de Voogt] 2017).	See response to comments on 5281
2019/04/25	
		-		
5283
2019/04/25	VEWIN,
Other contributor,
Netherlands	3 Comments on the decision on substance evaluation of GenX as SVHC (Milou M.L. Dingemans and Thomas ter Laak, KWR Watercycle Research Institute, Nieuwegein, the Netherlands).

It has been proposed to classify substances used in GenX technology (2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides; covering any of their individual isomers and combinations thereof) as a substance of very high concern (SVHC) via the REACH article 57f route. This proposal (in the form of a annex XV report) has been submitted in March 2019 by the EU memberstate the Netherlands. In response, ECHA has decided that the registrants are obliged to supply addition hazard and biomonitoring information to maintain the REACH registration for use of these substances. We have reviewed the decision on substance evaluation and would like to share the following comments:

1) Human relevant mechanisms may not be excluded based on the requested carcinogenicity study in mice.
• The registrants argue that the effects observed in the submitted rat study are not relevant for humans. The registrants are to submit the results of a carcinogenicity study in a second species (mice) with the aim to be able to exclude human relevant mechanisms. It is important to design an adequate experimental plan (Testing Proposal) that is fit to obtain the needed information. ECHA has included guidance on the test methods that should be used in the decision on substance evaluation document. We strongly suggest to also include studies on cellular and molecular mechanisms using New Approach Methods (in vitro models). These methods have the potential to compare the activity of these substances on the PPAR-receptor and other, more human relevant, receptors potentially associated with carcinogenicity (the current knowledge gap for which the additional mouse study is requested).

2) The REACH status of these substances is unclear
• The registrants should submit the additional hazard and biomonitoring information in March 2021 and November 2022. Until then, it is unclear whether this substance will remain on the list of chemicals that are proposed Substances of Very High concern, or whether they will be transferred to the Candidate List of Substances of Very High Concern. ECHA requests additional information on hazards and bioaccumulation of this substance to be able to exclude that these substances are unsafe (based on toxicology and bioaccumulation). In view of the precautionary principle the uncertainty on the absence of health effects and accumulation of internal exposure to these substances already urges risk management measures that need to be addressed by ECHA before the final outcomes of these studies are available. We suggest, based on the presented material and the precautionary principle, to transfer this substance on the Candidate List of Substances of Very High Concern until the additional research has proven that it is not a SvHC.

3) Persistence and mobility in the aquatic environment is not taken into account
• As these substances are persistent, pass natural barriers, are poorly removed in wastewater treatment and are mobile in the aqueous environment, their permitted emission into surface water is a threat to drinking water sources. It is therefore recommended to include criteria for fate and behavior in the water cycle in the REACH registration process. These criteria have been developed in the scientific field of environmental chemistry and researchers stress the relevance of these polar and very polar persistant substances for the environment and human exposure (Reemtsma et al. Environ Sci Technol. 2016; RIVM [Versteegh and de Voogt] 2017).	See response to comments on 5281
2019/04/25	
		-		
5291
2019/04/26	RIWA, Association of River Waterworks,
Industry or trade association,
Netherlands	RIWA, the Association of River Waterworks in the Netherlands and Belgium, welcomes the proposal by the Netherlands for the identification of HFPO-DA* as a substance of very high concern on the basis of the criteria set out in REACH article 57. We support the conclusions of the proposal and would like to stress several of the specific findings in it, such as:
• HFPO-DA is detected in finished drinking water at several locations downstream of the fluorochemical production plant in the Netherlands. This is of concern to the drinking water companies which are members of our association. Because HFPO-DA does not adsorb to sediment, soil and active coal, and does not show any (bio) degradation under environmental conditions, it is very difficult to remove HFPO-DA from water. Even advanced water purification techniques are mostly not able to remove HFPO-DA, or only to a very limited extent. RIWA would like to stress that one of the aims of the Water Framework Directive is to avoid deterioration of water quality in order to reduce the level of purification treatment required in the production of drinking water. As HFPO-DA is very difficult to remove from water with the current levels of purification treatment installed we strongly support to avoid any emissions to water.
• HFPO-DA is very persistent, very mobile in the water environment and shows adverse effects in humans. The available information on toxicity shows that some of these effects can be considered irreversible (i.e. acting as a potential human carcinogen). The current uncertainty regarding bioaccumulation adds to the conclusion that adverse effects of HFPO-DA may occur at lower concentrations than the available toxicity data currently suggests. RIWA is of the opinion that for exposure through drinking water the precautionary principal should be in effect for substances like HFPO-DA.
• In order to avoid similar situations such as with the presence of HFPO-DA in the water environment RIWA suggests looking at the criteria set in REACH for better protecting the sources of drinking water.
We also support the comments submitted by Vewin and KWR Watercycle Research Institute in this public consultation.

* 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof)	We thank you for your support.
Development of further criteria for the protection of drinking water is beyond the scope of the present Support Document. Further development of the UBA proposal for PMT criteria is also beyond the scope of the current Annex XV proposal. 

As is described in the Support Document, HFPO-DA is concluded by the Dossier Submitter to be more persistent and more mobile than the minimum criteria as these are proposed by UBA to prioritize substances for the evaluation of further regulatory action on the basis of vPvM characteristics. As these criteria are still under discussion and do not yet have any regulatory significance, we have not included these in the Support Document.

		Attachment: 5291_RIWA Position on UBA proposal for PMT criteria REACH.docx
		
5293
2019/04/27	Vewin,
Other contributor,
Netherlands	Vewin welcomes the proposal by the Netherlands for the identification of HFPO-DA* as a substance of very high concern on the basis of the criteria set out in REACH article 57. We support the conclusions of the proposal and would like to stress several of the specific findings in it:
• HFPO-DA is detected in finished drinking water at several locations downstream of the fluorochemical production plant in the Netherlands. This is of concern to the drinking water companies. Because HFPO-DA does not adsorb to sediment, soil and active coal, and does not show any (bio) degradation under environmental conditions, it is very difficult to remove HFPO-DA from water. Even advanced water purification techniques are mostly not able to remove HFPO-DA, or only to a very limited extent. Vewin would like to stress that one of the aims of the Water Framework Directive is to avoid deterioration of water quality in order to reduce the level of purification treatment required in the production of drinking water. As HFPO-DA is very difficult to remove from water with the current levels of purification treatment installed, we strongly support to avoid any emissions to water.
• HFPO-DA is very persistent, very mobile in the water environment and shows adverse effects in humans. The available information on toxicity shows that some of these effects can be considered irreversible (i.e. acting as a potential human carcinogen). Vewin is of the opinion that for exposure through drinking water the precautionary principal should be in effect for substances like HFPO-DA.
• In order to avoid similar situations such as with the presence of HFPO-DA in the water environment Vewin suggests to incorporate criteria in the REACH registration and assessment processes for better protecting the sources of drinking water.

We also support the comments submitted by RIWA and KWR Watercycle Research Institute in this public consultation.
* 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof)	See the response to comments 5291
2019/04/26.	
		-		
5297
2019/04/29	Finland,
Member State	-	See response to comments  5297
2019/04/29 in the “Specific comments on the justification” section of this RCOM.	
		Attachment: 5297_HFPO_DA_Annex_to_FI_CA_comments_BIOWIN.docx
		
5302
2019/04/29	EurEau,
Industry or trade association,
Belgium	N/A	Thank you for your support and your information with regard to the water production process. We have added this information to sections 3.2.3 and 6 of the Support Document.	
		Attachment: 5302_EurEau_Public Consultation_Ammonium 2333-tetrafluoro-2-(heptafluoropropoxy) propanoate.pdf
		
5303
2019/04/29	Chemours International Sàrl,
Company,
Switzerland	Please find comments for all Parts in the attached document.	Thank you for your comments and information provided.

Regarding your comment on use and alternatives: Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.

Regarding your comments and information on the process of SVHC identification in the absence of clear criteria: As is clarified in the Support Document section 6.3.2 we based our equivalent level of concern assessment on several documents providing support to interested parties on this topic. In the Support Document, we refer to the work prepared for sensitizer, neurotoxic and immunotoxic substances as well as on the ELoC environmental concerns stemming from substances that have been included on the Candidate list on the basis of endocrine disrupting effects and effects on target organ toxicity. We note that these all have their basis in the elements as laid down in the guidance for the identification of substances of very high concern (https://echa.europa.eu/support/authorisation/substances-of-very-high-concern-identification). 

Regarding your comment that there is a the need for more specific criteria in order to allow identifying HFPO-DA as SVHC according to Art. 57(f) under Regulation No 1907/2006, we agree that the assessment elements identified to support all stakeholders in the evaluation of an equivalent level of concern are of a generic nature. However, we disagree that this would limit the identification of substances as SVHC under art. 57(f) of 1907/2006. We would like to draw your attention to Case T-134/13 of the General Court who ruled in par. 96-97 with regard to the criteria laid down in the guidance (in the context of respiratory sensitizers; https://echa.europa.eu/documents/10162/13657/svhc_art_57f_sensitisers_en.pdf/a50728cc-6514-486c-9108-193a88b4bc9e) that  “Although it is true that those criteria are general in nature and are applicable not only to respiratory sensitisers, the fact remains that they are sufficiently precise to enable interested parties, properly and effectively, to make known their views as to the assessment of whether a substance gives rise to a level of concern equivalent to those of other substances listed in Article 57(a) to (e) of Regulation No 1907/2006”.

From this ruling, we take that the current guidance on ELoC assessment and SVHC identification according to Art. 57(f) is already specific enough to allow for this assessment. Furthermore, in this same Case T-134/13 par. 99, the General Court ruled that “Moreover, it is apparent from the comments submitted by the first applicant…that the assessment carried out … according to which HHPA gave rise to a level of concern equivalent to those of other substances listed in Article 57(a) to (e) of Regulation No 1907/2006, was sufficiently clear to enable that applicant, properly and effectively, to make known its views.” Hence, it is apparent that even though it is acknowledged that the guidance on ELoC assessment contains criteria that are general in nature, these criteria are sufficiently clear to support the dialogue on a possible equivalency of concern to articles 57(a) – (e) also for the applicant of the appeal. Since the work on the respiratory sensitizers and the neuro and immunotoxicants, more substances have been identified according to art 57(f) for which no specific criteria were developed beforehand but for which the ELoC assessment did build on the generic elements that were developed in the context of respiratory sensitizers.

In the Support Document, section 6.3 we have added a more detailed elaboration on our ideas regarding the equivalency of concern to art 57(a) – (e), showing that the equivelency in our view is straight forward.

Regarding your comment on widespread occurrence in water and biota: We have updated sections 3 and 6 with the information you provided.

We did not include the reference to the German Umweltprobenbank as the samples are very diverse and originate from a wide time span, including years in which HFPO-DA was not used in Europe and for which the LOD is not known.

We do not agree that any number that is presented in the figures as smaller than should be interpreted as misleading, especially not because the data are discussed in the text, also if not detected and including the LOD. We did change the legend to make clear that “≤” in the lowest category may also be n.d.

The figures and its subscripts have been amended according to your suggestion (i.e. Asia and North America were replaced by the countries, n.d. was added to the legends. 

Regarding your comments on distribution and abundance we would like to refer to our response to similar remarks by UK CA (comment 5305 below in relation to section 3.3 page 39).

Regarding your comments and information on Industrial emission reduction: We have included reference to your improvements of processes that in 2020 are said to lead to 99% reduction of emissions as they were in 2017 in the Support Document as part of section 6.3. We note that the fact that negative effects associated with the use of a substance can be controlled adequately does not preclude its identification as a substance of very high concern (see par. 61 of Case T-134/13 of the General Court). Furthermore, we note that monitoring data suggest the additional presence of diffuse emission sources that are as of yet of unknown nature. Reduction of industrial emissions will reduce at least part of the overall emissions to the environment, but the observed diffuse emissions are expected to be unaffected by your current improvements of the industrial processes.

Regarding your comments on toxicity: 

We observe that you conclude, based on all available information, that “there is sufficient data to conclude that HFPO-DA is not a human carcinogen or that exposure to it will not result in immune, hematological, liver, or kidney effects in humans.” Additionally, you are of the opinion that “there is a ponderance of evidence in the literature (see, for example, Felter et al. 2018) supporting the lack of relevance of this mechanism [PPARα activation] to humans.” For instance, you note, fibrates (known PPARα activators) provided to patients for therapeutic use, do not cause liver carcinogenicity in humans. You lastly note that “the study requested under Substance Evaluation will most likely not address concerns of carcinogenicity, as it is a descriptive toxicity test which is not designed to, and will not, elucidate the rodent carcinogenicity mechanisms which created the original concern.” We have taken note of your considerations and would like to point out several of our observations that lead us to the opinion that the observed effects may be of serious concern to human health. 

We note the reference you provide (Felter et al. 2018). This study describes that PPARα-induced liver carcinogenicity as observed in rodents is not relevant to human health (a point which we will address below). This study however does not extend this observation to other health effects (immunotoxicity, haematological effects, liver effects, and kidney effects) as you do. It is noted that PPARs (α, β/δ, γ), belonging to the nuclear hormone receptor superfamily, mediate a wide range of biological activities, such as certain aspects of immune function (e.g. inflammation), lipid metabolism, vascular functions, glucose control, hormone biosynthesis, and embryonic and foetal development, and these receptors are consequently expressed in numerous tissues and cell types in the body, also during the development (Feige et al. 2006, Abbott et al. 2009). RAC notes in review of PFOA-induced carcinogenicity and developmental effects, that “the relevance of PPARα expression for humans is well established for the liver, however much less is known for the relevance of PPARα-related effects in other organs and effects in offspring and juvenile” (ECHA, 2011). One review study shows that interspecies differences in other tissues than the liver, and during development, could be considered less apparent (Abbott et al. 2009). The mere fact that PPARα activators (such as fibrates) are provided to humans as therapeutics to treat hypercholesterolemia illustrates that this category of compounds is biologically active in the human body, and could, in a non-clinical setting (e.g. as environmental contaminants), give undesired effects. We furthermore would like to add to this argument that evaluation of the risks for therapeutics is fundamentally different from that of environmental contaminants, where the issue of benefit-risk in the context of human health hazard assessment is a prominent factor, which does not hold true for the latter. 

We note your interpretation of the study by Rushing et al. (2017), who assessed the immunomodulary potential of HFPO-DA. In answer to comment 5297 2019/04/29, regarding page 86 in section “Specific comments in the justification” of this document, we further elaborate on the link between PPARα activation and potential immune modulation. Our assessment of the results by Rushing et al. (2017), as well as our assessment of other indications that HFPO-DA acts upon the immune system (changes in spleen weight, A/G ratio changes), and the evaluation of current datagaps, was summarized in the Support Document, and gives in our opinion concern for adverse effects to human health.

In answer to your comment that “the effects noted in the liver are PPAR alpha mediated and are therefore not relevant to humans”, we would like to refer to the article by Hall et al. (2012), which summarizes the outcome of an expert pathology workshop on how to assess whether liver pathological changes are PPARα-mediated (and therefore not relevant to humans) or not. Hall et al. (2012) note that liver weight increases, liver hypertrophy, steatotic macro-vascuolation without any other cellular damage, altered hepatic foci, and primary liver tumors are likely rodent specific phenomena if induced by PPARα. However, if there is histological evidence of structural degenerative or necrotic changes (such as necrosis, inflammation, and/or fibrosis), these effects (i.e. liver weight increases and hypertrophy) should be considered relevant to human health. In almost all repeated dose toxicity studies, in mice as well as in rats, liver necrosis was observed (Wang et al. 2017, Edwards 2010a, Haas 2008b, Haas 2008a, Haas 2009, Edwards 2010b, Craig 2013), as well as accompanied liver steatosis in one study (Wang et al. 2017). 

Lastly, we note you do not mention any effects on reproductive and developmental toxicity in this context. For new relevant findings with regard to HFPO-DA induced developmental toxicity, we would like to refer to our answer to comment 5297 2019/04/29 in the “Specific comments on the justification” section of this RCOM, where we address the findings by Conley et al. 2019.

In conclusion, regardless of whether the effects observed in the repeated-dose toxicity studies (liver, kidney, immunological, and haematological effects) are PPARα mediated or not, these effects are considered serious and relevant for human health. Chapter 4 of this Support Documentforms the basis of why the DS regards the effects observed in animal studies serious and adverse for humans, including data gaps still to be identified. This section now also includes a short discussion on mode of action in relation to the repeated-dose toxicity effects observed, based on the above. 

Then, with regard to the carcinogenicity study in mice as requested in the substance evaluation, you comment that this study will not elucidate the rodent carcinogenicity mechanisms. This argument was also brought up by the Registrant during the MSC-62 meeting, where the substance evaluation request was discussed and agreed upon by the MSC members. We cite the conclusions from MSC-62 underneath, concerning the ways this study will provide new information on the carcinogenicity of the substance:

“The possibility of a carcinogenicity study in mice leading to a Carc. 1B classification of the substance was discussed by MSC. It was acknowledged that sufficient evidence that the effects seen were not relevant to humans was needed in order to make this conclusion for classification. In this case, apart from liver tumors there were also pancreatic tumors and tumors in leydig cells. Hence, a study in mice, could be helpful to confirm or remove the concern for pancreatic tumors. It was also recognized that any mechanistic studies to understand other possible modes of action of Gen-X would be useful.” 

To that respect, we would also like to mention the effort of the Registrant to conduct any study underlying the carcinogenicity mode(s) of action for HFPO-DA until December 2018: 

“Regarding the carcinogenicity study, they [the Registrant] agreed with the assessment from the PfA submitter that since the observed tumors suggested to result via a PPARα mode of action, they are rodent specific and appear not to be relevant to humans. Hence, they agreed that there was no value in conducting a second carcinogenicity study as it was
expected that rats and mice would react similarly. However, in the meeting, when questioned, they responded that no studies with regard to carcinogenic mode of action had been carried out on the registered substance.” 

About the modes of action underlying the carcinogenicity of this substance in specific, still only limited data exists. Indeed, Wang et al. (2017) and Conley et al. (2019) show that HFPO-DA exposure leads to increased activity of PPARα-associated genes in rodent livers. And, as you mention, PPARα-mediated liver carcinogenicity being a relevant mechanism for human health is under debate (Felter et al. 2018, Guyton et al. 2009). Recently however, a study was published by Li et al. (2019) showing that HFPO-DA is also able to induce the human and murine nuclear receptor PPARγ. As indicated in the Decision Document of the substance evaluation, more information is required to exclude possible other MoAs leading to HFPO-DA observed liver carcinogenicity, and to further clarify the link between PPARα activation and pancreatic- and Leydig cell tumor formation. 

The burden of proof to conclude on the relevance/irrelevance of a tumor type to human health is very high. Consider also the framework as developed by Meek et al. (2014) on mode of action (MoA)/species concordance. The authors state that quantitative mechanistic evidence is required for each Key Event underlying the hypothesized Adverse Outcome Pathway, all supporting the observed tumor type. Furthermore, other relevant Adverse Outcome Pathways leading to the same tumor type need to be excluded based on mechanistic data, taking into account all underlying Key Events. This information should also contain human specific data (e.g. using human cells in vitro). And last, knock-out studies are preferred to confirm the suspected mechanism is indeed responsible for the effect of concern. These type of studies are not available for the HFPO-DA induced tumors in the liver, the pancreas, and the testes. Therefore, based on the currently available information, it cannot be excluded that the tumors observed in rodents are relevant for human health.   

Lastly, we welcome your reference to Thompson et al. (2019) but regret that this study has become publicly available only a few days before the MSC. Nevertheless, we have taken note of this study and reflect the findings below.

Thompson et al. (2019) derived an oral reference dose (RfD) and a maximum contaminant level goal (MCLG) for drinking water for GenX using the existing repeated dose toxicity studies as presented in Chapter 4 of the Support Document. A probabilistically derived oral reference dose of 0.01 mg/kg bw/day was calculated based on a BMDL10 of 6.4 mg/kg bw/day for liver cystic focal degeneration observed in male rats upon chronic exposure. Assessment factors used for input in APROBA, were assessment factors correcting for allometric scaling and toxicokinetic/toxicodynamic differences, and an assessment factor correcting for differences in sensitivity between individuals in the human population. Afterwards, an assessment factor correcting for database uncertainties of 3 was applied to the output of APROBA. Based on the same information, a MCLG for drinking water of 70 μg/L was established assuming a relative source contribution of 20%. 

Additionally, Thompson and colleagues performed a re-analysis of the liver histopathology for the 5 mg/kg bw/day dosed male mice in the reproduction/developmental screening study. After re-evaluation of the images, the single cell necrosis observed in this dose-group was re-interpreted as apoptosis. It was suggested that this effect would be caused by the PPARα mode of action, since Corton et al. (2014) hypothesised that increased liver apoptosis in vivo in rodents would be a feedback response to increased cell proliferation, which is in line with the proposed adverse outcome pathway for PPARα induced liver carcinogenicity. 

We note in this context that you conclude, based on our BMD analysis and the BMD analysis by Thompson et al. (2019) that “there is consistency between the two analysis in that liver effects [liver weight and liver lesions] drive the risk assessment rather than any of the parameters described by the CA”. We would like to reply that the BMD analysis we performed shows that all EDLs for liver weight (abs and rel), liver hypertrophy, liver focal necrosis, and liver single cell necrosis in male mice are in the order of 0.08-1.55 mg/kg bw/day. Also the effect of liver cystic focal degeneration, which Thompson et al. (2019) used as their point of departure, was in this range in our analysis (EDL10 = 0.674 mg/kg bw/day). In male rats, the EDLs for 10% increase in A/G ratio and 5% decrease in absolute spleen weight were 0.4 and 0.11 mg/kg bw/day respectively, which are effects occurring approximately at the same dose level. We therefore do not agree with you that liver effects seem to be the only effects relevant for BMD risk assessment. There is a large difference between the oral RfD of Thompson et al. (2019) [10 μg/kg bw/day] and the oral tTDI of Janssen et al. (2017) [0.021 μg/kg bw/day], which can mainly be explained by the different points of departure, and the absence of an additional assessment factor of 66 correcting for bioaccumulation potential.

We note the re-analysis of the liver single cell necrosis in Thompson et al. (2019), which is suggested to be in line with the PPARα mode of action. As we have described in the section on mode of action in Chapter 4 of the Support Document, there is still uncertainty that PPARα is the sole mode of action by which HFPO-DA may cause liver toxicity. There is for instance liver necrosis observed in female mice in the reproduction/developmental screening study at 5 mg/kg bw/day, for which cannot be concluded that this effect fits within the adverse outcome pathway for PPARα-induced liver carcinogenicity . The argumentation is further explained in Chapter 4 of the Support Document. 

Abbott, B. D. 2009. Review of the expression of peroxisome proliferator-activated receptors alpha (PPARα), beta (PPARβ), and gamma (PPARγ) in rodent and human development. Reproductive toxicology, 27(3-4), 246-257.

Corton, J.C., Cunningham, M.L., Hummer, B.T., Lau, C., Meek, B., Peters, J.M. … Klaunig, J.E. 2014. Mode of Action Framework Analysis for Receptor-Mediated Toxicity: The Peroxisome-Proliferated Receptor Alpha (PPARα) As a Case Study. Critical Reviews in Toxicology, 44, 1-49. 

Feige, J.N., Gelman, L., Michalik, L., Desvergne, B., Wahli, W. 2006. From Molecular Action to Physiological Outputs: Peroxisome Proliferator-activated Receptors are Nuclear Receptors at the Crossroads of Key Cellular Functions. Progress in Lipid Research 45(2): 120-159. 

Guyton, K.Z., Chiu, W.A., Bateson, T.F., Jinot, J., Scott, C.S., Brown, R.C., Caldwell, J.C. 2009. A reexamination of the PPAR-α activation mode of action as a basis for assessing human cancer risks of environmental contaminants. Environmental Health Perspectives 117 (11): 1664-1672.  

Hall, A. P., Elcombe, C. R., Foster, J. R., Harada, T., Kaufmann, W., Knippel, A., ... & Nolte, T. 2012. Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes—conclusions from the 3rd International ESTP Expert Workshop. Toxicologic pathology, 40(7), 971-994.

Meek, M.E., Boobis, A., Cote, I., Dellarco, V., Fotakis, G., Munn, S., Seed, J., and Vickers, C. 2014. New developments in the evaluation and application of the WHO/IPCS framework on mode of action/species concordance analysis. Journal of Applied Toxicology 34: 1-18.

MSC-62 minutes derived from: https://echa.europa.eu/documents/10162/23843530/msc-62_minutes_en.pdf/e15afa65-f298-783f-4d21-0d62692a4bf4

Regarding your comments on bioaccumulation: 

We observe that you conclude that “all available data [experimental and monitoring data] clearly demonstrate that HFPO-DA is not a bioaccumulative substance”. Furthermore, you wonder why the lack of a definitive half-life for the substance is so prevalent in the thinking of the DS, as “it is generally a true statement that industrial chemicals lack definitive measures of human half-life”. We have taken note of your considerations and would like to point out several of our observations that lead us to the opinion that there is concern for bioaccumulation. We would however like to note that the ongoing substance evaluation on FRD-902 (and thereby HFPO-DA) aims to generate further insight in the half-life in humans. We furthermore add to this that the current Support Document solely deals with the SVHC identification of the substance and stands apart from the ongoing substance evaluation. Bioaccumulation in humans is of concern but is not part of the motivation for equivalent level of concern.

As indicated in the Decision Document of thesubstance evaluation, the bioaccumulation potential of the substance in humans cannot be estimated with sufficient certainty based on the currently available information. This concerns the available experimental study in animals (Gannon et al., 2016) as well as the available monitoring data (Van den Berg 2017, Pan et al. 2018, NCDHHS 2018). 

With regard to the study by Gannon et al. (2016), we note that the study authors did not provide a measure to illustrate the goodness-of-fit of a two-compartment model in comparison to a one-compartment model, nor have shown the fit of a one-phase elimination model or a two-phase elimination model through the serum concentration data. These elements, together with a visual inspection of the data, and the fact that the data contains non-detects, give us reason to doubt the exact parameter estimations provided in Table 2 of the publication, and the width of their confidence intervals. Therefore we conclude in the Support Document that the available animal data indicates that the half-life of the substance in these species (mouse, rat, monkey) varies between one and several days. We provide our assessment of this research to point out the uncertainties the analysis of the data by Gannon et al. (2016), but it does not change our concern for bioaccumulation in humans.

We have amended the text of the Support Document to indicate that “this raises the question whether a distinction should be made between alpha and beta phases for this dataset or whether one-phase elimination would illustrate a better fit.” Prior reference to the term one-compartment model in this sentence was incorrect. 

Regarding the recent human biomonitoring study conducted by the NCDHHS (2018), the authors conclude that “GenX was not detected in blood or urine from any of the 30 participants. Although GenX was not detected, people have still been exposed in the past through drinking water from private wells. These results may indicate that GenX doesn’t stay in the body for a long period of time since all participants had stopped using their well water for drinking.” People switched to bottled water 9 months (average time) prior to first sampling, but the authors acknowledge that no individual exposure history is available. Therefore, the statement by the authors on the half-life of the substance is surrounded by significant uncertainty, as exposure was identified by the fact that participants had been living near the production plant for over 10 years and the mean concentration in their wells was 680 ppt. You also note, based on these data, that “it [the human half-life] is clearly not years or the exposed population would have had measurable amounts of HFPO-DA in their blood”. We acknowledge, however also pointing to the uncertainties, that these data provide a first indication that the human half-life may not be in the order of years. This is now added to the Support Document. However, whether the half-life is months, weeks or days can still not be concluded from the data.

We are aware of a Powerpoint circulating on the internet with more information on follow-up sampling after six months, from which was concluded that also during second sampling, GenX was not detected in blood or in urine. This information was however not included in the Support Document yet, since this Powerpoint is considered preliminary research which was not taken up in the report (NCDHHS 2018). Other than that, this knowledge does not change our conclusion that these data provide merely an indication that the human half-life may not be in the order of years.

What can be concluded from the North Carolina study (NCDHHS 2018) is that people in this area were not internally exposed to the substance during the time of sampling at concentrations above LOD. The other available human biomonitoring data prove the contrary, namely: HFPO-DA is detected in blood of workers and the general population, which indicates that humans are internally exposed to the substance (Van den Berg 2017, Pan et al. 2018). As these data are point measures lacking any detailed external exposure estimates, derivation of a half-life based on these data is surrounded with high uncertainty as well. 
	
We are interested in the exact half-life of this substance, as data from other PFASs (e.g. PFOA, PFOS, and PFHxS) indicate that humans have much higher half-lives relative to other species than would have been expected based on allometric scaling. As the human half-life for HFPO-DA is currently unknown, we have concern this value would be higher than expected based on animal data solely. We note you refer to additional information on the half-lives of two other PFASs (PFBA and PFBS) in humans, which are 3.1 days and 25.8 days respectively (Chang et al. 2008; Olsen et al. 2009). According to you, the half-lives of these substances provide prove HFPO-DA also has a short half-life in humans. Upon review of these publications, it was decided not to add these references to the Support Document, but rather to add the article by Pizzurro et al. (2019). This article makes reference to the publications by Chang et al. (2008) and Olsen et al. (2009), but discusses the toxicokinetics of PFBS and PFBA in relation to intermediate and long-chain PFASs (PFHxS, PFOA, PFOS). Providing information for PFBA and PFBS does not take away our concern for bioaccumulation of HFPO-DA in humans, since information for other PFASs (e.g. PFOA, PFOS, and PFHxS) makes that we have concern the human half-life would be higher than expected based on animal data solely. Hence, the fact that other industrial chemicals do not have a definitive half-life does not justify there is no need for a definitive half-life of the substance in this particular case.

Regarding your comments on BAF/BCF: We agree with your reasoning about the mechanism of aquatic bioaccumulation in fish. We do not state in the dossier that the internal concentration in fish increase with decreasing exposure concentrations and we do not think that this is suggested in the dossier. Neither do we use BCFs or BAFs as such to identify a risk in risk assessment. BCF/BAF values are used to calculate at which water concentration a threshold value in fish is exceeded. To calculate this, it is necessary to know the BCF/BAF changes with exposure concentration. For PFASs and also for HFPO-DA, the BCF/BAF values do increase with decreasing exposure concentrations. This is also exemplified by your reference to the study by Liu et al. (2011) for some other PFASs. A concentration dependent BCF results in internal concentrations in fish that decrease with decreasing exposure concentrations, but not proportionate to the exposure concentrations. The results of the recent BCF study by Chemours (Goodband, 2019) are included in the dossier. We agree that the bioaccumulation in fish is low, but an analysis of the results shows that the BCF is indeed concentration dependent as expected. Actually the data fit in rather well with the data already presented in the dossier. We do however, not agree on the remark that a risk assessment is conservative, if this is based on laboratory BCF values, which are derived for high exposure concentrations. This was the case for the existing BCF values. The new bioconcentration study gives more insight on the BCF at low and more relevant concentrations. Moreover, it is important to note that a kinetic reanalysis of the data in the study resulted in a BCF of 21 L/kg in the lowest concentration.

Regarding your comments on enrichment of plants: Enrichments in plants is not only a concern if the BAF values are higher than one, the exact value is also dependent on the way the BAFs are expressed (dry weight/wet weight). Here, plant concentrations are expressed on the basis of wet weight, BAFs based on dry weight would be higher. This is further explained based on comparison with other existing data on dry weight basis. Transfer of HFPO-DA from soil into plants leads to an additional exposure route for humans and wildlife and that is the concern addressed. We agree with your remark that BCF in pore water concentrations could be  more relevant. This is already indicated in the dossier, but these data are unavailable.
	
		Attachment: 5303_20190429_SVHC_Comments_Chemours_HFPO-DA.pdf
		
5305
2019/04/29	United Kingdom,
Member State	page 8 (also p116): The statement “HFPO-DA adversely impacts human health at a daily intake that could be as low as 21 ng/kg bw/day (tTDI)” is misleading. A Tolerable Daily Intake (TDI) is an estimate of the quantity of a chemical contaminant to which a person may be exposed through environmental contamination, and which when found in food can be ingested daily over a lifetime without posing a significant health risk. Whilst the value calculated here is a ‘tentative’ TDI due to the various uncertainties having a daily intake of the TDI should not ‘adversely impact human health’. Please consider rephrasing.

Section 1.4 (page 17-18): Editorial – The vapour pressure of the dried ammonium salt is stated to be 0.0117 Pa and 0.017 Pa at different points in the text. Please confirm which value is correct.

Section 1.4 (page 18): Log Kow values are reported from QSAR predictions. Please provide an indication of the reliability of these predictions, and whether they are for the ionised or unionised form. Three different QSAR software packages were used, and it would be helpful to understand the differences and whether the training sets contain relevant substances/fragments. Please consider which value is most appropriate, also taking account of the pKa information.

Section 3.1 (page 21): HFPO-DA is compared to perfluorinated substances with a carbon chain length of 8 or higher (e.g. PFOA). Are data available for any per- or polyfluoroether carboxylic acids with similar chain lengths to HFPO-DA?

Section 3.1.1.3.2 (p 23): Data presented in the phototransformation in water study are not comparable to that produced in an OECD 316. The total Wm-2s-1 that the substance was exposed to should be provided, along with the temperature at which the study was performed.  No extrapolation to daylight (as per OECD 316) at relevant latitudes has been performed. Additionally comparison to the AOP/ARP studies is irrelevant as these were not performed under environmentally relevant conditions.

Section 3.1.2.1.2 (page 24): It is noted that the toxicity of H-28397 to inoculum in a respiration inhibition test was measured. However, no results from the study are included. Please include these in the report.

3.2.1 The discussion of adsorption to powdered activation carbon and sub-bituminous granulated activated carbon is not relevant within the adsorption-desorption section. These are non-standard materials in the assessment of kd.

Section 3.2.2 (page 27): Editorial – The Henry’s Law Constant taken from the ECHA dissemination portal has the incorrect units (should be Pa·m3/mol not “mol Pa·m3/mol”). Please correct this.

Section 3.2.6 (page 38): Is it possible to provide a calculation based on a steady state emission and no removal mechanisms to estimate how long it would take for the concentration of HFPO-DA to reach levels in drinking water that would result in unacceptable risk to humans (e.g. using the FOCUS model)? It would be useful to have this hypothetical information to provide some further context to the proposal in terms of the urgency for action. This modelling could also be used to determine the effect of the emission reduction from the Dutch manufacturing plant.

Section 3.2.5 (page 38): If 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)propanoyl fluoride (C3 dimer acid fluoride) is a known pre-cursor of HFPO-DA then should this substance also be included in this SVHC proposal as a “related substance”?

Section 3.2.6 (page 39): The dossier notes that HFPO-DA has been detected in areas large distances from known point sources, but that the concentrations that have been detected are very small. We think it would be helpful to provide some benchmark for comparison.

Section 3.3 (page 39): We do not consider that the summarised monitoring data support the statement that HFPO-DA “is wide spread over Europe, the US and China”. Only a small number of sampling programmes have been undertaken, generally around a known point source. The available data are not sufficient to conclude on the distribution of this substance in these areas. Please amend the text accordingly.

Section 3.3 (page 40 and 41): Based on the pKa, the log Kow and log Kaw used in the modelling should be for the ionised form.

Section 3.3 (page 40 and 41): The table and text states that the lower bounds of the vP criteria were used to set the DT50 for soil and water. However, the soil DT50 used is the lower bound of the P criteria (i.e. 120 days instead of 180 days). The justification for using either the P or vP criteria should be made clearer. As the DT50 values are unknown the dossier submitter could have modelled a number of half-lives ranging from the modelled ‘optimistic’ values to longer DT50 as this would have demonstrated the range of possible model outputs and the uncertainty associated with this. This would aid the discussion on page 41.

Section 3.3 (page 41): Please add the LRTP model boundary lines to Figure 11 to allow easier interpretation of the model output. What type of error results from compounding predicted values with a model? (See previous comment in Section 1.4 and 3.3 with regards to the reliability of QSAR predictions for ionised/non-ionised substances.)

Section 3.4.1 (page 42): Editorial – The SVHC report states “HFPO-DA could not be detected in fish at none of these two concentrations”. The meaning of this sentence is unclear as it includes a double negative. Do you mean that HFPO-DA was detected in fish at both exposure concentrations, or that it was detected in neither?

Section 3.4.1 (page 44): The final paragraph of this section states that there is “uncertainty in this [aquatic] bioaccumulation potential of HFPO-DA”. However, the reported BCF and BAF are so low that even if there is uncertainty associated with them this would have to be very high to result in values of concern. Please also move this paragraph to a separate section as it relates to human exposure via consumption of fish, rather than bioaccumulation.

Section 3.4.2 (page 44): Please document the range of BCF and BAF values reported in this summary section. It appears that even the higher BAFs observed at the lower exposure concentrations are extremely low when compared to B/vB thresholds and this comparison should be added to the report. The final sentence of this section suggests that bioaccumulation in fish could pose a high level of concern to humans via consumption. Please move this line as it relates to human exposure via consumption of fish, rather than bioaccumulation. It also needs to be clear why the level of concern arising from human exposure indicates ELoC.

Section 3.5 (page 46): The final sentence of this section suggests that accumulation in vegetables could pose a high level of concern to humans via consumption. We do not believe this is warranted as the BAF in vegetables is low and the clearance times of HFPO-DA in monkeys, rats and mice indicate it should be readily excreted after consumption by air-breathing mammals. We note that the human biomonitoring study requested under Substance Evaluation will provide more information on the half-lives in humans to allow a more detailed assessment of this. In addition, the dossier does not include an overall assessment of human exposure so the relative contribution from different sources cannot be assessed. Please remove or amend this text.

Section 3.5: The BAF calculation for plants does not document which part(s) of the plant HFPO-DA was located in. For example, it should have been possible to determine whether uptake was via air or water from the distribution in the plant. We do not agree that these BAF values reflect the mobile character of the substance. Enrichment really just demonstrates the solubility of the substance.

Section 4.11 (page 100): We are of the opinion that the need for a human health hazard classification for specific target organ toxicity or CMR endpoints that would meet the Annex XIII T criteria has not yet been demonstrated. We note that there is a self-classification of STOT RE 2 mentioned in Section 2, but in the RMOA the NL-CA states that this classification is not warranted. We also note that a carcinogenicity study has been requested under Substance Evaluation, so this may alter the classification. It would be helpful to include a clear statement about this within the dossier.

Section 6.3 (page 102): The SVHC dossier states that HFPO-DA shows “adverse effects on human health”. However, if a substance does not meet the Annex XIII T criteria, why should they be considered especially significant to justify an ELoC? We think that for consistency, a level of toxicity equivalent to the Annex XIII criteria should be used as an essential element of the ELoC argument, unless a very good justification is provided.

Section 6.3 (page 102): The SVHC dossier states that HFPO-DA shows “a widespread occurrence in the Netherlands and in other EU Member States, in drinking water, fish and in home grown vegetable”. This statement is not supported by the data presented in the dossier, which only reports monitoring data from the Netherlands for these three media.

Section 6.3 (page 102): The SVHC dossier states that HFPO-DA is “ubiquitously present in the global environment at low background concentrations”. Although the summarised monitoring studies have detected HFPO-DA at low concentrations in the USA, China and Europe we do not consider that this is sufficient to state that this substance is ubiquitous globally.

Section 6.3 (page 102): The SVHC dossier states there is an “impossibility to remove the substance from the environment after release”. We do not think it is entirely fair to say that the substance is “impossible” to remove as Section 3.2.3 indicates that high pressure membranes can be effective. However, we agree that it may be difficult to remove in a cost-effective way using common treatment methods.

Section 6.3 (page 103): The SVHC dossier states that the hazard of these substances leads to a “societal concern for irreversible and intergenerational effects on humans and the environment for which as of yet no safe limit of exposure can be derived and which exposure cannot be predicted, controlled nor reversed”. If this statement is based on pre-empting the outcome of carcinogenicity and human biomonitoring studies that have been requested under Substance Evaluation then this should be made clear. In this case the ELoC argument would be based on the precautionary principle, rather than scientific data, and so this should be clearly stated and as a policy-based decision should be considered by the REACH Committee rather than the MSC.

Section 6.3.1.1 (page 103): We agree that this substance can be considered to meet the criteria for vP. It is stated that HFPO-DA is more persistent that PFOA. Neither HFPO-DA nor PFOA have data from definitive persistence studies in all compartments. There are not enough data from studies that trace transformation of these substances to make this statement.

However, the last sentence states that HFPO-DA has been found in remote areas with no indication of a point emission source, and so attributes these detections to long range transport. We do not know all the uses of the substance or non-European sites of use and manufacture, and so cannot state this conclusively. We would also not consider locations at which HFPO-DA has been detected to be ‘remote’, compared to the Antarctic for example.

Section 6.3.1.2 (page 103): Please summarise the range of BCF and BAF values reported in this summary section as they are extremely low when compared to B/vB thresholds and this comparison should be included in the report. Please also remove the text relating to human exposure via consumption of fish from this section on bioaccumulation.

Section 6.3.1.4 (page 104): See our previous comments where we disagree with the use of the term ‘ubiquitous’. We do not think that it surprising that a persistent and mobile compound is detected in monitoring programmes, and we see this monitoring data as further support for the persistence ELoC argument, not a separate point.

Section 6.3.1.4 (page 105): In the RMOA for this substance it is noted that the manufacturing plant in the Netherlands is adding measures to reduce its emissions by up to 99 % by 2020. Please add this information to the dossier.

Section 6.3.1.5 (page 105): We do not think that it surprising that a persistent and mobile compound is detected in monitoring programmes, and we see this monitoring data as further support to the persistence ELoC argument, not a separate point.

Section 6.3.1.7 (page 106): This section is largely a repeat of the bioaccumulation section 6.3.1.2, and as such should be removed if it does not add an additional ELoC argument. Has HFPO-DA been looked for or found in biota (especially mammals or birds) in monitoring programmes? Is there any evidence for HFPO-DA (not PFOA) that higher levels in biota would be observed than predicted based on the aquatic BCF and BAF?

Section 6.3.1.8 (page 106): The SVHC dossier states that “Due to the considerable uptake in vegetables and fruits, consumption of these by humans contributes significantly to the total exposure to HFPO-DA”. This statement is not supported by the data presented in the dossier that reports BAF<1.62 gdwt/gfwt, and the dossier does not include an overall assessment of human exposure so that the relative contribution from different sources can be assessed.

Section 6.3.1.10 (page 107): As stated previously, we consider that a conclusion on human health effects should wait until the carcinogenicity and human biomonitoring studies requested under Substance Evaluation are available and can be considered together with the repeat dose toxicity data via the CLH process.

Section 6.3.1.12 (page 109): We do not think that co-exposure with similar substances is a relevant argument for ELoC. The relative importance of this will depend on a variety of factors, and we did not take co-exposure with other PBT/vPvB substances into account for previous SVHC cases.

Section 6.3.2.1 (page 111): Please remove the sentence on intergenerational effects from this section. No evidence has been provided that intergenerational effects will occur and this text is not relevant to this section on persistence.

Section 6.3.2.1: Please remove or re-word the sentence “Consequently, once HFPO-DA has entered the environment, it will not be removed by any natural processes e.g. bio- or photodegradation”. We do not agree that this statement can be made as not all natural processes of degradation are represented in the testing presented here. Additionally, photodegradation was observed as noted in Section 3.1.1.3.2.

Section 6.3.2.1 (page 111): See our previous comments on the use of the term ‘ubiquitous’.

Section 6.3.2.1 (page 111): The dossier states “The wide spread occurrence in the environment and the low background concentrations in water observed world-wide raise a concern for impact on migratory species and show that the substance has the potential to impair population level structure and recruitment or ecosystem function and stability at remote and pristine areas”. Again, we do not believe that the monitoring data presented allows for a conclusion of world-wide concern. In addition, exposure alone does not have the potential to cause effects – hazard would also have to be shown, which we do not believe to have been demonstrated for this substance.

Section 6.3.2.2 (page 111): This Section notes that the concern for carcinogenicity and the current uncertainty regarding bioaccumulation adds to the conclusion that “the effects of HFPO-DA on human health may be more severe than can be concluded on the basis of the currently available toxicity data alone”. However, a carcinogenicity study and human biomonitoring data have been requested under the Substance Evaluation of FRD-902 (and thus HFPO-DA). It would seem sensible to wait for the results of these studies before proceeding to SVHC identification,

Section 6.3.2.3 (page 112): The majority of chemicals enter the biosphere and humans via a variety of routes. This in itself is not a reason to identify a substance as an SVHC. Due to its persistence and mobility it is not surprising that HFPO-DA has been detected in monitoring programmes of environmental compartments, fish and vegetables. However, exposure alone is not sufficient to identify a substance as SVHC and we see this monitoring data as further support to the persistence ELoC argument, not a separate point.

Section 6.3.2.4 (page 114): The RMOA for this substance notes that the manufacturing plant in the Netherlands is adding measures to reduce its emissions by up to 99 % by 2020. Please add this information to the dossier together with details of how this is being achieved and whether this will reduce emissions to air or water.

Section 6.3.2.4 (page 114): The dossier states in Section 9 that the very high concentration (up to 3 mg/L) at a waste facility is being further investigated. It therefore seems premature to conclude that exposure is difficult to regulate when data to support this assertion have not yet been published and the sources not determined.

Section 6.3.2.5 (page 114): We do not consider that HFPO-DA is of equivalent concern to PBT/vPvB substances as T has not been demonstrated.	Thank you for your comments and information.

Regarding p.8 and p.116 we agree that what is written may be interpreted wrongly and have changed the text. 

We corrected the typo on p.17-18

Regarding section 1.4: Discussion on the log Kow estimates has been added, showing considerable agreement among the different estimation routines, and a recommendation including the pKa on the value to be preferred (the completely ionized form of HFPO-DA) is included.

Regarding p.21: As far as we know there is not much data available on other perfluoro ether carboxylic acids. ADONA could be an exception, but this compound is still under investigation as well. The best compound to compare HFPO-DA with is thus one with structural similarities that is tested in the same test set-up, and  that which results have been concluded.  PFOA is currently thought to be the candidate that best matches these requirements.

Regarding p.23: We agree that this study is not a standard study comparable to the OECD 316 and certainly it is not representative for environmental conditions as indicated in the dossier. The temperature is not reported.  

Regarding p. 24: The details and the interpretation of the study have been added to the dossier.

Regarding section 3.2.1: The adsorption desorption section describes relevant findings for these processes, not only for the assessment of Kd. Adsorption to powdered activated carbon is relevant information in the light of possible remediation techniques.

Regarding p.27: The typo in the unit has been corrected.

Section 3.2.6 (page 38): We note your point. However, a calculation on steady state emission is direct risk based assessment. In this dossier one of our important concerns in the equivalent level of concern is built up around the uncertainties of such an assessment. These uncertainties include many steps in the risk assessment. It starts with the possible diffuse sources of HFPO-DA next to the direct emission to water from the plant. These could include air emissions and deposition, soil run-off to water, but also yet unknown diffuse sources. Second, the environmental distribution, requires a high level of knowledge of the hydrological systems to estimate concentration in different compartments including the river bank filtrates. Last, as pointed out in the toxicology section, also the assessment of what is urgent or not for action is complicated because of uncertainties around the assessment of effects. Hence, we are of the opinion that the exercise you propose may give the misleading impression that we may be able to anticipate and control possible risks. We have therefore not added this to the Support Document.

Section 3.2.5: The C3 dimer acid fluoride is indeed included in the SVHC proposal: “…and its acyl halides…”

Section 3.2.6: We note your point. However, a benchmark is only useful if the pattern of emission and the period of emission are the same. There is no such substance for HFPO-DA, at least not in such quantities that it can be traced over large distances and is unique for this point of emission at the same time. However, we are of the opinion that the fact that HFPO-DA is found in such far-away water bodies, where extensive dilution is self-evident, is ultimate proof of its persistence and mobility. The fact that HFPO-DA is detected at those locations above the level of detection is therefore the most important observation from this information.

Section 3.3: We have amended the text such that the observations and related concerns are now better described. We are of the opinion that the substance is widespread. It is true that the highest concentrations are found near known point sources. However, if the most recent monitoring data are considered (Heydebreck 2017, Pan et al. 2018), it appears that HFPO-DA does not only occur downstream of point sources, where it can be transported by water (e.g. the sea). Also upstream of point sources or in water without an evident point source HFPO-DA is detected in low concentrations. In Europe, this concerns the river Thames in UK, waterways near Stockholm and the upper part of the river Rhine. In USA, the Delaware river has not a known source of HFPO-DA. Moreover, the data from the river Rhine suggest that concentrations are increasing. In conclusion, the text of the dossier is not changed on this subject.
We have cited findings of HFPO-DA as far as the open sea more than 200 km out of the Norwegian coast far away from any known point source. It seems rather stringent if this is not considered remote anymore. Moreover, recent yet unpublished research (website, SETAC Helsinki abstract) by the same research group (Helmholtz Institute that detected HFPO-DA in the Norwegian Sea, North Sea and Baltic Sea) was able to detect it even further away, in the Arctic region in the Fram Strait (between Svalbard and Greenland).  

Section 3.3: The calculations for the ionized form were initially given in a footnote – but we agree that those are actually more relevant for the environmental situation. These calculations are now presented in the main body text, the calculations with the neutral species are not presented anymore. The log D at neutral pH (7) and adapted log Kaw are used for the LRTP calculations in the OECD LRTP tool.

Section 3.3: Thanks for correcting this obvious mistake. All calculations have now been performed with the vP criterion for soil, i.e. a half life of 180 days. As soil is not a very relevant compartment this does not change the conclusions, it only strengthens them. In the text now also the results are included where half-lives for HFPO-DA in both water and soil are set at 1 year and 3 years (being less optimistic). The results using the lower boundary of the vP criterion already clearly shows the LRTP potential and support the monitoring observations. This is indicated in the text.

Section 3.3: In the figure 11 caption the model boundary line is now explained. The figure is adapted to show the results of the calculations for the completely ionized substance. The reliability of the QSARs (for log Kow / log D) is now discussed in section 1.4. Annex I (detailed information from the LRTP tool calculation) has also been updated to show the results for the completely ionized species.

Section 3.4.1: Editorial is clarified.

Section 3.4.1 and 3.4.2: With regard to the BCF/BAF values.
This section starts with the remark that the BCF/BAF values for HFPO-DA are low. It has been further amended to reflect the results of the new BCF study. A comparison with the B/vB criteria is not within the scope of this dossier.

Actually, with the defaults used in quality standard setting (2 L drinking water per day, 115 g fish per day), the route fish consumption becomes critical at a BCF/BAF value of only 17 L/kg. For PFOA this is indeed the case, where the BAF are not high but high enough to make fish consumption the most stringent route. We removed the last paragraph as you suggested. It is indeed not directly related to bioaccumulation, but to standard setting. Further, it has become less relevant due to the newly provided BCF study. 

We do not provide a comparison with the B/vB criteria, because this is not part of the ELoC. Part of the ELoC however, is still the contribution of fish consumption to the overall exposure of humans and wildlife.

Section 3.5: The section now mentions that the BAFs refer to the edible parts. Solubility and mobility seems to be strongly connected. The fact that a plant accumulates a substance from the soil in its leaves indicates mobility throughout the plant via the roots and stems. Compared to other chemicals, the uptake in these edible parts is moderate to high. Some results for benchmarking with other chemicals have been included, although not exhaustive.

Section 4.11: Although we agree that expressing concern in terms of meeting criteria for classification would support assessing the overall equivalency of concern for HFPO-DA, we would like to stress that we are not addressing any classification in terms of Regulation No 1272/2008 as this would be inappropriate in the context of a Support Document. Any statement in this direction is therefore excluded from the current Support Document. 

For further details on the Substance Evaluation process, we would like to refer you to the relevant response to comments 5280
2019/04/25 

Regarding your comments on the need to meet the T criterion of Annex XIII (section 6.3, p.102), Art. 57(f) of REACH clearly states that a substance should be of equivalent level of concern and not of “the same concern”. The Candidate List contains several SVHCs identified according to Art. 57(f) based on Endocrine Disruption for the Environment that do not meet the T criterion of Annex XIII. See also the response to comments 5280
2019/04/25 for further details. 

Against the background of the concerns we have today, we are of the opinion that it is not opportune to await the results from the Substance Evaluation and when appropriate a follow-up proposal for Classification under 1272/2008, which may easily take another 6 years. 

Section 6.3 (page 102): Regarding your comment on a wide spread occurrence in NL and other EU member states, we agree with your point and have corrected throughout section 6 accordingly.

Section 6.3: Regarding your comment on the ubiquitous presence in the global environment, we agree that this rather reflects our very high concern and expectations fo future spread of the substance than that this reflects the exact monitoring data available. We have amended the text to make this clear.

Section 6.3: Regarding your comment related to the removability of HFPO-DA from the water phase. We agree with you that it may be possible to remove HFPO-DA from drinking water but that this process is very costly and energy intensive. We however are of the opinion that it is impossible to remove HFPO-DA from the water environment without seriously impacting the ecosystem integrity. We have amended the text.

Section 6.3: Regarding your question whether or not the ELoC assessment is based on a precautionary approach awaiting the SEv results, we motivate in section 6 that we base our ELoC assessment solely on the information we have on the Phys Chem properties, behavior and fate in the environment, monitoring data and toxicity of HFPO-DA today. Where this might have been confusing the text has been amended to make clear that we are not pre-empting any results that may come out of the Substance Evaluation process. 

Section 6.3.1.1: Relative persistence compared to PFOA has been removed from this section. Further details on the assessment are included in Section 3. However, it was not stated in the dossier that HFPO-DA is more persistent than PFOA. This is an incorrect interpretation of the dossier. It is stated that experimental data suggest that under abiotic conditions HFPO-DA is more persistent than PFOA. This statement is correct (see 3.1.1).

Regarding its presence in remote areas, please see our previous reflections on this issue to your early comments on Section 3.

Regarding section 6.3.1.2: We have removed the concern for human exposure through fish consumption from this section as it is already included in the assessment of ELoC. Although we see your wish to include an overview of quantitative BCF and BAF values in the assessment of ELoC, we decided to not further include those at that level because we find that the BCF and BAF values may be strongly influenced by the actual water concentration of HFPO-DA and the presence of co-exposure of other PFAS. Hence, we conclude that not the quantitative measure but the ability to enrich plants is of importance to the ELoC. 

Section 6.3.1.4: Comment addressed, see earlier.

Section 6.3.1.4: We have added the industrial emission reduction initiatives to the Support Document in the context of the availability of water remediation techniques. We have also added information on the societal costs to section 3.2.3.

Section 6.3.1.5: Comment addressed, see earlier.

Section 6.3.1.7: We have merged the essential information with section 6.3.1.2. To the best of our knowledge, there is no information available on biota like mammals or birds that may be used to address your question, apart from the cited monitoring data from remote areas. Non-detects are difficult to interpret in the absence of more detailed knowledge of the food pattern and possible other routes of exposure. The data summarized in the bioaccumulation section indicate that the use of a BCF obtained at high concentrations indeed may result in erroneous results if applied to low environmental relevant concentrations. 

Section 6.3.1.8: We are of the opinion that consumption of fruits and vegetables may be an exposure route of concern. However, we agree with your comment and amended the text.

Section 6.3.1.10: We kept the information on carcinogenicity and have indicated in Section 6.3.2 that this effect is included in the weight of evidence of the ELoC assessment as supportive information.

Section 6.3.1.12: Regarding your comment on co-exposure: As is being summarized in Section 4, for many PFAS very similar effects are observed (at different potencies). HFPO-DA is likely to remain in the environment for a very long time due to its very high persistence. As a consequence, co-exposure with other PFAS is of concern. The fact that co-exposure has not been taken into account (yet) in the assessment of PBT/vPvB substances does not exclude this concern to be included in the ELoC assessment under art. 57(f). Combined toxicity as a consequence of co-exposure to multiple chemicals is an area of high concern flagged by the European Commission and environmental quality standards for the group of PFAS are currently under discussion under the Water Framework Directive.

Section 6.3.2.1: Regarding your comment on intergenerational effects: we have clarified the text where needed.  

Section 6.3.2.1: The text has been adjusted.

Section 6.3.2.1: Comment addressed, see earlier.

Section 6.3.2.1: Comment addressed, the text is amended. See also our earlier response to your comments on this issue of worldwide occurrence.

Section 6.3.2.2: We have removed the concern for bioaccumulation from the weight of evidence for ELoC and included the concern for carcinogenicity as supportive information. See also our response to comment 5280  2019/04/25.

Section 6.3.2.3: We agree that exposure alone is not sufficient for ELoC and we do not suggest something along these lines. All information provided in section 6.3.2 is used in a weight of evidence assessment in section 6.3.3.

Section 6.3.2.4: Thank you for your comment.  The information included in section 9 is indeed part of further investigation. However, the monitoring data presented in section 3 already provide sufficient information to conclude the possible presence of diffuse emission sources (see also our previous response to this comment and also in 5280
2019/04/25. Regarding your more detailed comment on the reduction of industrial emissions  Section 6.3.2.4 (page 114): we note that comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process. 

Section 6.3.2.4: The monitoring data clearly show the possible presence of HFPO-DA in regions without an apparent emission source. It’s mobile character will make it extremely difficult to manage environmental exposures once HFPO-DA is released into the environment. Waste treatment is just one of the concerns for environmental release. The text has been amended to clarify this.

We take note of your reservations regarding the ELoC assessment and HFPO-DA being of ELoC. We hope that the further elaborations on our concern for adverse effects that are now included in Section 6 may change this view.	
		-		
5309
2019/04/29	American Chemistry Council,
Industry or trade association,
United States	-	Thank you for your comments and information.

On your first comment that the substance characteristics are not of ELoC to PBT/vPvB, vPvB, we note that an equivalent level of concern under Art. 57(f) is about concern for substances which effects on humans or the environment is so serious that we rather prevent these effect from happening than to remedy them. We argue in Section 6 that this is the case for HFPO-DA and that HFPO-DA is of equivalent level of concern not only to Art. 57(d) and (e) like you state in your comment but also to Art. 57(a) – (c).

For further details in response to your comment, please find our responses to comments 5303 2019/04/29 and 5280 2019/04/25 for further interpretation of the ELoC assessment, including a reflection on the the availability of criteria to perform an ELoC assessment and the ruling of the Court on that issue.

We are of the opinion that it is disproportionate to regulate our present concern with end-of-pipe measures like water purification techniques. We argue that once water concentrations will become critical in terms of actually causing a risk to human health or the environment, it will be very difficult to reverse exposure. This because water remediation techniques are difficult and energy intensive and because the substance is so persistent that it will remain in the environment for very long times. Legislative instruments like the Water Framework Directive and the Drinking Water Directive are therefore in our opinion less well suited in this case to address our concern.	
		Attachment: 5309_FINAL_ACC Comments to ECHA 042919.pdf
		
5314
2019/04/29	European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	-	Thank you for your comments and considerations.

Regarding your comment on the absence of well-defined criteria for addressing ELoC according to Art. 57(f) for the environment, we would like to refer you to our responses to comments 5303 2019/04/29 and 5280 2019/04/25 in which we detail that the available guidance for ELoC assessment is ruled by Court to be define well enough for this purpose. We stress that the fact that at least 9 substances are agreed and put onto the Candidate list based on a concern for Endocrine Disrupting effects on the environment suggests that the guidance for ELoC assessment is defined enough to deal with environmental concerns. ELoC considerations used in these cases typically relate to (but are not restricted to) severity and irreversibility of effect, broad environmental relevance and difficulty to set safe exposure levels. Similar arguments are brought up in section 6 of the Support Document.	
		Attachment: 5314_2019 04 29_Cefic updated reflection on SVHC_ELoC for env.pdf
		
5315
2019/04/29	FluoroCouncil,
Industry or trade association,
United States	-	Thank you for your comments and considerations. Regarding your comment on the absence of well-defined criteria for addressing ELoC according to Art. 57(f) for the environment, we would like to refer you to our response to comments 5314
2019/04/29 and references therein.

In your comment you refer to UmweltBundesamt, Assessment of persistence, mobility, and toxicity (PMT) of 167 REACH registered substances, 09/2018, stating that already 167 REACH registered substances meet the criteria proposed in this document. Also on this point, we stress that the ELoC assessment according to art 57(f) is a case-by-case assessment and that until now, Regulation No 1907/2006 is not restrictive to any detailed, quantitative criteria for the assessment of ELoC according to Art. 57(f). 

We like to point out that the criteria for PMT brought forward by UBA are in their work used solely for the purpose of prioritizing substances for evaluation of a possible need for further regulatory management measures. They are not positioned as to be defining criteria for SVHC identification on the basis of an ELoC according to Art. 57(f). This is clearly laid down in the Abstract of this work ”Consequently, a total of 134 substances based on suspected PaqMT properties combined with expected environmental emissions are recommended to the German Environment Agency (UBA) for further investigation and scientific and regulatory scrutiny. However, this result may not be suitable to indicate the need for regulatory measures.“ and in somewhat different wording in the Conclusions. The conclusions also highlight the added value of the assessment for registrant to evaluate a possible need for research and development towards substances of possible less concern.
	
		Attachment: 5315_FINAL FluoroCouncil response HFPO-DA SVHC consultation 29-4-19.pdf

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5269
2019/03/26	Oasen drinkwater,
Other contributor,
Netherlands	P 28. Values of HFPO-DA were detected in our individual wells for drinking water with concentrations up to 120 ng/l downstream of the Chemour factory. Indicating that the substance is very persistent and mobile and is not degraded during river bank filtration.	Thank you for this information.	
5270
2019/04/12	European Environmental Bureau,
International NGO,
Belgium	EEB welcomes the SVHC dossier submitted by The Netherlands. The dossier provides a comprehensive motivation for the identification as SVHC of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof). EEB supports the proposal to identify HFPO-DA as a substance of equivalent level of concern (art 57f) to those of other substances listed in points (a) to (e) of Article 57 of the REACH Regulation.

HFPO-DA should be identified as a substance of very high concern because of the combination of extreme persistency, high mobility and evidence of a wide range of toxicological effects on kidney, liver and immune system at low levels of exposure. In addition the substance may be carcinogenic. The substance is ubiquitously present in the environment, including pristine areas, groundwater and drinking water. It is difficult to remove from drinking water with current water treatment techniques. Its widespread occurrence in the environment and occurrence in drinking water, in combination with toxic effects at low exposure levels give rise to identification as SVHC according to Article 57f of REACH.	Thank you for your support.	
		-		
5275
2019/04/18	Health and Environment Alliance (HEAL),
International NGO,
Belgium	See full comments in attachment	Thank you for your support and information.	
		See the corresponding embedded attachment in table 1 of Part I: 5275_HEAL-Comments-GenX.pdf		
5279
2019/04/25	ANSES,
National Authority,
France	ANSES agrees that these substances are very persistent and very mobile in the environment. The monitoring data presented in the dossier show a widespread occurrence of the substances. Indeed, it is found in freshwater systems such as groundwater, drinking water, tap water and marine water. It is proven by scientific data that removal of the substances in water is not possible by both conventional methods and by advanced water treatment processes. The substances exhibit a high long –range transport potential, which is supported by monitoring data and modelling estimations. Emissions of the substances or their precursors to the air compartment lead a subsequent wet and/or dry deposition into the environment (and their mobilization), where humans and biota can be exposed to the substance also by this route. This finding is supported by the concentrations found in rainwater and soils.

A range of serious effects are identified on the basis of experimental studies in rodents.
- In repeated dose-toxicity studies, in particular in mice, the most sensitive effects appear to be significant adverse effects on blood cells (substantial decrease in haemoglobin, haematocrit, increase in reticulocytes) and on the liver (necrosis). These effects are observed at low dose (≤ 10 mg/kg in 90-day studies). Other effects are also identified (effects on kidney and immune system) but it is noted that they are less severe and/or occurring at higher doses.
- HFPO-DA induces tumors in different organs in rats. In particular, liver, pancreas and testis are organs that have already been described as sensitive to carcinogenesis after PFOA exposure. This consistency brings further support to the identification of the carcinogenic potential of HFPO-DA. In addition, in contrast to PFOA that is classified Carc 2 because observed tumors are benign only, malignant tumors are observed after exposure to HFPO-DA in the liver and pancreas. Carcinogenic properties of HFPO-DA are therefore acknowledged.  Harmonisation of  carcinogenic classification will be  justified once the ongoing study will be completed.
- In addition, it is noted that one of the major effect of PFOA is developmental toxicity. PFOA is classified Repr 1B for development based on positive results mainly in mice but not in rats. For HFPO-DA, it is noted that effects on early deliveries and decreased foetal body weight in the rat PNDT study are observed from the mid-dose onward. No significant general toxicity is observed at this dose. Therefore, this effect cannot be attributed to general toxicity. In particular, the decrease in gravid uterine weight should not be seen as a sign of maternal toxicity as it can be consistent with the decrease of foetal body weight (magnitude of the two effects should be compared to confirm this). Unfortunately, no relevant developmental data on mice are available for HFPO-DA as only an OECD-421 screening study with insufficient dose is available. The potential of HFPO-DA to induce developmental toxicity is detected based on the findings in the rat study and may be underestimated by the lack of relevant mice data.

These data indicate that HFPO-DA has the capacity to induce serious health effects. Importantly, these effects are relevant for human health as well as for mammals of the environment. The relevance of the data gathered on rodents for their relatives in environment should be underlined in the rationale for the identification.

The main concern related to these substances is that due to their very important persistence and mobility, the continuous use of these substances will lead to an irreversible contamination of environment and result in uncontrolled sources of exposure for humans and biota at large (drinking water, food).
As the substances will remain bioavailable for long periods of time due to their persistence in the environment, exposures of organisms (including humans) will occur across generations, even if the emissions have ceased.
By itself, this concern is considered sufficient to support an SVHC identification according to 57(f) as it is not realistic to consider that a chemical substance can accumulate and disperse in the environment without ultimately generate risks. The level of concern is therefore not only driven by the level of severity of the effect in this case but also by the level of ability of the substance to persist and contaminate the environment.

In addition, because of their serious hazardous properties, the risks related to these substances are especially substantiated.
On this basis, the dossier proposed by the Netherlands is supported.

The latter point supports an equivalent level of concern and should be discussed in more details. It is also consistent with the recommendation to discuss for HH ELoC the factor “is derivation of a safe concentration possible?”. In general, the dossier would benefit for a more structured presentation of the elements that are discussed in the introduction of the ELoC assessment and why some factors listed in introduction 6.3.2 are not discussed and/or considered relevant.	Thank you for your support and further information. 

More clarification on the developmental effects in the rat (e.g. gravid uterine weight) have been provided in section 4.8.2 and chapter 4 of the Support Document. Additionally, we also would like to draw your attention to a recent abstract that provides more information on a follow-up study by Conley et al. mentioned in our answer to comment 5297 2019/04/29 in the “Specific comments on the justification” section of this RCOM:
Conley, J.M., Lambright, C.S., Evans, N., Medlock-Kakaley, E., Wilson, V.S., Gray, E. 2019. Adverse effects of gestational exposure to hexafluoropropylene oxide dimer acid (GenX) in the Sprague-Dawley rat. Birth Defects Research 111: 502-538. Poster abstract No. 29.

With regard to the ELoC assessment, we have further structured the assessment in the Support Document along the different elements of concern and discussed these in more detail. We have also included more detail on possible environmental concerns, in particular for secondary poisoning, in Chapter 5 and included this in our ELoC assessment.
	
		-		
5280
2019/04/25	Germany,
Member State	The German CA supports the proposal to identify 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides as substances of very high concern (SVHC).
Based on the information provided in the dossier we agree that the substances are very persistent and very mobile and meet the criteria of being of an equivalent level of concern to those substances mentioned in Article 57 a-e.
The German CA would like to remind that in order to identify substances as SVHCs according to Article 57 (f) a demonstration of two aspects is necessary:
1. Demonstration of probable serious effects on human health and/or the environment
2. Demonstration of an equivalent level of concern to substances listed under points (a)   (e) of Article 57
For the first part, the German CA agrees that the substances are very persistent and very mobile and therefore of high environmental concern. However, with regard to adverse effects on human health, the German CA notes that the substances are not listed in Annex VI of the CLP Regulation and no harmonized classification and labelling is yet available. Therefore, the German CA is of the opinion that the SVHC identification should not be based on these properties in first place. Nevertheless, the adverse effects described in the dossier can be used as supporting evidence to underpin the equivalent level of concern argumentation.	Thank you for your comment and support to propose these substances as SVHC according to Art. 57(f) of No 1907/2006. 	
		-		
5284
2019/04/26	the city of Dordrecht,
Regional or local authority,
Netherlands	We welcome the proposal and can largely agree with the way the different properties of the substances are assessed. We particularly agree with the conclusion that the substances should be identified as SVHC.
With respect to the applied criteria, we submit that persistency in the environment, or, in the case of these substances: the unability to degrade under ambient conditions, should in itself already be a reason to designate the substance as an SVHC. In that respect we refer to a recently published paper by Cousins et al (Environ. Sci.: Processes Impacts, 2019. DOI: 10.1039/C8EM00515J). The substances that are now proposed to be identified as SVHC have very long half-lives under environmental conditions, exceeding the vP criteria by far. When released into the environment, such substances will ultimately lead to human and environmental exposure, the effects of which may not yet be known.
Furthermore, we would draw the attention of ECHA to the recent study by Conley et al (Env Health Persp., 2019. DOI: 10.1289/EHP4372). In this study, the effects of oral exposure to HFPO-DA in rat is compared to the effects of other known PFAS. The results of this study give additional evidence about the toxicity of HFPO-DA.	Thank you for your support and informormation 

We have added the information (Conley et al. 2019; Cousins et al. 2019) to Section 4 and Section 6 of the Support Document.	
		-		
5288
2019/04/26	Ireland,
Member State	We understand that the proposal to identify HFPO-DA as a SVHC under Article 57(f) is based on a weight of evidence approach taking into account a number of hazard and fate properties, including that HFPO-DA adversely affects human health. Our comments relate only to the human health aspects of the proposal.

With respect to the effects on human health, the Annex XV report includes a number of repeated dose toxicity studies and a carcinogenicity study in rats.  We note that in the discussion of this data, no conclusion is drawn regarding whether the data is sufficient to meet the classification criteria as STOT RE or carcinogenic under CLP. We appreciate that harmonised classification is not a requirement to identify a substance as an SVHC in accordance with Article 57(f). However, we consider that where classification criteria exist for the endpoints under consideration, as in this case, some discussion of whether the classification criteria are met would assist in assessing the severity of the effects observed and thus the impact on the equivalent level of concern assessment.

With respect to the carcinogenicity data in particular, there is some uncertainty regarding the weight applied to this potential hazard in the equivalent level of concern assessment. We note that on page 8 of the Annex XV report, the limitations of the available carcinogenicity data are noted: “HFPO-DA may also be a human carcinogen, but data are currently insufficient to fully determine its carcinogenic potential. The carcinogenicity of FRD-902 is currently under investigation in an ongoing Substance Evaluation.” However, the (potential) concern for carcinogenicity is used to justify an adverse effect on human health for HFPO-DA in various places in the Annex XV report, for example:

• Summary of how the substance meets the criteria set up in Article 57 of REACH (page 8): “The effect on human health may come with a possible delay between the moment of exposure and the onset of any observable adverse effect (i.e. cancer)…” (the same sentence is used on page 112)
• Section 6.3.1.10 Effects on human health – toxicity (page 108): “Therefore, HFPO-DA is considered potentially carcinogenic to humans and the information available is concluded by the dossier submitter to possibly meet the CLP criteria for a category 2 carcinogen. Data are however currently insufficient to conclude on the full carcinogenic potential of HFPO-DA.”
• Section 6.3.2.2 HFPO-DA causes adverse effects on human health (page 112): “Based on the effects on carcinogenicity it is concluded that HFPO-DA causes adverse effects on human health that can be considered irreversible.”
• Section 6.3.3 HFPO-DA is of equivalent level of concern (page 115): “The available information on toxicity shows that some of these effects can be considered irreversible (i.e. acting as a potential human carcinogen).”

We note that the substance evaluation decision for FRD-902 includes a request for a carcinogenicity study in mice (OECD 451) which is justified as “the current data for the registered substance are not sufficient to conclude whether classification for carcinogenicity is triggered, and to differentiate between carcinogenicity classification in CLP Cat. 1B or Cat. 2”.

As the carcinogenicity of HFPO-DA is currently under evaluation, we consider that the proposal should be clearer regarding the weight given to the carcinogenicity concern in the equivalent level of concern assessment.	Thank you for your comments and suggestions for further improvement of the Support Document.

Regarding your comment on adding the criteria for Classification under Regulation No 1272/2008 we agree that adding these criteria would help interpreting the severity of effects. We have not included these here to avoid confusion because assessing a need for Classification is beyond the scope of this Support document. However, we have included a short reflection in Section 6.3.2.6 on different opinions expressed by various Member States on the possibility to classify effects during this RCOM, by the Netherlands in their RMOA, and by the registrant in their registration dossier under REACH. We are of the opinion that whether the effects observed in laboratory tests meet the classification criteria is neither definitive nor sufficient for SVHC identification according to Art. 57(f). For further details, we would like to refer you to our relevant responses to comment 5280 2019/04/25

This concern adds on to the concern for the other effects observed in laboratory animals i.e. on the liver, blood, immune- and reproductive system that together form our concern that effects on human health may be probable.  In combination with its very high persistency and mobility, this makes HFPO-DA a substance of equivalent level of concern according to Art. 57(f). We have clarified the text in the Support Document accordingly. 

Regarding carcinogenicity, we have added the weight this effect has in the Equivalent level of concern assessment. The potential effect is of high concern and is added as supportive information in the present ELoC because of the uncertainties being under further evaluation in the ongoing SEv. 
	
		-		
5290
2019/04/26	Sweden,
Member State	General comments
The Swedish CA is concerned about the following properties of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof), further denoted HFPO-DA:
• the extreme persistence, which results in that HFPO-DA will remain in the environment for indefinite time and background concentrations will increase.
• the mobility in water and soil, which may result in, among other things, further contamination of drinking water resources and together with the extreme persistency and other physicochemical properties result in potential long-range transport and contamination of pristine areas.
• difficulty of remediation, which means that contaminated compartments, such as e.g. drinking water resources, will remain contaminated for very long periods of time and attempts to remove HFPO-DA, from e.g. drinking water resources, will be costly and inefficient.
• the toxicity-profile, which is similar to that of PFOA, and includes liver toxicity (incl. necrosis) at dose levels relevant for STOT RE1-classification, and tumors in the liver, pancreas and testes.	Thank you for your support and expressed concern.

With regard to the comment about possible harmonized classification as STOT RE1, we refer to the response to comment 5280 2019/04/26 in the section “General comments on the SVHC proposal”.
	
		-		
5291
2019/04/26	RIWA, Association of River Waterworks,
Industry or trade association,
Netherlands	-	See our response to comment 5291
2019/04/26 in the section “General comments on the SVHC proposal”.	
		See the corresponding embedded attachment in table 1 of Part I: 5291_RIWA Position on UBA proposal for PMT criteria REACH.docx		
5292
2019/04/26	CHEM Trust Europe,
National NGO,
Germany	CHEM Trust supports the identification of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof) as SVHC.  The group of substances has been shown to be of high persistence, very high mobility and having adverse effects on human health. The very good dossier makes a convincing case that there is scientific evidence of probable serious effects to the environment and humans, which gives rise to an equivalent level of concern according to article 57(f) of REACH.

The high persistence of HFPO-DA combined with its high mobility means that potential impacts will continue even after cessation of emissions, thus presenting a threat also to future generations. The intrinsic properties and connected uncertainties in the assessment regarding the potential serious and irreversible effects makes it unlikely that deriving a safe concentration is possible.

Taken together with the evidence of adverse effects provided on human health, the potential for long-range transport and the fact that structurally similar perfluorinated substances have already been included as PBT or vPvB chemicals in the REACH candidate list this dossier convincingly identifies this compound group as SVHC according to REACH 57 f.

On the issue of high persistence we would note that scientists have argued for decades that high persistence in itself is a major concern as highly persistent chemicals accumulate in the global environment and have the potential to reach critical concentrations at which negative unexpected effects can be triggered (Cousins et al., Environmental Science: Processes & Impacts, 2019, DOI:10.1039/C8EM00515J.)  The paper emphasizes that “these increasing concentrations will result in increasing probabilities of the occurrence of known and unknown effects and that, once adverse effects are identified, it will take decades, centuries or even longer to reverse contamination and therefore effects.”

To demonstrate the very high mobility the dossier has compiled important studies reporting findings in drinking water and surface water and has highlighted results illustrating the ineffective removal of the substances in water treatment steps. It is indeed very concerning that the environmental occurrence of HFPO-DA has developed over just a few years (2012-2018) since the start of using these compounds in Europe. The increased exposure via drinking water mobility should be considered of equivalent concern to bioaccumulability (see also Reemtsma, et al., 2016. Mind the Gap: Persistent and Mobile Organic Compounds – Water Contaminants that Slip Through. Environ. Sci. Technol., 50, pp. 10308-10315. http://doi.org/10.1021/acs.est.6b03338)
In CHEM Trust`s view it would be important to pursue a general policy discussion to ensure that the identification and regulatory controls  of  PMT/vPvM chemicals under REACH are improved (see also proposal by the German Environment Agency UBA (UBA, 2017. Protecting the sources of our drinking water: A revised proposal for implementing criteria and an assessment procedure to identify Persistent, Mobile and Toxic (PMT) and very Persistent, very Mobile (vPvM) substances registered under REACH. German Environment Agency, 20pp. https://www.umweltbundesamt.de/sites/default/files/medien/1410/publikationen/171027_uba_pos_pmt_substances_engl_2aufl_bf.pdf	Thank you for your support and information. 

We have amended the Support Document to further elaborate on the concern for highly persistent substances that are mobile in the environment and have the potential to have adverse effect on humans.

We acknowledge that further policy discussion may be needed to further strengthen regulatory measures for substances of concern due to their high persistency, mobility and possible adverse effects on human health or the environment. We stress that this policy discussion is beyond the scope of this Support Document. The present assessment of ELoC of HFPO-DA is a case-by-case assessment. Further development of criteria for PMT/vPvM is neither a necessity, nor will it influence the equivalent level of concern assessment of HFPO-DA according to art. 57(f).

We also thank you for providing additional information (Cousins et al. 2019; Reemtsma et al. 2016), these references have been added to the Support Document. 	
		-		
5294
2019/04/27	Individual,
Finland	The report produces a commendable effort to provide an overview of the available data on GenX.  Unfortunately, the authors allow themselves speculations and unfounded statements, present hypotheses and raise questions.  With some cleaning of the text this report could be a reasonable proposal to fund further research to address the scientific questions raised.  However, the available substance specific facts presented may raise a (societal) concern but not an alarm.  It is premature to take regulatory risk management actions at this moment, and there is sufficient time to address the outstanding scientific questions by appropriate data generation on the substance itself.  The identification of GenX as an SVHC should therefore not be supported for the moment.  Several arguments are presented that underpin this position.

1) Some of the questions raised are currently under investigation with data being generated on human biomonitoring (which will address uncertainties in the human half-life of GenX) and a mice carcinogenicity has been requested under the substance evaluation process (to follow-up on mode of action uncertainties).
2) The dossier heavily relies on a read-across based on structural similarity, but does not produce a hazard data matrix to compare different endpoints, their effects and potencies of the substances used in the read-across.  This violates the approach advocated in the ECHA’s RAAF. Furthermore, the physico-chemical fate and behaviour information presented introduces a circular argumentation. The model calculation (e.g. EPIWIN) are based on the premise that structural components contribute to the calculated property value. However, for PFASs these values have not been independently derived, and the model calculations are speculative (as acknowledged in the dossier) since they are outside the models’ domain of applicability. If the read-across is accepted by MSC then the approach used here for the SVHC identification of GenX introduces a discrepancy in the standards applied to registrants and regulators regards read-across.  ECHA uses a slightly leaner approach in substance evaluation, since this results in data generation and a possible confirmation of the read-across concern, however, it is dis-proportional to take regulatory action mainly on the basis of structural similarity.
3) Some of the data on occurrence mentioned (Expertise centrum PFAS, 2018) are non-peer reviewed, not published and thus untraceable.  This is a violation of the right of the public to be heard since they cannot be commented upon.
4) The limit value derived by the Janssen et al (2017) is not necessarily directly comparable to the DNEL value derived by the Registrants according to the REACH methodology and uses an additional assessment factor for additional uncertainty on the substance’s half-life in humans.  Firstly, the introduction of an additional assessment factor in the DNEL derivation would be an unprecedented move by ECHA The assessment  factors provided in the REACH guidance documents already cover many uncertainties and are considered to provide a reasonable worst-case approach for DNEL or toxicological limit value derivation. Secondly, it is highly speculative that the GenX half-life in humans is analogous to that of PFOA, and data are currently being generated to further follow-up on that speculation.
5) The protection target for the SVHC identification of GenX are humans. As mentioned, key elements of the hazard database for GenX are still under development (see above). The human exposure routes presented are exposure through drinking water and food (e.g. plants and fish), and some data are presented on the occurrence of GenX in these exposure sources. Several questions arise on the topics presented.
5a) The authors speculate on the dependence of bioaccumulation in aquatic organisms on the exposure concentration. The general concern is that in such instances the bioaccumulation increases with increasing exposure concentrations due to saturation of active elimination processes. In effect, the substance specific data presented suggest an exposure concentration dependence, however, somewhat unexpectedly this goes in the opposite direction.  An average BAF in muscle of carp of 4.1 L/kg at a median concentration of 369 ng/L in water (Pan et al, 2017) whereas at a significantly higher exposure concentration of 6800 ng/L a BAF in muscle of carp of 0.31 L/kg is reported (Van Bentum et al, 2017).  This dependence of the bioaccumulation in aquatic organisms on the exposure concentration will lead to an overestimation of the human exposure via fish if the more conservative BAF value is used and should therefore not be an element of concern.
5b) Enrichment in plants is not an element of concern as such, and criteria for when plant accumulation is to be considered as an independent assessment element are not available. The authors do not provide comparative information from other substances to further benchmark the substance’s accumulation.  Therefore, this information can only be used in a quantitative risk assessment with realistic assumptions on the plant food basket contribution.
5c) Both properties are fate and behaviour related, not intrinsic hazard properties, and similarly degradation is not a hazard property.  In the context of ED-identification ECHA excludes fate and behaviour properties from case-by-case equivalent level of concern assessments. Including them here suggests an inconsistent approach taken.
6) The aquatic mobility and long-range transport potential (LRTP) are based on monitoring in the aquatic (marine) environment from sources with significant direct releases. The LRTP provides support for the mobility in aqueous environments, but it subsequent occurrence in pristine and remote areas is not a relevant element in this SVHC identification as the protection targets are humans (exposed via the food and water.  If the protection targets were organisms living in those pristine and remote environments the LRTP could be considered in a weight of evidence approach, however, the dossier does not contain an environmental hazard assessment.
7) No information is provided on soil mobility, other than screening level studies, and higher tier leaching studies are not available/presented.

8) A comparison with PBT/vPvB substances is not relevant for this case. Environmental food-chain transfer to higher trophic levels would require that the dossier contains an environmental hazard assessment.
9) Irreversibility of effects has not been demonstrated.

10) Continuous exposure to a substance with toxicological effects that act through threshold mechanisms is not an element of equivalent level of concern. Humans are always and continuously exposed to different types of natural and man-made substances.  This a general issue that can be addressed through the established risk assessment methodologies. The monitored upper-level exposure concentration in drinking water is 30 ng/L.  Even when taking the extremely low TDI of Janssen et al (2017) of 21 ng/kg bw/day as a worst case DNEL, then a human of 70 kg would need to drink 42 liters of water per day to arrive at a risk characterisation ratio (RCR) of 1.  Please note that the average intake of water by humans is 2 liters of water, and also that water has an LD50 in the range of 5.4-6.3 liters per day.
11) The dossier lacks information on (expected) time trends in substance concentrations. No increase over time has been reported. Hence, it can only be speculated that cessation of emissions do not lead to a reduction in environmental or the more relevant drinking water concentrations.

In conclusion, it is acknowledged that there is a high public and political concern, specifically in the Netherlands, fueled by media coverage of the general press.  However, based on the above arguments there is no scientific argumentation to consider this alarming and requiring an immediate regulatory risk management.  It is still unclear how the substance affects human health, and the body of science is not robust enough as it needs to be. The data generation processes of REACH should, specifically in this case, be finished first before moving onwards with irreversible regulatory actions.  The costs and benefits need to be carefully balanced.	Thank you for your comments and your opinion on the equivalent level of concern of HFPO-DA according to Art. 57(f) of 1907/2006.

Regarding your comments:

1.	See response to comment 5280 2019/04/26 in the section “General comments on the SVHC proposal”

2.	As is lined out in Sections 3 and 4 and summarized further in Section 6, the equivalent level of concern assessment builds on data generated on HFPO-DA. The resulting view on ELoC is then further supported by the available knowledge on some other PFAS.

3.	Data that have been published in the meantime are updated, which includes the cited one. The data on fish have been published.

4.	The DNELs were brought up solely for the purpose of illustrating some further perspective on the possible evaluation of effects observed in mammals, their representativeness for possible effects on human health and the existing uncertainties. They are not definitive in the ELoC assessment. It is our opinion that the effects observed in mammalian studies are already of sufficient concern in the absence of further information on bioaccumulation.

5.	We note that the environment (wildlife, birds and mammals via secondary poisoning) is addressed as a protection goal in the Support Document. Given the very high persistence of HFPO-DA, its mobility and its current insight in possible effects on human health we are of the opinion that it is disproportionate to await further insight development on the many outstanding issues for which there is still significant uncertainty. 5a. See our response to comment 5305 2019/04/29. 5b. The enrichment in plants demonstrates the possibility of exposure of humans to HFPO-DA through food.

6.	LRTP is relevant for the possibility of a world wide spread of the substance and hence the possibility for humans to get exposed.

7.	Comment noted. Section 1.4 and 3 provide an overview of the information of the sorption potential of HFPO-DA. These data clearly show that sorption to soil is highly unlikely.
8.	We do not agree with your view as art. 57(f) indicates ELoC to 57(a) – (e).

9.	The fact that HFPO-DA is so very persistent that eventually environmental concentrations are expected to remain over long periods of time, will result in continuous exposure and consequently effects that are reversible may in practice turn out to be irreversible due to this continued exposure.
10.	Continuous exposure may lead to effects that remain unobserved in standard toxicity tests (Cousins et al. 2019). See also Section 6 of the Support Document.

11.	The substance shows no to negligible degradation under environmentally relevant conditions. It is therefore to be expected that environmental concentrations will rise upon continued emissions. The uncertainty regarding when concentrations will be reached at which effects will occur is a reason not to wait for concentrations to further rise.

The ELoC assessment lined out in Section 6 motivates that effects on human health will occur once exposures become high enough. The very high persistency and mobility of HFPO-DA make it likely that there will be a point in time at which such exposure levels will be reached when environmental concentrations will rise with continued emissions. 	
		-		
5295
2019/04/29	Norway,
Member State	General comment:
We thank the Dutch authorities for the SVHC-dossier for HFPO-DA, its salts and its acyl halides, and appreciate the opportunity to comment on the dossier. We share the concern for the findings of HFPO-DA in the environment and for the properties of the substance which represent a risk to human health and the environment.
HFPO-DA is highly persistent and is not expected to degrade under environmentally relevant conditions. It is highly mobile in the aqueous environment, and contamination of water resources and drinking water has been observed. Furthermore, HFPO-DA has a potential for long-range transport.
In our opinion HFPO-DA exhibits properties that taken together are of an equivalent level of concern as PBT/vPvB substances. According to the REACH PBT Guidance the specific concerns related to PBT/vPvB substances is due to their potential to accumulate in parts of the environment and to the fact that the effects of such accumulation for human health or wildlife may be unpredictable in the long term. With continuous emissions of HFPO-DA, environmental concentrations will increase, including the levels in drinking water sources and even an enrichment in edible plants. An increasing human exposure will be accompanied by increasing HFPO-DA levels in human blood and organs. At some point a concentration may be reached at which the currently known and unknown health effects of the substance may be realized. HFPO-DA should therefore be identified as a substance of Very High Concern (SVHC) according to REACH article 57 f) and included in the Candidate List.

Detailed comments:
We suggest adding a recent study by Conley et al. (2019) on developmental toxicity;
The study is a combined in vitro and in vivo study in Sprague-Dawley rats concerning potential maternal and postnatal toxicities of oral HFPO-DA. The study demonstrated that HFPO exposure produced higher maternal liver weights, lower maternal serum thyroid hormone and lipid profiles, and up-regulated gene expression related to PPAR-signaling pathways in maternal and fetal livers during gestation. The pilot postnatal study indicated lower female body weight and lower weights of male reproductive tissues in F1 animals.
Reference: Conley, Justin M., et al. "Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats." Environmental health perspectives 127.3 (2019): 037008.
We also suggest including another recent study by Cousins et al. (2019) on persistency and the concern on high persistent compounds:
This paper argues that the higher the persistence of a chemical, the greater emphasis should be given in chemicals assessment and decision making. The study demonstrates that if a chemical is highly persistent, its continuous release will lead to continuously increasing contamination irrespective of the chemical's physical-chemical properties. Thus, increasing concentrations, will result in increasing probabilities of the occurrence of known and unknown effects and that, once adverse effects are identified, it will take decades, centuries or even longer to reverse contamination and therefore effects.
Reference: Cousins, Ian T., et al. "Why is High Persistence Alone a Major Cause of Concern?." Environmental Science: Processes & Impacts (2019).
The substance FRD-902 (CAS no 62037-80-3) was included in a Norwegian environmental monitoring study in 2016. Samples were collected from locations within the Oslofjord area, Lake Mjøsa and in the vicinity of the City of Oslo. Samples were taken from a STP (VEAS), seawater and sediments near the outlet from VEAS, moreover samples from snail and shore crabs and cod liver (Gadus morhua) were analysed.  Also from a lake (Mjøsa) samples from a STP (HIAS), sediments in the vicinity and liver samples from several fish species in the lake (perch (Perca fluviatilis), roach (Rutilus rutilus), bream (Abramis brama), grayling (Thymallus thymallus) and whitefish (Coregonus lavaretus)) were analysed. Moreover, liver samples from rats captured from the sewage system of Oslo, from the streets of Oslo and from indoor areas at a waste treatment plant and dust and air samples from a hotel and two shopping centres were analysed. The substance was not quantified in any of the samples. However, it should be recognized that there are no known companies producing or using the substance (or the acid (HFPO-DA) or other of its salts) in this area.
Reference: The Norwegian Environment Agency. Screening programme 2016: Suspected PBT    compounds. M-806 | 2017	Thank you for your support, additional studies and more detailed information on monitoring data on HFPO-DA in Norway. These data have been added to the Support Document.

We have amended the Support Document with this information. Additionally, we also would like to draw your attention to a recent abstract that provides more information on a follow-up study by Conley et al. mentioned in our answer to comment 5297 2019/04/29 in the “Specific comments on the justification” section of this RCOM:

Conley, J.M., Lambright, C.S., Evans, N., Medlock-Kakaley, E., Wilson, V.S., Gray, E. 2019. Adverse effects of gestational exposure to hexafluoropropylene oxide dimer acid (GenX) in the Sprague-Dawley rat. Birth Defects Research 111: 502-538. Poster abstract No. 29.

Reference to The Norwegian Environment Agency. Screening programme 2016: Suspected PBT    compounds. M-806 | 2017 is included in the Support Document.	
		-		
5297
2019/04/29	Finland,
Member State	We thank the Netherlands for this proposal.
Please note that in addition to the comments to the Annex XV report listed below there is a separate document regarding the biodegradation predictions using the BIOWIN models (file name: HFPO_DA_Annex_to_FI_comments_BIOWIN.docx). This document gives additional information to the comments below.
Comments:
We would like to draw your attention to the recent publication by Conley et al. Please discuss these findings in relevant sections of the document.
Conley, Justin & S. Lambright, Christy & Evans, Nicola & Strynar, Mark & McCord, James & Mcintyre, Barry & Travlos, Gregory & Cardon, Mary & Medlock-Kakaley, Elizabeth & Hartig, Phillip & S. Wilson, Vickie & Gray Jr, Leon. (2019). Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats. Environmental Health Perspectives. 127.
page 6. List of abbreviations. Please include “HFPO” in the list
page 8. (summary): ”HFPO-DA adversely impacts human health at a daily intake that could be as low as 21 ng/kg bw/day (tTDI).”  Please, rephrase this sentence to: HFPO-DA may adversely impact human health at a daily intake…”. Reasoning: The wording gives impression that there are reported cases of people suffering from HFPO-DA toxicity.
page 8: “which will become irreversibly affected”: Comment: This refers to concentrations and distribution. Therefore, we think that “affected” should be replaced by “exposed” as effects are not discussed in this paragraph

page 8: “chronic background concentrations” (used also in other parts of the document): Comment: The word “chronic” seems to be redundant and misleading as it is often associated with effects and here it is used in relation to exposure. An alternative wording could be e.g. “expected continuous presence in the environment”.

page 9. Please extend the summary to include reasoning why there is considered to be an ELoC to the environment and humans, taking into account that there are no indications that the T criterion of PBT assessment would be fulfilled and that information on environmental hazards is not included in the proposal at all. In our view this should include considerations related to PBT/vPvB substances. This is discussed in more detail in our other comments (e.g. comments regarding pages 111 and 114).
page 9: “effects will not only occur at the point of release…”. Comment: This sentence is about distribution and not effects. Therefore, it could be replaced by “the substance will not only be present at the point of release but…”. In addition, “will affect a very large number of people” should be changed, e.g. to “a very large number of people may be exposed to the substance”.

page 9: “…such as PFOA, PFHxA and PFBS present in the environment lead to combination effects on human health, which add further onto the societal concern for this substance.” Please modify to: …may lead to combination effects on human health,… Reasoning: as stated on page 113: “Effects resulting from combined exposure are of concern but are as of yet unknown.”

page 21: ”For HFPO-DA there are no studies on its degradation potential available that follow a standardized and generally accepted study design, such as the OECD test guidelines”
Comment: “HFPO-DA” apparently refers here to the dimer acid of HFPO. Please specify this in the sentence because based on the list of abbreviations (page 6) and Chapter 1.1. (page 11) HFPO-DA can also refer to the group of 2,3,3,3-tetrafluoro-2- (heptafluoropropoxy)propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof).

page 21: “A number of studies for the PFOA confirm that this substance is very persistent and does not undergo abiotic or biotic degradation at all under environmental conditions (ECHA, 2013b).”
Comment: Please modify to:“…and does not undergo abiotic or biotic degradation at all in studies conducted under environmentally relevant conditions (ECHA, 2013b).”. Reasoning: there are studies indicating biodegradation of PFOA conducted in optimised conditions, i.e.:

Luo, Q. et al. 2015. Laccase-Catalyzed Degradation of Perfluorooctanoic Acid. Environ. Sci. Technol. Lett., 2015, 2 (7), pp 198–203 https://pubs.acs.org/doi/10.1021/acs.estlett.5b00119
Luo, Q. et al. 2017. Factors controlling the rate of perfluorooctanoic acid degradation in laccase-mediator systems: The impact of metal ions. Environmental Pollution. Volume 224, May 2017, Pages 649-657 https://doi.org/10.1016/j.envpol.2017.02.050
Yi et al. 2016. Isolation, identification, and degradation performance of a PFOA-degrading strain.
Genetics and Molecular Research 15 (2): gmr.15028043. http://dx.doi.org/10.4238/gmr.15028043.  https://www.geneticsmr.com/articles/6361.

page 21: “The difference between these PFCAs and HFPO-DA is the ether bond in the perfluoro chain (see also Annex II). This ether bond is not expected to lower the persistence substantially. QSARs included in BIOWIN v4.10 of EpiSuite generally have a negative fragment contribution of the ether bond on the degradation included. Further, also the length of the perfluorochain does not influence the degradability of the substances”
Comment: We propose to modify and extend this, for example as follows:
“There are structural similarities between HFPO-DA and PFCAs, such as the high degree of fluorination, the carboxylic acid group, steric conformation, and bond angles (see Annex II). One difference between HFPO-DA and PFCAs is the HFPD-DA’s ether bond which is located between two C3 moieties. Due to the ether bond the fluorinated carbon chains in HFPD-DA are shorter than in e.g. perfluorohexanoic acid (PFHxA) which has the same number of fluorine atoms. There are no indications available in the literature that the ether bond or other differences between these compounds would have an influence on the degradability/stability of these substances in the environment. QSARs included in BIOWIN v4.10 of EpiSuite generally have a negative fragment contribution of the aliphatic ether bond on the degradation included (see ‘Comparison of BIOWIN QSAR results for HFPO-DA, PFHxA, and PFOA’). This indicates that ether bond in HFPO-DA is not expected to lower the persistence substantially. BIOWIN results suggest that HFPO-DA, PFHxA, and PFOA have a low biodegradability and that there may be some differences in biodegradability between these compounds. However, the reliability of the BIOWIN models to predict differences between these compounds is questionable (see ‘Comparison of BIOWIN QSAR results for HFPO-DA, PFHxA, and PFOA’).
Reasoning: This change is proposed to take into account that there is no information on long-term degradation rates of perfluorinated substances with different chain lengths or with different functional groups (such as carboxyl or ether) in environmentally relevant conditions. Also other differences between HFPO-DA and PFCAs than the ether bond may be significant and therefore are briefly discussed in the proposed text.
Regarding BIOWIN models we agree that (aliphatic) ether fragments in BIOWIN are mostly negative indicating that an addition of an aliphatic ether to a molecule generally decreases the predicted degradability according to BIOWIN. However, as the purpose here is to estimate the effect of an ether fragment in relation to PFCAs (that are considered vP) we do not think that the fact that ether bond has a negative coefficient in BIOWIN is a sufficient argument for equal persistence of HFPO-DA to PFCAs. All structural differences should be considered as well as the values of the coefficients. Therefore, we suggest to include the comparison of BIOWIN results (submitted here as separate document, file name: HFPO_DA_attachment_to_FI_comments_BIOWIN.docx) e.g. as an appendix.

page 24:
“In particular, the perfluorinated carbon chain is counted as four units of “carbon with 4 single bonds & no hydrogens”, while only BIOWIN 1-4 and 7 predictions include an additional fragment for a trifluoromethyl group.
Comment: Please modify e.g. to “In particular, there is no fragment coefficient for a subterminal perfluorinated carbon in the BIOWIN models. For example, for EC 236-236-8 the perfluorinated carbon chain is counted as three units of “carbon with 4 single bonds & no hydrogens”, while BIOWIN 1-4 and 7 predictions include an additional fragment for a trifluoromethyl group and BIOWIN 5-7 include a fluoride fragment. It should also be noted that in BIOWIN 1-4 the trifluoromethyl fragment is based on only one compound in the training set. In the case of BIOWIN 1-2 the amount of trifluoromethyl fragment exceeds the maximum number of fragments in the training set compounds and in this situation the predictions may be less accurate according to BIOWIN User’s Guide.”.

Reasoning: There are three (not four) units of “carbon with 4 single bonds & no hydrogens” in HFPO-DA. In addition, BIOWIN 5-7 in principle cover the whole perfluorinated chain as they include also a fluoride fragment (in addition to the “carbon with 4 single bonds& no hydrogens”).

page 24:
“The toxicity of H-28397 (88% ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)
propanoate, 13.3% water and an impurity of 3.4 ppm perfluorooctanoic acid) to inocula was
tested separately in a respiratory inhibition test according to OECD TG 209.”
Comment: Please include an explanation and the results or move to microbial toxicity section or delete the sentence. It is not clear why this information is included in the degradation section. In addition, the toxicity results are not given.

page 25: Please specify in the report whether the screening studies by Kawashima and Lili include toxicity controls.

page 25: “Based on the predictions on biodegradation by BIOWIN and the lack of any primary degradation in the screening tests available on biodegradation, it is concluded that HFPO-DA does not biodegrade.”
Comment: In line with the arguments presented above, we propose to modify, e.g., to:
“Based on the lack of any primary degradation in the screening tests available on biodegradation, predictions on biodegradation by BIOWIN, and the very high degree of fluorination it is concluded that the biodegradation of HFPO-DA in the environment is likely to be very slow or negligible”.

page 26: Please include discussion of reliability of KOCWIN 2.00 prediction for HFPO-DA.

page 39, last paragraph of 3.2.6. Comment: Please modify to take into account that there are many uncertainties in the use of monitoring data in P/vP assessment. According to the ECHA guidance R.11. “conclusions should be drawn on the basis of monitoring data only when there is sufficient understanding of the substance distribution and transport behaviour and under the condition that the uncertainties in the monitoring data presented are adequately addressed.”. We note that in the degradation section monitoring data is not used as the main argument. The same considerations may be relevant for mobility as well.

page 41: first paragraph:”lower boundary of the half-life criterion for very Persistent (vP substances)” : Please delete “lower boundary of the” as there are no lower boundaries for vP (for each of the compartments the vP criterion is indicated by one half-life value).

page 41: last paragraph. “This makes these estimations less reliable.”  Comment: please specify, what are these estimates (the same ones as in Table 8 or other?) and what is the comparison point meant by “less reliable than”?

page 42: last paragraph. Please specify “aqueous exposure concentrations”; what is the difference between this parameter and “water concentrations” in the same paragraph? Is it the same measurement but only on different sampling date?

page 43: “Other data for BCF and BAF of PFOA in carp (Verbruggen et
al., 2017) show that the expected BAF value for PFOA is higher than what as observed for HFPODA at the same external water concentration.”. Comment: This is a difficult sentence. Would the following modification be in accordance to the meaning of the sentence?: “Other data for BCF and BAF of PFOA in carp (Verbruggen et al., 2017) show that at the same external water concentration a higher BAF would be expected for PFOA than for HFPO-DA”?

page 43: Figure 12. In the figure caption, could you explain what is the meaning of “Arrows denote values smaller than indicated”? What values does it refer to? and what does it mean (e.g., that the values are out of the scale of the graph?). There is only one arrow that is linked to a data point.

page 43: “The water concentrations of PFOA in the studies cited by Verbruggen et al. (2017) were always amongst the highest observed in the field studies (roughly about half of the total concentration of PFASs or more).”. Comment: What does “amongst the highest observed” refer to (highest of PFASs studied?). Please specify.

page 44: “Taking into account the uncertainty surrounding the joint exposure of PFAS, the aquatic bioaccumulation of HFPO-DA might still be very similar to that of PFOA.”. It could be explained why the BCF study by Hoke et al. 2016) (with FRD-903 only) seems to be given a low weighting in this assessment and instead the effect of joint exposure of PFAS is emphasised. Are the BCFs reported in that study (<30 and <3 L/kg) considered reliable? Is there any information on biotransformation in fish and whether it could affect the result?

Page 86: “Decreased globulin and corresponding increases in A/G ratio are considered early signs of potentially reduced immune function.” This effect was reported quite consistently and at already low dose levels in both rats and mice in repeated dose toxicity studies and is thus interesting. Moreover, the lowest reference values for humans (tTDI) were derived from this effect. Could you please elaborate briefly in the document (possibly including literature references) why you consider this finding as early signs of potentially reduced immune function.

page 87 (carcinogenicity). The tumor findings are important part of the dossier. This section would benefit of more detailed information which would enable the reader to conclude on carcinogenic properties of the substance. Please modify the section as follows:

The Table 32 is difficult to read since different dose levels were used for males and females.
Please modify the table 32 by including dose levels as mg/kg bw/day. Moreover, incidences for males and females could be in separate columns for clarification.
The tumor findings are compared with historical control data but no information on historical control data is given. Thus, it is not possible to judge the relevance of the historical data. Please include in the text the necessary information on historical control data, i.e. whether the data is from the same laboratory that conducted the study in question, strain and origin of the animals (same breeder?), how many studies and animals, from what time period (preferably within 5 years to study in question).
Second paragraph. Please consider modifying accordingly: “The incidence of Leydig cell tumors was not statistically significant, amongst others due to a relatively high incidence of these lesions in the controls. However, the incidence of interstitial cell hyperplasia was increased at 50 mg/kg bw/day and outside the historical control range suggesting that increased incidence of Leydig cell tumors in high dose males was treatment-related.

pages 92-93. In rat developmental toxicity study early deliveries and reduced pup weights were observed at 100 and 1000 mg/kg bw/day while also maternal toxicity was evident at these doses. Please include brief comparison of maternal toxicity and foetal effects/early deliveries and discuss whether you consider these effects (foetal effects, early deliveries) to be a secondary non-specific consequence of other toxic effects (maternal toxicity) or not. Consider also findings of the mice reproduction/developmental screening study and the findings of the recent publication by Conley et al and conclude on developmental toxicity (i.e. whether you consider that the data currently available fulfils CLP criteria for Category 2/Category 1B developmental toxicant. When appropriate, please include this conclusion also in section 4.8.3 (summary and discussion of reproductive toxicity), section 4.11 (summary and discussion on human health hazard assessment, page 100), section 6.3.1.10, pages 108-109, section 6.3.2.2

page 100. First paragraph: “In summary, the data illustrate that HFPO-DA induces tumors in the liver, pancreas, and testes in rats upon chronic exposure.” Please conclude clearly on carcinogenic potential based on the currently available data. For example:  This indicates that HFPO-DA may also be a human carcinogen… the data is considered to fulfil CLP criteria for Category 2 carcinogen. Please include this conclusion also to section 6.3.2.2 page 112.

page 101: “The environmental health hazards…”. Comment: apparently, “health” should be deleted (as the title of the Chapter is Environmental hazard assessment).

page 101: “The environmental health hazards of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid,its salts and its acyl halides (covering any of their individual isomers and combinations thereof) are considered not relevant in the context of the present Annex XV proposal to motivate the very high concern for these substances that lead to propose these substances as SVHC according to art. 57(f) of REACH. Subsequently, no environmental hazard assessment has been performed.” Comment: The report states on page 116 that there is scientific evidence of probable serious effects to the environment and humans, which gives rise to an equivalent level of concern according to article 57(f) of REACH. The text on page 101, claiming that environmental hazards are not relevant, therefore seems inconsistent with the proposed SVHC identification. Please consider including a justification why environmental hazards are not considered relevant.

page 102: 6.3. “All publicly available information was taken into account and no information was given additional weight in relation to other information”.
Comment: Please check whether this statement is correct. At least based on the degradation section there were differences in the relevance of the studies as it is stated: “All studies and publications are considered relevant to evaluate the degradation of HFPO-DA, and are used in the weight of evidence assessment of persistence. Despite the fact that some studies are not conducted according to OECD guidelines, or may not be considered highly relevant as standalone studies to assess the persistence, the study results show an overall consistent pattern of degradation for HFPO-DA. Hence, the dossier submitter sees no reason to discard any study on the basis of reliability.”

page 102: “…are irreversibly present in the environment due to the absence of degradation and the impossibility to remove the substance from the environment after release…”
Comment: Please modify to “…are irreversibly present in the environment due to the absence of degradation in environmentally relevant conditions and the impossibility to remove the substance from the environment after release…”

page 103: “The Substance Evaluation decision addresses concerns of carcinogenicity which could lead to a potential classification and the half-life in humans (bioaccumulation potential) which could lead to identification of the substance as PBT/vPvB and/or a different DNEL for workers and consumers.”. Comment: Please clarify whether it means that different DNEL might be derived for workers compared to consumers, or whether it means in general a refinement of DNEL for workers and consumers.

page 103: 6.3.1. The title refers to “hazardous properties” whereas many of the subtitles are more related to observations that are related emissions and distribution of the substance. “Summary of the data on the identified concerns” could be more suitable.

page 110: In Section 3.1 it is shown that HFPO-DA is so very persistent that the substance practically does not degrade in the environment. Comment: Please modify to be consistent with 3.1.4, e.g. to: 1 “it is shown that degradation potential of HFPO-DA in all compartments can be concluded to be very low or negligible.”

page 110: “Based on the available experimental and QSAR information on
HFPO-DA and on the information of structurally related substances, it is expected that HFPO-DA will meet the P and vP-criteria of REACH Annex XIII.”: Comment:  Perhaps the words “expected” and “will” can be deleted as it is already said in the subtitle 6.3.2.1 (and in summary section of the report) that the substance is very persistent.

page 110:” it will not be removed via any natural process such as e.g. bio- or
photodegradation.”. Comment: we propose to modify “its removal via any natural process such as e.g. bio- or photodegradation will be negligible or very slow.”

Page 111: “Due to the very high persistence of the substance, the exposure will remain over multiple generations and hence will lead over time to inter-generational effects.” and “Irreversible concentrations in the environment will furthermore lead to inter-generational effects”.
Comment: Please modify to “Due to the very high persistence of the substance, the exposure will remain over multiple generations and hence can lead over time to inter-generational effects.” and later “Irreversible concentrations in the environment can furthermore lead to inter-generational effects”.  No certain predictions can be done for inter-generational effects with current knowledge, but as a precaution there is a concern that inter-generational effects might occur in the future.

page 111: “The wide spread occurrence in the environment and the low background concentrations in water observed world-wide raise a concern for impact on migratory species and show that the substance has the potential to impair population level structure and recruitment or ecosystem function and stability at remote and pristine areas.” Comment: Please delete or modify the sentence. Reasoning: It is unclear from the present text why the occurrence in the environment is of particular concern to migratory species compared to other species and what evidence there is for impairment of population level structure and recruitment or ecosystem function and stability at remote and pristine areas, considering that no data on environmental hazards is included in the document at all. If the available mammalian toxicology data is considered relevant for the environment this should be explained in the report. If a similar argumentation as for vPvB substances (i.e. that regulatory action is warranted even though the T criterion is not fulfilled) is considered relevant here, it should be described.

Page 111: “once released any amount will persist and environmental occurrence will only
increase with continued production, use and emission of HFPO-DA and any of its precursors.“
Comment: Please modify to: “once released any amount is likely to persist and environmental occurrence will increase with continued production, use and emission of HFPO-DA and any of its precursors”. Reasoning: There are studies indicating that degradation of perfluorinated substances is possible in optimised conditions. Therefore, it is not completely excluded that some degradation would occur in the environment. We also note that the environmental half-lives of HFPO-DA or other perfluorinated componds in the environment are not known and there are no standard simulation tests available for these compounds.

Page 111: “Irreversible concentrations in the environment will furthermore lead to inter-generational effects ”. Comment: Please modify to: “High persistence and continuous presence in the environment can furthermore lead to inter-generational effects”. Reasoning: As discussed in comments above.

page 112: “HFPO-DA enters the biosphere and humans via several routes”
Comment: Please change the term biosphere to biota or for example “HFPO-DA enters the biosphere via several routes”. We think that biosphere, by definition, would also include humans.

page 112: Second paragraph: “Based on the effects on carcinogenicity it is concluded that HFPO-DA causes adverse effects on human health that can be considered irreversible.” Please modify to: “Based on the currently available data on carcinogenicity it is concluded that HFPO-DA may cause adverse effects…”

page 113: ”Independent of the half-lives in humans, irreversible background concentrations of HFPO-DA in water, which may lead to the contamination of drinking water and food and feedstuff, lead to long-term continuous human exposure, that can be expected to be inter-generational.”
Please modify to: “Independent of the half-lives in humans, irreversible background concentrations of HFPO-DA in water may lead to the contamination of drinking water and food and feedstuff and hence to long-term continuous human exposure, that can be expected to be inter-generational.”. Reasoning: as discussed in comments above.

page 113: “bioaccumulation in humans cannot be ruled out due to the absence of data in humans”: Comment: We do not think that a concern which is not confirmed can be used as an argument for EloC. This would not be appropriate for SVHC identification under 57 (a) to (e).

page 114:, 6.3.2.5
“The environmental abundance of HFPO-DA is considered to be impossible to
reverse in practice, and hence exposure of humans and the environment will continue after
cessation of use.”
Comment: “The environmental abundance” is unclear. In addition, as indicated in comments above, the possibility for degradation in the environment cannot be completely excluded. We propose to change to “Once released and distributed to the environment, the presence and amount of HFPO-DA in the environment are expected to be long-lasting, and hence exposure of humans and the environment will continue after cessation of use”.

page 114, 6.3.2.5. We think that this section is crucial for the report and should be more informative.  To justify an ELoC it should be explained why the combination of environmental fate properties and other properties, together with the documented level of toxicity, causes a concern that is of equivalent level to a PBT and/or vPvB substance. The only explanation in 6.3.2.5 currently is that the environmental concentrations of HFPO-DA will increase in the aquatic environment when the use continues (and also for remote and pristine environments) and that the environmental abundance is considered to be impossible to reverse in practice.  We think that the relationship between environmental half-life, bioaccumulation, environmental concentrations and internal concentrations should be discussed in more detail to evaluate whether there is an exposure potential comparable to PBT/vPvB substances which would be supportive of ELoC.

Reasoning:
We think that the potential ELoC of HFPO-DA should be compared to PBT and vPvB substances because the exposure of humans is via the environment and because the justifications for ELoC to humans have similarities to PBT and vPvB substances. There is no proper explanation why the substance is considered an ELoC to the environment.

Currently, there are no generally agreed principles in the EU on what level of evidence of toxicity in combination with high persistence (vP) and mobility is considered to form an ELoC under REACH. We note that the toxicity properties of HFPO-DA are not equivalent to Art. 57 points (a) to (d) as neither the classification criteria for CMR Category 1 nor the T criteria of PBT assessment are fulfilled based on currently available information. As the level of toxicity of HFPO-DA is lower than that of PBT substances based on currently available information, it should be explained why it is still considered that there is an equivalent level of concern to PBT substances.

It might be more straightforward to justify a comparison of HFPO-DA to vPvB substances than PBT substances. We note that according to ECHA guidance R.11, “In the case of vPvB substances, there is concern that even if no toxicity is demonstrated in laboratory testing, long-term effects might be possible since high but unpredictable levels may be reached in man or the environment over extended time periods.”. Therefore, it should be explained why very persistent and mobile substances will reach similar levels in humans or in the environment over extended time periods as vPvB substances.

The internal concentration (and exposure) of PBT/vPvB substances can be expected to increase in organisms along the food chain due to the persistence in the environment and accumulation in lipids. Regarding a very persistent and mobile substance (but with no significant bioaccumulation potential) the concentrations may increase in water and in food, which may lead to increasing exposure to the substance based on the lines below:

-assuming continuous emissions there will be an increase in environmental concentrations (e.g. due to the lack of degradation or adsorption) which leads to a continuous exposure of environmental organisms, as well as humans via environment, drinking water, or food
-assuming that there is no bioaccumulation the internal concentrations in organisms will depend on the concentrations in the environment, drinking water, or food
-therefore, the internal concentrations will increase with increasing environmental/drinking water/food concentrations
-it should be further discussed whether the expected increase in internal concentrations of HFPO-DA will lead to similar levels as expected for PBT/vPvB substances
We propose these issues to be included in more detail in the report.

page. 115. first paragraph: ”…shows adverse effects in humans.” Could you please rephrase this sentence: shows potential for adverse effects in humans / may cause adverse effects in humans. Reasoning: the sentence gives impression that there are reported cases of people suffering from HFPO-DA toxicity.

page 115:  “The current uncertainty regarding bioaccumulation adds to the conclusion that adverse effects of HFPO-DA may occur at lower concentrations than the available toxicity data currently suggests.”. Comment: It is not clear from this sentence how the bioaccumulation might explain that effects may occur at lower concentrations (e.g. does it refer to internal concentrations or concentrations in the environment). In addition, we do not think that a concern which is not confirmed can be used an argument for EloC. This would not be appropriate for SVHC identification under 57 (a) to (e).
page 115: “Further concern also arises as a consequence of the very high persistence and chronic background concentrations in the environment, resulting in continuous exposure that may lead to the irreversibility of adverse effects that are normally considered reversible upon the removal of exposure in standard toxicity studies.”
Comment: Please clarify whether this refers to effects in humans or in environmental species.
Page 115: “The combination of very persistent and very mobile characteristics means that with continuous emission into the environment, the concentrations of HFPO-DA in the environment will increase, the substance will be distributed world-wide and pristine areas and groundwater will become irreversibly affected.”. Comment: Please consider clarifying whether this refers to the presence of the substance or to the effects of the substance, or both. As no environmental hazards are included in the report, meaning of “affected” is unclear here in the environmental context. One option would be to consider only the presence of the substance, e.g.”…the substance will be distributed world-wide, including pristine areas and groundwater.”

Page 115: 2nd paragraph, “As HFPO-DA adversely affects human health, continuous exposure …” Please modify the sentence by deleting “As HFPO-DA adversely affects human health..”. Reasoning is the same as for the sentence considering HH effects in first paragraph of page 115.

Page 115 and 116: please modify to: “may lead to combination effects”. Reasoning: As stated on page 113: “Effects resulting from combined exposure are of concern but are as of yet unknown.”	Thank you for your detailed comments, information and suggestions for improvement of the Support Document. 
We have seriously considered all your input and updated the Annex XV dossier where this was appropriate. Most of your suggestions for increasing the readability of the text are taken up in the Support Document. 

Where this was not so or where we are of the opinion that we cannot accommodate your suggestions, we have included a specific response in this RCOM.

Regarding your comments on p.21: Thank you for the text suggestion, which we have included and slightly adapted. The comparison of the BIOWIN results for GenX PFOA and PFHx on the detailed level is in our opinion over interpretation of the BIOWIN predictions, given the fact that a number of arguments are given why BIOWIN is not expected to be well parametrized for predicting the persistence of perfluorinated alkyl substances. We agree on the trends observed, and especially the lack of non-terminal (per)fluorinated carbon fragments seems to indicate an underestimation of persistence in the environment. Therefore, these predictions used in an indicative manner, and we prefer not to compare them on the detail level suggested by the discussion in the annex provided with this comment.

The proposed change was added to the Support Document. The cited references ( Luo et al. 2015; )were considered as examples only of studies under optimized conditions, thus the opposite of those mentioned in the Support Document. Fot this reason they were not included.

Thank you for suggestion. The text was amended according to your suggestion with some revisions.

Regarding your comments on p.24: See the response to the previous comment. Thanks for the text suggestion which has for the largest part been implemented.

Page 24, OECD 209: The reference and test results have been further clarified in the test. An explanation of meaning of the results for the other tests has been given as well.

Page 25: No toxicity controls were performed in these tests. This has been added. It makes the results of the OECD 209 (and the toxicity controls in other tests) more important.

Page 25: Your suggestion for the concluding remark has been incorporated in the dossier.

We have included some discussion on the reliability. We still think that it is hard to say which value is most reliable.

Page 39: Some remarks about the interpretation of monitoring data have been added.

Regarding p.41: We tried to indicate that the vP criteria are the lower values in our estimations for persistence. We deleted lower boundary in relation to the vP criteria to prevent further confusion.

Regarding p. 41: The estimations are the outcome of the LRTP tool, less reliable refers to the fact that the QSAR predictions of the input data have uncertainty itself. 

Regarding p.42: We changed the wording to water concentrations to make sure there is no confusion. It concerns water concentrations from the same lake that were sampled 9 days before the simultaneous sampling of water and carp (by another institute). The text was amended to make it clearer.

Regarding p.43: Thank you for your suggestion. The sentence was indeed changed to improve readability with a different wording.

Regarding p.43, figure 12: The figure is updated as a result of the discussions during the Member State Committee meeting 65. The arrows have been removed for clarity reasons.

Regarding p. 43: Yes, indeed, this sentence has been clarified.

Regarding p. 44: Biotransformation does not influence the results. The dissemination website mentions a study with trout hepatocytes and this is mentioned now in the dossier as well. The inclusion of the new BCF study as mentioned in comment 5303 has led to substantial revision of the section, including the sentences referred to in your comment. The new BCF study confirms the concentration dependent BCF as earlier hypothesized. The study by Hoke et al. 2016 is in principle reliable and this has been added.

Regarding p.86: As part of a systemic inflammatory response, cells produce and secrete increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6), which results in changed transcription of genes responsible for the acute phase response. This process leads to a cascade of downstream actions, among which induced differentiation of B-lymphocytes into plasma cells to produce immunoglobulins, and decreased albumin production in the liver (Gervois et al. 2004; Hachiya et al. 2018). 

It is known that PPARα activators inhibit the IL-6 induced inflammatory response, leading to decreases in acute phase proteins (which contribute to the globulin fraction) and increases in negative acute phase protein (albumin) (Gervois et al. 2004). Thus, the A/G ratio is a clinical biomarker which indicates activation or perturbation of this process. However, it must be acknowledged that a change in A/G ratio, without accompanying pathology or haematology markers, is a rather non-specific indicator for immune effects, as the globulin and albumin serum levels are affected by many different processes (e.g. stress, liver failure and dehydration) (Hachiya et al. 2018).   

For HFPO-DA however, there are more indications of changed immune function accompanying the observed change in A/G ratio, as noted in Section 4.5 of the Support Document.

Regarding your comments on carcinogenicity (e.g. Table 32, historical control data, text corrections), Section 4.7 of the Support Document has been adapted accordingly to reflect your suggestions, with the exemption of a possible conclusion on harmonized classification (see the answer to comment 5280). 

Regarding your comment on the developmental toxicity of the substance, in Section 4.8.2 more information has been provided on the magnitude of effects as reported in Edwards (2010b). Furthermore, a study summary of the results from Conley et al. (2019) have been added to the Support Document in Section 4.9.1.3 and to the summary on reproductive and developmental toxicity (section 4.8.3). 

Findings relevant for reproductive and developmental toxicity in Conley et al. (2019) are generated through a non-guidance pilot study administering one dose (125 mg/kg bw/day) to dams within a 4-day timeframe. However results from this study (F1 rat male decreased epididymis weight, F1 rat female decreased anogenital distance and body weight decrements during development) were significantly changed from control (on an individual basis), the authors mainly conclude that more research is needed, e.g. a study with an expanded dosing period which includes the entire period of foetal development, to further examine the mode of action underlying HFPO-DA toxicity and to study potential effects on foetal and neonatal development that are not covered by the exposure regimen of the pilot study. 

In an abstract submitted to the Teratology Society’s 59th meeting, taking place June 22-26 2019, Conley et al.2019 share the preliminary results of their follow-up study in rats covering a wider dosing interval (GD8-PND3) and a larger sample size (N = 5), administering HFPO-DA at a dose-range of 10-250 mg/kg bw/day. They describe their results as follows: 

“In utero exposure resulted in a significant dose-responsive increase in neonatal mortality at ≥62.5 mg/kg/d. Pup mortality
occurred shortly after birth (<24 hrs). Further, there was a significant decrease in pup body weight measured at birth, PND1, and PND2 at ≥30 mg/kg/d and increased liver weight
(relative to body weight) of pups at necropsy (PND2) in all
dose groups (≥10 mg/kg/d). Dam weight gain during gestation
was significantly reduced at ≥125 mg/kg/d and liver weight
(measured on PND2) was increased at all doses (≥10 mg/kg/d)”  (Conley et al. 2019).

Most important finding in this study is a significant treatment-related increase in neonatal mortality in pups shortly after birth (no magnitude of effect given), which may provide further evidence that HFPO-DA could follow in the line of other PFASs with regard to developmental toxicity. PFOA for instance, is classified as Repr. 1B for development based on full litter resorptions, reduced postnatal survival, and delays in growth and development. Since these are preliminary results, presented in an abstract, they have not been added to the Support Document. 

Conley, J.M., Lambright, C.S., Evans, N., Medlock-Kakaley, E., Wilson, V.S., Gray, E. 2019. Adverse effects of gestational exposure to hexafluoropropylene oxide dimer acid (GenX) in the Sprague-Dawley rat. Birth Defects Research 111: 502-538. Poster abstract No. 29.

With regard to the comment about possible harmonized classification as developmental toxicant 1B or 2, we refer to the answer to comment 5280.

Regarding p. 101: concern for secondary poisoning is added to the Support Document.

page 102: 6.3: This text has been amended to better reflect the weight-of-evidence approach.

Regarding your comment on p.113 and p.115 where you indicate that you “…do not think that a concern which is not confirmed can be used as an argument for ELoC.“ We stress that in our opinion precaution could in principle be an argument under art 57(f) as a high level of protection of human and environmental health is one of the cornerstones of REACH 1907/2006 (aArt. 1). We do agree that the equivalent level of concern assessment should be based on a weight of evidence of available information.. A suspected property which has not been confirmed can be understood as supportive information to the weight of evidence, when it triggers, in combination with other (confirmed) concerns, an additional concern element. 
Regarding your specific comment, we understand that we have not been sufficiently specific on our concern regarding long term bioavailability and exposure to humans and we have amended the text accordingly.

	
		See the corresponding embedded attachment in table 1 of Part I: 5297_HFPO_DA_Annex_to_FI_CA_comments_BIOWIN.docx		
5298
2019/04/29	Austria,
Member State	PFAS compounds are resistant to degradation and the degradation potential of HPFO-DA is negligible. The Austrian REACH CA supports the vP status of the substance. Additionally, the substance in its anionic form is very mobile based on the very high water solubility and the calculated log KOC for HFPO-DA (2.48 and 1.92), hence the substance can be widely distributed via water. With conventional methods during drinking water treatment, no substantial removal for HPFO-DA is possible. A special concern is the presence in drinking water.

The LRTP tool from OECD indicates that the substance has a potential for long range transport. The properties of the substance in combination with the toxicity (concerns related to potential carcinogenicity, immunotoxicity and developmental toxicity as well as endocrine disruption) leads to a very high concern for human health and the environment and therefore qualifies the substance to be identified as 57 (f). Therefore the Austrian CA strongly supports the Dutch proposal to identify 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof) as Substance of very high concern as a substance of equivalent level of concern according to Article 57 (f) of the REACH Regulation, also to prevent undesired substitution of other PFASs.	Thank you for your support.	
		-		
5301
2019/04/29	Provincie Zuid-Holland,
Regional or local authority,
Netherlands	We welcome the proposal and can largely agree with the way the different properties of the substances are assessed. We particularly agree with the conclusion that the substances should be identified as SVHC.
With respect to the applied criteria, we submit that persistency in the environment, or, in the case of these substances: the unability to degrade under ambient conditions, should in itself already be a reason to designate the substance as an SVHC. In that respect we refer to a recently published paper by Cousins et al (Environ. Sci.: Processes Impacts, 2019. DOI: 10.1039/C8EM00515J). The substances that are now proposed to be identified as SVHC have very long half-lives under environmental conditions, exceeding the vP criteria by far. When released into the environment, such substances will ultimately lead to human and environmental exposure, the effects of which may not yet be known.
Furthermore, we would draw the attention of ECHA to the recent study by Conley et al (Env Health Persp., 2019. DOI: 10.1289/EHP4372). In this study, the effects of oral exposure to HFPO-DA in rat is compared to the effects of other known PFAS. The results of this study give additional evidence about the toxicity of HFPO-DA.	Thank you for your support.

As is lined out in the Support Document, we argue that HFPO-DA is of equivalent level of concern because of its very high persistence, its high mobility and its possible effects on human health. 

We acknowledge that there may be substances that may be of equivalent level of concern based solely on their very high persistence. However, this discussion is less opportune in the assessment of HFPO-DA since for HFPO-DA our concern also involves its mobility (uncontrollable spread in the environment, possibility for wide dispersive exposure, difficulty to remove the substance from the environment/drinking water) and its adverse effects on human health.  	
		-		
5302
2019/04/29	EurEau,
Industry or trade association,
Belgium	N/A	See our response to comments 5302
2019/04/29 in section “General comments on the SVHC proposal”.	
		See the corresponding embedded attachment in table 1 of Part I: 5302_EurEau_Public Consultation_Ammonium 2333-tetrafluoro-2-(heptafluoropropoxy) propanoate.pdf		
5303
2019/04/29	Chemours International Sàrl,
Company,
Switzerland	-	See our response to comments 5303
2019/04/29 in section “General comments on the SVHC proposal”.	
		See the corresponding embedded attachment in table 1 of Part I: 5303_20190429_SVHC_Comments_Chemours_HFPO-DA.pdf		
5305
2019/04/29	United Kingdom,
Member State	We thank The Netherlands for producing this dossier and have the following comments;

We agree with the proposed grouping of the substances presented in this SVHC dossier, based on the formation of HFPO-DA in the environment at relevant pH.

We agree that even though no simulation studies are available, the available evidence indicates that HFPO-DA can be considered to be a very persistent (vP) substance. It is likely to significantly exceed the Annex XIII criterion by analogy with similar substances.

We agree that it is mobile and likely to move from terrestrial to aqueous compartments. We also agree that it may be difficult to remove significant amounts of HFPO-DA from waters using many current treatment technologies.

However, we do not agree that the data presented in the dossier allow us to state that HFPO-DA is ubiquitous in the environment. The monitoring data presented are from a relatively small number of studies, from a limited number of countries, generally around known point sources.

The SVHC dossier also notes that there are numerous CLP notifications of FRD-902, FRD-903 and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoyl fluoride, and Section 9 refers to unknown sources of HFPO-DA in the environment. There is also the potential that HFPO-DA or the parent compounds are present as an impurity in fluoro-polymers. It is therefore unclear whether the monitoring data truly indicate long-range transport from known point source industrial sites, or are due to other unknown point or diffuse sources. On the other hand, highly persistent substances are likely to be able to reach remote environments eventually. Whether this might be in sufficient amounts to cause harm over relevant timescales is a different question.

There is currently no clear evidence that HFPO-DA is significantly toxic in either aquatic or mammalian studies and there is no evidence of significant bioaccumulation potential in humans or wildlife. Scientific evidence of a high degree of likely harm to the environment or human health is therefore lacking. All other SVHCs have demonstrated high toxicity potential as shown by their classification or by meeting the criteria to be considered T (the vPvB category exists because the physico-chemical properties of such substances may prevent toxicity being observed in the relatively short durations of laboratory experiments, e.g. due to the time needed to reach steady state); this does not seem to be the case for HFPO-DA.

The SVHC dossier states “Based on the information available, it is concluded that the effects of HFPO-DA [on human health] are severe”. However, HFPO-DA does not currently have any human health classifications that would trigger regulatory action. We agree that the key target organs in repeat dose studies are the liver, blood, and to a lesser extent the kidney. There are some indications of effects on the immune system, although this is less convincing. The registrants apply the self- classification STOT RE 2 (liver, blood) however, the data are not consistent across the studies. For example, necrosis is reported in the liver in the 28 day study in rats, but not at higher doses in the 90 day study. Furthermore, effects on haematological parameters which are seen in male rats after 28 days and 90 days are not seen after 12 months (in the carcinogenicity study). Ideally, the repeated dose toxicity needs to be properly assessed (i.e., through the CLH process), with full consideration given to whether the effects are relevant to humans (some of the liver effects are consistent with PPARα). In the associated RMOA the NL-CA dismisses this classification.
A guideline carcinogenicity study is available in rats in which tumors were seen in the liver, pancreas and testes. In our opinion, this could support classification in Carc Cat 2 at most (the substance is non-genotoxic, and there is evidence for a PPARα MoA).

The dossier refers to a tentative Tolerable Daily Intake (tTDI) which has been calculated using various uncertainty factors including an additional uncertainty factor of 66 to cover the unknown differences between bioaccumulation in humans and animals. This is based on data from PFOA but no justification for using this, rather than any other analogous substance, is given. A second carcinogenicity (in mice) and human biomonitoring studies have been requested under Substance Evaluation. These studies may provide evidence of toxicity that could be taken into account in future (or it could confirm a low level of toxicity). It could also allow for a more realistic TDI to be calculated. We therefore consider that it would be more appropriate to wait for this information, prepare a CLH proposal to thoroughly assess the human health data, recalculate TDIs and then assess whether the ELoC criteria are met.

Turning to other points made in support of the “equivalent level of concern” (ELoC) argument:

• Long-term exposure of organisms: This argument could apply to any substance that is emitted continuously into the environment. Whilst an uncertainty, we do not think this is a good ELoC argument.

• Co-exposure with other per- and polyfluoroalkyl substances:  We do not think this is a relevant argument for ELoC. The relative importance of this will depend on a variety of factors, and we did not take co-exposure with other PBT/vPvB substances into account for previous SVHC cases.

• Plant enrichment: There is no benchmark provided to indicate how HFPO-DA compares with non-PFAS substances, or description of the levels that can be achieved in edible plant tissues. Unless such enrichment leads to a toxic effect in plants (not described), we do not see how this can be a particular concern for a substance that does not accumulate in consumers and is of relatively low toxicity. What level of plant bioaccumulation should constitute ELoC and why? (For example, in fish, regulatory triggers are only met at 500 L/kg or higher.) Why is plant bioaccumulation not part of the PBT assessment, but relevant here? We are not convinced that bioaccumulation or occurrence in plants demonstrates “mobility” in the usual sense. The data presented do not clarify how the substance entered the plant, e.g. via uptake through groundwater/irrigation, through respiration in the gaseous phase or a mixture of both.

The main concerns seem to be around the release of this substance from known industrial point sources, which could be controlled in other ways. Proposing this substance as an SVHC appears premature, given that key data have been requested under Substance Evaluation. The ELoC argument in this case therefore appears to be governed by the precautionary principle in the absence of significant toxicity from the substance itself. There is no prior EU-wide policy agreement on the use of this principle for low toxicity perfluoroalkyl substances (PFAS) or any agreed scientific criteria on which to base the decision. It is therefore questionable whether the MSC is an appropriate forum to take this type of decision, especially given the precedent that this would create for other (non-PFAS) substances and the resulting uncertainty that would entail for industry stakeholders. We therefore believe that such a policy-based decision should be taken by the REACH Committee, with an understanding of the uncertainties involved and (ideally) an impact assessment.	Thank you for your comments and further information.

Thank you for your support on:
1.	The grouping of substances relevant for this Support Document
2.	The persistency of HFPO-DA significantly exceeding the Annex XIII criteria for vP
3.	The mobility of HFPO-DA and the difficulty to remove the substance from water using current treatment technologies

Regarding your comment on ubiquitous presence of HFPO-DA in the environment, we have adjusted the text in section 3 and section 6 (see also addressed under 5305
2019/04/29 “General information on the SVHC proposal”).

Regarding your comment on the long range transport potential (LRTP), see also our response to your comment 5305
2019/04/29 made in the section “General information on the SVHC proposal”. Indeed unknown or diffuse sources are of concern to use. The available monitoring data together with the modelling data for LRTP however build a clear case that LRT is of concern for this substance.

Regarding your comment on toxicity we argue in the assessment of equivalent level of concern that the effects observed in mammalian studies do show a concern for serious effects on human health, see also our response to comment 5303 2019/04/29, 5297 2019/04/29 and 5280 2019/04/25. All information taken together, HFPO-DA shows a consistent pattern of toxicity that is considered relevant for human health. The fact that HFPO-DA does not have a harmonized classification under 1272/2008 and may not meet the criteria as laid down in Annex XIII of the 1907/2006 is neither a necessary nor a definitive argument for ELoC according to art. 57(f).

With regard to your comment on the tTDI, we included this reference solely for the purpose of illustrating some further perspective on the possible evaluation of effects observed in mammals, their representativeness for possible effects on human health and the existing uncertainties. With regard to your proposal to await the results from the Substance Evaluation, we would like to refer to our response to comment 5280 2019/04/25 made in the section “General information on the SVHC proposal”. 

With regard to long term exposure, for HFPO-DA concern is that exposure will not cease when emission ceases because of its very high persistence. As a consequence exposure becomes uncontrollable. We are of the opinion that this is one element that leads to a very high concern for HFPO-DA.

See our earlier response to your comment 5305 to the “General comment to the support document”, response to your comment on Section 6.3.1.12. As is described in Section 4.9.1.4, monitoring data indicate that often more than one PFAS can be identified in environmental samples suggesting that PFASs are likely to co-occur as contamination in soil, groundwater or drinking water. Zeilmaker et al. (2018) derived so-called Relative Potency Factors (RPFs) for several perfluorocarboxylic acids (PFCAs), perfluorosulphonic acids (PFSAs) and HFPO-DA, to allow for risk assessment of combined toxicity to a mixture of PFASs based on the principle of dose-addition. This concept is developed assuming that the PFAS act in a similar manner, with the same mechanism/mode of action, resulting in dose-responses with the same shape but with different potencies for each of the individual substances. Because of the very high persistence of HFPO-DA chances are high that coexistence remains for long times. Based on the fact that PFASs often occur together in environmental samples and result in the same type of effects, we consider co-exposure to PFASs a relevant argument for ELoC. 

Regarding your comment on plant enrichment. The enrichment of plants demonstrates the possibility of uptake of HFPO-DA in plants and shows that exposure through the food-chain is possible. This is only one element of the total weight-of-evidence of the ELoC assessment. We have elaborated further in section 6 on why we are of the opinion that the concern we have for HFPO-DA is of an equivalent level to the concern for substances identified as PBT/vPvB.

Regarding your comment of industrial emissions being the focus of our concern: Monitoring data do point at industrial emissions for being an important source of HFPO-DA in the environment. However, over the last years, more and more data appear that suggest the presence of diffuse emission sources being of concern (see also chapter 3 for a description of different locations where HFPO-DA is found).

The fact that there are no pre-agreed criteria specifically discussed to identify concerns like we conclude for HFPO-DA as ELoC, does not limit the identification of HFPO-DA as a substance of very high concern according to art. 57(f) of 1907/2006. See further, our response to comment 5303 on this topic, which also refers to the Court ruling that clarifies this issue.	
		-		
5306
2019/04/29	Denmark,
Member State	DK CA would like to thank the NL CA for submitting this Annex XV dossier. The dossier submitter proposes to identify 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid, its salts and its acyl halides as substances of equivalent level of concern according to Article 57 (f) of the REACH Regulation. The DK CA supports the proposal and believes that the dossier presents sufficient evidence for the identification of these substances as being substances of very high concern.

We would like to draw your attention to two recently published studies on persistency and on toxicity relevant for the evaluation of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid which can be used to further strengthen the argumentation used in the dossier.
A recently published study by Cousins et al. (2019) argues why high persistency alone may cause a major concern. The authors uses model predictions to demonstrate that if a chemical is highly persistent, its continuous release will lead to continuously increasing contamination irrespective of the chemical's physical–chemical properties. Based on this the authors argues that high persistency, without considering any other hazardous properties, is a sufficient basis of regulation of a chemical.
Another recently published study has identified maternal, fetal, and postnatal effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid following oral exposure in Sprague-Dawley rats (Conley et al., 2019). A reference to this study can be used to strengthen the argumentation for the toxic properties of this substance.
References:
Cousins, I. T., Ng, C. A., Wang, Z. and Scheringer, M. (2019): Why is high persistence alone a major cause of concern? Environ. Sci.: Processes Impacts, 2019. DOI: 10.1039/c8em00515j
Conley, J. M., Lambright, C. S., Evans, N., Strynar, M. J., McCord, J., McIntyre, B. S., Travlos, G. S., Cardon, M. C., Medlock-Kakaley, E., Hartig, P. C., Wilson, V. S. and Earl Gray Jr, L. (2019): Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats. Environmental Health Perspectives 127(3). https://doi.org/10.1289/EHP4372.	Thank you for your support and information. 

We have included the information in the Support Document in section 6.3 to further strengthen the motivation for ELoC.	
		-		
5309
2019/04/29	American Chemistry Council,
Industry or trade association,
United States	1. The Proposal Does Not Demonstrate That Conditions Have Been Met for SVHC Identification on the Basis of Equivalent Level of Concern (ELoC) to PBT/vPvB

The Proposal argues that HFPO-DA should be identified as a SVHC under REACH on the basis that the materials represent an ELoC to other substances identified in Article 57(a) through (e), that is, ELoC to carcinogens, mutagens, reproductive toxicants, persistent, bioaccumulative and toxic (PBT) substances and very persistent and very bioaccumulative (vPvB) substances, respectively, for having “probable serious effects to human health and the environment.”   This Proposal argues that for HFPO-DA, “there is scientific evidence of probable serious effects to human health”  due to a combination of properties, including extreme persistence and mobility, which will result in contamination of drinking water sources.   However, the Proposal does not provide sufficient policy or technical justification to warrant the conclusion that the materials demonstrate an ELoC.

The persistence and mobility information presented in the Proposal are not equivalent to the vPvB criteria in Article 57(e).  The comparison of persistence and mobility to persistence and bioaccumulation suggests that mobility is of equivalent concern to bioaccumulation.  A case has not been made in the Proposal that “M” and “B” are equivalent; rather that both criteria are elements of potential exposure.  There is no consensus in the scientific community regarding this point, nor have there been sufficient policy discussions of it in Europe, to establish common understanding.

Artificially limiting the mobility criteria to intrinsic substance properties, such as soil adsorption coefficient (Koc), may misclassify a large range of substances that present no concern for exposure from sources of drinking water, which will then create a potentially unnecessary burden for both authorities and industry.

2.  Assessment of Mobility and Exposure Via Drinking Water Can Be Achieved Using Existing Risk Assessment Methods and Tools.

As discussed above, the Proposal’s underlying rationale for identifying HFPO-DA as persistent and mobile is to address concerns for exposure to the substance from drinking water.  However, it is possible to use existing risk assessment and risk management to address mobility and potential exposure via drinking water.   Therefore, additional screening criteria for SVHC ELoC that would lead directly to restriction or authorization under REACH are not warranted.

The concept of mobility is currently assessed as part of the exposure assessment required under REACH.  The environmental risk assessment aims to evaluate the exposure from the uses registered by the applicant, which includes consideration of release rates  and environmental transport in the environment.  As such, the mobility of a substance is already incorporated in the exposure assessment, since properties such as environmental fate and partitioning to and between different media are key input parameters. Narrowing the evaluation of mobility to a single intrinsic property, such as Koc, may generate false positives inadvertently implicating many substances that are not a real-world concern for exposure from sources of drinking water.

Environmental risk assessment under REACH addresses all environmental compartments, including the groundwater compartment, as illustrated in the ECHA guidance for predicted environmental concentration (PEC) derivation.  In particular, predicted exposure in groundwater (PEClocalgrw) is used in the exposure modelling for humans with indirect exposure via the environment. As indicated by the guidance, monitoring information may be used when it is representative and within the scope of the risk assessment.  These points should be addressed in Section 3.2.4 of the Proposal.

In addition, there are existing regulatory frameworks outside of REACH that should be utilized for protection of drinking water, including the Water Framework Directive.  This allows for environmental monitoring to be used to determine if chemicals are present in drinking water at levels that raise concern.

ACC supports the use of tiered, risk-based approaches for assessment of chemicals.  Regulatory action should not be based solely on screening-level, hazard criteria or intrinsic properties without the opportunity for risk assessment.  Based on the above considerations, including the possibilities for addressing concerns for drinking water with existing risk assessment tools and methods, in general, the combination of properties including mobility should not be considered as ELoC for SVHC.

4.  Need for General, Agreed-Upon Criteria

Finally, before identifying any ELoC for the environment, general criteria should be developed. These criteria should include demonstration of how a substance being proposed as ELoC for the environment has serious and irreversible effects on human health or the environment.  Before any substance-specific case based on ELoC for the environment is assessed, a policy discussion on the applicability of ELoC criteria to the environment is required, and agreement needs to be reached on any relevant assessment methodologies.  In general, where possible, hazard information must be put into appropriate context of realistic exposures.

The EU Commission recently addressed this issue in response to the Parliamentary question for written answer E-000641-19.  In response to questions regarding if there is a mutual agreement and understanding of what constitutes an equivalent level of concern under Article 57(f), the EU Commission indicated that while criteria have been agreed upon in the case of sensitizers, criteria have not been agreed upon for other effects. The EU Commission states:

"Due to that, the Commission announced in 2018 in the REACH Review that it will ensure  together with ECHA and Member States that criteria for the identification of substances of very  high concern (SVHC) requiring an assessment of ELoC are developed and applied in a consistent  manner."

ACC supports the adoption of clear criteria before Article 57(f) can be used for evaluating substances based on environmental criteria.	Thank you for your comments and considerations.

Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.

On your comment that the Equivalent level of concern is insufficiently substantiated: we have further elaborated on our concern and the equivalent level thereof to PBT/vPvB and CMR.

Regarding the comparison between “B” and “M”: we have elaborated about the equivalency in level of concern in section 6.3.2.11. We stress that proposing criteria for “M” for the purpose of SVHC identification is outside the scope of this Support Document. The current SVHC proposal should be considered as a single case assessment.

Regarding your comment on mobility criteria: The ELoC assessment as is made in section 6 clearly shows the combination of phys chem properties, monitoring data and toxicity studies together constitute the very high concern that we have for this substance.

Regarding your comment on the possible assessment of exposure through assessment methods and tools: We argue in Section 6 that due to the very high persistecy of this substance and high mobility, this type of exposure assessment becomes highly uncertain like is the case for PBT/vPvB substances.

Regarding your comment that screening criteria would directly lead to restriction or authorisation: The development of such a system is not within the scope of this Support Document.

On your comment on mobility: See our response to your earlier comment on mobility. Our ELoC assessment is maded on a multitude of concerns, see for details Section 6.3 of the Support Document.

Regarding the use of monitoring data in the ELoC assessment: Earlier ELoC cases have shown that exposure based elements can be part of the ELoC assessment. This does not have to be in the form of a risk assessment.

We note your point that beside the REACH Regulation there are other regulatory frameworks that work together to regulate safe use of chemicals.

Regarding your concern for drinking water: We note that we have concern for drinking water and for HFPO-DA for the environment.

For your comments regarding criteria under ELoC we would like to refer you to our response to comment 5303 2019/04/29 in the section “General comments to the SVHC proposal”.	
		See the corresponding embedded attachment in table 1 of Part I: 5309_FINAL_ACC Comments to ECHA 042919.pdf		
5312
2019/04/29	ChemSec,
International NGO,
Sweden	ChemSec´s agrees with the identification of this substance as an SVHC.
The dossier well summarizes the evidence showing extreme persistency and high mobility in, resulting in widespread and concerning occurrence in the environment. In addition the substance has shown an array of toxicological effects, including being a potential carcinogen.
ChemSec supports the idea of identifying substances that are persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM) as SVHCs. This is an important and problematic group of substances that need more regulatory attention in order to halt and prevent further pollution of valuable water resources.	Thank you for your support.	
		-		
5314
2019/04/29	European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	Cefic comment relates to the general approach proposed and not on sustance specific aspect.	See our response to comment 5314 2019/04/29 in the section “General comments to the SVHC proposal”	
		See the corresponding embedded attachment in table 1 of Part I: 5314_2019 04 29_Cefic updated reflection on SVHC_ELoC for env.pdf		
5315
2019/04/29	FluoroCouncil,
Industry or trade association,
United States	See attached contribution.	See our response to comment 5315 2019/04/29 in the section “General comments to the SVHC proposal”	
		See the corresponding embedded attachment in table 1 of Part I: 5315_FINAL FluoroCouncil response HFPO-DA SVHC consultation 29-4-19.pdf		
5316
2019/04/30	Swedish Society for Nature Conservation,
National NGO,
Sweden	2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propionic acid (HFPO-DA), its salts and its acyl halides (covering any of their individual isomers and combinations thereof)

Swedish Society for Nature Conservation welcomes the SVHC dossier submitted by The Netherlands. The dossier provides extensive background information for the identification of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propionic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof) as a SVHC. SSNC supports the proposal to identify HFPO-DA as a substance of equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 of Regulation (EC) No 1907/2006 (REACH) according to Article 57(f) of the REACH Regulation.

HFPO-DA should be classified as a substance of very high concern due to the combination of extreme persistency, high mobility and evidence of a wide range of toxicological effects on kidney, liver and immune system at low levels of exposure. In addition there is some evidence that the substance may be carcinogenic.  The substance is ubiquitously present in the environment including groundwater and drinking water and current water treatment techniques are not capable of removing HFPO-DA. Since HFPO-DA is used in the production of fluoropolymers, there is a risk that it could be present in consumer products such as cosmetics. Also, scientific data shows that fluoropolymer manufacturing is a
source of emission of per- and polyfluoroalkyl substances such as HFPO-DA into the environment (Song et. al 2018 ).
The widespread occurrence together with the documented toxic effects at low exposure levels is evidence that HPPO-DA meets the criteria as SVHC according to Article 57f of REACH.	Thank you for your support.

Regarding Song et al. 2018, we have evaluated the study and concluded that the representation on the data on HFPO-DA do not allow easy interpretation in its current form as these are aggregated for several HFPO-copolymers. Going into the further study details was not possible within the time available to address this comment and would require to request further details from the authors. However, we do note that comments regarding use, exposure, alternatives and risks, of which we are of the opinion that this may be one, may, when relevant, be considered at later stages of the risk management process.

	
		-		
5317
2019/05/02	Belgium,
Member State	Belgian comments to the Annex XV SVHC report for GENx
--------------------------------------

Belgium would like to thank the NL CA for submitting this Annex XV dossier. We recognize that the dossier submitter proposes to identify GENx:

2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid, its salts and its acyl halides (covering any of their individual isomers and combinations thereof)

as a SVHC according to Article 57(f) of REACH Regulation.

Belgium, as a Member State, is of the opinion that enough evidence is available in the Annex XV dossier to identify GENx as being of equivalent level of concern, because amongst others:

a) Regarding the toxicity of the substance, effects seen in liver are severe and irreversible (Haas 2008a, MacKenzie, 2010 and Edwards, 2010a), and could warrant a classification as STOT RE1.  Moreover the concern is further supported by effects seen in the available carcinogenicity study. We draw the attention on the fact that new information is available in Conley (2019).

b) GENx fulfils the persistent (P) and very persistent (vP) criterion of Annex XIII to REACH. This is based on its structural properties, QSAR estimates, read-across, screening test, and monitoring.

c) GENx gives rise to an equivalent level of concern to the bioaccumulation (B) criterion of Annex XIII of REACH. This can be shown by recalling that the legislator included B in REACH as a concern because irreversible or poorly reversible internal exposures to a substance can potentially lead to toxic effects that are not already known, as it appeared in several historical cases. GENx indeed raises equivalent concerns regarding internal unavoidable exposure: (1) GENx is a very mobile substance (low adsorption to organic matter / soil) with a high distribution towards aquatic systems, and can be transported over long distances in short timeframes, and is currently already found in surface water, groundwater and oceans, and (2) if emissions are not reduced, concentrations will only increase in the aquatic compartment due to the high persistence of the substance, and due to the residence time in aquifers and the lack of water treatment methods available at large scale for drinking water, such exposures can be considered irreversible in practice (as shown by existing cases of tap water contamination with other PFAS where the only solutions found in the midterm are the change of water sources or providing bottled water). This concern is further substantiated more generally in Cousins (2019) for compounds that are persistent and poorly adsorbed in organic matter and sediments.

REFERENCES
---------
CONLEY et al, 2019. Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats. Environmental Health Perspectives. https://doi.org/10.1289/EHP4372

COUSINS et al 2019, Why is high persistence alone a major cause of concern? Environmental Science: Processes & Impacts

EDWARDS, T. L. 2010a. An Oral (Gavage) Reproduction/Developmental Toxicity Screening Study of H-28548 in Mice

HAAS, M. C. 2008a. A 28-day Oral (Gavage) Toxicicty Study of H-28397 in Rats with a 28-day Recovery.

MACKENZIE, S. A. 2010. H-28548: Subchronic Toxicity 90-Day Gavage Study in Mice.	Thank you for your support and information. All references were considered and included in the Support Document. 

We have included the information in the Support Document in Section 6.3 to further strengthen the motivation for ELoC.

With regard to the comment about possible harmonized classification as STOT RE1, we would like to refer you to our response to comment 5280.

PART II: Comments and responses to comments on uses, exposures, alternatives and risks

Specific comments on use, exposure, alternatives and risks
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5269
2019/03/26	Oasen drinkwater,
Other contributor,
Netherlands	Both US-EPA and RIVM derived drinking water standards for HFPO-DA in the same order of magnitude as PFOA. Both extremely low (around 0,1 microgram/liter)which indicates that this is a substance with a high toxicity. Added to the Persistency and Mobility of this substance, it is very clear that HFPO-DA is a threat for the public through drinking water and should be classified as SVHC.	Thank you for addressing this. We have added the drinking water standards derived by the RIVM (Janssen, 2017) and the North Carolina Department for Human Health Services (NC DHHS 2017) to Section 4.10 of the Support Document. 	
5275
2019/04/18	Health and Environment Alliance (HEAL),
International NGO,
Belgium	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
We especially note your comment on the possibility that HFPO-DA could be present in food contact materials. A recent report published by the RIVM (Bokkers et al. 2019) notes that FRD-903 is on the positive list of Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food. The substance is restricted to be used as a polymerization aid in the polymerization of fluoropolymers that are processed at temperatures at or above 265 °C and are intended for use in repeated use articles. The authors did not find any evidence for the presence of HFPO-DA in food contact materials reported in the public literature on PFAS concentrations in food contact materials, however HFPO-DA was not part of the analysis in most of the publications. 

Bokkers, B.G.H., van de Ven, B., Janssen, P., Bil, W., van Broekhuizen, F., Zeilmaker, M., and Oomen, A.G. 2019. Per- and Polyfluoroalkyl Substances (PFASs) in Food Contact Materials. RIVM Letter Report 2018-0181	
		See the corresponding embedded attachment in table 1 of Part I: 5275_HEAL-Comments-GenX.pdf		
5284
2019/04/26	the city of Dordrecht,
Regional or local authority,
Netherlands	As a local government, we are responsible for the health and well-being of our citizens. At the same time, we have to deal with the emissions, among which HFPO-DA, from a major fluorochemical plant. The proposal already takes into account a number of studies about environmental concentrations that were measured in the vicinity of this plant. We find HFPO-DA in soil, ground water, surface water, drinking water and in crops in vegetable gardens, often along much higher concentrations of PFOA, the predecessor of HFPO-DA which was used and emitted for over 40 years from the same fluorochemical plant. We are still facing the consequences of these PFOA-emissions. People living near the plant still have elevated levels of PFOA in their blood even though emission ended in 2012.
The similarities between HFPO-DA and PFOA, including the health concerns and their behaviour in the environment, urge for swift action and justify designation of HFPO-DA as a SVHC. We have to prevent the long-term effects we are facing now because of the emission of PFOA that went on for decades. We owe our citizens and the future generations the best protection and have to learn from the past. Therefore we shouldn’t delay the designation of HFPO-DA as a SVHC.	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		-		
5285
2019/04/26	Gemeente Sliedrecht,
Regional or local authority,
Netherlands	As a local government, we are responsible for the health and well-being of our citizens. At the same time, we have to deal with the emissions, among which HFPO-DA, from a major fluorochemical plant. The proposal already takes into account a number of studies about environmental concentrations that were measured in the vicinity of this plant. We find HFPO-DA in soil, ground water, surface water, drinking water and in crops in vegetable gardens, often along much higher concentrations of PFOA, the predecessor of HFPO-DA which was used and emitted for over 40 years from the same fluorochemical plant. We are still facing the consequences of these PFOA-emissions. People living near the plant still have elevated levels of PFOA in their blood even though emission ended in 2012.
The similarities between HFPO-DA and PFOA, including the health concerns and their behaviour in the environment, urge for swift action and justify designation of HFPO-DA as a SVHC. We have to prevent the long-term effects we are facing now because of the emission of PFOA that went on for decades. We owe our citizens and the future generations the best protection and have to learn from the past. Therefore we shouldn’t delay the designation of HFPO-DA as a SVHC.	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		-		
5286
2019/04/26	Unie van Waterschappen,
National Authority,
Netherlands	The Unie van Waterschappen  from the Netherlands  supports the proposal  for identification of HFPO-DA and its salts/Acyl Halides as SVHC on the basis of the criteria set out in REACH article 57

The Dutch water boards have many problems with HFPO-,also known as GenX .  GenX is found in increased concentrations in the surface water, in effluent from WWTPs , groundwater, aquatic soils.  GenX has similar properties to substances that are on the SVHC list. The waterboards have high economic costs because of stopping work by the presents of GenX.
There are also concerns about the health of the people who come into contact with GenX due to, among other things, air deposition.   Through air deposition , GenX deposits on soil and water and affects people in their living environment who swim, eat fish, live in, consume vegetables and dairy products.  Temporary standards have been derived because of the lack of information.  GenX is the substitute for PFOA which is already identify as an SVHC substance. GenX have persistent, mobile en toxic characterics( PMT). Substances with PMT characterics are defined bij their inabiltiy to break down under environmental conditions, their affinity for water, and, when toxic  their adverse impacts to human health and the environment.   It has been proven that these substances have harmful effects on the environment and human health.  That is why we support the proposal to put GenX on the SVHC list to prevent harmful effects of GenX on the environment and public health.	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		-		
5291
2019/04/26	RIWA, Association of River Waterworks,
Industry or trade association,
Netherlands	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		See the corresponding embedded attachment in table 1 of Part I: 5291_RIWA Position on UBA proposal for PMT criteria REACH.docx		
5292
2019/04/26	CHEM Trust Europe,
National NGO,
Germany	The dossier provides ample evidence of exposure via diffuse emissions to the general population via drinking water, fruits and local air emissions which is very concerning. The fact that the registrant has replaced the use of PFOA by FRD-902 as processing aid in the so-called GenX technology points to a bigger, very common problem: restricted hazardous chemicals are replaced by similar substances which are often identified as harmful some time later. It is clear that a more systematic solution needs to be found to prevent this failure of human health and environment protection. CHEM Trust has highlighted this topic in the report From BPA to BPZ: a toxic soup? How companies switch from a known hazardous chemical to one with similar properties, and how regulators could stop them  (https://www.chemtrust.org/wp-content/uploads/chemtrust-toxicsoup-mar-18.pdf).

The dossier addresses a group of structurally related substances which is a very welcome approach for this SVHC identification. However, we do see the urgent need to apply more effective regulatory approaches, such as covering an even larger group of substances in the subsequent control measures to break the vicious circle of moving from one to the next PFAS.  (see also Wang et al, Environ. Sci. Technol. 2017, 51, 2508−2518, A Never-Ending Story of Per- and Polyfluoroalkyl Substances (PFASs)? DOI: 10.1021/acs.est.6b04806).	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		-		
5297
2019/04/29	Finland,
Member State	-	See our response to comments 5297
2019/04/29 in the Specific comment section of this RCOM.	
		See the corresponding embedded attachment in table 1 of Part I: 5297_HFPO_DA_Annex_to_FI_CA_comments_BIOWIN.docx		
5301
2019/04/29	Provincie Zuid-Holland,
Regional or local authority,
Netherlands	As regional government we are the competent authority for a major fluorochemical plant where release of HFPO-DA is a concern. The proposal already takes a number of studies into account about environmental concentrations that were measured in the vicinity of this plant. We find HFPO-DA in soil, ground water, surface water, drinking water and in crops in vegetable gardens, often along much higher concentrations of PFOA, the predecessor of HFPO-DA which was used and emitted for over 40 years from the same fluorochemical plant. We are still facing the consequences of these PFOA-emissions. What remains a concern to us is the co-exposure of humans and the environment to several PFAS simultaneously. As there is not yet an agreed scientific approach on how to assess such exposure, we consider this an additional argument to designate HFPO-DA as SVHC.	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		-		
5302
2019/04/29	EurEau,
Industry or trade association,
Belgium	N/A	See our response to comments on 5302
2019/04/29 in the General section.

Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.	
		See the corresponding embedded attachment in table 1 of Part I: 5302_EurEau_Public Consultation_Ammonium 2333-tetrafluoro-2-(heptafluoropropoxy) propanoate.pdf		
5303
2019/04/29	Chemours International Sàrl,
Company,
Switzerland	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		See the corresponding embedded attachment in table 1 of Part I: 5303_20190429_SVHC_Comments_Chemours_HFPO-DA.pdf		
5305
2019/04/29	United Kingdom,
Member State	Section 11 (page 120): The Dutch manufacturing plant appears to be a key source of the substance in the European environment. It would be useful to describe the level of emission from the plant to air, wastewater, etc., and if possible the historical trends. This would then help to explain (or not) the findings around the vicinity of the plant and beyond. It would also be useful to understand what risk management has been put in place to reduce emissions. The RMOA stated that the site operator is taking steps to reduce emissions by up to 99 % by 2020. Can additional details be provided?

Section 11.2: Please provide further information to support your statement that the potential alternatives to these substances will “most likely be similar in their properties with regard to persistence, mobility and possibly toxicity”.	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.		
		-		
5309
2019/04/29	American Chemistry Council,
Industry or trade association,
United States	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		See the corresponding embedded attachment in table 1 of Part I: 5309_FINAL_ACC Comments to ECHA 042919.pdf		
5314
2019/04/29	European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		See the corresponding embedded attachment in table 1 of Part I: 5314_2019 04 29_Cefic updated reflection on SVHC_ELoC for env.pdf		
5315
2019/04/29	FluoroCouncil,
Industry or trade association,
United States	-	Thank you for your comment and the information provided. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process.
	
		See the corresponding embedded attachment in table 1 of Part I: 5315_FINAL FluoroCouncil response HFPO-DA SVHC consultation 29-4-19.pdf