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

Substance name: Perfluorohexane-1-sulphonic acid and its salts (PFHxS)
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: vPvB (Article 57(e))

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. The RCOM has not been agreed by the Member State Committee, nor has the document been modified as result of the MSC discussions.  

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	
4803
2017/04/11	ANSES,
National Authority,
France	Page 18
3.1.1.3 Summary on abiotic degradation
Please add the reference about the half-life >42 reported for hydrolysis of PFOS.	Reference added and >42 is corrected to >41.	
4804
2017/04/14	Mineraloelwirtschaftsverband,
Industry or trade association,
Germany	See the corresponding embedded attachment in table 1 of Part I: 
	Thank you for the information.	
4809
2017/04/21	Individual,
China	All material provided to the customer does not contain the above substances	Thank you for the information.	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
4802
2017/03/29	F. O. BAGS GmbH,
Company,
Germany	FOND OF BAGS as a Cologne based bag producer has to follow the cosumer wish that is having 'waterproof' backpacks. The whole industry now swithches from long chain to short chain PFCs as there is 'no alternativ' than using PFCs.

Therefore, FOND OF BAGS asks to put all PFCs on the REACH list in order to reduce the customer expecations and not having a disadvantage against competitors that would still use PCS. We need the politics here in order to really change the industry and as a next step the consumer expectations on everyday products.
Best wishes,
Michael Damm
CR Manager
FOND OF BAGS, Cologne, Germany	Thank you for the information.	
4803
2017/04/11	ANSES,
National Authority,
France	Perfluorohexane-1-sulphonic acid and its salts (PFHxS) belong to the substance group of PFSAs in which the well-studied PFOs has been already included on the UNEP POP list of chemicals and also fulfils the vPvB criteria under REACH. Furthermore, the substances in this group have a similar chemical structure with a perfluorinated carbon chain and a terminal acid group, sulphonic acid (PFSA) or carboxylic acid (PFCA). Moreover, eight entries of PFCAs have already been included in the candidate list for PBT and vPvB properties.

A weight of evidence approach was applied to identify the substance as vPvB, according to the requirements of Annex XIII.  This approach includes the evaluation of all available and relevant information from modelling, standard and non-standard tests, QSARs and read-across with PFOS and long chained PFCAs.

In the document, the abbreviation PFHxS refers to the acid Perfluorohexane-1-sulphonic acid as well as to its salts, for instance ammonium and potassium salts.

Persistence
PFHxS exhibits a stable perfluorinated structure and it is not expected to undergo abiotic or biotic degradation under relevant environmental conditions. Concerning abiotic degradation, one study about photolysis is available for PFHxS, which shows no significant degradation of the substance. Furthermore, as no study on biodegradation is available for PFHxS, data from PFOS is presented for biodegradation screening tests and for the simulation tests, the read across with PFOS and PFOA is applied. The persistence behaviors of PFOS and PFOA have been already confirmed, both substances are persistent and do not undergo any further abiotic or biotic degradation, thus they meet the criteria for persistent and very persistent.

Considering the available knowledge on the high stability of the C-F bonds and using the read–across approach with PFOA and PFOS, PFHxS fulfill the P and vP criteria according to the provisions set out in Annex XIII of REACH.

Bioaccumulation
Studies with aquatic organisms report BCF and BAF values for PFHxS below to the threshold value of 2000 or 5000 to consider a substance as bioaccumulable (B) or very bioaccumulable (vB) respectively, only one study with fish (Leuciscus cephalus) shows a BAF value of 1995 in plasma. This value allows to consider the substance as a borderline B.

BCF values reported with the analog PFOS for fish are higher than 2000 and for PFOA the values are below to 2000.  The BCF values as indicator of bioaccumulation following the classic accumulation into fatty tissues have been questioned in both reports. Furthermore, several studies revealed that perfluorinated compounds preferentially bind to proteins in blood and liver. In the case of PFHxS and of others PFSAs and PFCAs, the bioaccumulation does not follow the classic pattern of traditional hydrophobic compounds with partitioning into fatty acids.

There is evidence that PFHxS preferentially bioaccumulates in air breathing mammals including endangered species and humans, rather than water breathing organisms.

- According to data, BFM values are found in liver from polar bears and ringed seal, ranged between 20 and 373.
- In humans, elevated concentrations of PFHxS have been found up to 1790 µg/L in blood serum. Furthermore, the elimination half-life for this substance is greater than 7 years, being longer than perfluoralkyl and polyfluroalkyl substances (PFAS) for which data is available.

Concerning biomagnification in food chains, even if it is not possible to conclude about the TMF values found in the literature, the BMFs reported for several species, considered both as predator and prey, are higher than 1. These values show an indication of the potential biomagnification of the substance. This finding is supported by the fact that the concentrations levels of PFHxS increase along the food-chains.

Taking into account all this information in a weight of evidence approach, PFHxS fulfils the vB criterion of Annex XIII of REACH.

In summary, the Annex XV report shows enough information in a weight of evidence approach that allows to conclude in the vPvB properties of PFHxS.  Considering all these information, ANSES supports its identification as a substance of very high concern.	Thank you for your support.	
		-		
4804
2017/04/14	Mineraloelwirtschaftsverband,
Industry or trade association,
Germany	See the corresponding embedded attachment in table 1 of Part I: 4804_PFC-in-AFFF.zip 	Thank you for the information.	
4809
2017/04/21	Individual,
China	All material provided to the customer does not contain the above substances.	Thank you for the information.	
4810
2017/04/21	Norway,
Member State	We support the Swedish proposal to identify Perfluorohexane-1-sulphonic acid and its salts (PFHxS) as substances of very high concern in accordance with Article 57(e) of Regulation (EC) 1907/2006 (REACH) due to its very persistent (vP)) and very bioaccumulative (vB) properties.

The data on persistence are indisputable; PFHxS and its salts are very persistent (vP) substances.

The data presented in the proposal clearly show that PFHxS and its salts must be identified as very bioaccumulative (vB). We support that the human data (e.g. Olsen et al. 2007) demonstrate a human half-life of PFHxS of more than 8 years (Olsen et al. 2007). This is the longest half-life demonstrated for perfluoroalkyl and polyfluoroalkyl substances (PFAS) for which data are available. Furthermore, BMFs up to 373 are indicated (Butt et al. 2008) for Arctic food webs. This BMF is higher than for other long-chained PFCAs that have already have been identified as vB on the Candidate List.

In addition to the data presented by Sweden, a Norwegian study has demonstrated that PFHxS is more efficiently transferred from the mother to the foetus via umbilical cord blood than PFOS (Gutzkow et al. 2012).	Thank you for your support.

The report by Gützkow et al. (2012) is now included in the report.	
		-		
4812
2017/04/21	Germany,
Member State	DE supports the Swedish proposal for identifying PFHxS as a vPvB substance.

In the human health hazard assessment the following concern is identified: PFHxS is transferred to the foetus through the placenta in humans and is excreted via lactation and breast milk may therefore be an important source of exposure to breast-fed infants. This important concern should also be considered in the summary.

Environmental fate properties:
Since the vB is strongly associated with protein binding and human blood elimination half-lives, we would advise to crosslink this information also in the bioaccumulation chapter.	Thank you for your support.

New text is added in the summary on gestational and lactational exposure.

New text is added in section 3.3.4 
	
		-		
4814
2017/04/21	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust agrees with the identification of perfluorohexane-1-sulphonic acid and its salts as a substance of very high concern according to REACH article 57 e) based on its vP and vB properties.
The dossier compiled a whole range of relevant information, including results from environmental analysis, calculations c from modelling studies as well as read-across.
Thus, the dossier makes a very convincing weight of evidence determination according to Annex XIII of REACH to conclude that perfluorohexane-1-sulphonic acid has vP and vB properties. This is of particular relevance given the data from environmental monitoring results, including in Arctic wildlife as well as the evidence concerning accumulation potential in humans.
First findings of perfluorohexane-1-sulphonic acid in human serum were made over a decade ago and the substance has been on the SIN list since 2014. More information can be found in the SIN list database, here: http://sinlist.chemsec.org/search/search?query=355-46-4 

CHEM Trust considers that regulatory action is long overdue and should swiftly follow the identification of this substance as SVHC.	Thank you for your support.	
		-		
4818
2017/04/21	United Kingdom,
Member State	We thank Sweden for submitting this SVHC dossier, and the comprehensive resume of the data.

We agree that the substance is vP. The more difficult question is whether there is a sufficient weight of evidence to support the substance meeting the vB criteria. We are very mindful of the previous MSC decisions taken for different perfluorinated substances, for example PFOA (which was determined to be B), the bioaccumulation evidence for these and how the evidence for PFHxS compares. This is important as we should understand the trends that exist in this category of substances.

For PFHxS there appear to be no unequivocal aquatic bioaccumulation data to demonstrate vB is met directly. The data are compromised by several issues, including the number of samples taken and significant uncertainty such as extrapolation between organ and whole body concentrations. This is in addition to the substance appearing not to conventionally accumulate to B or vB levels in fish (we think the BAF of 1900 in Chub should be treated with caution given this only relates to five fish).

PFHxS is detected in the environment. However the lack of knowledge about the supply of the substance makes it difficult to set this in context for B or vB. This is in contrast to PFOS and PFOA where the trend in supply volume is reasonably well understood.

PFHxS is detected in humans, however it is difficult to benchmark the concentrations to determine whether the elevation represents B or vB levels. The main data (Olsen et al, 2007) supporting the claimed human half-life appear to be significantly compromised as it is not possible to determine where on the elimination curve the half-life analysis was performed for the study.

The remaining bioaccumulation information is the mammalian half-life data. In the absence of other data, and also evidence to the contrary, this indicates that PFHxS does have a particularly long half-life in monkeys and pigs compared to other perfluorinated substances in the same experiments. The studies appear to be reliable, and therefore we take them to be unequivocal. However, there is no definition to relate mammalian half-life to the B or vB criteria. 

There is also a consistency issue for how we have evaluated (or will evaluate) other substances for bioaccumulation, where a half-life in a pig or monkey is not available.

For the points above, we do not think fundamental changes to the dossier are possible as what is presented is the available information. 

One of the difficulties in submitting the SVHC dossier at this point is the substance is not registered. This means it is not possible to request any further information about supply or seek additional data regarding bioaccumulation or toxicity. Overall, the question for us is whether the long mammalian half-life and detection in human blood constitute a sufficient weight of evidence to indicate the substance is vB rather than B. 

We remain to be fully convinced that it is, but wait to hear other MS opinions.	Thank you for your comment.

Thank you for your support on vP. We agree that the main point for the discussion is how to interpret the toxicokinetic data and the half-life in the context of the criteria for vB. We note, same as you do, that PFOA previously have been agreed to fulfil the B criterion based on data including toxicokinetic data without having data on fish BCF sufficient to fulfil the B criterion. 

Our conclusion when taking all available information together in a weight-of-evidence approach is that PFHxS fulfils the vB criterion of REACH Annex XIII. This information includes that PFHxS has a very long human elimination half-life and the longest observed non-rodent mammalian elimination half-lives among PFAS substances agreed to be PBT and/or vPvB.,In addition an indication of field bioaccumulation in air-breathing mammals, which based on the data in this dossier is similar or higher than for PFOS and the long-chained PFCAs which have already been identified as vB. 

In this category of perfluorinated substances, there are trends with e.g. increasing elimination half-lives in mammals and bioaccumulation in fish with increasing length of the carbon backbone. But the blood elimination half-lives for PFHxS in humans and non-rodent mammals presented in the dossier - which are longer than those for PFSAs and PFCAs with longer carbon backbones - seem to be a deviation from these trends.

As is described in the dossier, PFHxS, like other PFSAs and PFCAs, do not follow the behaviour of traditional hydrophobic compounds with partitioning into fatty tissues, but instead bind to proteins in blood and liver. Hence, bioconcentration in gill breathing organisms and the accumulation in lipids is not the most relevant endpoint to consider for these types of substances. Field studies show that air-breathing organisms are more likely to bioaccumulate PFHxS and other PFAS compared to water breathing organisms. Therefore, assessment based on a bioaccumulation study on aquatic species does not sufficiently address the bioaccumulation potential of PFHxS.

It has not been possible to find information on historical and present global production and use volumes of PFHxS to compare with those of PFOS and PFOA. PFHxS has been detected as an impurity in PFOS in the range of 4-10% ((Seacat et al., 2002), (Jiang et al., 2015)). However, we do not believe that specific knowledge about levels in the environment and supply volumes are useful for and important instruments to discriminate between B and vB.

Despite the fact that PFHxS has not been registered within the EU, it has been and are found in humans and in the environment in Europe and there is evidence that PFHxS preferentially bioaccumulates in air-breathing mammals, including endangered species and humans. 

We consider that the studied part of the overall time-concentration curve in Olsen et al. (2007) sufficiently represents elimination of PFHxS in humans and therefore can be used for the calculation of a biological half-life. This is further explained below.

For first order processes, the elimination half-life is independent of concentration. The more time that has passed since the external exposure ended, the more likely it is that the elimination has entered a terminal phase, i.e. the least steep slope on the semi-log concentration versus time plot. This part of the curve tend to follow first order kinetics and is usually the part best suited for calculations of biological or terminal half-life. This applies to data on PFHxS (see below).

In general when elimination half-lives are calculated at blood concentrations that is in the range of background levels, then exposure from other sources might influence the time-concentration curve, making the calculations of half-life uncertain, but this is not a case for PFHxS where blood levels of the retired workers are well above that of the general population (see below). 

In the article by Olsen et al. (2007), the human half-life of PFHxS is estimated by using a one-compartment model describing the decrease of blood levels of PFHxS in human blood from retired industry workers. The onset of the study (blood samples at time point 0) was 0.4-11.5 (mean 2.6) years after the time of retirement, i.e 0.4 - 11.5 years after the cessation of occupational exposure to PFHxS. Eight blood samples per studied individual were taken on a regular basis for 5 years. As there is no correlation between PFHxS elimination half-life and time since retirement, this clearly indicates that the studied part of the curve only is affected by elimination processes and has entered the terminal phase. It is not considered likely that the calculated half-lives from the studied part of the curve is influenced by exposure from other sources, such as the environment. This since the end-of-study blood levels for PFHxS (117 µg/L) remained substantially above comparable levels (2.1 µg/L) for a statistically representative population (non-occupationally exposed). In addition, during a literature search a study by Olsen et al. (2003)* was found that includes measured concentrations of PFHxS in blood serum in employees working in the same chemical plant as the retirees in Olsen et al. (2007) previously worked in. Measurements of PFHxS in blood serum in the two studies, Olsen et al. (2003) and Olsen et al. (2007), were performed during the same year 1998, as the measurements in Olsen et al. (2007) started in 1998. The concentration of PFHxS detected in blood serum in the two studies are practically identical. The 3M employees worked in the same 3M plant in Decatur as the retirees previously had worked in, having the same type of work.

Olsen et al. (2003)	
Olsen et al. (2007)	

Population	
Employees (n=126) working in the 3M plant in Decatur

Years worked: 1-38	
Retirees (n=23) from the 3M plant in Decatur. 

Retired between January 1995 and the onset of the study in November 1998 (≥ 5 Months)	

Type of work	
Cell operator, chemical operator, maintenance, …	
Same as in Olsen et al. (2003)	

Measure-ments	
Blood serum
1998	
Blood serum
November 1998 – March 2004	

Conc. (µg PFHxS/L)	
180 (geom. mean)
5 – 1880 (min-max)	
186 (geom. mean)
16 – 1295 (min-max)	

Elimination half-lives	
-	
Estimated for PFHxS, PFOS and PFOA	

Note: Olsen et al. (2007) also includes data from 3 retires from a 3M plant in Cottage Groove, with similar types of job categories, which had blood concentrations that were within the range of values measured in the retirees from the 3M plant in Decatur.

The data by Olsen et al. (2007) does not constitute the only available data on long human elimination half-lives and is used together with other data in a weight-of-evidence approach. In addition to the study by Olsen et al. (2007), there are also other sources supporting that PFHxS has a very long human elimination half-life:

1. The study by Zhang et al. (2013) who sampled and measured the concentration of several PFAS, including PFHxS, in paired blood and morning urine samples from volunteers (n = 86) in Shijiazhuang (capital city) and Handan (industrial city), Hebei province, China, in April to May 2010. Based on previous results from literature and an observed strong association between urinary and blood concentrations (except PFUnDA), renal clearance was assumed to be the major pathway for human elimination of PFCAs and PFSAs, with menstrual clearance being an important clearance pathway for PFAS in young females that was estimated and added to the renal clearance rate for young females. Using a one-compartment model resulted in the estimated biological elimination half-lives of PFHxS in young females of 7.7 y (arithm. mean)/7.1 y (geom. mean)/7.1 y (median) (range: 2.3-13 y) and in males & older females of 35 y (arithm. mean)/25 y (geom. mean)/29 y (median) (range 1.6-182 y). 

2. Human elimination half-lives of PFHxS, PFOS and PFOA have been estimated on a group basis in a population of 113 persons exposed via contaminated drinking water in Kallinge, Sweden, based on decreasing concentrations in blood serum (Scott, 2016) to 6.8 y, 5.2 y and 4.5 y.

3. Another way to evaluate the relative human bioaccumulation potential of PFHxS is benchmarking against vB substances known to be highly accumulative in humans such as PCBs. Ritter et al (2011) calculated “intrinsic” human elimination half-lives for a number of PCB congeners using a population PK model. In their estimation of “intrinsic” elimination half-lives Ritter et al corrected their estimations by taking confounding factors such as changes in exposure and body weight into account. The longest intrinsic elimination half-lives estimated by Ritter et al were 15.5 years for PCB-170 and 14.4 years for PCB 153. The shortest elimination half-life 2.6 years was estimated for PCB-52. Ritter also claims that their results, together with results from other studies (Kreuzer et al., 1997; Shirai and Kissel, 1996 which indicated that plausible maximum elimination half-lives of PCBs and dioxins are probably not much larger than ten years), gives further evidence that a maximum intrinsic elimination half-life for persistent chemicals exists and lies within the range of 10-15 years. 

Wong et al. (2014) estimated the intrinsic elimination half-life in human males of PFOS to 4.7 years. This corresponds well with the apparent elimination half-lives of 5.4 years/3.8 years (arithm. mean/geometric mean) derived from retired occupational workers (Olsen et al. 2007). It can therefore be assumed that also the apparent elimination half-life of 8.5/7.3 years (arithm. mean/geometric mean) for PFHxS derived by Olsen et al. may be in good agreement with the intrinsic elimination half-life and, thus, be comparable with the intrinsic elimination half-lives estimated for the PCB congeners. PCB-153 has a very high log BCF in fish of 5.0 – 5.3 (= 100000 – 199526). The log BCF in fish for PCB-52 has been reported to be 4.8  - 4.9 (= 63096 - 79433). Both PCB-153 and-52 fulfil the vB-criterion of REACH based on their high BCF in fish. 

The apparent elimination half-life of PFHxS in humans (8.5 years), are expected to be in fair agreement with an intrinsic elimination half-life, and is not much shorter than the intrinsic elimination half-lives of some of the most bioaccumulating PCB-congeners in humans which have intrinsic human elimination half-lives in the range up to 15 years. It should be noted that elimination half-lives exceeding 15 years have been estimated for PFHxS in some of the studied human populations (Zhang et al., 2013).

Regarding the lack of B/vB criteria for mammalian half-life data: In the context of presenting a dossier for the identification of a substance as SVHC it is not possible to define new specific criteria for vB. Therefore, the dossier uses a weight-of-evidence approach including all the available and relevant information to assess whether PFHxS fulfils the B or vB criterion of REACH. This is following from the approach defined by REACH Annex XIII that PBT/vPvB-assessment should be performed as a weight-of-evidence assessment. Thus it should be possible to come a conclusion even though a specific criterion has not always been set for all kinds of data included in the weight-of-evidence assessment. 

The weight-of-evidence assessment approach also implies that there will often be considerable differences in the kind of data and information available in the different cases to be assessed and compared with PBT/vPvB criteria. We do not see this as an issue of consistency or an argument for not using data that may not necessarily be available in other cases.  

We agree with that view. 

We acknowledge the fact that the substance is not registered. One of the aims of this dossier for identification of PFHxS as SVHC is to avoid “regrettable substitution” and that the substance will be manufactured and marketed in the EU. 

We note that you remain to be fully convinced and we also note that 6 out of 7 MS providing comments in the Public consultation on the PFHxS dossier supported the identification as vPvB. We await further discussion at the MSC.

* Olsen, G.W., Logan, P.W., Hansen, K.J., Simpson, C.A., Burris, J.M., Burlew, M.M., Vorarath, P.P., Venkateswarlu, P., Schumpert, J.C., & Mandel, J.H. (2003). An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: Biomonitoring. AIHA Journal, 64, 651-659	
		-		
4825
2017/04/24	TE Connectivity,
Company,
United States	p.1 On cover page and p.11 Name and other identifiers of the substance, Substance Name and CAS/EC Number does not match. Substance Name "Perfluorohexane-1-sulphonic acid and its salts" covers a group of substances, while CAS/EC Number only represents a single substance "Perfluorohexane-1-sulphonic acid". There is also NO table in Annex XV to list example substances of Perfluorohexane-1-sulphonic acid salts. This conflict will cause confusion and problems for industry to conduct SvHC communication through supply chain. As some companies may follow a whole group of substances, while others may just follow a single substance. Critical issue to solve, suggest ECHA to revise Annex XV by adding a table with substance examples and indicate the table is not exhaustive. Thanks for your consideration!
	Thank you for your question relating to the identifiers used for describing the substances covered by this proposed Candidate List entry.
 
Indeed, we acknowledge your concern regarding the correct use of substance identifiers. The aim of the proposed entry is to cover both Perfluorohexane-1-sulphonic acid and any salts thereof. The proposed entry therefore does not refer to a closed list of substances. Currently, for this type of entries, the EC and CAS identifiers are normally not listed in the Candidate List. This is to avoid misunderstandings in relation to the substances meant to be covered by the entry. Information on the identity of substances that are covered by such entries, instead, may be given in a separate document (as it has been done for instance in the case of the group entry for ‘4-Nonylphenol, branched and linear’). A non-exhaustive list of identifiers that may be used for describing these substances would be included in such a document. A link to the document would be made available in the Candidate List table on the ECHA website.
 
This practice can be adopted also for this proposed entry.	
4826
2017/04/24	Austria,
Member State	The Austrian CA strongly supports the Swedish proposal to identify  PFHxS as Substance of very high concern on the basis of the criteria set out in REACH Article 57e.
vP:
PFHxS it is not expected to undergo abiotic degradation under relevant environmental conditions due to the stability of the C-F bonds. Estimated data with the Biowin models demonstrate that PFHxS clearly fulfills the P/vP criterion, supported by Read across data with longer chain compounds like PFOS.
vB:
Shorter-chain PFCs are generally assumed to have shorter half-lives, although PFHxS is an exception, with an estimated mean half-life in humans of 8.5 years[1] .The half-lives of PFHxS are substantially longer than of PFOA in all species and are actually longest of all the PFAS in pigs, monkeys and especially in humans. The PFHxS elimination half-life in 26 retired production workers was estimated to be 8.5/7.3 years (arithmetic/geometric mean) years, suggesting poor elimination of PFHxS in humans  [2]. This elimination half-life was higher than for PFOS and PFOA (arithmetric mean: 5.4 and 3.8 yr). Maximal elimination half-lives  of up to 35 years were reported in the SVHC dossier. PFHxS can be detected in human blood globally, studies indicate increasing concentrations. PFhxS has been demonstrated to be transferred from the mother to the fetus and accumulates in breast milk. Analysis of autopsy tissue samples revealed detectable concentrations in brain, liver, lung, bone and kidney. The highest median concentrations were found in the kidney 18 μg/kg wwt., followed by the lung (5.7 μg/kg wwt.) In humans PFHxS bioaacumulates to at least to the same extend than PFOS (vB fulfilled) and PFOA (B fulfilled). Accumulation in air-breathing food chains has been demonstrated, e.g. levels above 500 µg /kg have been detected in polar bears according to the SVHC dossier.
Therefore, taking together Austrian CA clearly supports the Swedish conclusion that the substance fulfills the vB criterion.

[1] Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115:1298–1305.
[2] Academic Article- Comparative pharmacokinetics of perfluorohexanesulfonate (PFHxS) in rats, mice, and monkeys, Reproductive Toxicology 33 (2012) 441–451	Thank you for your support.	
		-		
4830
2017/04/24	ChemSec,
International NGO,
Sweden	ChemSec supports the inclusion of PFHxS on the Candidate List because of its vPvB properties. ChemSec included this substance in the SIN List already in 2014.
This substance is among the most commonly detected PFCs in the environment and in biota, and an increasing trend over time has been observed. It belongs to the same family as PFOA and PFOS and a number of other fluorinated compounds that have already been identified as being SVHCs. The evidence laid out in the dossier is clear and well presented with a transparent weight –of-evidence approach using measured, experimental and calculated data as well as read-across.

The additional studies below further show the concern and the need for regulatory action on this substance:

Calafat et al. measured 11 PFCs in 23 pooled serum samples collected in the United States (US) and Peru. The results show that PFOS and PFOA were the most detected PFCs in all the pooled samples followed by PFHxS, which was detected with median concentrations of 2 µg/L in samples from the US and <0.3 µg/L in samples from Peru.
(Calafat, A. M., L. L. Needham, et al. (2006). "Perfluorinated chemicals in selected residents of the American continent." Chemosphere 63(3): 490-496.)

PFHxS was detected in reclaimed wastewater from four WWTPs in California (US) that produce tertiary treated effluent for landscape irrigation and other reuse purposes. PFHxS measured concentrations range between 6.5 to 24 ng/L  Additionally, PFHxS was found in groundwater from San Jose, CA (US) with a maximum concentration of 11 ng/L.
(Plumlee, M. H., J. Larabee, et al. (2008). "Perfluorochemicals in water reuse." Chemosphere 72(10): 1541-1547)

In water, sediment and air samples from three Arctic lakes on Cornwallis Island, Canada, PFHxS was found at concentrations ranging from 2.9 to 20.8 ng/L in water, ≥ 1.2 ng/g in sediments, and a mean concentrations of 0.2 pg/m3  in air
(Furdui, V. I., N. L. Stock, et al. (2007). "Spatial Distribution of Perfluoroalkyl Contaminants in Lake Trout from the Great Lakes." Environmental Science & Technology 41(5): 1554-1559.)

Breast milk collected from seven Asian countries (Japan, India, Malaysia, Philippines, Indonesia, Vietnam, and Cambodia) was analyzed to determine concentrations of nine PFCs PFHxS was the second predominant PFC after PFOS, followed by PFOA. PFHxS was detected overall in more than 50% of the breast milk samples with a mean concentration range between 6.5 and 92 pg/mL.
(Tao, L., J. Ma, et al. (2008). "Perfluorinated Compounds in Human Breast Milk from Several Asian Countries, and in Infant Formula and Dairy Milk from the United States." Environmental Science & Technology 42(22): 8597-8602.)	Thank you for your support.	
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4834
2017/04/26	Netherlands, Member State	NL supports the proposal to include PFHxS and its salts in the candidate list of SVHC in accordance with Article 57(e) of Regulation (EC) 1907/2006 (REACH) given the vPvB properties. 
NL does however have reservation with conclusion in section 6.2.1.3 on the toxicity of PFHxS  that "the toxicity data available are not sufficient for classification for reprotoxicity or for specific target organ toxicity after repeated exposure in category 1 (STOT RE1)". It would still be useful to explore the possibility to classify PFHxS similar to PFOA and PFOS based on read-across. When this read-across is justified PFHxS would also be classified as Repro 1B and consequently be identified as SVHC in accordance Article 57(c) and 57(d) as well 
Therefore, we would like to propose to soften the statement "Although PFHxS can induce toxic effects, it is concluded that the toxicity data available are not sufficient for classification for reprotoxicity or for specific target organ toxicity after repeated exposure in category 1 (STOT RE1)". into "Although PFHxS can induce toxic effects, at present PFHxS has not been classified for reprotoxicity or for specific target organ toxicity after repeated exposure in category 1 (STOT RE1), further assessment of these end-points could considered" 

Identity of the substance and physical chemical properties
 Hardly any information is available on the toxicity of PFHxS. In fact only three mammalian toxicity studies are discussed in the Annex XV dossier. One study did not observe reproductive or developmental toxicity in rats. Two other studies reported that PFHxS affects mice behavior and levels of brain neuroproteins in similar fashion as PFOA and PFOS. Both PFOA and PFOS have been (amongst others) classified as STOT RE 1 (for PFOA target organ is liver, for PFOS not specified) and Repr. 1B, and thus meet the T-criterion. The lack of effect caused by PFHxS in rats could be due to the species tested (mice vs. rat). Considering the higher bioaccumulation potential of PFHxS and that it also binds to proteins, it would seem likely that PFHxS would at least meet the STOT RE with liver as target organ classification. Furthermore, ECHA’s Annex III inventory states the following with regard to toxicity: “The Toolbox profiler DART scheme v.1.0 gives an alert for toxicity to reproduction; Developmental/Reproductive Toxicity library (PG) in VEGA (Q)SAR platform predicts that the chemical is Toxicant (good reliability)”. Thus, the toxicity section should be extended by read-across to mammalian toxicity of PFHxS to at least PFOA and PFOS. If the read-across is robust enough, PFHxS and its salts could possibly also be identified as meeting the T criterion based on Repro 1B Article 57(c), and thus as SVHC in accordance with Article 57(d) as PBT. 
In the PBT factsheet discussed at the PBT EG it was stated that it has not been assessed whether PFHxS would be classified as specific target organ toxic after repeated dose cat.1 (STOT RE 1).	Thank you for your support.

The text in section 6.2.1.3 is modified. However, the wording is not exactly as proposed, this since it is unclear what further assessment of these endpoints using read-across may result in.	
4836
2017/05/05	Finland,                Member State	The Finnish CA supports the proposal to identify Perfluorohexane-1-sulphonic acid and its salts (later referred to as PFHxS) as a SVHC substance according to REACH Regulation Article 57(e) of the REACH regulation.   

Identification according to Article 57(e)

A weight-of-evidence determination according to the provisions of Annex XIII of REACH has been used to identify the substance as vPvB according to Article 57(e). 

The conclusion on vP is based on the stabile structure of highly fluorinated carbon chains that are not expected to undergo abiotic or biotic degradation under relevant environmental conditions, and read across to other similar substances (PFOS and PFOA). Although the numerical criteria of the REACH Regulation for the B/vB are not directly applicable to PFHxS, other information relevant for the B assessment (Annex XIII section 3.2.2.) shows that the vB criterion is fulfilled. This information includes monitoring data, field data on bioaccumulation and elimination half-lives from humans and other mammals. Based on the information available, it seems justified to conclude that PFHxS fulfils the vPvB criteria in Annex XIII to the Regulation. 

Regarding persistence assessment, we have the following comments to the Annex XV report:

It is mentioned in the Annex XV report (3.1.2.1.1. Estimated data, p. 18-19) that “Not all of the molecular fragments of the molecule are included in the training sets of the model. The confidence that may be put on BIOWIN predictions under such circumstances would not be clear in case no other information would be available for the substance as such or relevant analogues (if such are available). However, in this case the missing molecular fragment holds true not only for PFHxS but also for the close structural analogue PFOS, which is an agreed persistent substance (UNEP, 2006). The screening assessment on persistence on PFHxS, based on BIOWIN predictions, can add to the weight-of-evidence
that PFHxS is persistent.”

We are of the opinion that for evaluating the role of BIOWIN predictions in a weight-of-evidence, each BIOWIN prediction should be assessed separately for reliability and relevance (as needs to be done also in the case of each experimental study), taking into account model specific information and guidance, such as the list of fragment coefficients included in the model and the composition of the training set of the model. The results of this assessment can then be used to evaluate how much weight the BIOWIN predictions can have in the weight of evidence assessment. 

Therefore, we would suggest to replace the paragraph cited above, e.g., as follows:

“Not all of the molecular fragments of the molecule are included in the training sets of the BIOWIN models 2,3, and 6. Regarding the BIOWIN 2 and 3 predictions, the trifluoromethyl group is included in the prediction whereas the remaining part of the perfluorinated carbon chain is counted as eight units of “carbon with 4 single bonds & no hydrogens”. Considering that only one of the 17 fluorine atoms is included in the prediction and that the perfluorinated carbon chain is expected to be very stable but has no coefficient in the model, it can be concluded that BIOWIN models 2 and 3 are more likely to underestimate the persistence rather than overestimate it. Therefore, it is considered that BIOWIN 2 and 3 can be used for the estimation in this case, despite the missing fragments. These models indicate that PHFxS “Does not biodegrade fast” (BIOWIN 2) and that the ultimate biodegradation rating is “Recalcitrant” (BIOWIN 3).

Regarding the BIOWIN 6 model, the model recognized all the 17 fluorine atoms (as “Fluorine [-F]") and 7 of the 8 carbon atoms (as “Carbon with 4 single bonds & no hydrogens”) whereas the sulfonic acid fragment is not recognized. The fragment coefficient for “Fluorine [-F]" is -3.99 (which is multiplied in the prediction by the amount of the Fluorine fragments) whereas, for comparison, the coefficient for “Sulfonic acid / salt -> aromatic attach” is 0.678. This suggests that the missing sulfonic acid fragment would not influence the outcome of the prediction (readily biodegradable/NOT readily biodegradable), even taking into account that the sulphonic acid is not attached to an aromatic group in PHFxS. Therefore, BIOWIN 6 model indicates that PHFxS is not readily biodegradable in the MITI test. 

Considering the above, the screening assessment on persistence on PFHxS, based on BIOWIN predictions, can add to the weight-of-evidence that PFHxS is persistent."

We note that even though the proposed changes to the justifications for the use of QSARs do not change the outcome from the BIOWIN models in the present case, the situation could be different in other cases. E.g. in some cases fragments not covered by the prediction may have a high influence on degradability of the substance and can therefore have a significant influence also on the reliability of the prediction. Therefore, we think it is important that the justifications for use of QSARs are valid. We also consider that using two models in combination as instructed in ECHA guidance should not be a reason for not taking into account model reliability separately for each individual model. 

Further considerations on the BIOWIN models: 

BIOWIN 2: In addition to the above-mentioned “Trifluoromethyl group [-CF3]”, the set of fragment coefficients included in BIOWIN 2 includes one fluorine-containing fragment (“Aromatic fluoride [-F]”), which, however, is not included in PHFxS. We also note that the training set for BIOWIN 2 contains 259 compounds and it seems that only two of these includes fluorine (2-fluorophenol, fluridone) The prediction for these two compounds is "Does not biodegrade fast" which is in accordance with the result of the expert evaluation used for deriving the model. 

BIOWIN 3: In addition to the above-mentioned “Trifluoromethyl group [-CF3]”, the set of fragment coefficients included in BIOWIN 3 includes one fluorine-containing fragment (“Aromatic fluoride [-F]”), which again is not included in PHFxS. We also note that the training set for BIOWIN 3 contains 200 compounds and it seems that only two of these include fluorine (3'-Methyl-4'-chloro-2,2,2-trifluoroacetophenone, 2-Acetamido-7-fluorofluorene). The prediction for these two compounds is "months", which means that the compound is predicted to biodegrade completely in a time frame of months. The predictions match with the degradation times from expert evaluation used for deriving the model.
 
BIOWIN 5-6:
The BIOWIN 5-6 training set (589 compounds) contains at least eight substances with include fluorine . The BIOWIN 5-6 validation set (259 compounds) contains at least two such substances. For all of these substances, the biodegradability evaluation (based on MITI test) is “0=does not biodegrade fast”. For all of these substance, the prediction matches with the evaluation (A Probability Less Than 0.5 indicates --> NOT Readily Degradable). Some of these substances are highly fluorinated (2-Propanol, 1,1,1,3,3,3-hexafluoro- and Propane, 1,1,1,2,2,3,3-heptafluoro-3- (trifluoroethenyl)oxy -). 

The Finnish CA notes that a Risk Management Option Analysis (RMOA) conclusion document has been published on the ECHA website. According to the RMOA, "although PFHxS or its related substances do not fulfil the relevancy criteria according to the SVHC Roadmap 2020 (no full registration yet), the identification of PFHxS and its related substances as vPvB and also as a possible replacement for PFOS are reasons for inclusion in the Candidate List. Furthermore, an inclusion of PFHxS and its related substances in the Candidate List would clearly establish that the substance has vPvB properties and should therefore be substituted wherever possible. PFHxS would have a low priority for inclusion in Annex XIV and inclusion in Annex XIV would not cover PFHxS in imported articles. After the inclusion of PFHxS and its related substances in the Candidate List, a restriction might be considered as a next step, provided that sufficient information on e.g. occurrence in articles and exposure of humans and the environment is available."	Thank you for your support.

Thank you for the text proposal. The text in section 3.1.2.1.1 is changed.	

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	
4804
2017/04/14	Mineraloelwirtschaftsverband,
Industry or trade association,
Germany	We want to point out that on 11/3/2016, German competent autority BAuA has started an RMOA on undecafluorohexanoic acid. In the course of this RMOA, we have communicated attached information about concentration levels of several PFCA impurities in fire fighting foams. These data were also communicated als input to the public consultation on restriction of PFOA in 2015. Please take these information into account.	Thank you for the information.	
		See the corresponding embedded attachment in table 1 of Part I: 4804_PFC-in-AFFF.zip 		
4809
2017/04/21	Individual,
China	All material provided to the customer does not contain the above substances	Thank you for the information.