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

Substance name: 4,4’-isopropylidenediphenol (bisphenol A; BPA)
CAS number: 80-05-7
EC number: 201-245-8

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Endocrine disrupting properties (Article 57(f) environment)

Disclaimer: Comments provided during public consultation are made available as submitted by the commenting parties. It was in 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.

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
of dossier submitter	
4848
2017/10/13	Sensopolis Ltd,
Company,
United Kingdom	Page 136 last paragraph conclusions fundamentally flawed. Generally the report is highly biased and completely ignores data from other sources (including the American Chemical Society, the FDA and the European Food Standards Agency and German BfR which would contradict the view, the report in fact gives the impression that the conclusion was already made and they went off to try and find data to substantiate the pre defined conclusion. This type of muddy thinking and reporting brings the work of the ECHA into disrepute and leads to a complete lack of trust in all the work carried out. There have recently been several cases where the reports seem to have been written to support a specific set of pre conceived conclusions rather than science.	We thank the Sensopolis Ltd, Company for the comments provided.

Assessment 
We adapted the hazard assessment and conclusion sections in accordance with the comments received. The assessment was done in accordance with agreed guidances and procedures. See further responses.
 
Reports from other authorities
The cited sources address human health, but not environmental aspects. BPA is already identified as SVHC according to 57f with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment. 	
4849
2017/10/16	Berceo Chemicals,
Company,
Spain	The report states in multiple areas that there is scientific evidence that Bisphenol A causes probable serious effects  - however, other studies from across the world dispute this and consider BPA safe even in food contact due to more than 50 years of real exposure experience in the environment and in food contact with humans through packaging coatings and water containers.  It is therefore unsafe to use the report. The studies taken to support the inclusion of BPA as a substance of very high concern do not correlate with real life experience.
The study is full of assumptions which do not match actual experience and the summary contains many statements which “might, maybe and probable”  with no real life evidence to support the studies despite the enormous amount of real life data.
Consequently, there is no real scientific evidence that Bisphenol A causes serious effects in the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 REACH and classification as a Substance of Very High Concern would be against the public interest.	We thank the Berceo Chemicals, Company for the comments provided. 

“Real life data”/human health 
The comment mainly addresses human health aspects and experiences with food contact materials. This dossier aims towards an identification as SVHC with respect to the environment.
There is not an enormous amount of “real life data” for the environmental compartments as “real life experiments”, i.e. field experiments with direct exposures of ecosystems or natural habitats are not conducted on purpose in the EU. 
Assumptions
The assessment was done transparently, differentiating between can be clearly concluded or demonstrated and where there still are open questions.	
4874
2017/10/20	Norway,
Member State	Attachment: 4874_Comments SVHC BPA ED ENV.docx

Text of the document inserted by UBA:
We would like to thank Germany for the proposal and the comprehensive Annex XV document on the endocrine effects of Bisphenol A (BPA) in the environment.  We support the conclusion that BPA should be identified as a substance of very high concern in accordance with Article 57(f) of REACH. This is  because BPA is a substance with endocrine disrupting properties for the environment for which there is scientific evidence of probable serious effects to the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 REACH.
As documented in the Annex XV report there is convincing evidence from both in vitro and in vivo data that BPA acts via an estrogenic mode of action (MoA) in fish. Adverse effects such as a skewed sex ratio has been observed in fish and a direct link between the estrogenic MoA and adverse effects has been established in several studies of fish species. The skewed sex ratio towards females is an effect that is both diagnostic for an endocrine MoA and an adverse effect. In amphibians a thyroid MoA and a link between the in vitro and in vivo data on this MoA and spontaneous inhibition of metamorphosis has been established in several amphibian species. There is also evidence that BPA may act as an endocrine disruptor via the thyroid MoA in fish and via an estrogen MoA in amphibians.  Moreover, the ED activity of BPA is also supported by effects observed in invertebrate taxa.  
All the data presented in the Annex XV proposal clearly show that BPA fulfils the WHO/IPCS definition of an endocrine disruptor and the recommendations from the European Commission`s Endocrine Disruptor Expert Group (JRC 2013a) for a substance to be identified as endocrine disruptor.
Thresholds of adversity for EDs may exist but may be very low for individual EDs, depending on the mode of action, potency and toxicokinetics (JRC 2013b).  Moreover, thresholds may be particularly low during foetal development (i.e. critical windows of sensitivity) due to the immaturity of homeostatic mechanisms, the immature metabolism as well as the absence of some endocrine axes during sensitive periods of foetal life as compared to adult life stages. 
The effects documented for BPA are considered to have the potential to adversely affect wildlife population stability and recruitment in a number of species. The endocrine-mediated effects have been observed in the low μg/L range. Based on the current database it does not seem possible to derive a safe level of exposure. Environmental monitoring data demonstrate that BPA is ubiquitous in the environment and has been detected in all environmental compartments, including in fresh and marine waters, sediments and biota. We would also like to mention a recent study where BPA was detected in Arctic biota (Svalbard) in eggs of kittiwake and glaucous gull. BPA was among the most quantitatively abundant compounds found in seabird eggs in this study.  (Lucia, M. et al 2016). BPA has also been detected in eggs of herring gull in a series of monitoring reports of an Urban Fjord in Norway.
Taken together all the data presented support the conclusion that there is scientific evidence of probable serious effects to the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 REACH (and to substances identified as SVHCs and already listed in the candidate list due to ED for ENV).  
References: 
JRC (Joint Research Centre) 2013a. Key scientific issues relevant to the identification and characterisation of endocrine disrupting substances. Report of the Endocrine Disrupters Expert Advisory Group.
JRC (Joint Research Centre) 2013b. Thresholds for Endocrine Disrupters and Related Uncertainties. Report of the Endocrine Disrupters Expert Advisory Group.
Lucia, Magali, Gabrielsen, Geir W., Herzke, Dorte, Christensen, Guttorm. Screening of UV chemicals, bisphenols and siloxanes in the Arctic. 2016. M-598
http://miljodirektoratet.no/Documents/publikasjoner/M598/M598.pdf
http://www.environmentagency.no/Documents/publikasjoner/M375/M375%20komplett%20liten.pdf	We thank Norway for these supportive and helpful comments.

Thresholds of adversity
We agree that it might be possible to determine no effect concentrations in individuals or single species.  We also fully agree to the statement made that at present the existing uncertainties related to environmentally relevant ED substances do not allow for deriving a safe concentration level in the environment.

Environmental Monitoring data
We included the results for BPA in arctic biota and herring and the respective references in chapter 3.3 and Annex I. This evidence for arctic biota is indeed important and interesting, and was not included in the data compiled by JRC in 2016. 	
4880
2017/10/20	PC/BPA Group of PlasticsEurope cosigned by BPA REACH Consortium and Epoxy Resins Committee of PlasticsEurope ,
Industry or trade association,
Belgium	Attachment: 4880_Attachments PCBPA Group comments Annex XV dossier.zip
	See responses to your comments below. 	
4892
2017/10/20	Individual,
Switzerland	Attachment: 4892_Huntsman_Release to ENV_Toilet_paper_Oct_2017.pdf
	Thank you for your comment.

Releases from Toilet paper
Additional information on releases to the environment from toilet paper is appreciated and will be used during further RMO-decisions, but is not part of the SVHC dossier.	
4906
2017/10/20	United Kingdom,
Member State	• Section 3 (Degradation): We do not agree with the dossier’s conclusion that BPA is “not generally readily degraded in the environment”. Three standard ready biodegradation studies indicate a high level of mineralisation. Such tests are stringent, so it is not surprising that some fail. Unless it is known that the positive studies all used pre-adapted inoculum, we would normally conclude that the substance is readily biodegradable. High levels of removal have also been observed in several river water simulation tests, some sediments, and also soil (bearing in mind that further work is underway to determine whether non-extractable residues should be of concern or not). Some longer half-lives have been determined in a few studies, which mostly seem to involve low temperature or limited microbial populations. We therefore think the weight of evidence points to the substance being rapidly degradable in general (and this was also the conclusion of the assessment performed under the Existing Substances Regulation (ESR), which contains additional details). We think this is an important point, because of decisions about what constitutes an equivalent level of concern in a hazard context under REACH.

• Section 5.4.1 (In vitro tests), Table 8 (p. 28): One of the EC50s from the Kunz and Fent (2006) test was 8460 µM, which is around 2000 mg/L. This is significantly above the water solubility limit (300 mg/L), and we wonder whether it has any relevance (e.g. fish would be dead at such a high concentration in water). Including such information without some consideration of relevance might be misleading.

• Section 5.5.2 (In vivo tests with fish): We think that identification of a “Substance of Very High Concern” (emphasis added) based on environmental endocrine disruption should be consistent with the most stringent environmental hazard classification band under the CLP Regulation (Aquatic Chronic 1). For a rapidly degradable substance that is not bioaccumulative, this would mean long-term NOEC/EC10s for adverse population-relevant apical effects related to ED of ≤ 0.01 mg/L (10 µg/L).

• We believe that reliable (fish) full life cycle studies provide the most informative data, because the level at which adverse apical effects occur can be more easily related to that at which ED effects arise, giving an indication of the likely impact. Reported effects at or below 10 µg/L are as follows:

- Common Carp: testis structure affected after 14 d at 1 µg/L (no FFLC study).

- Rare Minnow: female VTG and sex hormone levels significantly elevated at 1 µg/L after 7 d (unclear if effect on ovarian weight was significant at this concentration from the information provided) (no FFLC study).

- Japanese Medaka: male VTG induction LOEC = 10 µg/L (nominal) after 35 d (N.B. no adverse apical effects below 100 µg/L from FFLC test).

- Zebrafish: female-biased sex ratio, reduced sperm count/quality and embryo malformations/mortality at 0.228 µg/L (one study, single test concentration); LOECs for F1 VTG induction and reduced growth in F0 96 dpf (FFLC) = 10 µg/L; adult male VTG induction LOEC = 10 µg/L (nominal) after 4 d in one study but 200 – 1 000 µg/L (nominal) in a second study.

- Fathead Minnow: LOECs for testicular histology in F0 and F1 generation in range 1 – 16 µg/L (all other end points in FFLC test have LOECs above 100 µg/L). Further comments on this are provided below.

- Brown Trout: NOEC for weight 2.4 µg/L, LOEC for inhibition of ovulation = 1.75 - 5 µg/L (no FFLC study). Further comments on this are provided below.

- Goldfish: LOEC for sperm quality parameters and sex hormone levels = 0.2 – 0.6 µg/L (few details of these studies are provided; no FFLC study).

- Rainbow Trout: no adverse effects reported below 10 µg/L (limited studies).

- Green Swordtail: LOEC for tail length (male secondary sexual characteristic (SSC)) = 2 µg/L.

- Guppy: no adverse effects reported below 10 µg/L (limited studies).

• Most of the effects below 10 µg/L are either non-apical or non-specific to an ED mode of action. The only diagnostic apical effect was a skewed sex ratio in one study with Zebrafish (Chen et al., 2015) at a low concentration of around 0.2 µg/L (the only concentration tested). None of the other studies with this species – including a FFLC study – appear to have reported any effect on sex ratio or embryos at higher concentrations. We therefore wonder how reliable the Chen et al. (2015) study is – is the exposure concentration validated, and can handling and other factors (e.g. small variations in temperature, oxygen level and stocking density, which are known to affect sex ratio in this species) be excluded as causes of the reported effects? We also note that this would seem to be a key study for any future classification and labelling proposal, so we think full details and a critical review should be provided in this dossier. If valid, it would seem to be an important piece of evidence that is missing from the summary in Section 5.14.1.

• The effects on Green Swordtail may be important, but the dossier notes that it is difficult to conclude on the level of adversity (i.e. what degree of change should be considered as significant). In addition, the link to estrogenicity is not clearly established in the dossier. A paper on the use of SSCs has been tabled at the Endocrine Disrupter Expert Group, but conclusions have not yet been agreed (e.g. natural variability needs to be well understood, including the role that non-chemical factors play, such as responses to female behaviour and other environmental factors).

• Some of the reported effects (e.g. Fathead Minnow testicular histology (Sumpter et al., 2001), and Brown Trout sperm quality and ovulation (Lahnsteiner et al., 2005)) were discussed in detail in either the original risk assessment report under the ESR (EC, 2003 and its 2007 addendum) or in the REACH transitional dossier prepared by the UK REACH CA (2008) (see https://echa.europa.eu/information-on-chemicals/transitional-measures/annex-xv-transitional-reports). For example, the Sumpter et al. (2001) study was reviewed by independent experts who had significant concerns about the reliability of the sperm cell results; it was also noted that based on the hatchability results these changes did not appear to have any effect on the ability of the male fish to fertilise eggs successfully (i.e. they were not population-relevant). A number of drawbacks were highlighted for the Lahnsteiner et al. (2005) study (e.g. use of wild caught fish that might not have been fully acclimated to lab conditions, lack of suitable replication, unknown appropriateness of the statistical analysis and possible influence of environmental factors). Therefore whilst this study appears to show a dramatic effect (cessation of ovulation at the highest dose (which was above 10 µg/L)) its reliability is uncertain. We think these drawbacks – which have been discussed in previous EU reports – should be mentioned in the study descriptions, since they affect the weight that should be given to these end points.

• In conclusion, if the Chen et al. (2015) study can be shown to be fully reliable, we agree that fish can be considered to respond to the substance via an endocrine mode of action at concentrations that are consistent with a high level of concern. In our opinion the other evidence does not point to sufficiently reliable ED-mediated adverse population-relevant apical effects at concentrations that are consistent with a high level of concern.

• Section 5.7 – 5.8 (In vivo tests in amphibians): For amphibians, adverse apical effects generally appear to occur at concentrations above 100 µg/L (and some effects appear to occur around the level of fish LC50 values). The study of Kashiwagi et al. (2008) points to effects on metamorphosis with a NOEC in the range 2.3 – 23 µg/L (the effect compared to the controls should also be provided), but in Table 19 this study is given a rating as 3 (unreliable). If the validity rating is appropriate, we do not think this study should be used in the weight of evidence assessment or cited in the summary Table 20 (i.e. it should be assigned a low weight). This leaves three studies that seem to show effects below 10 µg/L:

- Levy et al. (2004) reported a 120-d LOEC for sex ratio and reproduction in Xenopus laevis of 7.3 µg/L (as a geometric mean of two experiments – the ESR RAR noted that it could be higher still). We think further details of this study (and that of Pickford et al., 2003) should be included, including the critique provided in the previous ESR RAR and addendum (for example, pooling the data effectively reduced the number of replicates to one so the experimental error associated with the sex ratio end point cannot be estimated, there is a lack of concentration-response relationship, some potential for statistical bias, and the absence of significant incidences of gonadal abnormalities at the histological level does not seem to be consistent with the presumed effect of BPA on gonadal development). This creates difficulties for interpretation. It appears that the age of exposure may be very important (and this should be noted for other substances), but still, the overall NOEC that was adopted in the previous EU assessment for this species was above 10 µg/L.

- Iwamuro et al. (2003) reported a 22-d LOEC of 2.3 µg/L for “spontaneous inhibition and (of?) TH-induced metamorphic changes” in Xenopus laevis (according to Table 19). This appears to be from in vitro work only and it is not clear what this effect actually involved (other effects appear to have occurred at much higher exposure concentrations) or whether concentrations were maintained in the study. We note that the summary in the ESR RAR Addendum said that the parameters measured in this study cannot be readily related to demographic effects. We are therefore unsure about its relevance, and as a key study, we think much more information should be provided in the dossier (e.g. the magnitude of in vivo changes, and how they related to controls).

- Oehlmann et al. (2009) reported a 21-d LOEC for increased growth and body weight in male Xenopus laevis of 2.28 µg/L (NOEC 0.228 µg/L). There might have been effects on testicular structure in the same concentration range, but Table 22 says the LOEC is 0.228 µg/L and the NOEC is 228 µg/L (presumably a transcription error). It is unclear whether increased growth is a hormonal effect in this case.

• We think it would help to provide an overview of the effects in Xenopus laevis (all studies) to see if there is a clear and consistent pattern of effects (or if not, can variations be explained?). The study of Iwamuro et al. (2003) might provide sufficient evidence of a population-relevant adverse effect, if the in vivo effect on metamorphosis was significant with a NOEC below 10 µg/L.

• Section 5.10 (Molluscs): Reproductive effects were observed in Marisa cornuarietis in one laboratory at a nominal concentration of 0.25 µg/L, with an EC10 possibly as low as around 5 ng/L (we have not reviewed the paper of Oehlmann et al. (2007) in detail, but it does not appear to present any additional data compared to that previously considered under the ESR). The strain used by this group is of uncertain origin (the breeding population was originally established using snails obtained from Dusseldorf Zoo, with “occasional” inputs of snails from an unnamed source in Florida – the level of inbreeding is therefore unknown). A tropical strain was used by the Forbes et al. group, but it is not clear whether this particular strain would be susceptible to seasonal influences on reproduction or not. A great deal of care and effort was taken to ensure that the Forbes et al. studies were carried out to a high standard with a suitable level of replication, so the failure to observe similar effects as the Oehlmann group does highlight an issue with the choice of this species as a model test organism in our opinion. It should be noted that reproductive traits are more variable in this species at lower temperatures, which could have some influence on the Oehlmann et al. findings due to the test design and method of statistical analysis. Still, the continued observation of “super-females” in the Oehlmann laboratory – which is completely antagonised by an anti-estrogen – does seem to be relevant. The calculated EC10 reported by Oehlmann et al. (2006) may be an artefact of the statistical approach and the choice of values used to represent the exposure concentrations. Nevertheless, as reported in the ESR RAR addendum, van der Hoeven (2005) calculated an alternative EC10 of 2.1 μg/L at 20 °C (with a 95 % confidence interval from 1.0 to 11 μg/L), based on a simple linear two-parameter model and nominal test concentrations. This is consistent with a very high level of concern.

• We also note the effects on embryo production in Potamopyrgus antipodarum occurring below 10 µg/L. The additional mollusc studies carried out in the UK and reported in the transitional dossier (Benstead et al., 2008) could also be mentioned – although they were inconclusive for a variety of reasons, they did report a significant effect on reproductive output in Potamopyrgus antipodarum over 28 days, at least at a nominal concentration of 0.2 μg/L (0.168 μg/L measured). Ideally we would prefer a fully valid study performed in accordance with the OECD TG for this species using a suitable concentration range. However, we should not ignore the existing findings.

• In conclusion, apical population-relevant effects occur in molluscs below 10 μg/L, which is consistent with our interpretation of what constitutes a “very high” concern, and we agree that the available evidence points to a potentially plausible link between the observed apical effect and the involvement of an estrogen-like receptor. Nevertheless, our understanding of molluscan endocrinology is still developing, and ideally we would like to have an adverse outcome pathway mapped out. We therefore hesitate to conclude that BPA is definitely causing its effects via endocrine disruption based on this information.

• Section 5.11 (insects): We thank the German CA for providing an overview of the evidence. We note that the Watts et al. (2001) study reported an adverse effect on F1 emergence for Chironomus riparius at a concentration of 0.078 μg/L. The ecological consequences of the mouthpart deformities observed in the Watts et al. (2003) study on the same species at similarly low concentrations are unclear (in this case, effects on emergence were only seen at high concentrations). We also note the apparently important effects on Euborellia annulipes at or below 1 μg/L, although the potential impact of other factors and consequences for reproduction are less clear. Similar to the case with molluscs, we think there is a potentially plausible link between the observed apical effects and the involvement of the ecdysteroid receptor, but we hesitate to conclude that BPA is definitely causing its effects via endocrine disruption based on this information.

• Section 5.12 (crustacea): We note the apparent similarity to insects, but that effects generally seem to occur at relatively high exposure concentrations. A single study points to effects below 10 μg/L – an apparent 103-d EC10 (brood size) of 5 μg/L was reported for Gammarus fossarum, based on a test which only had three exposure concentrations. There is no clear link to the endocrine system for this effect, so we do not believe that the crustacean data represent a very high concern.	We thank UK for the extensive and helpful comments.

Degradation
We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). 
We agree to your rationale that the substance is to be assessed as “rapidly degradable” on basis of the screening tests. 
However, we cannot conclude on degradability in all compartments based on the information available.
The study descriptions and assessment of the studies in the support document are in line with the EU RAR (European Comission, 2010), although we partly come to different conclusions. Few new studies were added and the conclusions of the CSTEE described in Bakker et al. (2014) were taken into account. 
We come to the conclusion that: The screening tests show that Bisphenol A can be rapidly removed from surface waters by biotic degradation processes and therefore is rapidly degradable. 
In surface waters, on the basis of the information available, Bisphenol A is rapidly removed. 
In sediments under aerobic and anaerobic conditions, on the basis of the available conflicting data, currently no definite conclusion on degradation of Bisphenol A is possible.
In soil, under aerobic conditions, Bisphenol A is removed rapidly. On the basis of the available conflicting data, currently no definite conclusion on removal of Bisphenol A in soil under anaerobic conditions is possible.
We have revised the text accordingly and added more information on the test methods and conditions in the tables.

In vitro tests
Thank you for your comment. It is correct that the tested concentration is significantly above the water solubility limit and the result has therefore no relevance. We added this in the Support Document.

In vivo tests with fish 
We tried to address the raised questions and concerns with respect to the fish studies in the support document and added more details on the studies (e.g. test conditions): 
-	Rare minnow: As described in the Support Document (Zhang et al., 2016b) only the expo with 15 µg BPA/L resulted in a significant elevation of ovarian weight not 225 µg BPA/L. At 1 µg BPA/L the ovarian weight was elevated but not significantly.
-	Zebrafish: concerning (Chen et al., 2015) we have added some details on test conditions and think that this study is reliable.
-	Fathead minnow: We recognized that the reliability of the effects on sperm cells were discussed in previous assessments. Therefore we mentioned this also in the report. The effect on sperm cell development was also seen in other fish species as Poecilia reticulate.
-	Goldfish: we added some details in the report.
In our view, there is not only one single study (Chen et al., 2015), demonstrating the oestrogenic mode of action of BPA in fish.

In vivo tests with amphibians 
We tried to address the raised questions and concerns with respect to the amphibian studies in the support document and also added more details on the studies (e.g. test conditions: 
-	We agree that the study of Kashiwagi et al. (2008) is not reliable due to its poor documentation. The results described in this study are also described in Goto et al. (2006). Here the study description is sufficient. The study was also used in the ESR RAR (2010). As the LOEC reported for effects on metamorphosis is 22.8 µg BPA/L the NOEC results in 2.28 µg/L (which is below 10 µg/L.
-	Levy et al. (2004): We added further details of this study and of Pickford et al. (2003) and also the critique provided in the previous ESR RAR. The overall NOEC adopted in the previous EU assessment was 60.4 µg/L as a result of pooling the results from Levy et al. with Pickford et al. 
-	Iwamuro et al. (2003): There was a transcription error. The LOEC for testicular structure effects was 2280 µg/L. We corrected this in the report. Therefore this study does not proved a NOEC below 10 µg/L for an in vivo effect on metamorphosis. This is given by Goto et al. (2006). Here the NOEC for inhibiting the metamorphosis was 2.3 µg/L.

Molluscs 
We tried to address the raised questions and concerns with respect to the mollusc studies in the support document
-	We added the points you made with respect to the Oehlmann and Forbes studies (e.g. uncertain origin of the strain in the studies, high standard of Forbes study) 
-	We added the information from the Benstead et al. 2008 study.
We are aware that the current knowledge on mollusc endocrinology is still fragmentary and would also like to have an AOP mapped out or further studies. However, we could not provide a comprehensive review on mollusc endocrinology here, but referred to the reviews available and highlighted the studies which analysed the effects of BPA. As we received comments from FR with this respect, we adapted the chapter on the in vitro evidences and added the receptor studies proposed by FR. We adapted the section and differentiated better between what can clearly be demonstrated and where there are still open questions.

Insects
We tried to address the raised concerns with respect to the insect studies in the support document and made more clear that data is of course still fragmentary. One study was added to address a comment from Plastic Europe. We adapted the section and differentiated better between what can clearly be demonstrated and where there are still open questions.

Crustaceans
We tried to address the raised concerns with respect to the crustacean studies in the support document and made more clear that data is of course still fragmentary and that effects often occurred at very high concentrations. We adapted the paragraphs with respect to the long-term study with gammarids. We adapted the section and differentiated better between what can clearly be demonstrated and where there are still open questions.
	
		-		
4938
2017/10/27	Finland,
Member State

	We thank the German CA for the comprehensive and systematic SVHC proposal on the environmental endocrine disrupting properties of bisphenol A. The German proposal to identify 4,4’-isopropylidenediphenol (bisphenol A, BPA) as SVHC according to Art. 57 (f) is based on the oestrogen agonistic/androgen antagonistic effects of BPA on fish and on the thyroid antagonistic effects on amphibians, supported by observed endocrine mediated effects on other trophic levels.
Bisphenol A has already been included in the SVHC candicate list based on 'Toxicity for reproduction (Article 57(c))' and 'Endocrine disrupting properties (Article 57(f) - human health)'. BPA has a harmonised classification for the hazard class reproductive toxicity category 1B (H360F ‘May damage fertility’) based on effects on reproductive function.
The Finnish CA notes that the available data set for endocrine mediated effects in the environment is considerable and fulfils the WHO/IPCS criteria for identification of endocrine disrupting substances. The mode of action, apical effects and a plausible link between them have been demonstrated in several studies. In many cases the relevant effects occur at or below the Aquatic Chronic 1 classification threshold <0.1 mg/l for not rapidly degradable substances, but again many of the studies show higher effective concentrations. Nonetheless the available evidence for estrogen mediated effects on fish seems evident, while the data set for thyroid effects is somewhat less exhaustive and more variable.
We also thank the German CA for including environmental fate properties in the assessment. However, could you please include more information of the methods of the simulation tests in order to consider their relevance. For example, were these standard OECD tests?
The Finnish CA supports the identification of bisphenol A as a substance of very high concern according to Article 57(f) as giving rise to an equivalent level of concern because of its endocrine disrupting properties to the environment.	We thank Finland for the valuable comments.

Degradation
We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). 
Please also refer to the responses given there.
We have revised the text accordingly and added more information on the test methods and conditions in the tables.

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
4844
2017/10/12	Austria,
Member State	We thank Germany for compiling a dossier demonstrating that BPA is an endocrine disruptor for the environment. The evidence is provided for a rather wide range of taxa and includes exceptionally many studies: In fish, amphibians as well as in several invertebrate taxa endocrine mediated effects are described – many of these effects need to be considered adverse. These effects are shown to occur already at low concentrations for many taxa - particularly several invertebrate species seem to be very sensitive to the detrimental effects of BPA.
Moreover, evidence is strengthened by mammalian data on fertility, mammary gland, neurodevelopment and metabolic effects described in the support document , which led to identification of BPA as an endocrine disruptor for human health. The support document also states that BPA may alter also other physiological functions, e.g. immune function, through ED modes of action. The adverse effects identified in mammals are also considered relevant for the mammalian species in the environment and are therefore considered supportive for the identification of BPA as an ED for the environment.
In conclusion, we agree that BPA fulfils the WHO/IPCS definition of an endocrine disruptor also for the environment and support the identification of BPA as an endocrine disruptor for the environment according to article 57(f) in REACH.	We thank AT for this supportive comments.

Human health/mammalian data 
Comments in this respect were received from Austria, Denmark as well as France and generally supported from Sweden.
It is correct, that the mammalian data is important to be considered also with respect to the environment. We added a summary of the conclusions from the support document for SVHC identification with respect to human health in chapter 4. 
We also explicitly referred to the relevance of this data to wildlife mammals and non-mammalian vertebrates in chapter 6.3.1 and 6.3.3. 
The present Support Document focuses on the evaluation of the available ecotoxicological studies for fish, amphibians and invertebrates mainly in the aquatic environment. A thorough assessment of mammalian data from the human health data base is not provided. – And cannot be achieved in the short time frame set for the dossier submitter responding to the comments.  	
4845
2017/10/12	Denmark,
Member State	1)
We support the proposal to identify BPA as a SVHC in accordance with Art 57(f) of REACH with respect to the environment. We acknowledge the comprehensive assessment done by Germany.
2)
Page 21:
We acknowledge that the focus of the Annex XV document is assessment of endocrine activity and effects in animals in the environment. However, we do not agree that the database to assess human health effects is not relevant for the environmental assessment, as claimed at page 21 under the heading “4. Human health hazard assessment“, with the following text: “not relevant for the identification of the substance as SVHC in accordance with art 57(f) REACH with respect to the environment”.
On the contrary, we find the mammalian database very important, and recommend to include an overview/review of the available data/conclusions from the human health (ED) Annex XV dossier in this Annex XV dossier.
In the draft revised OECD ED GD No 150 it is reflected that indications of ED related activity or effects from data on mammalian species (e.g. rat, mice) also causes concern for occurrence of such in non-mammalian vertebrate species (such as fish or amphibians). This is due to large degree of conservation of the primary amino acid sequences in proteins which implies large commonalities between non-mammalian and mammalian vertebrate species in regard to hormones, enzymes and receptors involved in the EATS modalities. Therefore, the data from mammals can be used to provide further/supportive information on endocrine modes of action and/or indication thereof in terms of adverse effects plausibly linked to an endocrine mode of action.
Another point is, as also now reflected in the draft revised OECD ED GD no. 150, that rodent data are generally not only relevant for humans but also for mammalian wildlife (i.e. ecotoxicity in mammalian species).
3)
Page 12-13 AND
Page 130-134
The argumentation for “Equivalent level of concern” (Eloc) is very long in our view. This is both the case at page 12-13 and the longer version on page 130-134. We propose to reduce this argumentation to a minimum.
We do agree that all the points mentioned in the Eloc are true for BPA. But we do not agree that all the arguments used for Eloc for BPA are necessary  - or even appropriate - for a substance to be regarded as being of Eloc. Therefore, the Eloc argumentation should in our view be reduced to a minimum, preferably along the same lines as in the decision documents for previous cases as e.g. DEHP. Furthermore, we disagree to list all arguments as Eloc considerations, since we do not find some of them necessary and we are afraid that such a comprehensive listing will create precedence for future cases. Finally in respect to some of the not needed arguments for Eloc we note that BPA is so well investigated compared to most other suspected endocrine disruptors. It therefore is foreseen that the amount of available information will be much smaller for most or all future cases.
Therefore we propose in general and also for BPA only to include the absolutely needed Eloc arguments.
4)
Observed effects of BPA on many different taxa are reviewed in the Annex XV dossier and used in the argumentation for identifying the substance as an ED in the environment. We propose to reduce the number of taxa included. Especially for molluscs, it is generally acknowledged (c.f. OECD STA No.121, Detailed Review Paper on Life cycle testing on Gastropods,  2010) that the endocrine system is so poorly known that defining endpoints to assess endocrine disruptors is currently not possible. The information of molluscs should therefore, in our view, not be included in this dossier. For other invertebrate taxa we have similar reservations about how well known the endocrine systems are. This applies to the following taxa mentioned in the assessment: cnidarian, porifera, echinodermata and annelida. In our view the current general knowledge is too weak to be able to conclude on an endocrine mode of action (and their plausible links to adverse effects) in also these taxa to be able to make any definitive conclusions even by WoE. We therefore suggest to leave the information on effects on these taxa out of this evaluation.
Specific comment:
Page 22 (5.2 General approach for the assessment of endocrine properties):
“In vitro and non-testing data were used to demonstrate the endocrine modes of action and pathways. The assessment of in vivo data focuses on the question whether adverse effects can be inferred to originate from the presumed modes of action or to be a consequence of general systemic toxicity”.
This description of the general approach does not acknowledge that mechanistic information can also be obtained from in vivo studies, where some endpoints are considered to be specific for substances affecting the hormonal systems. It is for example well known that Vtg increase in the blood (serum) in male fish or reduced AGD or Nipple Retention in newborn male rats in absence of clear general toxicity is a sign of  interference with the sex hormone system in fish (indicating “estrogenicity”) and rats (indicating “anti-androgenicity”), respectively.  Please reconsider the wording and the approach accordingly.	We thank DK for the extensive and very useful comments.

2. Human health/mammalian data
Comments in this respect were received from Austria, Denmark as well as France and generally supported from Sweden.
It is correct, that the mammalian data is important to be considered also with respect to the environment. We added a summary of the conclusions from the support document for SVHC identification with respect to human health in chapter 4. 
We also explicitly referred to the relevance of this data to wildlife mammals and non-mammalian vertebrates in chapter 6.3.1 and 6.3.3. 
The present Support Document focuses on the evaluation of the available ecotoxicological studies for fish, amphibians and invertebrates mainly in the aquatic environment. A thorough assessment of mammalian data from the human health data base is not provided. – And cannot be achieved in the short time frame set for the dossier submitter responding to the comments.  

3. EloC too long 
We think that it is - in this case – appropriate to refer to the evidences we have for BPA as we cannot ignore the available data. In light of the (compared to other substances) enormous amount of data for BPA we added a “disclaimer” to make clear that BPA is a special case.
We tried to made clear which evidence is sufficient for the ELOC assessment and which data is additionally presented as supporting evidence. Hence, we adapted the chapter, tried to prioritize and make it more stringent with a focus on the clear evidences with respect to ELOC (fish), supported by further studies.

4. Reduce the number of taxa included. 
In our opinion the data on molluscs gives valuable insight that also invertebrates are affected by BPA, that effects are most plausibly endocrine-related and in most cases development and reproductive parameters are affected leading to malformations or reproductive/developmental deficiencies. In particular molluscs have been discussed intensively with respect to BPA, so we would not ignore – but present and discuss - the available data in the document. 
Also for arthropods some evidence is provided and discussed, although also here data is of course still fragmentary.  
The data on Cnidaria, Porifera, Echinodermata and Annelida summarize the few examples that are available. 
Nevertheless we evaluated and considered the available data in the hazard assessment part and hence also referred to it later, being conscious that the indications for an ED MoA are weaker and no agreed specific guidance exists yet for the assessment of endocrine disrupting effects in invertebrates.  
In chapter 6, we also set a stronger focus on the vertebrate taxa, i.e. the oestrogen MoA in fish and thyroidal MoA in amphibians, with clear evidence (see above).
We follow the line of argumentation as in previous dossiers and refer to the data as a whole. We included a paragraph in 6.3.2 and 6.3.3 to make clear that due to the large amount of data a number of arguments can be provided, which are used in a WOE. None of the arguments alone is decisive and not all of them are needed to conclude on the ELOC. We decided to present the available evidences to get an overall picture on the data analysed.  

Specific comment: Wording in general approach 
Of course mechanistic information can also be obtained from in vivo studies. We adapted the paragraph accordingly: “Non-testing, in vitro and mechanistic information obtained from in vivo studies were used to demonstrate the endocrine modes of action and pathways.”	
		-		
4848
2017/10/13	Sensopolis Ltd,
Company,
United Kingdom	The comments made initially on page 13 of the report are disputed based on real life experience with the material. The report states in multiple areas that the is scientific evidence that Bisphenol A causes probable serious effects  - however, other studies from across the world dispute this and consider BPA safe even in food contact and hence direct ingestion experience over more than 50 years. It is therefore unsafe to use the limited and highly skewed studies taken to support the inclusion of BPA as a substance of  very high concern when the contrary appears to be the case and it would appear instead that this is purely a politically motivated attempt to exclude BPA, a molecule which has proven itself over the last 50+ years in real life exposure to be beneficial to the world’s population and de facto the environment due to its various applications including food packaging and reduced waste of food products. The study is full of unsafe extrapolations and even in the summary it is full of might, maybe and probable without a single piece of hard evidence to support it – see below:

Based on the current data and knowledge it appears difficult to derive and quantify a safe level of exposure for BPA, although it might exist. Effects on non-traditional endpoints and in specific species occurred at lower concentrations than those considered by standard OECD test guidelines. Moreover, as effects often occur in certain species, or after exposure during specific time windows or life stages, some effects might be overlooked. Effects of BPA are very complex and effects are provoked via different modes of action. Hence, a greater variety of species could be affected. Consequently, there is scientific evidence that Bisphenol A causes probable serious effects in the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 REACH.

And again on Page 17, again no hard evidence even on something as readily established as biodegradability (and hence dwell time in the environment), real life experience shows that there is little if any bio-persistence. This has again been ignored especially in products which are the primary environmental vectors for BPA in the real world namely packaging materials and polycarbonates including use in drinking water bottles on large global industrial scale with no evidence of any damage to life or the environment from the BPA (refer to page 20 - Hence, BPA reaches habitats continuously from various sources and may be defined as “pseudo-persistent”. Organisms are exposed more or less continuously to Bisphenol A and cannot avoid exposure. And with a low potential for bioaccumulation (Page 21 of the report)) It is therefore clearly incorrect to assume that a substance which by the reports own admission is widely dispersed in the environment, and with no tangible negative effects should be considered a substance of very high concern.

Concerning the environmental hazard classification, there is no harmonised classification available. From 1798 self-classifications, 1444 notifiers have no environmental hazard classification. The available ecotoxicity data for Bisphenol A is sufficient to propose a classification with Aquatic Chronic 1 (based on a NOEC of 2.4 µg/L for reduced egg production in Salmo trutta) ((Lahnsteiner et al., 2005) reliability 2, assessed with CRED).

There is conflicting information on the ready biodegradability of Bisphenol A. Three screening tests show that Bisphenol A is readily biodegradable while three other screening tests show that Bisphenol A is not readily biodegradable.

Page 33
5.4.4 Summary and Conclusions from in vitro data show very inconclusive results and only indicate: “The in vitro data suggests that Bisphenol A may affect a variety of endocrine
processes via multiple modes of action.”   That is to say there is absolutely no conclusive evidence that is viable to substantiate this from the data provided in the report and indeed in many other reports which have been conveniently ignored here the contrary is shown as has the study of (Kang et al.,2002 page 52) where again the results do not follow the reports bias and in fact show no effects – and this report is considered to be one of the most reliable even by Annex XV report: 1 – reliable without restriction: guideline study (OECD 230); extended.
Similarly (Keiter et al., 2012) showed no deviations from the controls.  Thus the summary on page 62 is flawed  as it ignores the most reputable reports.

Finally when considering the work of a=other authorities insufficient emphasis is placed on work which demonstrates clearly the safety of BPA (page 146  11.4 Previous assessments by other authorities). No comment is made to contradict the highly controversial French work and no reference made to the confirmation of the safety BPA by the European Food Standards Agency or U.S. National Toxicology Program including:

October 2016 - New data confirm EFSA’s previous conclusion that BPA might affect the immune system in animals, but the evidence is too limited to draw any conclusions for human health.

Hence the conclusions of 6.3.3 do not satisfy the question “Is there scientific evidence of probable serious effects to the environment which give rise to
an equivalent level of concern compared to CMR or PBT substances? (6.3.2) “ and the classification as a substance of very  high concern is not valid.	SVHC identification Environment
The cited sources address human health, but not environmental aspects. Additionally, BPA is already EU-wide identified as SVHC according to Art. 57 (c) and (f) of the REACH regulation based on its reproductive toxic and endocrine disrupting properties with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment.
The Art. 57 (f) of the REACH regulation explicitly states that: substances - such as those having endocrine disrupting properties… - for which there is scientific evidence of probable serious effects to human health or the environment… can be identified as SVHC. In our point of view the data and conclusions presented within our Support Document provide sufficient scientific evidence to identify BPA as an endocrine disruptor in the environment. We cannot exclude probable serious effects on wildlife species and see the need for action on an EU-wide level.

Degradation
We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). Please also refer to the responses given there.
We have revised the text accordingly and also added more information on the test methods and conditions in the tables.

Pseudo-persistence
We removed the term “pseudo-persistence” in the document and adapted the paragraph in chapter 3.3. 

In vitro studies
Please see our extensive response made below to the issues raised by the PC/BPA Group of PlasticsEurope. 

Studies ignored
(Kang et al., 2002): We did not ignore the results of this study. At page 43 we concluded that “Other studies conducted with O.latipes reported no effects on sex ratio. That could be because organisms were not exposed during their sensitive window of development but as adults, or the exposure duration was too short (Shioda and Wakabayashi 2000, Kang et al. 2002, Kashiwada et al. 2002, Tabata et al. 2001, Yamaguchi et al. 2005).” This study also reported effects on testis, which we considered also in our summary.
(Keiter et al. 2012): This study was described on page 44 of the report in more detail and the results were included in table 13. Effects of BPA reported in this study and included in the Support Document were e.g. VTG induction in F1 generation at 400 µg/L and in F2 at 10 µg/L, no effects on growth in F1 but in F2 generation at 400 µg/L.

Reports from other authorities
The cited sources address human health, but not environmental aspects. BPA is already identified as SVHC according to 57(f) with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment. 	
		-		
4849
2017/10/16	Berceo Chemicals,
Company,
Spain	The conclusions of 6.3.3 do not satisfy the question “Is there scientific evidence of probable serious effects to the environment which give rise to an equivalent level of concern compared to CMR or PBT substances? (6.3.2) “ and the classification as a substance of very  high concern is not valid. Consideration to the work of other authorities which demonstrates clearly the safety of BPA (page 146  11.4 Previous assessments by other authorities) is ignored. The French work does not correlate with other studies and no reference is made to the confirmation of the safety BPA by the European Food Standards Agency or U.S. National Toxicology Program.
5.4.4 Summary and Conclusions from in vitro data show very inconclusive results and only indicate: “The in vitro data suggests that Bisphenol A may affect a variety of endocrine processes via multiple modes of action.”   There is no real evidence to substantiate classification as an SVHC from the data provided in the report or other reports. The study of (Kang et al.,2002 page 52) in fact show no effects – and this report is considered to be one of the most reliable even by Annex XV report: 1 – reliable without restriction: guideline study (OECD 230); extended. Also (Keiter et al., 2012) showed no deviations from the controls.  Thus the summary on page 62 is cannot be taken as it does not represent the results from the most reputable reports.
Page 17, again no hard evidence even on something as readily established as biodegradability (and hence dwell time in the environment), real life experience shows that there is little if any bio-persistence.
There is no evidence of damage to life or the environment from BPA (page 20 - Hence, BPA reaches habitats continuously from various sources and may be defined as “pseudo-persistent”. Organisms are exposed more or less continuously to Bisphenol A and cannot avoid exposure and with a low potential for bioaccumulation (Page 21 of the report)) it is incorrect to assume that a substance widely dispersed in the environment, and with no negative effects should be considered a substance of very high concern.	Reports from other authorities
The cited sources address human health, but not environmental aspects. BPA is already identified as SVHC according to 57(f) with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment. 

Conclusions on in vitro studies
Please see our extensive response made below to the issues raised by the PC/BPA Group of PlasticsEurope. 

No real evidence from studies
Keiter et al. (2012) and Kang et al. (2002):
These studies did show deviations from controls and therefore effects resulting from exposure with BPA. The endpoints for which there was no deviation from control we described them also and dealt with this in the text of the Support Document.
For instance (Kang et al., 2002): At page 43 we concluded that “Other studies conducted with O.latipes reported no effects on sex ratio. That could be because organisms were not exposed during their sensitive window of development but as adults, or the exposure duration was too short (Shioda and Wakabayashi 2000, Kang et al. 2002, Kashiwada et al. 2002, Tabata et al. 2001, Yamaguchi et al. 2005).” This study also reported effects on testis, which we considered also in our summary.
Or (Keiter et al. 2012): We described this study on page 44 of the report in more detail and the results were included in table 13. Effects of BPA reported in this study and included in the Support Document were e.g. VTG induction in F1 generation at 400 µg/L and in F2 at 10 µg/L, no effects on growth in F1 but in F2 generation at 400 µg/L.

No hard evidence for effects in environment
Please refer to our response made above to the comments received by the Sensopolis Ltd,
Company. 

Degradation
We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). Please also refer to the responses given there.
We have revised the text accordingly and also added more information on the test methods and conditions in the tables.

Pseudo-persistence
We removed the term “pseudo-persistence” in the document and adapted the paragraph in chapter 3.3. 	
		-		
4855
2017/10/19	ChemSec,
International NGO,
Sweden	ChemSec supports the identification of Bisphenol A as an endocrine disrupting chemical for the environment, thereby being of equivalent level of concern. The evidence presented in the dossier is well presented and show ED mediated effects of BPA in a wide range of organisms, implicating probable serious effects on populations and ecosystems.	We appreciate your support.
	
4874
2017/10/20	Norway,
Member State	We would like to thank Germany for the proposal and the comprehensive Annex XV document on the endocrine effects of Bisphenol A (BPA) in the environment.  We support the conclusion that BPA should be identified as a substance of very high concern in accordance with Article 57(f) of REACH. This is  because BPA is a substance with endocrine disrupting properties for the environment for which there is scientific evidence of probable serious effects to the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 REACH. Please see the attachement for more details.	We appreciate your support.

Environmental Monitoring data
We included the results for BPA in arctic biota and herring and the respective references in chapter 3.3 and Annex I. This evidence for arctic biota is indeed important and interesting, and was not included in the data compiled by JRC in 2016.	
		Please see attachment embedded in table 1 of Part I  
4874_Comments SVHC BPA ED ENV.docx		
4880
2017/10/20	PC/BPA Group of PlasticsEurope cosigned by BPA REACH Consortium and Epoxy Resins Committee of PlasticsEurope ,
Industry or trade association,
Belgium	The PC/BPA Group of PlasticsEurope welcomes the opportunity to comment on the Annex XV dossier proposing to identify Bisphenol A (BPA) as a Substance of Very High Concern (SVHC) in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) based on alleged endocrine disrupting properties for the environment. The PC/BPA Group opposes the Annex XV dossier on the basis of the non-conclusive scientific evidence and the weakness in the scientific assessment brought forward in the dossier and because the legal requirements for SVHC identification pursuant to Article 57(f) of REACH are not respected.
In addition to our more targeted feedback on the Annex XV dossier in the sections below, we want to make a more general remark at the outset about the requirements for data quality used for regulatory purposes.
REACH and other EU legislation provides clear guidelines and requirements for the validity and quality of studies to be used for regulatory purposes. We note with concern that these requirements have not been followed in the Annex XV dossier, which raises questions about the basis on which conclusions are drawn by the authorities.
The precondition for any data evaluation as well as for a weight of evidence approach is a robust and transparent data reliability assessment which is based on defined and clear criteria.
The REACH Regulation defines the criteria which have to be applied to identify reliable data for any regulatory activity under REACH. These are outlined in Article 13(3) and Annex XI of the REACH Regulation. We have listed below the key requirements but provide further details in the attached document titled “Reliability assessment”.
In accordance with REACH, it is necessary to evaluate the overall adequacy of the data for the respective regulatory purpose. The reliability assessment has to evaluate the inherent data reliability which includes that “preferably standardized methodology” was used (listed in (EC) No 440/2008 and Directive 67/548/EEC, Annex V”), there is sufficient documentation (GLP ), there must be “evidence of the clarity and plausibility of the findings”, and the data reliability should be based on the Klimisch code scoring system.
Moreover, the REACH Regulation clearly defines thresholds for the use of non-standard (exploratory) data.
An exploratory study typically is based on a method that has been developed or adapted for just this purpose. As such little or no information is available on confounding factors in the assessment or on the actual relevance of the finding in an overall context. REACH acknowledges that in order to generate reliable, reproducible and relevant information, a method needs validation by multiple laboratories and proof that all the laboratories produce the same result on the same substances for all endpoints that are assessed. Only after such a validation, a method is approved for regulatory use).
The use of non-standard exploratory data is only adequate if the preconditions of Article 13(3) of REACH are met, which means that the criteria mentioned above apply in general. Additionally, the data must be adequate for the regulatory purpose, adequate and reliable key parameters of the corresponding standard test methods have to be covered, exposure duration is at least as long as the standard method and “adequate and reliable documentation of the study is provided”.
Beyond these general data quality criteria, we consider that the substance properties of BPA (e.g. ready biodegradability; for more details please see the attachment “Environmental fate properties”) and the explicit variability of certain chronic test systems under long-term conditions (e.g. snails) necessitate considering additional specific criteria:
- Use of an optimum exposure system to permit maintenance of steady BPA concentrations in long-term studies (preferably static-renewal or flow-through systems)
- Use of  reliable and sensitive analytical procedures to check adherence of measured BPA concentrations to nominal ones
- Use of test systems which are sufficiently replicated to characterize their inherent variability and to determine robust NOECs based on solid statistical considerations.

On the following pages of this document we present 5 key arguments substantiating our position towards part I of the Annex XV dossier, and a further argument regarding part II; each key argument being supported by several sub-arguments (listed A,B, C etc.), as relevant. Further detailed scientific comments are provided in the 10 Annexes attached to this submission, and referenced inside this document.

Comments on Part I of the Annex XV dossier “Identity of the substance and proposed SVHC property”
1. THE ARGUMENTATION AND ANALYSIS PUT FORWARD BY THE RAPPORTEUR IS NOT BASED ON AN APPROPRIATE WEIGHT OF EVIDENCE APPROACH
In several chapters of the Annex XV dossier it is emphasized that a weight of evidence approach is important in the process of an SVHC assessment. Chapter 6.3 “Assessment under Article 57(f)” underlines that a weight of evidence approach is not only required but is also employed to prove fulfilment of the requirements of Article 57(f) of REACH. However, we note with concern that the argumentation and analysis put forward by the rapporteur in this Annex XV dossier is not based on an appropriate weight of evidence approach because of an inadequate assessment of studies’ reliability and inappropriate selection of studies used in the effect assessment.
A. The Annex XV dossier follows an apparently inconsistent and selective approach in assessing the relative weight of specific scientific studies. It uses two scoring systems without making transparent the underlying reasoning for the individual categorisations. This leads to an argumentation being based on studies with major shortcomings while not appropriately taking into account high ranking valid studies, overall resulting in incorrect conclusions.
The assessment of reliability of the scientific evidence provided in the Annex XV dossier is scientifically inadequate and does not meet regulatory requirements. The dossier includes a non-transparent use of two scoring systems (adapted Klimisch and CRED) to assign reliability and validity to particular studies. The reliability assessment of several in vivo studies, which are critical for the Annex XV dossier conclusion, contradicts former assessments under EU RAR without providing appropriate explanations or justifications. This has resulted in an argumentation based on studies which have major shortcomings, whereas high ranking, valid study results are not at all or not appropriately taken into account. The inadequate assessment of the reliability and validity of the studies used in the dossier and the inadequate application of a weight of evidence approach for all information gathered, has resulted in incorrect conclusions.
In the attached document, titled “Reliability assessment”, we further elaborate on concerns regarding the reliability assessment and the impact on the overall quality of the Annex XV dossier. We anticipate detailed feedback from the rapporteur on these fundamental comments.

B. The selection of studies by the rapporteur for the effect assessment is considered inappropriate. BPA is a data-rich substance with many high quality chronic studies for all major taxonomic groups. The Annex XV dossier, however, rates some of these highest quality studies as low, or even does not take them into account at all, without providing any transparency why this has been done. Instead, mainly exploratory studies, with major shortcomings, have been used in the Annex XV dossier.
The current database (Oct 2017) of highest quality chronic studies with comprises 14 studies with freshwater species, 3 studies with sediment species, 3 studies with soil species, and 3 studies with marine species (please see our attachment titled “High Quality Chronic Studies Bisphenol A”). All long-term key toxicity studies for the aquatic compartment that included the measurement of apical endpoints related to population relevant effects on survival, growth, development and reproduction, are shown in the attached document titled “High quality chronic studies”.  This rich and valid dataset should be the basis of any regulatory action addressing BPA.
However, the Annex XV dossier does not rely on this dataset. Some of the studies listed in the attached table are not discussed at all (Lee, 2010: Americamysis bahia; Picard, 2010a: Leptocheirus plumulosus; Picard, 2010b: Chironomus riparius; Picard, 2010c: Lumbriculus variegatus), while others are disqualified on the basis of low Klimisch scores (Pimephales promelas: Rhodes et al. 2008 and Mihaich et al. 2012) without any details given on the basis of this assessment.
Only high quality studies (Klimisch score 1 or 2) should be used for regulatory purposes. Although such Klimisch 1 or 2 studies are available for freshwater and sediment, studies with major deficiencies were used by the rapporteur to assess these endpoints:
For both freshwater and sediment compartments, high quality studies are available. These high quality studies, considered Klimisch score 1, have been performed according to the state of science and are therefore suitable for regulatory purposes. However, we note with concern that results of these studies have not been taken into account in the Annex XV dossier. The dossier either disqualifies them without appropriate explanation or neglects them entirely. Instead, exploratory studies have been used while major deficiencies should preclude their use in a regulatory context. The most prominent examples are shortcomings of snail studies (for freshwater compartment) and oligochaetes studies (for sediment compartment) which are discussed in further detail in the attached document, titled “Invertebrate effect assessment”.
For example, for the freshwater compartment, several papers of Oehlmann and co-workers (e.g. Oehlmann et al. 2006) are discussed in the Annex XV dossier as providing evidence for extremely high sensitivity of prosobranch molluscs for BPA in the lower µg/L range.  However, thorough reviews of the Oehlmann et al. (2006) study with Marisa cornuarietis revealed significant weaknesses in the study design and in the details provided in the study. Criticisms concerning these studies were identified in the EU Risk Assessment (EC, 2010) and published in peer reviewed literature (Dietrich et al., 2006). Similar comments apply to the snail studies by Duft et al. (2003) and Jobling et al. (2004).
In view of many open questions related to earlier snail studies regarding BPA, EU Member States requested a snail research program with the subtropical prosobranch snail Marisa cornuarietis to address knowledge gaps in husbandry and basic biology of this species, as well as deficiencies in design and statistical assessment of earlier toxicity studies. The definitive study of this effort (Forbes et al., 2007, 2008; Warbritton et al., 2007a and 2007b), showed no effects of BPA on adult fecundity, egg hatchability or time to hatch. A slight, but significant decrease in female growth at 640 μg/L was observed as the only relevant effect.
Furthermore, during the OECD validation process of what became test guideline 242 (Potamopyrgus antipodarum Reproduction Test; adopted July 2016) it became apparent that the test system could not be validated for “superfeminization” effects which had been described by Oehlmann and other authors in earlier publications (Oehlmann et al. 2000; Oehlmann et al. 2006). This conclusion of the OECD snail experts casts strong doubts on the validity of studies reporting on reproduction-enhancing effects of BPA in prosobranch molluscs.
As shown in detail in document “Invertebrate effect assessment” the Oehlmann studies on BPA in snails are not sufficiently robust to be used for regulatory purposes.
For the sediment compartment, examples of inappropriate selection of studies relate to Lumbriculus variegatus: A reproduction test method was validated by the OECD (Test guideline 225). However, the results of the high-quality study on BPA using this method (Picard 2010c; Klimisch scoring: 1) are not even mentioned in the Annex XV dossier. Instead, the results of a non-standard, exploratory study in an “artificial indoor stream” (Ladewig 2006), have been taken into account in the dossier. The purpose of this study was to introduce a new technical approach and not to provide robust data for risk assessment. Notably, the high quality study indicates a NOEC that is four orders of magnitude higher than that of the exploratory study from Ladewig (Annex XV dossier section 5.13.3, page 111).
In the attached document, titled “Invertebrate effect assessment”, we provide a more detailed assessment of the studies and their shortcomings.
Studies selected in the Annex XV dossier to support fundamental conclusions have multiple and severe shortcomings (which would indicate a Klimisch 3 or 4 rating).  However, those studies are rated as Klimisch 1 or 2 by the rapporteur without providing an explanation.  These studies are repeatedly referenced in the dossier, while other, high quality studies, which cover similar endpoints but found no effects, are neglected or ranked low:
Chapter 5.5.1 of the Annex XV dossier details the principles reported as being the basis for the Annex XV dossier and the ED identification. Frequently, the careful selection and use of reliable data is stressed in the dossier as basis to ensure a transparent and comprehensive assessment. However, various chapters use weak data to support fundamental conclusions which are presented in a definite manner.
Despite the rich database of high quality studies, in many sections on vertebrates the Annex XV dossier is only based on very few, often just two, studies (chapters 5.5.2.1, 5.5.2.2, 5.8.1, 5.8.2 of the Annex XV dossier). Furthermore, the selected studies often reveal severe shortcomings, but despite these shortcomings, they are still ranked high (Klimisch 1 or 2) by the rapporteur. It is concerning to note that this weak evidence is repeatedly used to draw fundamental conclusions.
For example, the data by Bowmer and Gimeno (2001) in chapter 5.5.2.1 is only supported by an extended abstract. No report or publication is available. Yet, the evidence was assessed as a reliability 2. An unbiased assessment would suggest a reliability of 4 “documentation insufficient”. The only other study in this chapter, Mandich et al. (2007), is even rated as reliability 1, although it is an exploratory study with several shortcomings. Again, an unbiased assessment would suggest a reliability of 3 “not reliable”. Despite the fact that for lack of documentation or quality both studies provide weak evidence only the rapporteur concluded chapter 5.5.2.1 “effects on carp (Cyprinus carpio) related to an oestrogen/androgen MOA” as follows:
“These results lead to a strong evidence for in vivo oestrogenic activity of BPA in the fish species Cyprinus carpio” (emphasis added).
Another example of the use of poor quality data to suggest strong evidence relates to the amphibian assessment in chapter 5.7.2. Despite acknowledged availability of limited data of poor quality, the dossier again suggests strong evidence overstating the underlying data:
“This results … is strong evidence for a thyroid disrupting mode of action of BPA (anti-thyroidal) and a plausible biological link between the mode of action and the adverse effects can be established” (emphasis added).
Yet another example is the study of Lahnsteiner et al. (2005) on brown trout, which apparently is perceived as a key study selected by the rapporteur. Again, this study has severe shortcomings, e.g. poor quality of test fish, poor replication, lack of analytical confirmation, novel endpoints without validation, etc. and has a low reliability. Already the EU Risk Assessment Report from 2010 (EU RAR 2010) concluded that this study was inadequate for regulatory purpose. Still the study is referenced in the Annex XV dossier, while studies on the same species, such as Bjerregaard et al. (2008), are again neglected.
Also further studies on fish (e.g. Chen et al. (2015) and Mandich et al. (2007)) used in the Annex XV dossier suffer from severe limitations like poor replication, lack of control, analytical inconsistencies, insufficient documentation. Thus they are not suitable for regulatory purposes.
Furthermore, the Annex XV dossier fails to evaluate consistency and plausibility of reported effects. Whenever there is evidence that suggests an effect on a specific endpoint and there is contradicting evidence that there is no such effect (same endpoint, at comparable conditions, and at similar test concentrations, etc.), the regulation requires a careful assessment of the contradictory evidence. However such an assessment is lacking in the Annex XV dossier. A prominent example for such an omission of an assessment of contradictory results is the sex ratio in Medaka as described in chapter 5.5.2.3 in the Annex XV dossier.
In the attached document, titled “Vertebrate effect assessment”, we provide a more detailed assessment of the studies and their shortcomings.
None of the in vitro studies that are emphasised in the Annex XV dossier as basis for the estrogen and androgen receptor pathway rely on validated OECD guidelines or validated US EPA protocol – even though such guidelines and protocols are available:
None of the in vitro studies in the Annex XV dossier are based on a validated OECD test guideline nor a validated US EPA protocol even though such guidelines for the ER pathway as well as for the AR agonist pathway are available.
For some endpoints, i.e. on androgenic activity and on thyroid hormone like activity, only a very limited number of studies is presented in the Annex XV dossier. In addition, several quoted studies, i.e. on “transcriptional activation or reporter genes under control of the ER, AR and TR…” but also on “MCF-7 cell proliferation” are used to draw conclusions for BPA while these studies did not present any data on BPA.
In the attached document, titled “In vitro studies”, we provide a more detailed assessment of the studies and their shortcomings.
2. THE ANNEX XV DOSSIER FAILS TO PROVIDE THE SCIENTIFIC EVIDENCE FOR AN IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN AS REQUIRED IN ACCORDANCE WITH ARTICLE 57(f) OF REACH
A. The Annex XV dossier lacks a scientifically sound proof of relevant endocrine activity and mode of action in the selection of in vitro studies and their assessment.
The Annex XV dossier lacks a scientifically sound proof of relevant endocrine activity and mode of action (MoA) in the presented in vitro studies. Based on sound science and high quality measures, there seems no convincing evidence to classify BPA other than having very weak estrogenic activity for environmental taxa. This data is not sufficient for an SVHC identification under Article 57(f).  All evidence for other endocrine-mediated pathways is either extremely weak or highly speculative – and is not underpinned by valid test results. For vertebrates, the suggested induction of cross talk by BPA among various signalling pathways and the respective suggestion of in vivo relevance of the observed in vitro findings is very speculative (Annex XV dossier, section 5.4.4).
For invertebrates (molluscs), available valid in vitro data do not support a conclusion of an endocrine mode of action for BPA. Firstly, there is an apparent lack of knowledge about the endocrine system of most invertebrate groups. Secondly, the interpretation of the study results of exploratory studies is highly speculative. This does not allow drawing far-reaching conclusions on potential endocrine activity of BPA.
Throughout the document, relative receptor binding affinities (RBA) and relative estrogenic potency (REP) are often reported by a factor 100 too high – and thus led to erroneous conclusions.
Wrong calculations applied to in vitro tests for estrogenic activity resulted in gross overestimation of effects, while corrected calculation annuls these wrongly suggested effects:
Binding to sex steroid binding protein (SSBP) cannot be considered as an in vitro test for binding to the oestrogen receptor (ER): SSBP is a simple transport protein in blood, not a functional receptor. Oestrogen receptors are much more complex proteins that after activation by ligand binding form homodimers that interact with DNA and recruit co-activators resulting in the formation of the basal transcriptional complex. In the context of the study, incorrect figures for relative binding affinities (RBA) and relative estrogenic potencies (REP) were often given. After adequate correction of relative binding affinities (RBA) the statement that BPA showed higher RBA to the human receptor than to fish receptor is no longer valid. With properly corrected REPs it becomes obvious that induction of vitellogenin synthesis in fish and African clawed frog hepatocytes by BPA is very low when compared to estradiol. Based on properly corrected REPs it is also obvious that the relative transcriptional activity of BPA in recombinant yeast (human ER) and vertebrate cell lines (fish ER) compared to estradiol is very low. Except for a single reference (Olsen et al. 2005), only very limited evidence is presented to substantiate a statement that BPA acts like a full agonist in the MCF-7 cell proliferation assay. When applying the properly corrected REP the reported activity of BPA on proliferation in MCF-7 is very weak compared to estradiol (ref.2). For none of these studies a validated OECD test guideline or a validated US EPA protocol was used.
In vitro studies used to assess androgenic activity show inconsistent and unclear results, and do not provide evidence of such BPA-induced effects:
Some of the publications cited (e.g. Kunz & Fent 2006; Schreurs et al. 2005) are used to draw conclusions for BPA while these studies do not present experimental data on BPA. In other studies there was no evidence for AR agonistic activity of BPA. The small number of studies presented provides only limited evidence for weak antagonism of BPA at the AR in vitro (Sohoni & Sumpter 1998; Lee et al. 2003; Ekman et al. 2012; Xu et al. 2005). Information on the assessment of cytotoxicity, which is an important aspect when screening for antagonism, was not sufficiently clarified in these publications. For none of these investigations a validated OECD test guideline or a validated US EPA protocol was used.
Referring to TTR binding to show thyroid hormone-like activity in in vitro tests is inadequate:
Binding to transthyretin receptor (TTR) cannot be considered as an in vitro test for binding to the thyroid receptor (TR): TTR is a simple transport protein in blood, not a functional receptor. Thyroid hormone receptors are much more complex proteins that after activation by ligand binding form heterodimers that interact with DNA and recruit co-activators resulting in the formation of the basal transcriptional complex.
At the very best, these studies provide evidence for a very weak antagonism of BPA at the TR in vitro. However, the data presented are not reliable as the signals were either weakly positive or weakly negative, and thus contradictory. Some of the publications cited did not present experimental data on BPA or presented scientifically unverifiable data.
In the attached document, titled “In vitro studies”, we provide a more detailed assessment of the studies and their shortcomings.
B. High effect levels in many of the reported (vertebrate and invertebrate) studies are not suitable to conclude on a specific, i.e. endocrine, mode of action.
In 2013, ECHA`s ED Advisory Group (ED EAG) clearly expressed that an ED identification must be based on data which report on so-called “primary”, endocrine-mediated, effects (ref.3). This condition strongly challenges the undifferentiated inclusion of many data in the Annex XV dossier.
Testing at elevated concentrations which are in the range of acute toxicity is basically only valid to determine the apical endpoint mortality/survival and the lethal concentration of a substance. Any other effects in the acute toxicity range should not be assigned to a specific MoA which includes endocrine system mechanisms. The physiology of an organism which is exposed to lethal concentrations of a substance is completely out of control. Therefore, it does not provide reliable information on sequences of a specific mode of action like the endocrine system. Endocrine system mediated effects should be assessed differently, if observed at high exposure concentrations i.e. in the range of acute toxicity. In the Annex XV dossier, however, these results were treated the same way as effects detected at sub-lethal concentrations.
Examples for invertebrates are for instance the studies of Jeong (2013), Mu (2005) and Hassold (2009), reporting on gene expression and various developmental abnormalities in Daphnia magna, at sublethal to lethal BPA concentrations. The Annex XV dossier concludes “…Although concentrations are comparatively high for most crustacean species and often close to lethal toxicity (mg/L range) as seen for daphnids, this gives at least indications that effects of BPA also in crustaceans may be endocrine mediated. Furthermore, the effects on reproduction and development may lead to adverse and unpredictable effects on the long-term population development.”
The same applies to the assessment for vertebrates where effects where only reported at high concentrations, i.e. in the range of acute toxicity. Examples are: Yokota et al. (2000), Shioda et al. (2000), Kang et al. (2002), Yagamuchi et al. (2005), and Iwamuro et al. (2003).
In the attached documents, titled “Introduction Effect Assessment”, Invertebrate effect assessment” and “Vertebrate effect assessment” we provide a more detailed assessment of the studies and their shortcomings.
C. Low Acute-to-Chronic-Ratios (ACR) of BPA do not support the occurrence of specific (i.e. endocrine-mediated) modes of action.
In case of specific mode of actions, i.e. endocrine-mediated ones, very high ACRs would be expected (e.g. for natural or synthetic hormones ~ 5,700,000). The comprehensive database of BPA studies does however not suggest that chronic reactions in organisms are far more sensitive than acute toxicity effects on BPA, as expressed by the low ACRs (< 290).
In the attached document, titled “Acute to Chronic Ratio”, we provide a more detailed assessment of this issue.
3. THE ANNEX XV DOSSIER FAILS TO DEMONSTRATE THAT BPA CAUSES PROBABLE SERIOUS EFFECTS TO THE ENVIRONMENT WHICH GIVE RISE TO AN EQUIVALENT LEVEL OF CONCERN AND THEREBY FAILS TO MEET THE CRITERIA FOR SVHC IDENTIFICATION ACCORDING TO ARTICLE 57(f) OF REACH
Article 57(f) of the REACH Regulation specifies the requirements for the identification of substances as SVHC´s “substances - such as those having endocrine disrupting properties … for which there is scientific evidence of probable serious effects to ... 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 basis in accordance with the procedure set out in Article 59” (emphasis added). Therefore, an Annex XV dossier proposing SVHC identification pursuant to Article 57(f) of REACH should meet two requirements: 1) scientific evidence of probable serious effects and 2) an equivalent level of concern. Both of these requirements should be met, whether a substance is identified for its endocrine disrupting properties or for others. We consider that based on the evidence and assessment put forward by the rapporteur, the requirements of Article 57(f) are not met.
A. Based on the steadily improving environmental quality of major European waterways over the last decades, there is no evidence for “probable serious effects” on survival, growth, development, and reproduction of wild-living taxa in the aquatic environment on the long term, due to industrial chemicals with alleged endocrine activity.
We are not aware of any sites in major European streams where single compounds or mixed chemicals of suspected endocrine activity are causing reproductive disorders of natural populations, nor are there any data to this effect put forward in the Annex XV dossier. Quite the contrary, increasing species richness is observed in freshwater and sediment compartments, including those species which are being discussed in the Annex XV dossier as extremely sensitive to oestrogen agonists. Therefore, the real world situation in the environment positively contradicts the suggestions and assumptions made in the Annex XV dossier.
Taking the Central European Rhine River as a “freshwater example”, with its well-documented history of ecosystem development, it becomes obvious that environmental quality, e.g. expressed as species richness or population density of sensitive taxa, has steadily improved over the last decades. Starting from a severely impacted biocoenosis (fish, macroinvertebrates, algae) of the Middle and Lower Rhine in the late 70s of the last century (with roughly 30 macrobenthic species and less than 30 fish species), the regularly published reports of German state and federal agencies (so-called “Gewässergüteberichte”, e.g. LUA 1997) clearly document ecological progress as reflected by increased species numbers of all relevant taxonomic groups, including sensitive key species of the ecosystem.
On their webpage (ref.3), the Commission for the Protection of the Rhine (ICPR) recently pointed out that “The last biological inventories showed that many species of fish as well as invertebrate fauna (including snails, insect larvae, and mussels) that were regarded as extinct in the Rhine have returned.” In terms of more quantitative numbers, experts of the German Federal Institute of Hydrology found more than 500 species from all major macrobenthic groups in the Rhine River (ICPR 2015a (ref.4)). The situation for the Elbe River, and the development of its fauna over time, is comparable to the Rhine River, and equally well documented. Even species classified in this report as highly susceptible to BPA are meanwhile well-established members of the aquatic communities (e.g. Potamopyrgus antipodarum (ref.5); many other Prosobranch molluscs, Chironomid midges and many other insect species are abundant).

In the attached document, titled “Assessment environmental relevance”, we provide a more detailed assessment.
B. Contrary to the conclusion of the rapporteur, a safe threshold (PNEC) for BPA can indeed be derived – based on the most sensitive chronic endpoints of key species from all major taxonomic groups derived from valid high quality studies. On that basis, a probabilistic approach for PNEC derivation was agreed by all EU Member States in the EU RAR (2010).
More details of the database used, and the conclusions drawn by the Existing Chemicals Group (EU RAR 2010) and in the CSR (2015) are provided in the attached document titled “Introduction Effect Assessment”.
C. Effect levels in many of the studies reported in the Annex XV dossier, including studies regarded as valid also in the EU RAR (2010), are significantly higher than actually detected levels of BPA in European environment which makes the relevance of such data in this SVHC ED assessment questionable.
When concluding on the “evidence of probable serious effects” the realistically foreseeable exposure concentration in the European environment should be taken into account. During the recent Review of the Priority Substances under the Water Framework Directive (2000/60/EC), the 95th percentile of BPA in EU surface water was derived based on EU wide monitoring data. The 95th percentile BPA concentration was calculated as 0.32 µg/L. Comparing this rather low conservative real world exposure concentration with effect levels in many of the data used in the Annex XV dossier – or more appropriately with derived PNECs based on valid data (i.e. 18 µg/L for freshwater in the CSR) – questions whether probable serious effects on environment occur. Given the use of the substance over extended period of time the dossier should be providing evidence of serious effects in the environment related to BPA exposure as required to fulfil the preconditions of an equivalent level of concern as set out in Article 57(f) of REACH.
D. BPA as an alleged endocrine disrupting substance for the environment does not meet the conditions of Article 57(f) of REACH in terms of demonstrating an “equivalent level of concern” to other substances identified under Article 57(a)-(e).
Article 57(f) of REACH covers all other substances – such as those having endocrine disrupting properties - which do not fulfil any of the criteria listed in points 57(a)-(e),  but “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 basis in accordance with the procedure set out in Article 59” (emphasis added).
The requirement of demonstrating an equivalent level of concern as the substances listed in points (a) to (e) for these “other” substances - such as those having endocrine disrupting properties – highlights that endocrine disrupting properties are not automatically considered as being of “equivalent level of concern”. If this was not so explicitly stated, it would have been sufficient to provide in Article 57(f), that substances with endocrine disrupting effect qualify for being identified as SVHCs under 57(f) without any further conditions, such as scientific evidence of probable serious effects to human health or the environment, equivalent to those of CMR, PBT or vPvB substances or effects.
Article 57(f) of REACH does not lay down any criteria, nor provide any clarification with regard to the nature of the concerns that may be taken into consideration for the purposes of identifying a substance other than CMR, PBT or vPvB, including substances with endocrine disrupting properties.
The European Court of Justice has however held (ref.6)  that in the wording of Article 57(f) of REACH, “the scope of that provision encompasses the possibility of taking into consideration, for the purposes of comparison, material going beyond merely the hazards arising from the intrinsic properties of the substances concerned.”
For any substance falling outside of the CMR, PBT or vPvB hazard categories (specifically identified by the legislature as being of very high concern), the identification as SVHC under Article 57(f) of REACH, on account of a level of concern equivalent to those of CMR, PBT or vPvB substances, also involves ensuring considerations related to the fact that authorisation is necessary in order to control the risks arising from the use of that substance in an appropriate fashion. Such a decision requires a range of factors to be taken into account, going beyond the technical exercise of categorizing effects or intrinsic properties of a substance.
The Court further held that, by providing that substances may be identified as SVHCs, on a case-by-case basis, if their serious effects on human health give rise to ‘an equivalent level of concern’ to those of CMR substances, Article 57(f) of REACH does not prohibit taking into consideration data other than those relating to the hazards arising from the intrinsic properties of the substances concerned (ref.7).
In this context, the very limited environmental exposure to BPA, which is mainly used as an intermediate and is being transformed into other substances, is a factor which needs to be considered when judging the relevance of an “equivalent level of concern” of BPA to the environment compared to PBT and vPvB substances of very high concern, which are assumed to persistently remaining present in the environment.
Another aspect that should be taken into account in this context is the realistically foreseeable exposure concentration in the environment. As addressed in our comments in the following section, comparing rather low conservative real world exposure concentrations with effect levels in many of the data used in the Annex XV dossier - or more appropriately with derived PNECs based on valid data – questions whether any serious effects on the environment do occur. We therefore consider that there is no evidence of probable serious effects in the environment as required to fulfil the conditions of Article 57(f).
The recent assessment as to whether BPA constitutes a priority substance or a priority hazardous substance for the aquatic environment under Directive 2008/105/EC on environmental quality standards in the field of water policy further supports the lack of “equivalent level of concern”. BPA was not deemed to be a priority substance, and achieved a low-ranking as part of the assessment process. Consequently, it appears unjustified to claim “an equivalent level of concern” based on endocrine disrupting properties, when the substance is not even considered a priority substance under another EU regulatory regime.
In summary, the identification of BPA as an SVHC based on its alleged endocrine disrupting properties affecting the environment does not fulfil the conditions of Article 57(f) in terms of demonstrating that the alleged effects are of equivalent level of concern to that of other substances, for instance identified due to their PBT or vPvB properties.

4. THE PROPOSED SVHC IDENTIFICATION IS UNNECESSARY AND DISPROPORTIONATE
A. Because of various existing regulatory measures in the context of REACH, the proposal to identify BPA as an SVHC based on alleged endocrine disrupting properties for the environment does not provide regulatory value and could be considered premature. Also in view of the existing legal framework beyond REACH, the SVHC identification seems an unnecessary and disproportionate regulatory route for addressing any potential concerns about BPA in the environment.
Following the first Annex XV dossier submitted in August 2016, BPA was included in the Candidate List as an SVHC on 12 January 2017. The French authorities submitted a second Annex XV dossier for BPA a few months later. Following the MSC agreement, the Candidate List entry for BPA was updated in July 2017 to also include alleged endocrine disrupting properties for human health.
Confirmed by the German authorities in their Risk Management Option Analysis (RMOA) conclusion document, “the authorisation procedure itself would not address the manufacture of BPA or use of BPA as intermediate” and “the majority of uses is out of scope of authorization” (ref.8). Therefore, if authorisation is not the foreseen regulatory route, an additional SVHC identification of BPA as first step of the authorisation process is considered unnecessary and disproportionate, even more as BPA is already identified as SVHC.
Within the context of REACH, it is further important to note that the use of BPA in thermal paper is already the focus of a targeted restriction which entered into force in January 2017 and will be fully applicable as of 2 January 2020. This restriction is expected to result in further reduced presence of BPA in the environment.
Beyond REACH, it is important to note that a robust regulatory framework exists at EU level in order to deal with potential concerns for the environment. As already addressed in our comments in the previous sections, BPA has recently been thoroughly assessed in the context of the Directive 2008/105/EC on environmental quality standards in the field of water policy. BPA was not deemed to be a priority substance and achieved a low-ranking as part of the assessment process. Considering these existing assessments and recent conclusions in the context of other pieces of legislation, we question the regulatory added value of the proposed SVHC identification.
B. Based on the legal interpretation of the relevant REACH provisions and relevant case law, a substance should not be identified as an SVHC under Article 57(f) when it has already been designated as SVHC under that provision.
Article 57 of REACH provides different criteria (listed in entries from (a) to (f)) for the purpose of identifying substances that may be included in the Candidate List (and eventually in Annex XIV of REACH as substances subject to authorization). Article 57(a) to (c) cover substances meeting the criteria for classification in the hazard classes carcinogenicity, mutagenicity or reproductive toxicity (“CMR”) category 1A or 1B, in accordance with sections 3.5 to 3.7 of Annex I to Regulation No 1272/2008. Article 57(d) and (e) cover substances which are persistent, bioaccumulative and toxic (“PBT”) and those which are very persistent and very bioaccumulative (“vPvB”), in accordance with the criteria set out in Annex XIII to REACH.
Primarily, that Article 57(f) of REACH targets specifically all other substances which do not fulfil any of the criteria under Article 57(a) to (e). Only substances that do not fall within the CMR, PBT and vPvB hazard categories specifically identified by the legislature as being of very high concern pursuant to Article 57(a) to (e), may be identified as SVHC pursuant to Article 57(f).
As confirmed in a recent Judgement of the Court of Justice of the European Union (“CJEU”), Article 57(f) of REACH targets specifically all other substances which do not fulfil any of the criteria under Article 57(a) to (e) (ref.9). The Court held that “Article 57 provides, at point (f), for an independent mechanism that makes it possible to identify, as being of very high concern, substances which have not already been designated as such under that provision” (emphasis added) (ref.9). The Court therefore held that, where a substance has been already identified as an SVHC pursuant to Article 57(a) to (e), it may not be identified as an SVHC pursuant to Article 57(f).
Further, Article 57(f) covers substances “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 basis in accordance with the procedure set out in Article 59” (emphasis added).
Hence, the provision is designed to capture substances with probable serious effects to either human health or the environment, which give rise to equivalent level of concerns to the other substances identified according to Article 57(a)-(e).
We have already presented arguments above, why the condition of “equivalent level of concern” is not fulfilled for BPA as an alleged endocrine disrupting substance adversely affecting the environment. We further argue, that as BPA has already been proposed by France for being identified as an endocrine disrupting substance adversely affecting human health under Article 57(f), the condition of Article 57(f) in terms of determining other substances with probable serious effects have already been satisfied. Identifying probable serious effects for the environment is not a further requirement, as probable serious effects to human health OR the environment are not listed as cumulative requirements, but two individual endpoints; each of them alone being sufficient to capture a substance as a SVHC, provided the other conditions of Article 57(f) are fulfilled.
We understand from the Risk Management Option Analysis Conclusion Document submitted by Germany, the eMSCA on 13 June 2017 that the eMSCA will consider to propose harmonized classification for BPA as Aquatic Chronic 1 to account for its alleged ecotoxicity and adverse effects to aquatic organisms. The eMSCA acknowledges that its intention with the identification of BPA also as a SVHC for its alleged environmental properties would only “increase the pressure that BPA is to be progressively replaced by suitable alternative substances or technologies.” It is argued that established provisions of the REACH Regulation, such as the identification of substances as SVHC for certain specific properties as determined in Article 57 should not be used without appropriate legal basis.
Therefore, it must be inferred that from a legal interpretation of REACH, BPA may not be identified as an SVHC under Article 57(f) when it has already been identified as an SVHC under Article 57(c).

5. DECISIONS SHOULD BE TAKEN ON THE BASIS OF DATA THAT ARE AVAILABLE AND SPECULATIVE STATEMENTS REGARDING SAFE THRESHOLDS SHOULD BE AVOIDED IN ANNEX XV DOSSIERS
The Annex XV dossier put forward by the rapporteur suggests on page 133 that “it is not possible to derive and quantify a safe level of exposure for BPA”. While the dossier admits that a safe threshold might exist, it argues that on the basis of the available data “it appears not to be possible to derive a safe level in the environment”. These speculative statements are highly concerning and should be avoided in Annex XV dossiers.
The de facto conclusion of “non-threshold” due to “a lack of data” creates a huge stigmatization of a particular substance as it implies that the only route would be for the substance to be non-detectable in the environment, given that any risk could not be adequately controlled. This means that any chemical substance with a “non-threshold conclusion” could be effectively restricted in its entirety without proper valid scientific reasoning. For BPA, this comes despite being one of the most data-rich and most investigated substances ever in the regulatory process, where numerous peer-reviewed long-term studies, covering sensitive time windows and life stages, have shown that there is no risk to the environment.
The approach of the rapporteur is also of concern given that a proper substance specific weight of evidence approach is not applied (as mentioned earlier in this submission). The “non-threshold conclusion” in the dossier is based on the presence of certain studies that suggest a generic “non-threshold conclusion” for alleged EDs. However, the Competent Authority did not weigh these studies accordingly with large scale guideline studies that have assessed BPA’s impact on the environment specifically, and by which, other regulatory processes have long relied (e.g. EUR RAR). This approach, namely asserting a conclusion of scientific uncertainty based on the mere presence of studies that are contradictory and a subjective and general perception of uncertainty around thresholds for EDs, would be a clear departure from the established Risk Management Measure procedures and norms.
Basing speculative conclusions purely on availability not quality of studies is fundamentally flawed. A decision on this point should only be made at the relevant policy level or by the Risk Assessment Committee (if needed). The conclusions of the dossier should be taken on the basis of data that are available. For BPA, numerous peer-reviewed long-term studies, covering sensitive time windows and life stages, have shown that the conclusion of non-threshold is not justified. Moreover, in the REACH Regulation it is clearly stated that “Data generated by any of these methods (ref.10) are per se considered adequate for regulatory use” (emphasis added).
In previous cases on substances other than BPA, the rapporteur has applied similar conclusions of non-threshold, based on a general assessment for alleged EDs. The authorities have, in response to comments questioning this approach made by other Member States, justified the non-threshold conclusion on the basis of the general statement, that “it may be difficult (albeit not impossible) to determine a safe threshold with reasonable certainty for endocrine disruptors, taking into consideration all uncertainties related to EDs” made on a policy level by the European Commission at CARACAL (Doc. CA/25/2014, March 2014). However, It should be noted that in this statement by the Commission, it is stated that it is up to the REACH registrant to demonstrate that a threshold exists, and the ECHA Risk Assessment Committee to examine the validity of the assessment and decide if it does or not, on a case-by-case basis. Therefore, it is not appropriate for, nor the role of, Member States’ Competent Authorities to make generic conclusions on the existence or not of thresholds and applying that systematically to all alleged EDs.

References
1. Directive 2004/10/EC or other international standards recognised as being equivalent by the Commission or the Agency and with the provisions of Directive 86/609/EEC
2. Odum et al. (1998) demonstrated the potentially unpredictable nature of MCF-7 cell lines when used as a screening test for xenobiotic oestrogens. Neal et al. (2017) have recently re-emphasized that the proliferation of MCF-7 cells can occur via either an estrogen-related pathway or a non-estrogen-related mechanism. Therefore, a positive response in an MCF-7 cells assay is not necessarily a reliable indicator of a compound´s estrogenic potential.
3. https://www.iksr.org/en/topics/ecology/plants-and-animals/index.html
4. https://www.iksr.org/uploads/media/227_d_01.pdf
5. So far, population-level impacts on molluscs from exposure to endocrine-active substances have only been demonstrated for a few specific cases in marine environments, e.g.  gastropod population declines following TBT exposure, and subsequent recovery of biocoenosis after chemical ban (Marty et al. 2017; Santillo et al. 2001; )
6. Case C-323/15 P, Polynt SpA v ECHA (see supra), para. 34.
7. Case C-323/15 P, Polynt SpA v ECHA (see supra), para. 40.
8. https://echa.europa.eu/documents/10162/816f026b-e24c-5600-3beb-6696976d5044
9.  Case C-323/15 P, Polynt SpA v ECHA (see supra), para. 36.
10. “The new Test Methods Regulation (Council Regulation (EC) No 440/2008) contains all the test methods previously included in Annex V to Directive 67/548/EEC”

Supporting information – List of Annexes
Please find below the list of documents quoted in this commenting document. These documents can be accessed in the attached zip-file, including two additional documents with comments addressing the topics of Environmental fate and Classification & Labelling:
PlasticsEurope submission-comments-public consultation SVHC ED env_final_2017-10-18: Executive summary of comments
1. Data reliability assessment_2017-10-10: Discussion on the reliability assessment of data used in the Annex XV dossier
2. High quality chronic studies BPA_2017-10-18: High quality chronic studies on Bisphenol A (table)
3. In vitro studies_2017-10-18: Detailed discussion of in vitro studies
4. Introduction effect assessment_2017-10-18: Introduction to the discussion of effect assessment in the Annex XV dossier
5. Invertebrate effect assessment_2017-10-18: Detailed discussion of the invertebrate effect assessment in the Annex XV dossier
6. Vertebrate effect assessment _2017-10-18: Detailed discussion on the vertebrate effect assessment in the Annex XV dossier
7. Acute-to-Chronic Ratio_2017-10-18: Detailed discussion of Acute-to-Chronic Ratio
8. Environmental relevance_2017-10-18 : Detailed discussion of environmental relevance
9. Environmental fate properties_2017-10-18: Detailed discussion of environmental fate properties
10. CLP classification proposal_2017-10-18: Discussion of the CLP classification proposal in the Annex XV dossier	Thank you for the comprehensive and valuable comments. We considered them in the respective sections as appropriate. 

Data quality does not meet requirements
The use of non-standard data certainly also needs to meet the REACH requirements (with respect to key parameters, documentation, exposure duration, replication, etc.). However, further and to some extent other endpoints (addressing for example effects on sex ratio, development/ metamorphosis in amphibians, measurements of VTG or hormone levels, effects on the second generation to name a few) need to be considered during an evaluation of ED effects and may in many cases not be part of the information obtained from standard test protocols or be part of the standard data requirements for ecotoxicity data.
It is also important to consider the substance properties of BPA (e.g. its biodegradability) in the studies by using flow-through or semi-static conditions and not static ones and so on. We assessed the studies reliability according to Klimisch, which also means that not only GLP studies can achieve Klimisch category 1. In some studies, one part is not as statistically robust as the rest of the study and therefore we took this result not into account for the assessment in our report. 

WoE approach/Selection of studies inappropriate 
The studies were selected and evaluated with respect to possible endocrine mechanisms and relevant endpoints. These endpoints may in many cases not be part of the information obtained from standard test protocols which are used for risk assessment purposes to derive PNECs. Hence further studies were considered.
The standard ecotoxicological data you mention is referred to in chapter 5.1 and in Annex 1. In some few cases single studies used for risk assessment purposes or UQN listed by us are not the same as in your list, as we simple come to different conclusions with respect to reliability and relevance of certain studies.
This is also true for the studies evaluated in the RAR. We considered the assessment and studies of the RAR, but also here the focus under the existing substances assessment was a PNEC derivation in a classical risk assessment. It is to be noted that a rating according to Klimisch is not provided in the RAR. 
The present evaluation is done under REACH and an analysis according to 57f with a focus on ED properties.
However, the same reliability criteria according to KLIMISCH were applied. The only difference is that, the relevance of the endpoints with respect to the indications for ED effect were taken into account.

Use of CRED/KLIMISCH (reliability rating) 
We assessed all studies according to Klimisch. Only few studies were additionally assessed with CRED as was indicated for the respective studies. Reasons were to include an additional evaluation of relevance with the CRED criteria. However, the reliability rating according to Klimisch remained. To make it more transparent and clear we decided to fully rely on and refer to the ratings according to Klimisch for all studies. The respective paragraphs were adapted accordingly.

Database with highest quality chronic studies
We appreciate the database and the thorough assessment of the ecotoxicological studies. However, the selection of studies and their assessment aim towards a PNEC derivation and use of the results for an SSD. Data therefore comprises standard ecotoxicological studies to determine the acute and long-term ecotoxicity for risk assessment purposes. Also in your database, several studies – which we think are of importance to be considered - are missing with respect to the ecotoxicological standard information. Furthermore, the focus of the present evaluation and document was an evaluation of the possible endocrine properties of Bisphenol A with respect to the environment. Relevant and reliable studies and consideration of endpoints with this respect are to a large extent missing in the database you refer to. 

Discussion of some studies are missing  
With respect to the invertebrate studies we added the study of Staples at al 2016 mentioned in your comments for chironomids to complete the picture on developmental effects for this species as this study is publicly available. Other studies are rather part of the standard ecotoxicological assessment (Section 5.1). 

Shortcomings of snail and oligochaete studies
We appreciate and considered your remarks with respect to the Oehlmann and Forbes studies as well as the Bannister Study and added some more explanations and references (Dietrich et al 2006 as well as the response of Oehlmann et al. 2006). We also adapted the sections after consideration of the other comments. Please refer to the comments made by DK and FR.

No scientific evidence for SVHC in fish (Detailed discussion on the vertebrate effect assessment in the Annex XV dossier)
Thank you for your comment on the misleading description for Shioda and Wakabayashi (2000). We corrected this in the report.
We studied your comments concerning the “assessment on presumed ED properties of BPA for vertebrates”. We used studies also used in previous risk assessments and which were considered reliable from all member states as Bowmer and Gimeno (2001) and Mandich et al. (2007). We reflected your comments on our wording for the conclusions and in some cases adapted them.
Concerning the “biased dataset”, we described in the report, e.g. why we did not use a result from one study or the fact that no effect occurred, what could be because adult fish was exposed and therefore the sensitive window was not met. 
Your comment on “limited evidence of data with only one test concentration”: We concluded that also these studies with only one test concentration are reliable as they were conducted according to basic scientific principles (control, replicates and so on).
Concerning your remarks on the reliability of some studies with fish and amphibians as Lahnsteiner et al. (2005) and Chen et al. (2015) we reflected the scientific critiques in the report and added more details there.
Concerning your comments on some formal errors: as you know the oestrogen agonistic adverse effects cannot be fully distinguished from the androgenic antagonistic adverse effects despite they result from different mode of actions. Therefore, we chose the headlines this way we did. Thank you for the comments on inconsistent reliabilities and on literature quotation. We checked and corrected this in the report when necessary.

In vitro studies
We appreciate your detailed comments on the presented in vitro data.
We agree that the studies mentioned in your response, which do not cite any effects of BPA, are erroneously cited within the Support Document due to a bug in our internal literature database. These studies are removed from the Support Document and we appreciate your comment regarding this issue.
Furthermore, we agree that some of the reported RBA values are not correct. We now recalculated and corrected the values to have comparable units for the effect concentrations.
It is true that the in vitro studies cited within the Support Document were not performed according to an OECD Guideline, but are high quality academic studies according to our quality assessment described within the Support Document.
We agree that in vitro data generally are not able to provide sufficient evidence to identify a substance as an endocrine disruptor according to the WHO/IPCS definition. That is why the identification of Bisphenol A as an endocrine disruptor in the environment is based on its oestrogenic adverse effects in fish. The skewed sex ratio towards females observed in the studies cited within the Support Document is an effect that is both diagnostic for an endocrine MoA and an adverse effect. The in vitro data presented are used in a weight of evidence approach as supporting information on our conclusion on the available in vivo data. By doing so, we are well aware of the shortcomings of some of the in vitro data presented (e.g. missing control with E2-antagonist in the MCF-7 assays, results from the androgen activity assays and the still limited knowledge on how to interpret results from invertebrate in vitro data). However, we think that the general picture drawn by the in vitro data available fits very well into the conclusions drawn from the observed in vivo effects (e.g. weak anti-androgenic effects observed in vitro support the occurrence of apical oestrogenic effects like a sex ratio skewed to females). Additionally, as stated in the Support Document, issues of hazard characterisation like potency should not be considered during ED identification. Thus, also weak (compared to E2 controls) in vitro effects must be considered here.
Despite these general remarks, we agree with your specific statement made about the interpretation of the TTR and SSBP assays. These tests cannot provide data on the receptor protein affinity of the compounds tested but show their binding affinity to specific hormone transport proteins. The results obtained from these assays hence point to a possible interference of BPA with the HPG and HPT axis upstream of the respective receptor proteins. The respective paragraphs of the Support Document were revised accordingly.    

No scientific evidence for ED in molluscs, etc.
It is clear that the available data of course is in some cases fragmentary, we summarized the available evidence. We adapted chapter 6. The evidence for an estrogen MoA and related effects in fish as well as the thyroidal effects in amphibians are however, clearly demonstrated. Please see other comments (e.g. FR, DK, UK).

High effect levels not suitable to conclude on a ED MoA 
In some cases effects were indeed first shown at high test concentrations. Nevertheless, these are studies were plausible and provide explanations for a plausible underlying mode of action. This was discussed and made clear in the respective sections. However, further studies also pointed towards low effect concentrations and adverse effects which cannot be neglected.   

Low ACR for BPA
We principally think that the ACR should only be used with great care for identifying endocrine mediated effects. Firstly, one has carefully to consider the underlying mode of endocrine action and subsequently the selection of appropriate endpoints and species from the chronic assays that are sensitive to this MoA. Transferring this to the BPA case, for example taking the concentration of 0.372 µg/L where Chen et al. 2015 detected a significantly skewed sex ratio towards females as a chronic effect in zebrafish and comparing this concentration with the acute EC50 of around 10 mg/L as it is reported for zebrafish embryos and larvae, one ends up with an ACR around 100,000.
Secondly, the ACR in our point of view is more a question of potency that should not be considered during ED identification. Crucial here is to show that ED mediated effects do not occur in parallel with systemic toxic effects. This is the case for BPA within the presented key studies in our Support Document. 
 
No evidence for serious effects in the ENV
Please refer to our response made above to the comments received by the Sensopolis Ltd,
Company. 

A safe threshold may be derived
We agree that it might be possible to determine no effect concentrations in individuals or single species. But we think that at present the existing uncertainties related to environmentally relevant ED substances do not allow for deriving a safe concentration level in the environment.

Effects are above conc. in environment
Actually, some studies point towards effects below 10 and even below 1 µg/L. This is also the range were BPA was measured in the environment. Further it needs to be considered that organisms may be continuously exposed towards low concentrations due to the ubiquitous and continuous occurrence of BPA in e.g. surface waters. 
The currently derived EQS is 0.32 µg/L (and still might not be protective in some species). Effects were in several cases demonstrated above the actual PNEC in the CSR of 18 µg/L PNEC.

EloC not met and 57f not applicable
The assessment whether or not an identified ED substance is, from an environmental point of view, of equivalent level of concern compared to PBT/vPvB substances should in our opinion reflect the following issues: Irreversibility of effects in wildlife species, delay between exposure and effects, sensitive windows of exposure in which even transient short term exposure can lead to irreversible effects, uncertainties arising from the currently restricted knowledge about species transferability of effect concentrations and endocrine modes of action. These aspects are all addressed and discussed for the specific case of BPA within the Support Document. Based on this discussion we come to the conclusion that BPA is of equivalent concern based on its endocrine disrupting adverse effects in wildlife species and hence the requirements of Art. 57 (f) are fulfilled.  

Appropriateness
The identification of BPA as SVHC is the only option to come to an EU-wide agreement on its endocrine disrupting properties in the environment. Thus, we see candidate listing of BPA as a specific tool to clarify this concern on an EU-wide basis and hence, SVHC identification of BPA is appropriate. 

Further SVHC identification legally not possible
Since SVHC identification of BPA as an ED in the environment will complete the SVHC identification of BPA according to Art. 57 (f) of the REACH regulation by adding the environment as a subject to protection, we do not see any non-compliance with the law here.

Decision-making process
SVHC identification is hazard-based measure in which the ECHA´s Risk Assessment Committee (RAC) and Socio-Economic Committee (SEAC) are not involved. RAC and SEAC will be involved in case that an application for authorisation is submitted to ECHA. During the authorisation process, it is up to the registrant to demonstrate that a threshold for the ED substance under question exists.  

Degradation
We received comments with this respect from UK, FIN, SE, NL,  Plastics Europe, Sensopolis, Berceo Chemicals). Please also refer to the responses given there.
We have revised the text accordingly and also added more information on the test methods and conditions in the tables.

	
		Please see attachment embedded in table 1 of Part I  
4880_Attachments PCBPA Group comments Annex XV dossier.zip		
4892
2017/10/20	Individual,
Switzerland	Please see attachment embedded in table 1 of Part I  
4892_Huntsman_Release to ENV_Toilet_paper_Oct_2017.pdf	Thanks for your information on releases from toilet paper. We will consider this with respect to the further risk management options.	
4893
2017/10/20	Sweden,
Member State	We thank the German CA for submitting a dossier on Bisphenol A (BPA) aimed at the inclusion on the candidate list as a SVHC based on its endocrine disrupting properties.

We find that BPA fulfills the WHO/IPCS definition of an endocrine disruptor, and that the substance can be considered an endocrine disruptor for the environment. The Swedish CA agrees that there is scientific evidence that BPA gives rise to an equivalent level of concern and should be identified as an SVHC according to article 57(f) in REACH.

We would for clarification and an exchange of views also like to comment on the wording in chapter 4 (Human health hazard assessment). The first sentence under this headline says: ‘Not relevant for the identification of the substance as SVHC… with respect to the environment’. We assume that this wording has been included based on the suggestion in the template for the Annex XV dossier that this phrase may be used “if this section is not relevant”.

Although we agree that the human health assessment as such is not relevant, we believe that the database used for that assessment in principle is relevant for mammals in the environment, and could be useful also for the identification with respect to the environment. In this case, however, the data available for other environmental taxa are sufficient for the identification as ED. Therefore, we see no need at this point in time to request inclusion of further data from that database in the Annex XV dossier, although they could potentially have supported an addition of mammals to the groups of organisms for which there are data warranting identification of BPA as an endocrine disrupter in the environment. Such an assessment and conclusion was for example included in the MSC agreement on DEHP as ED in the environment https://www.echa.europa.eu/documents/10162/ad79f939-cd8e-4eab-8fee-59288fecbf00.

Finally, based on the SVHC identification for BPA as ED for health and the MSC agreement on DEHP we suggest that you consider a different wording in Chapter 4 to explain why the human health database on ED properties of BPA has not been used in this Annex XV dossier.

Environmental fate properties
The conclusion on the ready degradability of BPA needs to be changed from not ready to ready. Among the different ready tests (pp 17-20 and 166-167) there is at least one ready test that is reliable, with non-adapted inoculum, which shows that BPA is readily biodegradable. Therefore, because of the stringency of the test parameters in TG 301, a positive result means that a substance should be considered readily biodegradable (despite negative results in other ready tests).	We appreciate your support.

Human health/mammalian data 
Comments in this respect were received from Austria, Denmark, as well as France and generally supported from Sweden.
It is correct, that the mammalian data is important to be considered also with respect to the environment. We added a summary of the conclusions from the support document for SVHC identification with respect to human health in chapter 4. 
We also explicitly referred to the relevance of this data to wildlife mammals and non-mammalian vertebrates in chapter 6.3.1 and 6.3.3. 
The present dossier focuses on the evaluation of the available ecotoxicological studies for fish, amphibians and invertebrates mainly in the aquatic environment. A thorough assessment of mammalian data from the human health data base is not provided. – And cannot be achieved in the short time frame set for the dossier submitter responding to the comments.  

Environmental fate properties/ Degradation
Thank you for the comment. 
We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). Please also refer to the responses given there.
We adapted the conclusion on ready degradability. We have revised the text accordingly and also added more information on the test methods and conditions in the tables.

	
		-		
4906
2017/10/20	United Kingdom,
Member State	• We thank the German CA for a very clear and well-structured report. We agree that there is ample evidence of effects on the endocrine system in fish and amphibians, which in turn lead to adverse population-relevant effects. However, we believe that the concentrations at which these occur in reliable standard tests are an important consideration about whether BPA should be considered to be a “substance of equivalent concern”.

• We do not agree with the dossier’s conclusion that BPA is “not generally readily degraded in the environment”. We think this is an important point, because of decisions about what constitutes an equivalent level of concern in a hazard context under REACH. Further detailed comments are provided below.

• Several of the aquatic toxicity studies were addressed under previous evaluations performed by the UK on behalf of the EU. Important drawbacks were identified for some (e.g. Sumpter et al., 2001; Levy et al., 2004; Lahnsteiner et al., 2005), and we think this information should be included in the dossier since it affects the weight that can be placed on some of the end points.

• We think that the Chen et al. (2015) study that reported significant effects on sex ratio in Zebrafish below 10 µg/L would provide sufficient evidence to identify BPA as an SVHC if it can be shown to be fully reliable (see further comments below). Similarly, the study of Iwamuro et al. (2003) might provide sufficient evidence of a population-relevant adverse effect in amphibians, if the in vivo effect on metamorphosis was significant with a NOEC below 10 µg/L (this is not clear to us from the description in the dossier). In our opinion the other evidence does not point to sufficiently reliable population-relevant apical effects in fish or amphibians caused by endocrine disruption at concentrations that are consistent with a “very high” level of concern.

• We note that the ED identification guidance being developed by EFSA and ECHA does not address invertebrate effects. We think this is an omission, and welcome the discussion of the invertebrate studies provided in this dossier. Our understanding of invertebrate endocrinology is still developing, and we are not aware of any adverse outcome pathways that provide a clear link between suspected endocrine modes of action and the reported adverse effects. Whilst we agree that the available evidence indicates adverse population-relevant apical effects in molluscs and insects occurring below 10 μg/L (consistent with our interpretation of what constitutes a “very high” concern), and there are signs that this may involve the endocrine system, we hesitate to conclude that this provides definitive evidence of endocrine disruption in these taxa. However, we would appreciate hearing the views of other Member States, and at the very least agree that it can be used as significant supporting information.	Thank you for your comments.

Test concentrations
We referred to the test concentrations below 10 µg/L in the document.

Degradation
See above. 
We received comments with this respect from UK, FIN, SE, NL, AT, Plastics Europe, Sensopolis, Berceo Chemicals). Please also refer to the responses given there.
We have revised the text accordingly and also added more information on the test methods and conditions in the tables.

Drawbacks of studies already evaluated in UK RAR
We considered the drawbacks of studies already evaluated in the RAR more clearly. We also referred to the RAR with respect to the comprehensive study summaries and evaluations. 
Fish data
See comment above. We included the drawbacks of studies already evaluated in UK RAR where it was missing in the report.
Invertebrate data 
See comment above. We also think that knowledge on invertebrate endocrinology is still evolving and it is difficult to conclude on definite evidence for a specific and certain mode of action. However, there is evidence for possible underlying MoA and adverse effects which should not be ignored. The observations fit in the overall picture. We see it as supporting information and made it more clear. 	
		-		
4908
2017/10/20	Netherlands,
Member State	We agree with the proposal to identify BPA as a substance of very high concern in accordance with REACH, Article 57(f) based on its endocrine disrupting properties for the environment.
NL does have some difficulties with the summary and conclusion of the degradation data in the justification document. First, a statement that a substance is or is not readily biodegradable in the environment is scientifically incorrect as this qualification is very much related to the test and not to the environment. Furthermore, several valid tests do show that the substance is readily biodegradable and in such case normally the substance is considered as readily biodegradable despite some contradiction, which could also be related to the test design, but this has not been discussed. The fast degradation observed in the ready tests is also supported by several aerobic simulation studies in freshwater and soil. Overall, we believe it is justified to conclude that under aerobic condition BPA is not persistent.	We appreciate your support.

Degradation
Thank you for your comment. We received comments with this respect from UK, FIN, SE, NL, Plastics Europe, Sensopolis, Berceo Chemicals). 
We agree to your rationale that the substance is to be assessed as “rapidlydegradable” on basis of the screening tests. 
However, we cannot conclude on degradability in all compartments based on the information available.
The study descriptions and assessment of the studies in the support document are in line with the EU RAR (European Comission, 2010), although we partly come to different conclusions. Few new studies were added and the conclusions of the CSTEE described in Bakker et al. (2014) were taken into account. 
We come to the conclusion that: The screening tests show that Bisphenol A can be rapidly removed from surface waters by biotic degradation processes and therefore is rapidly degradable. 
In surface waters, on the basis of the information available, Bisphenol A is rapidly removed. 
In sediments under aerobic and anaerobic conditions, on the basis of the available conflicting data, currently no definite conclusion on degradation of Bisphenol A is possible.
In soil, under aerobic conditions, Bisphenol A is removed rapidly. On the basis of the available conflicting data, currently no definite conclusion on removal of Bisphenol A in soil under anaerobic conditions is possible.
We have revised the text accordingly and added more information on the test methods and conditions in the tables.	
4914
2017/10/20	ANSES,
National Authority,
France	ANSES supports the identification of Bisphenol A as SVHC (57f) based on the studies on fish (and mammals) as there is convincing evidence that significant adverse effects for fish populations are caused by endocrine disruption, particularly via an estrogenic mode of action related to the interaction of BPA with the vertebrate estrogen receptors. In fact, the in vitro studies show that BPA can act as an estrogen receptor agonist in vertebrates (including fish and amphibians) and the in vivo data on several species of fish with varying sensitivities highlight unquestionable adverse effects, as skewed sex ratio and changes in secondary sexual characteristics, with clear indications supporting the estrogenic mode of action.
Concerning the other modes of action (androgen antagonist, thyroid antagonist) and the effects on other species (amphibians, insects, molluscs or crustaceans), the indications and mechanistic links are weaker than evidenced for the estrogen agonist mode of action in fish (and mammals). Especially in the case of invertebrates, the data allowing to attribute significant effects for the populations to the exposure to BPA and via an ED MoA are still very fragmentary. However these effects must alert to possible implications that are still poorly understood.
To our point of view, the data set has not been analysed sufficiently as a whole to determine the degree of certainty of each proposed MoA or effect. The authors included a very consistent set of results without prioritizing them.
Therefore, a prioritization should be made to better evidence the effects mediated undoubtly with an ED MoA, i.e.the estrogen agonist properties of BPA in vertebrates (mainly fish and mammals). The large quantity of other results dealing with multiple effects and on a large number of species should be highlighted, but in a second time. It indeed supports a high level of uncertainty regarding the extent of targets of BPA through potential ED MoAs and the difficulties to set any safe level of exposure. It is thus important to emphasize in the SVHC identification. More specific comments on these MoAs are included below.
Moreover, links to the in vivo mammal studies can support the identification of BPA as an estrogen agonist in vertebrates and these data should be shortly summarised and discussed in this dossier to strengthen the rationale.
Moreover we are of the opinion that neurodevelopmental studies on fish should be included in the proposal to make the link with what was observed in humans and rodents models and support the issue of increased neurodevelopmental disorders when organisms are exposed during brain developmental stages.
In fact, Kinch et al. (2015) show that exposure of zebrafish to very low doses of BPA (6.8 nM) during hypothalamic neurogenesis leads to changes in locomotor activity (i.e. hyperactive behavior) of larvae. This behavioral change would be an effect of a precocious neurogenesis linked to an increase of newly born neurons in the hypothalamus.  The elements of the study support the hypothesis that BPA might act on neurodevelopment by the increase of AroB transcription, as demonstrated by the reversal of the effects when gene expression of AroB is reduced.
Other fish compartmental studies are available as Wang et al. (2013, 2015) showing effects of BPA on the behavior of adult zebrafish. Zebrafishes were exposed for 6 months to low concentrations of BPA. Authors showed a lower adaptability to the environment and a modification of the circadian rhythm which can have consequences for the survival of individuals. Wang et al. (2013) showed that BPA-exposed zebrafish have altered neurodevelopment and locomotion suggesting potentially deleterious reflex loss for fish survival or to escape predator attack. More recently Basavaraj et al. (2017) showed that fishes exposed for 75 d to 5 ng/L of BPA exhibited reduced swimming time and increased freezing periods.

Comments on specific MoA/targets:
1. The (anti-)androgenic effects in fish
There is concordant and convincing evidence that BPA can interact with mammalian and fish androgen receptor. The anti-androgenic activities can contribute to the observed adverse effects (i.e. feminization of the organisms). Nevertheless the proposed  androgenic mode of action (Table 12, p 36) is more questionable. Additional data should be available to demonstrate this hypothesis and validate the link between some adverse effects and the proposed mode of action.

2. Thyroid effects
Fish
Concerning the thyroid axis, only two publications are mentioned. In 2008, Ramakrishnan and Wayne report an acceleration of embryonic development time and early sexual maturation. This effect could result from an interaction with the thyroid axis because it is inhibited by amiodarone, provided that this axis is involved in this development. In any case, this stimulatory action is not in agreement with the inhibitory effect of TRβ noted in vitro. The publication of Terrien et al. (2011) (using transgenic danios with GFP under the regulation of TR) is also in contradiction with the in vitro study (same species) because no transcription activity is obtained with BPA alone. A reduction in fluorescence (GFP) is obtained only in the presence of T3. Finally, as stated in the concluding case p 67, "plausible biological link but indications for a thyroidal effect can be concluded". Nevertheless, the relevance of these data in the file is uncertain.
Amphibians
Amphibians are acknowledged as a good model to detect thyroid disruptors. Many different protocols have been used such as exposure to BPA during natural thyroid hormone-dependent-metamorphosis (while a T3 peak occurs) or shorter assays where exogenous T3 is added.  All these assays showed a strong, dose dependent BPA antagonistic effect. However, all studies which were done more than 6 years ago using high concentrations of BPA from 10-5 M (or 2.28 µg/L) or higher which are not environmentally relevant. There are convergences to an anti-thyroid effect at high doses. However there is no data showing such an effect at actual environmental concentrations.
3. The effects on invertebrates
In the case of invertebrates, the data allowing to attribute significant effects for the populations due to exposure to BPA and via an ED MoA are still very fragmentary, although these effects are important and must alert to possible implications that are still poorly understood.
Molluscs
The report assumes that the mode of action is related to estrogen-mediated activation through the mollusc estrogen receptor, p. 81: "The assumed mode of action of Bisphenol A in molluscs is that of an estrogen receptor agonist". This assumption must be considered in the light of available data.
Published studies show that ER orthologues have been identified in several species of mollusc (Thornton et al., 2003; Keay et al., 2006; Kajiwara et al., 2006, Matsumoto et al., 2007). However, all of these studies show lack of binding of ER protein to vertebrate estrogens or xenoestrogens in vitro using reporter assays, and endogenous ligands have not been found.
It cannot be assumed that any compounds known for its estrogenic activity in vertebrates can be an active estrogen in molluscs. This is very obvious even with the natural hormone (of the vertebrates) that does not bind nor transactivate any response through the mollusc ER.
The proposal notes that a study with a reporter system comprising the ER of Marisa cornuarietis, mc-ER and mc-ERR, showed an increase in the fluorescence of the reporter gene under the action of BPA (Bannister et al., 2012). However, this induction is true only for mc-ERR, not for mc-ER.
The proposal notes pertinently that the possible roles of E2 are not known in molluscs (p.79, $ 5.9). Thus, this compound cannot be used as a positive control of activity in these organisms as suggested in the methodology (p. 80; $ 5.9).
It should be noted, however, that this does not imply that vertebrate estrogenic compounds cannot interfere with the physiology of molluscs, possibly via an endocrine mechanism to be discovered.
Moreover, the “superfemale” phenotype described by Oehlmann and collaborators, is controversial. These effects could not be verified independently, and were not observed in a high-quality study (Forbes et al., 2007).
In the present state of knowledge, and in the absence of firm evidence of an endocrine mechanism, effects on molluscs cannot be retained for the SVHC identification.
Insects
The proposed mode of action for insects is via the interaction of BPA with the ecdysteroid receptor. Four studies were selected for this mode of action in vitro. Among them, only one of quality 2 is really specific to the receptor and tends to indicate an antagonistic action of BPA on the ecdysteroid receptor for an EC50 of 22 mg/L (Dinan et al., 2001). A second publication indicates a positive regulation (factor 2) of the expression of the receptor mRNAs after exposure to 0.5 and 3 mg/L of BPA (Planello et al., 2008). The third publication shows an activation of the transcription, in particular of the ERR gene (Park and Kwak, 2010). The latter shows an induction of vtg (Hahn et al., 2002). Therefore the mode of action does not appear to be demonstrated by these studies but can be suspected.
The plausible consequences of an interaction with the receptor are developmental effects. Two publications report such effects (without showing any mechanistic link). Watts, 2013 reported an increased in moulting time in chironomes exposed to 1 mg/L BPA. Alti and Unlu (2011) observed a delay in time to transformation in Drosophila at 100 μg/L. The other mentioned publications have effects on the reproductive axis without the establishment of mechanistic links.
In conclusion, studies are few and the evidence remains to be well demonstrated in insects.
Crustaceans
The mode of action proposed in crustaceans is via the interaction of BPA with the ecdysteroid receptor. No in vitro studies have tested this hypothesis with crustacean receptors according to the proposal. The data are only indirect: modulation of gene expression (some of which are related to moulting) (Jeong et al., 2013), variation in 20E (20-hydroxyecdysone) concentration (Lemos et al., 2009) under the action of BPA.
Nineteen publications were selected to demonstrate an in vivo effect. Of these, 8 reported effects on moulting and/or transformation. Five are on daphnia, two of which are negative (concentrations too low according to the proposal). The effects are reported for high concentrations (higher than 1 mg/L). Copepods appear to be more sensitive with observed delayed moulting times at 0.1 μg/L. These effects are considered "of little impact on the demographic profile of the copepod" by the authors (Marcial et al., 2003). The second publication (Andersen et al., 2001) reports an EC50 of 550 μg/L (without analytical confirmation of the used doses). Two publications on Gammarus pulex indicate no effect on moulting (Johnson et al., 2005: up to 1mg/L, Ladewig et al., 2006: up to 0.5mg/L). In the isopod Porcelio scaber, BPA induces an acceleration of moulting (Lemos et al., 2009).
In conclusion, the proposal and the literature included suggest that endocrine-acting effects are plausible but the strength of the demonstration is limited. The paper argues with good reason that effects other than those involving development can occur by interfering with the endocrine system. This applies in particular to reproduction. However, data remains scarce.
Additional references
Basavaraj B. G., Pancharatna K., 2017; Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio), In Environmental Toxicology and Pharmacology, 54, 146-154.
Kajiwara, M., Kuraku, S., Kurokawa, T., Kato, K., Toda, S., Hirose, H., Takahashi, S., Shibata, Y., Iguchi, T., Matsumoto, T., Miyata, T., Miura, T., Takahashi, Y., 2006. Tissue preferential expression of estrogen receptor gene in the marine snail, Thais clavigera. General and Comparative Endocrinology 148, 315–326.
Keay, J., Bridgham, J.T., Thornton, J.W., 2006. The Octopus vulgaris estrogen receptor is a constitutive transcriptional activator: evolutionary and functional implications. Endocrinology 147, 3861–3869.
Kinch C.d., Kingsley I., Jeong J.-H., Habibi, H.R,Kurrasch M., 2015.Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish, Proceedings of the National Academy of Sciences 112 (5), 1475-1480.
Matsumoto T., Nakamura A., Mori K., Akiyama I., Hirose H., Takahashi Y. 2007. Oyster estrogen receptor: cDNA cloning and immunolocalization, Gen. Comp. Endocrinol. 151, 195–201.
Thornton, J.W., Need, E., Crews, D., 2003. Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science 301, 1714–1717.
Wang J., Wang X., Can Xiong C., Liu J., Hu B., Zheng L., 2015, Chronic bisphenol A exposure alters behaviors of zebrafish (Danio rerio), Environmental Pollution, 206, 275-281, Wang X., Dong Q., Chen Y., Jiang H., Xiao Q., Wang Y., Li W., Bai C., Huang C., Yang D., 2013,Bisphenol A affects axonal growth, musculature and motor behavior in developing zebrafish, In Aquatic Toxicology, Volumes 142–143, 104-113.	Analysis of data as a whole and prioritisation 
We evaluated and considered the available data for different taxa in the hazard assessment part and hence also referred to them later on to complete the picture. In chapter 6, we set the focus on the vertebrate taxa, i.e. the estrogen MOA in fish and thyroidal in amphibians, with clear evidences (see above). We made clear which evidence is sufficient and needed for the ELOC assessment and which data is additionally presented as supporting evidence. Hence, we adapted the chapter, tried to prioritize and make it more concise with a focus on the clear evidences with respect to ELOC (oestrogen MO in fish, thyroid MOA in amphibians), supported by further studies and evidences (other MOA in fish and amphibians, invertebrate data).

Human health/mammalian data 
Comments in this respect were received from Austria, Denmark as well as France and generally supported from Sweden.
It is correct, that the mammalian data is important to be considered also with respect to the environment. We added a summary of the conclusions from the support document for SVHC identification with respect to human health in chapter 4. 
We also explicitly referred to the relevance of this data to wildlife mammals in chapter 6.3.1 and 6.3.3. 
The present dossier focuses on the evaluation of the available ecotoxicological studies for fish, amphibians and invertebrates mainly in the aquatic environment. A thorough assessment of mammalian data from the human health data base is not provided. – And cannot be achieved in the short time frame set for the dossier submitter responding to the comments.  

Neurodevelopmental studies in fish
We included the studies of Kinch et al. (2015), Wang et al. (2013, 2015) and Basavaraj et al. (2017) with respect to neurodevelopment in fish in an additional section in chapter 5. These studies make a link to the observations made for human health aspects which have been summarized in chapter 4 and provides additional support. However, we could not further assess these findings together with the results for the clear oestrogen mode of action in fish. This is partly also due to the very short time frame incorporating the comments in the RCOM and update the Support Document.

Anti- androgenic mode of action in fish
As we described, effects attributed to the oestrogenic MOA cannot clearly be distinguished from an anti-androgenic mode of action. Therefore we often referred to an “oestrogen agonist/androgen antagonist action”. However, the focus is on oestrogen agonist mode of action, which is better substantiated.   

Thyroid effects fish
Data for this MOA in fish is fragmentary. We checked the data, added more details on the studies, and gave better explanations.  Indeed, the relevance of these data is weaker.

Thyroid amphibians
We adapted the section. Although test concentrations are higher than for fish, effects were found at low concentrations (approx. 3-20 µg/L). 

Invertebrates - Data fragmentary
It is true that knowledge on the endocrine systems of different invertebrate taxa are fragmentary. We highlighted this in several sections. Still, we provide a valuable overview of the existing knowledge and discuss the evidence for probable endocrine related effects and the possible underlying mechanisms.
We evaluated and considered the available data in the hazard assessment part and hence also referred to it later, being conscious that the indications for an ED MoA are weaker and no agreed specific guidance exists yet for the assessment of endocrine disrupting effects in invertebrates.  

Receptor Molluscs
We appreciate your comments on estrogen receptors and lack of functionality and included the studies you refered to (Thornton et al., 2003; Keay et al., 2006; Kajiwara et al., 2006, Matsumoto et al., 2007). However, they are not necessarily in contradiction to the other studies which found ER related receptors. 
We already referred to the estrogen related receptor (mc-ERR) in the Bannister study.  
We are of the opinion that although the precise roles of E2 are not known in molluscs, studies with known (xeno-)oestrogens can be helpful for comparison. Vertebrate-type steroids are found in mollusc and also seem to elicit effects. Still, as you note other and further endocrine mechanisms may play a role. We tried to adapt the section to make it more clear.  

Mollusc “superfemale” phenotype . 
The effects were replicated in different experiments, although in the same laboratory. The study surely has deficiencies but we cannot ignore the effects observed. (See also comments/responses to UK). There are plausible reasons why the effects may not have been verified and replicated in the later high quality study (Forbes) (such as for example the difference of the strain used, the high reproductive rate masking effects (seasonality not considered). Effects in the Oehlmann studies could in addition also be attributed to metabolites (which were occurring in relevant concentrations under semi-static but not flow-through conditions), which is not verified, but just a hypothesis based on a study with fish. These considerations are reflected in the Support Document.

Insects
We tried to address the raised concerns with respect to the insect studies in the support document and made more clear that data is of course still fragmentary. We adapted the section and differentiated better between what can clearly be demonstrated and where there are still open questions.

Crustaceans
With respect to the lack of receptor studies we referred better to the available study for the related insects. We are aware of the high effect conc. in daphnids and think this is stated clearly in the document. We also added the conclusion of the author in the copepod study (effects are considered "of little impact on the demographic profile of the copepod" by the authors (Marcial et al., 2003).	
		-		
4923
2017/10/20	Belgium,
Member State	Belgium would like to thank Germany for the preparation and submission of this annex XV dossier. We acknowledge the huge work done!
The adverse effects and the link to the ED modes of action are clearly reported. The equivalent level of concern to CMRs, PBT or vPvB is clearly demonstrated.
Endocrine disrupting effects are reported in the annex XV dossier for fish and amphibians (with oestrogen agonist, androgen antagonist and thyroid antagonist modes of action), but also in invertebrates.
Moreover, endocrine disrupting effects of BPA were also reported in rodents, in the annex XV dossier submitted previously by France.
Based on the provided data/arguments, Belgium supports the identification of BPA as SVHC in accordance with art.57(f) for ED effects.	We appreciate your support.	
4936
2017/10/20	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust considers that the dossier is of very high quality and provides very good evidence for identifying BPA as an endocrine disrupter to the environment. We agree that on the basis from high quality studies it can be demonstrated that BPA causes endocrine mediated adverse effects in several fish and amphibian species and that BPA affects a huge variety of ecologically important species in different ecosystems. CHEM Trust therefore supports identification of BPA also as an endocrine disruptor for the environment in addition to the identification of an ED for human health according to article 57 f of REACH.	We appreciate your support.	

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	
4848
2017/10/13	Sensopolis Ltd,
Company,
United Kingdom	Information from all sources demonstrating that over the last 5 decades there is no tangible and realisable risk have been ignored, and the weight of accepted reports giving the conclusions that there is no real evidence have been down played even in this report.	The cited sources mainly address human health, but not environmental aspects. BPA is already EU-wide identified as SVHC according to 57(c) and (f) based on its reproduction toxic and endocrine disrupting properties with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment.	
4864
2017/10/19	The Boeing Company,
Company,
United States	The Boeing Company submitted comments to ECHA during the 2016 public consultation period when BPA was initially proposed to be identified as an SVHC. Our assessment of the new proposal indicate no change to the previous comments and we are resubmitting to support ECHA’s new request:
“We acknowledge the use of Bisphenol A as a widely used epoxy resin. We concur with its use in aerospace sector as a composite prepreg and potting compound/edge filler for honeycomb structures. In addition, we have identified Bisphenol A in formulations used in parts marking ink and several types of adhesives (i.e. epoxy, rubber-based, for thread locking and structural bonding).  Many of these formulations must meet the EASA and FAA Flammability requirements and alternative materials are not currently available”.	We thank the Boeing Company for the comments provided.
We are aware of this issue and will reflect this within our risk management analysis.

4874
2017/10/20	Norway,
Member State	Please see attachment embedded in table 1 of Part I  
4874_Comments SVHC BPA ED ENV.docx	See response above. 	
4880
2017/10/20	PC/BPA Group of PlasticsEurope cosigned by BPA REACH Consortium and Epoxy Resins Committee of PlasticsEurope ,
Industry or trade association,
Belgium	The PC/BPA Group of PlasticsEurope further wants to make key legal comments with regards to the uses of BPA as identified by the rapporteur, supporting its overall position that the proposed Annex XV dossier is disproportionate and has limited regulatory added value:
1. THE ANNEX XV DOSSIER IS DISPROPTIONATE GIVEN THAT THE VAST MAJORITY OF USES OF BPA ARE AS AN INTERMEDIATE WHICH FALL OUTSIDE THE SCOPE OF TITLE VII OF REACH
In the vast majority of cases, BPA is used as an intermediate, and consequently exempt from authorisation, in accordance with Article 2 (8)(b) of REACH. Hence, given the very limited non-intermediate uses, an SVHC identification of BPA is not proportionate.
In the vast majority of cases, BPA is used as a monomer, which meets the definition of an on-site/transported isolated intermediate in the manufacture of polycarbonate and other polymers. Pursuant to Article 2(8)(b) of REACH, such intermediate uses are exempted from the entire Title VII (Articles 55 to 66 of REACH) and cannot, therefore, be identified as SVHCs under Article 59 of REACH.
The uses, which clearly meet the definition of “intermediate” under Article 3(15) of REACH, far outweigh the uses of BPA as an additive (which would subsequently be within the scope of authorisation), for example in the production of thermal paper. Given the use of BPA in thermal paper is already the focus of a targeted restriction under REACH, triggered by the French authorities, the ultimate merits and relevance of an SVHC process for the remaining non-intermediate uses of BPA does not seem proportionate. The German authorities in fact confirmed earlier in their Risk Management Option Analysis (RMOA) conclusion document that “the authorisation procedure itself would not address the manufacture of BPA or use of BPA as intermediate” and that “the majority of uses is out of scope of authorisation” (ref.8).
In summary, such low volume and adequately controlled uses should not result in the prioritisation of BPA for inclusion in Annex XIV based on the Article 58(3) criteria of REACH; hence, identifying BPA as an SVHC for these very limited applications only is not proportionate.

Reference
8. https://echa.europa.eu/documents/10162/816f026b-e24c-5600-3beb-6696976d5044	Thank you for this comment.
Please refer to our response made to your comments above under “specific comments” to Part I. 	
		Please see attachment embedded in table 1 of Part I  
4880_Attachments PCBPA Group comments Annex XV dossier.zip		
4892
2017/10/20	Individual,
Switzerland	We report in the attachment on the presence of free BPA in toilet paper as a source of BPA release to surface water via waste water treatment plants.	Releases from Toilet paper
Additional information on releases to the environment from toilet paper is appreciated and will be used during further RMO-decisions, but is not part of the SVHC dossier.	
		Please see attachment embedded in table 1 of Part I  
4892_Huntsman_Release to ENV_Toilet_paper_Oct_2017.pdf		
4903
2017/10/20	Individual,
Italy	by reading and analisyng the french report appears clearly that it is indicating data about risks very limited and in opposition to ther reputable sources like the American Chemical Society, the FDA and German BfR.
Furthermore, in absence of a clear and undeniable evidence the classification as SVHC is clearly a mistake.
Bisphenol A should not be classified in opposition to an evidence of the last 50 years.	This is actually a report from the German authorities. 

Reports from other authorities
The cited sources address human health, but not environmental aspects. BPA is already EU-wide identified as SVHC according to 57f based on its endocrine disrupting properties with respect to human health. This dossier aims towards an identification as SVHC with respect to the environment.	
4936
2017/10/20	CHEM Trust,
National NGO,
United Kingdom	For some uses, it is known that BPA has been replaced with bisphenol S (BPS), a substitution that may have similar or worse health effects. Therefore, for all subsequent risk management measures it would be desirable to take a group approach for a wider group of bisphenols to avoid regrettable substitution.
see e.g.
https://www.kemi.se/en/news-from-the-swedish-chemicals-agency/2017/new-report-37-bisphenols-may-be-endocrine-disruptors/

Qui W, Zhao Y, Yang M, Farajzadeh M, Pan C, Wayne NL, Actions of bisphenol A and bisphenol S on the reproductive neuroendocrine system during early development in zebrafish, Endocrinology 157:636-647, 2016

Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environ Health Perspect 123:643–650; http://dx.doi.org/10.1289/ehp.1408989
Chen D, Kannan K, Tan H, Zheng Z, Feng Y, Wu Y, Widelka M, Bisphenols analogues other than BPA. Environmental occurrence, human exposure, and toxicity—A review. Environmental Science and Technology 50:5438-5453, 2016	We thank CHEM Trust for the supportive comment and the citations provided.
We fully agree that taking a group approach is desirable here to avoid regrettable substitution. This issue is included into our risk management analysis.