30 November 2016

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

Substance name: p-(1,1-dimethylpropyl)phenol
CAS number: 80-46-6
EC number: 201-280-9

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

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	
4632
2016/10/19	United Kingdom,
Member State	• Overall summary (p. 5) and Section 6.3 (e.g. p. 72): The reference to the possibility of effects from transient exposure of sensitive life stages is unclear. What does “transient” mean in this context? We do not think such an argument needs to be made, but if it is kept, we think that the uncertainty in such a statement needs to be emphasised more.

• Overall summary (p. 5, third bullet point, second sub-bullet point) and Sections 6.3.2.2 and 6.3.3 (p. 72-74): There are no data on the substance itself to suggest that it causes endocrine effects on taxa other than fish. 

We would caution against making statements such as it is “nearly impossible” to estimate which species are most sensitive or that it is “difficult” to derive a safe level. A decision on this point should only be made at the relevant policy level or by the Risk Assessment Committee in due course (if needed). We think statements about the potential for thresholds should be deleted from the document. Decisions should be taken on the basis of data that are available.

• Section 1.5 (physico-chemical properties) (p. 24): Since branched 4-heptylphenol is surface active, it is possible that this substance is too. If information on this point is missing (and the critical micelle concentration (CMC) is unknown), we think that a note of caution should be added for any study where the dissolved concentration was not measured, and the measured log KOW value may also be unreliable.

• Section 3 (environmental fate) (p. 11): We thank the Dossier Submitter for including this section because, contrary to the opening remarks, we think that degradability (along with potency) is an essential component of any argument for equivalent level of concern on the basis of environmental endocrine disruption. In other words, when a substance is being assessed for equivalent concern on environmental grounds, the factors considered under Article 57(d) and 57(e) are still relevant.

We note that there is no section discussing the reliability of fish BCF data (which are mentioned in the table in Annex I). This is unfortunate, because bioaccumulation behaviour is an important aspect of fish toxicity (and may be useful in comparisons between substances).

• Section 3.1 (degradation) (p. 11): During discussions at the Risk Assessment Committee about the hazard classification of 4-tert-butylphenol, there was a reluctance to consider a substance that was readily biodegradable but failed to meet the 10-day window as “rapidly degradable” in a CLP context. 4-tert-Pentylphenol might therefore not be considered to be rapidly degradable, and we think this is an important consideration for the equivalent concern argument (in terms of whether the potency (NOEC) of the endocrine effect triggers the highest hazard classification band).

• Section 5.6.2.2 (in vitro) (p. 42-): As a general remark, it would be useful to know the purity of the test substance and state the actual test concentration (in terms of mg/L) in the various studies. Some of the reported test concentrations seem remarkably low (e.g. Akahori et al. (2008) use 1E-11 M, which is around 2 ng/L). How reliable are these, especially as alkylphenols are believed to adhere to glassware? Some consideration of relevance to likely fish tissue concentrations (e.g. based on BCF information) would also be helpful. Where comparisons are made with other substances, please confirm whether this is based on equimolar concentrations and the same dose spacings (as relevant).

• Section 5.2.1.3.1 (Pimephales promelas) (p. 27): It is not uncommon to find discrepancies between tables and text in published academic studies (such as the number of testis-ova at 188 µg/L in the case of the Panter et al. (2006) study). Whilst this does not invalidate the entire study, it would be helpful to mention if efforts were made to clarify such discrepancies with the study authors. This is an important part of the audit trail (and could be more easily done for GLP studies).

• Section 5.2.1.3.1 (Pimephales promelas) (p. 39): We agree that the feminisation of gonadal ducts and change in sex ratio are indicative of endocrine disruption, but the dossier itself indicates that effects on fecundity are not exclusively ED-mediated, and the following sentence in the same paragraph says they are not diagnostic. Therefore it would be better to emphasise just the gonadal and sex ratio changes in this paragraph.

• Section 5.2.1.3.2 (Danio rerio) (p. 46): The statement that changes in sex ratio (and histological findings) means that the substance is “almost certainly an endocrine disrupter” is odd in the context of this dossier. Elsewhere it is indicated that this finding is diagnostic.

• Section 5.2.1.3.3 (Ozyrias latipes) (p. 50-51): The summary table seems to suggest significant differences in effect concentration that lead to changes in sex ratio/gonadal histology between studies. Are there any explanations for this or is it just due to the way the information has been summarised?

Editorial: Section 5.2.2.1 (p. 14 -): We note that some of the general references given in this section (e.g. Kendall et al., 1998) are missing from the reference list at the end (presumably due to cut and paste from a previous report).

Section 5.2.1.3.1 (p. 39): “sex ratio” is mentioned twice on the third line.	Thank you for your comment. The text was revised.  

The support document was revised in order to make clear that the statement is based on read across and a sentence was included about the plausibility of the read-across

The text was revised but still revers to a safe level. Please note that a 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” has been made on a policy level by the European Commission at CARACAL (Doc. CA/25/2014, March 2014). Please also note that a similar sentence is included in the MSC Agreement on 4-tert-otcylphenol and 4-nonylphenol branched and linear. 

A note of caution was included.

Please note that neither potency nor degradability or bioaccumulation was considered when identifying 4-nonylphenol branched and linear and 4-tert-octylphenol as substances of very high concern.

A section was included.

A sentence was included to reflect this. However, please note that neither potency nor degradability or bioaccumulation was considered when identifying 4-nonylphenol branched and linear and 4-tert-octylphenol as substances of very high concern.

Molar concentrations were kept as they allow a better comparison on a molecular level. In vitro studies are used to provide information about a possible mode of action. They are not meant to discuss in vivo effect concentrations. Thus, no further information about relevance to tissue concentrations were provided and no additional information about spacing was included.

A sentence was included to reflect on this.

The text was revised to make clear that fecundity is not an indicator for an estrogenic mode of action.

As described in the heading of the table the conclusion “almost certain an endocrine disruptor” is based on the OECD GD 150 which states that if a shift in sex-ratio is observed in a fish sexual development test and in vitro data and other in vivo data support the mode of action the substance is almost certain an endocrine disruptor.

The difference can be explained by differences in the test design. The first test by Hagino et al. was based on sex reversal of fish whose genotypic sex was identified by body color; therefore the test was very sensitive. In the three following studies no high differences were in the sex ratio of males only (238-318). 
The sex ratio in the validation study of Lab 10 based on intersex at 94 µg/L.
A sentence was included to reflect this fact.

The references are included.

Sex ratio is mentioned two times, because it is both an indicative and adverse effect.	
		-		
4686
2016/10/20	Individual,
United Kingdom	PTAP

Comments to the German MSCA Annex XV report on
p-(1,1-dimethylpropyl)phenol
(EC No. 201-280-9, CAS No. 80-46-6)

- 12 October 2016 -

Sponsor:
Dr D Brassington Authors:
Vice President Regulatory Affairs
Tenax Road,
Trafford Park,
Manchester
M17 1WT,  UK
Andrew Cockburn, PhD, FRSB, FBTS, ERT
Francesca Tencalla, PhD, ERT

TABLE OF CONTENTS
1. Introduction 3
2. Comments to Annex XV report conclusions of PTAP 3
3. Conclusion 4
4. References 4

1. Introduction
On 26 March 2016, the German Member State Competent Authority (MSCA) published a document justifying the selection of p-(1,1-dimethylpropyl)phenol (EC No. 201-280-9, CAS No. 80-46-6), also known as 4-tert-pentylphenol or PTAP, as a substance for inclusion in the Community Rolling Action plan (CoRAP) list, identifying the substance as a potential candidate for authorization under REACH. The document states that PTAP gives evidence of being an endocrine disruptor for the environment. However, no clear conclusion on the ED properties were possible and a further substance evaluation was proposed.
On 30 August 2016, The German MSCA published a proposal (Annex XV report) for identification of PTAP as a substance of very high concern (SVHC) on the basis of criteria set out in REACH article 57f:
“substance – such as those having endocrine disrupting properties or those having persistent, bioaccumulative and toxic properties or very persistent, very bioaccumulative and very toxic properties, which do not fulfil the criteria of points (d) or (e) - for which there is scientific evidence of probable deleterious 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 procedures set out in Article 59.

Addivant, as downstream user of PTAP, wishes to submit comments to the German MSCA Annex XV report.
2. Comments to Annex XV report conclusions of PTAP
The German MSCA Annex XV report presents and discusses a number of in vitro and in vivo studies suggesting that PTAP acts as an estrogen receptor ligand in fish and that there are apical endocrine-mediated effects at the organism level.

Addivant agrees that the weight of evidence points to a weak estrogenic chemical potentially causing apical effects in fish under favourable exposure conditions. However, Article 57(f) of REACH explicitly applies to substances that cause probable serious effects. For the following reasons, Addivant believes that this does not apply to PTAP:

• PTAP is a weak estrogenic substance. In vivo, its estrogen binding activity is consistently orders of magnitude lower than that of 17β-estradiol in all tested systems.

• PTAP is readily biodegradable (albeit failing the 10-day window criteria) and not bioaccumulative, with a modelled BCF value of 229 L/kg (based on a Koc of 3.6). As such, bioavailability for aquatic organisms is likely to be limited.

• Article 58 (2) of REACH states that: “uses or categories of uses may be exempted from the authorisation requirement provided that the risk is properly controlled”. According to its REACH registration, PTAP does not have wide dispersive uses. In the EU, it is manufactured and used in industrial sites (in the context of polymer preparations and compounds) for the production of perfumes, fragrances and phenolic resins. Release to the environment in industrial settings is controlled and regulated by local pollution control legislation. The Chemical Safety Report for PTAP documents use conditions leading to acceptable Risk Characterisation Ratios (RCR).
 
3. Conclusion
In conclusion, Addivant does not believe that available information on PTAP supports its identification as an SVHC based on an endocrine mode of action. As the substance is not likely to persist in the environment, there are no wide dispersive uses and release to the aquatic environment is properly controlled (RCR < 1), the clause ‘of an equivalent level of concern’ is not met. This is in line with previous evaluations by the UK (Crane et al., 2008) and the US (US EPA, 2005) which considered the substance to be of low concern due to limited environmental exposure.
4. References
Annex XV report: PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE
BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57; Substance Name(s): p-(1,1-methylpropyl) phenol; Submitted by: Germany; Date: 30 August 2016

Crane M. et al. (2008). Environmental risk evaluation report: 4-tert-pentylphenol (CAS No. 80-46-6). UK Environment Agency.

Unites States Environmental Protection Agency (US EPA) (2005). Reregistration Eligibility Decision (RED) for 4-t-amylphenol. https://archive.epa.gov/pesticides/reregistration/web/pdf/
amylphenol_red.pdf

Dr Francesca Tencalla
Dr Andrew Cockburn

12.10.16
END	

Although the substance could be considered as a weak estrogenic substance, it results in adverse effects (e.g. change in sex-ratio) which are considered probable serious effects due to their influence on a population level.

This fact is mentioned in the dossier.

Thank you for this information. We will consider it when discussing further risk management options.

Thank you for your conclusion. Please note that the assessment of the equivalent level of concern is not based on risk considerations and exposure information. 	
		Attachment: 4686_PTAP - Registrant comments to Annex XV report - 12Oct16.docx
		
4760
2016/10/21	Norway,
Member State	-	Thank you for the information on monitoring data. We will consider them when discussing further risk management options.	
		Attachment: 4760_p-(1,1-dimethylpropyl)phenol.xlsx

4774
2016/10/21	Sasol Germany GmbH, as Lead Registrant,
Company,
Germany	-	Thank you for your comment. However, we do not agree with the conclusion by Sasol that the substance is not an endocrine disruptor and that the equivalent level of concern is not justified. See our more specific responses to comments below
1a) Scientific criteria not met: The following adverse effects which are considered population relevant have been observed for ptAP: change in sex-ratio.
1b)Eloc assessment missing: Please refer to chapter 6.3.2.  Potency is not part of the Eloc assessment in our point of view.
1c) Studies unreliable: Only Klimisch 1 or 2 studies were used for the conclusions
2) no effects at environmentally relevant concentrations: Please note that exposure is not considered for SVHC identification.
3) uses are not in the scope of SVHC identification: thank you for your information which is how ever not relevant for the actual SVHC identification itself.
With regard to wildlife data please note that the WHO definition which is used in REACH does not require proving effects in wildlife nor does it state that effects are considered not relevant if monitoring data indicate that effects might not be relevant on a population level. Despite this fact it is our opinion that the information provided by Sasol is not robust enough to prove that effects observed are not relevant on the population level. For instant literature cited for STP effluents include histological changes but not changes in sex-ratio. It is not possible to conclude for the endpoint sex-ratio from these studies.

With regard to reliability of data: We appreciate that in general the reliability assessment agrees with our assessment. Cases with different results are considered not relevant since they are used as supporting evidence only. As far as we understood the main concern is that the most sensitive endpoint is not clearly endocrine mediated and that effect concentrations are not environmentally relevant. Please note that both aspects are not relevant with regard to SVHC assessment in our point of view. 	
		Attachment: 4774_Letter Response to Annex XV Reports_211016_Pentylphenol_final.pdf
		
4790
2016/10/21	Health & Environment Alliance (HEAL),
International NGO,
Belgium	HEAL supports the adoption of p-(1,1-dimethylpropyl)phenol as an SVHC.  Although the relevance for human health has not been assessed in this dossier, we believe it should be assumed unless there is strong evidence that it is not.	Thank you for your support.	
4797
2016/11/01	Finland,
Member State

	The Finnish CA agrees that 4-tert-Pentylphenol meets the WHO/IPCS criteria for endocrine disruptors. There is scientific evidence of endocrine mode of action, adverse effects in the environment and a biologically plausible link between these, which probably gives rise to an equivalent level of concern in accordance with Article 57(f) of REACH Regulation.

In vivo evidence of estrogenic mode of action (increase of vitellogenin level, various indications of feminisation) and adverse effects (impacts on sex ratio, reproduction) is seen in four fish species. In addition several in vitro studies are available regarding estrogen receptor binding activity, transcriptional activation and E-Screen. The substance has been a part of the validation studies of the FSDT test (OECD TG 234). Consequently the Finnish CA considers the reasons given in the Annex XV report regarding identification of ED properties of 4-TPP well justified.

Other properties relevant for environmental concern

Under Chapter 3 of the Annex XV report it is stated that environmental fate properties are not relevant for the identification of the substance as SVHC in accordance with 57(f) of REACH. We consider that at least persistency and the potential for bioaccumulation are important intrinsic properties of a substance and relevant for the evaluation on whether a substance has probable serious effects to the environment giving rise to an equivalent level of concern in accordance with 57(f) of REACH. In order to strengthen the proposal, please add a short discussion and any further information on these properties.

We appreciate that screening level test results on biodegradation have been included in the proposal. Based on a ready biodegradability test results (Haener, A. 1999), it is assumed that the substance is readily biodegradable, failing the 10-day window. We note that the reported ready biodegradation test result is similar to some results reported for 4-nonylphenol (branched) (NP)(1)   and 4-tert-octylphenol (OP)(2)  . For NP and OP also aquatic simulation degradation results are available showing that the substances have a tendency to dissipate into sediment and have significant persistence in certain environments (sediments, sea water). Could you please include a comparison to NP, OP and other alkylphenols.

Regarding bioaccumulation, we note that there seems to be no measured data on bioconcentration/accumulation. Could you please add QSAR predictions and a comparison to other similar alkylphenols in the proposal.
-------------------
(1)Support document for 4-nonylphenol branched and linear. (https://www.echa.europa.eu/documents/10162/3024c102-20c9-4973-8f4e-7fc1dd361e7d)
(2)Support document for 4-tert-octylphenol. (https://www.echa.europa.eu/documents/10162/4c6cccfd-d366-4a00-87e5-65aa77181fb6)
	Thank you for your support.

Information on degradation was already included in the support document. Some additional information on BCF was included in chapter 3. However please note that neither potency nor degradability or bioaccumulation was considered when identifying 4-nonylphenol branched and linear and 4-tert-octylphenol as substances of very high concern.

A short comparison was included in the chapter.

Additional information was included in chapter 3.	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
4630
2016/10/19	Austria,
Member State	For 4-tert-pentylphenol there is strong evidence from good quality studies that the substance causes endocrine mediated adverse effects in several fish species:
In vitro data unambiguously show that 4-tert-pentylphenol acts interacts with estrogen receptors: The estrogenic mode of action is substantiated by the available in vivo data, as endpoints indicative for an estrogenic mode of action (VTG induction, feminization of gonadal ducts and other histological alterations, reduced male secondary sex characteristics, female biased sex ratio) were affected in all six fish species tested.
A female biased sex ratio was observed in five fish species: This is like the other observed adverse effects (reduced reproduction, reduced growth) also a serious population relevant adverse effect. Effects observed show that even transient exposure during sensitive life stages may result in effects that remain during the entire life and even in following generations. Thus local exposure of migratory species might not only locally affect population stability but also in other areas.
The data fit to the data provided for other alkylphenols in a weight of evidence approach: Two of these substances (4-tert-octylphenol, 4-nonylphenyl, branched and linear) are already identified as endocrine disruptors for the environment.
Therefore, 4-tert-pentylphenol is considered to fulfil the WHO definition for endocrine disrupters, Commission’s proposal for scientific criteria for endocrine disruptors for the Biocidal Products Regulation and the Plant Protection Products Regulation (European Commission, 2016 ) and is of equivalent level of concern to those of other substances listed in points (d) to (e) of Article 57 REACH.
The conclusion that there is scientific evidence that 4-tert-pentylphenol causes probable serious effects in the environment which give rise to an equivalent level of concern to those of other substances listed in points (d) to (e) of Article 57 REACH, is fully supported.

A change of the substance identity scope in analogy to 4-nonylphenol, branched and linear, could be envisaged.	Thank you for your support.

With regard to substance identity we think that such an approach is currently not required for this substance since the production process results in a mono-constituent substance which has also been registered as such. 	
		-		
4632
2016/10/19	United Kingdom,
Member State	• We congratulate the Dossier Submitter on a very thorough and clearly presented Annex XV dossier.

• Sex ratio change is a significant population-relevant adverse effect that is generally recognised as being endocrine-mediated. This has been reported in several fish species following exposure to the substance, including a full life cycle study, with LOECs below 100 µg/L (0.1 mg/L) for some. The substance is borderline “not rapidly degradable”, so this would trigger an Aquatic Chronic 1 classification under the CLP Regulation, signifying the highest level of chronic aquatic hazard under EU law. We therefore agree that 4 tert-pentylphenol has endocrine disruptive properties in fish that give rise to a level of concern equivalent to PBT/vPvB and CMR substances.

• The read-across from higher molecular weight 4-alkylphenols provides some supportive evidence, but the available evidence for the substance is sufficient by itself. We also think that the data for 4-tert-butylphenol from the Pike-perch (Sander lucioperca) study of Demska-Zakęś (2005) are of uncertain reliability (see our comments on that substance), so read across from the lower molecular weight 4 alkylphenol is more uncertain.

• Speculative statements about the lack of a threshold for endocrine disrupting effects are not helpful and we do not think that the final MSC opinion should present an approach that has not been agreed at a policy level, or which might prejudice the Risk Assessment Committee’s analysis of subsequent applications for authorisation or restriction proposals.	Thank you for your support.

We have not changed our statements on the difficulty to derive a safe level, because the statements refer to 4-HPbl specifically or to alkylphenols, for which our expertise is that it is difficult to derive a safe level although it may exist.

Furthermore, a 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” has been made on a policy level by the European Commission at CARACAL (Doc. CA/25/2014, March 2014).

Please also note that a similar sentence is included in the MSC Agreement on 4-tert-otcylphenol and 4-nonylphenol branched and linear. 	
4686
2016/10/20	Individual,
United Kingdom	PTAP

Comments to the German MSCA Annex XV report on p-(1,1-dimethylpropyl)phenol
(EC No. 201-280-9, CAS No. 80-46-6)

- 12 October 2016 -

Sponsor:
Dr D Brassington Authors:
Vice President Regulatory Affairs
Tenax Road,
Trafford Park,
Manchester
M17 1WT,  UK
Andrew Cockburn, PhD, FRSB, FBTS, ERT
Francesca Tencalla, PhD, ERT

TABLE OF CONTENTS
1. Introduction 3
2. Comments to Annex XV report conclusions of PTAP 3
3. Conclusion 4
4. References 4

1. Introduction
On 26 March 2016, the German Member State Competent Authority (MSCA) published a document justifying the selection of p-(1,1-dimethylpropyl)phenol (EC No. 201-280-9, CAS No. 80-46-6), also known as 4-tert-pentylphenol or PTAP, as a substance for inclusion in the Community Rolling Action plan (CoRAP) list, identifying the substance as a potential candidate for authorization under REACH. The document states that PTAP gives evidence of being an endocrine disruptor for the environment. However, no clear conclusion on the ED properties were possible and a further substance evaluation was proposed.
On 30 August 2016, The German MSCA published a proposal (Annex XV report) for identification of PTAP as a substance of very high concern (SVHC) on the basis of criteria set out in REACH article 57f:
“substance – such as those having endocrine disrupting properties or those having persistent, bioaccumulative and toxic properties or very persistent, very bioaccumulative and very toxic properties, which do not fulfil the criteria of points (d) or (e) - for which there is scientific evidence of probable deleterious 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 procedures set out in Article 59.

Addivant, as downstream user of PTAP, wishes to submit comments to the German MSCA Annex XV report.
2. Comments to Annex XV report conclusions of PTAP
The German MSCA Annex XV report presents and discusses a number of in vitro and in vivo studies suggesting that PTAP acts as an estrogen receptor ligand in fish and that there are apical endocrine-mediated effects at the organism level.

Addivant agrees that the weight of evidence points to a weak estrogenic chemical potentially causing apical effects in fish under favourable exposure conditions. However, Article 57(f) of REACH explicitly applies to substances that cause probable serious effects. For the following reasons, Addivant believes that this does not apply to PTAP:

• PTAP is a weak estrogenic substance. In vivo, its estrogen binding activity is consistently orders of magnitude lower than that of 17β-estradiol in all tested systems.
• PTAP is readily biodegradable (albeit failing the 10-day window criteria) and not bioaccumulative, with a modelled BCF value of 229 L/kg (based on a Koc of 3.6). As such, bioavailability for aquatic organisms is likely to be limited.
• Article 58 (2) of REACH states that: “uses or categories of uses may be exempted from the authorisation requirement provided that the risk is properly controlled”. According to its REACH registration, PTAP does not have wide dispersive uses. In the EU, it is manufactured and used in industrial sites (in the context of polymer preparations and compounds) for the production of perfumes, fragrances and phenolic resins. Release to the environment in industrial settings is controlled and regulated by local pollution control legislation. The Chemical Safety Report for PTAP documents use conditions leading to acceptable Risk Characterisation Ratios (RCR).
 
3. Conclusion
In conclusion, Addivant does not believe that available information on PTAP supports its identification as an SVHC based on an endocrine mode of action. As the substance is not likely to persist in the environment, there are no wide dispersive uses and release to the aquatic environment is properly controlled (RCR < 1), the clause ‘of an equivalent level of concern’ is not met. This is in line with previous evaluations by the UK (Crane et al., 2008) and the US (US EPA, 2005) which considered the substance to be of low concern due to limited environmental exposure.
4. References
Annex XV report: PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE
BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57; Substance Name(s): p-(1,1-methylpropyl) phenol; Submitted by: Germany; Date: 30 August 2016

Crane M. et al. (2008). Environmental risk evaluation report: 4-tert-pentylphenol (CAS No. 80-46-6). UK Environment Agency.

Unites States Environmental Protection Agency (US EPA) (2005). Reregistration Eligibility Decision (RED) for 4-t-amylphenol. https://archive.epa.gov/pesticides/reregistration/web/pdf/
amylphenol_red.pdf

Dr Francesca Tencalla
Dr Andrew Cockburn

12.10.16

END	See our response to your general comments.	
		Attachment is embedded in table 1 of Part I: 4686_PTAP - Registrant comments to Annex XV report - 12Oct16.docx		
4717
2016/10/20	ChemSec,
International NGO,
Sweden	p-(1,1-dimethulpropyl)phenol
ChemSec supports the identification of p-(1,1-dimethulpropyl)phenol as a Substance of Very High Concern, based on its properties as an endocrine disruptor for the environment. The dossier shows ED properties in several species of fish. The relevance for human health has not been assessed in this dossier, we believe however it would be of importance to more carefully investigate also the endocrine disrupting properties for human health, as there are indications that this substance could also interfere with mammalian endocrine systems.	Thank you for your support.	
4760
2016/10/21	Norway,
Member State	The Norwegian CA supports that p-(1,1-dimethylpropyl)phenol fulfills the criteria in Article 57(f) and should be identified as SVHC based on in vitro and in vivo data. The data demonstrate that the substance is an endocrine disrupting compound in fish, comparable to octylphenol and nonylphenol in the types of effects observed as well as the concentrations at which effects are elicited, which are widely recognized as ED substances.

Two reports can support the proposal. They document the presence of 4-tert-pentylphenol in the environment. (4-tert-PP is the IUPAC name for p-(1,1-dimethylpropyl)phenol.) Heemken et al., 2001 found up to 0.7 ng/l in the Elben river water and in sediment samples from Elben 17-66 µg/kg was found. The same study also reports low concentration in the North Sea (0.3 ng/l). 4-tert-PP has also been detected in water samples from landfill leachate in Sweden (Kalmykova et al., 2013).

For more details and full references, please see the attachment.	Thank you for your support.	
		Attachment is embedded in table 1 of Part I: 4760_p-(1,1-dimethylpropyl)phenol.xlsx		
4774
2016/10/21	Sasol Germany GmbH, as Lead Registrant,
Company,
Germany	p. 14 (5.2.1 Endocrine Disruption in fish):  We believe that:

1. The substance does not meet the criteria for Substances with an Equivalent Level of Concern (ELoC)

The evidence set out in the Annex XV document does not support the conclusion that the substance meets the criteria for substances with an equivalent level of concern, as set out at Article 57(f) REACH for the following reasons.

a. The scientific criteria espoused by the European Commission for identification of substances with the potential to pose a risk to human health and wildlife from the adverse effects of endocrine disruption are not met.

b. An Equivalent Level of Concern assessment has not been carried out (considering inter alia potency) to establish that the substance meets the criteria set out in Article 57(f) REACH in accordance with the procedure recommended by ECHA.
In addition:

c. The evidence base as presented is not robust.  Various studies presented are not reliable.  Therefore the findings do not accurately reflect the scientific weight of evidence. A conclusion that the substance meets the criteria for Substances with an Equivalent Level of Concern (in accordance with Article 57(f) REACH) in line with all scientific information is not possible.
2. The weight of scientific evidence does not support the conclusion that substance effects relating to an endocrine mode of action are observed at environmentally relevant concentrations.

There are various studies and lines of reasoning relating to the endocrine activity of this substance, evidence for endocrine disruption effects, and the mode of action for measured apical effects such as reproduction or size.  There is a lack of scientific consensus on these matters.  However, notwithstanding these various possible interpretations or positions, available evidence indicates that endocrine mediated effects, and indeed biomarkers for such effects, are not observed at exposures relating to environmentally relevant concentrations of this substance.

Detailed arguments relating to these points can be found in our attachment.	See our response to your general comment.	
		Attachment is embedded in table 1 of Part I: 4774_Letter Response to Annex XV Reports_211016_Pentylphenol_final.pdf		
4780
2016/10/21	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust supports the proposal to include  p-(1,1-dimethylpropyl)phenol as a substance of equivalent concern in the REACH candidate list based on Article 57f. The thorough dossier convincingly presents the evidence from several fish sexual development tests, reproduction assays as well as in vitro information. The studies found that the substance can cause endocrine mediated adverse effects in several fish species which are likely to manifest themselves at the population level. Additionally, in our view it would be important to look into the evidence for impacts on human health.	Thank you for 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	
4632
2016/10/19	United Kingdom,
Member State	• It could be helpful for (future) prioritisation purposes to know whether derivatives have the potential to degrade to the parent 4-alkylphenol in the environment. Lack of monitoring information means we do not know whether 4-pentylphenol isomers are a significant contaminant of water courses. They might also be a constituent of some of the other commercial alkylphenols that are used in higher amounts, which could complicate the interpretation of such data.

• The current proposal only refers to a specific isomer of 4-pentylphenol. In line with other 4 alkylphenols, would it be appropriate to ensure that the linear and other branched isomers are included in the SVHC identification, if possible, to avoid regrettable substitutions? We realise that this might require some further discussion of data from other 4-alkylphenols showing the in vivo equivalence of the various isomers. There is also a question about whether a linear substance would more likely be rapidly degradable, in which case, sex ratio NOECs would need to be below 0.01 mg/L to trigger an Aquatic Chronic 1 classification (the available data would trigger an Aquatic Chronic 2 classification under such circumstances, and so it is debateable whether a substance should be identified as an SVHC on this basis).	Thank you for this suggestion. We will consider it when discussion further risk management options.

With regard to substance identity we think that such an approach is currently not required for this substance since the production process results in a mono-constituent substance which has also been registered as such.	
		-		
4686
2016/10/20	Individual,
United Kingdom	-	See our response to your general comment.	
		Attachment is embedded in table 1 of Part I: 4686_PTAP - Registrant comments to Annex XV report - 12Oct16.docx		
4760
2016/10/21	Norway,
Member State	-	See our response to your general comment.	
		Attachment is embedded in table 1 of Part I: 4760_p-(1,1-dimethylpropyl)phenol.xlsx		
4774
2016/10/21	Sasol Germany GmbH, as Lead Registrant,
Company,
Germany	p. 75 (9 Information on uses of the substance):  We believe that:

The Uses of the Substance are not within the scope of Authorisation.  Therefore proposals to identify the substance as a SVHC cannot be considered efficient or effective policy.

As supported by Part II, Section 9 of the German MSCA Annex XV report, the substance is used as an intermediate or monomer.  No further uses are known to the registrants or indeed covered by the REACH registration.  Intermediate use is explicitly being out of the scope of authorisation under REACH. Therefore authorisation is an ineffective regulatory tool.	See our response to your general comment.	
		Attachment is embedded in table 1 of Part I: 4774_Letter Response to Annex XV Reports_211016_Pentylphenol_final.pdf