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

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

Substance name: Phenol, alkylation products (mainly in para position) with C12-rich branched or linear alkyl chains from oligomerisation, covering any individual isomers and/ or combinations thereof (PDDP)
CAS number: -
EC number: -

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Toxic for reproduction (Article 57c), Endocrine disrupting properties (Article 57(f) – human health), Endocrine disrupting properties (Article 57(f) – environment)

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	
5499
2021/04/22	Calicio Limited (Additives Technical Committee (ATC) Consortium, Task Force 33C),
Industry or trade association,
United Kingdom	Please see the comments in the attachment submitted in Section IV.	

Thank you for your comments. Specific parts are responded to below. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process of the SVHC dossier.
	
		Attachment: 5499_ATC TF33c Response to PDDP SVHC consultation_April 2021_Final.pdf

Confidential attachment removed 		
		The ATC Consortium position is that PDDP requires no additional regulatory actions beyond the existing harmonised classification1 and restrictions already in place under Annex XVII of REACH. The proposal fails to recognize that endocrine disruption is a mode of action (MoA) and not necessarily an adverse effect endpoint. Both ECHA and the Commission have been clear in their views that evidence should include an adverse effect, an endocrine MoA, and a link between both the adverse effect and MoA. The Annex XV report does not provide the necessary strong link.	Your disagreement is noted. The current restriction in place under Annex XVII only covers the use of PDDP as a substance or mixture by the general public, i.e. consumers. The concern regarding exposure of the environment cannot be addressed with this restriction entry. As the registered tonnage of PDDP is very high and given the open uses of the substance, it cannot be excluded that PDDP reaches the environment. This is confirmed by monitoring studies that show findings of PDDP in the environment and biota. Since it is not possible at the current state of scientific knowledge to derive a safe level of exposure for ED in the environment, every entry to environmental media poses a risk. Hence, SVHC identification of PDDP to come to an EU-wide agreement on its endocrine disrupting properties is a necessary first step to initiate further risk management measures to minimize environmental exposure.

To fulfil the WHO/IPCS criteria for an ED in the environment, a substance must show adverse effects, which can biologically plausible be linked to an endocrine mode of action. With respect to this PDDP shows endocrine activity in several in vitro and in vivo assays and the substance shows population relevant adverse effects in in vivo mammalian assays that can be linked to the observed endocrine modes of action. Thus, as described in the Annex XV dossier PDDP fully meets the WHO/IPCS criteria as an ED for human health and the environment. We commented on the detailed arguments in the below section ‚Specific comments on the justification‘.
	
		Furthermore, if the proposal that PDDP is an endocrine disruptor leading to adverse reproductive toxicity is accepted, then the substance would be double categorised by adding SVHC for endocrine disrupting properties.

To endorse the current proposal that PDDP should be identified as an SVHC of equivalent concern would ultimately double categorise PDDP for the same endpoint.	Based on the Commission’s Decision 2017/1210, and the Court ruling in Case T-636/17 (challenge of ECHA identification of BPA having endocrine disrupting properties with adverse effects to human health), “double identification” for the same adverse effects is possible under Article 57(f).	
		In addition, the European Commission has begun discussions with member states to classify endocrine disruptors into hazard classes under CLP ((EC) No 1272/2008). 	In our view and as presented in the dossier, the substance fulfills the criteria for an SVHC and should be identified as such. These potential new hazard classes could also be assigned to the substance after the respective entry into force. However, this issue is separate from the question of the fulfilment of the SVHC criteria which this Annex XV dossier addresses.	
		• The harmonised classification of PDDP ensures high visibility of the hazard. Furthermore, the substance is also subject to restriction in consumer applications as per Annex XVII of REACH.
• The substance is used only as an intermediate in the manufacture of other substances and polymers. Therefore exposure is extremely low due to the risk management measures in place throughout the life cycle of the substance and its extremely low volatility in water and low solubility. Experimental data on exposure from manufacture and use of PDDP-containing additives confirms this.
	Regarding harmonised classification: there are not enough consequences for protection of the environment; regarding the restriction in consumer applications, please see above.
	
		• In the EU market the substance is found mainly as an unintended impurity in lubricant oils. Significant efforts are being made by the industry to reduce both the concentration of PDDP and its use. In particular, the lubricant industry invested multi-million Euros to change the manufacturing process.
• Such efforts would be significantly hindered if regulatory actions such as SVHC listing were to be implemented and may encourage companies to move the manufacturing of lubricants containing this PDDP-impurity to outside the EU, such that the lubricants components containing a higher level would not face regulatory action. 
As electrification of transport progresses the volumes of lubricant oils used in the EU is expected to decrease over time anyway.
• There are environmental benefits in the use of PDDP containing additives in that they increase the lifespan of lubricating oils and engines and help reduce fuel consumption by improving the performance of combustion engines, thus also helping the EU achieving its climate goals.
	Thank you for your input regarding use and related exposure considerations. As mentioned above this information will be taken into account at a later stage in the regulatory process to identify the most appropriate risk management option or options to reduce environmental exposure. SVHC identification seeks to come to an EU-wide agreement on intrinsic hazardous properties of substances.	
		The substance is used only as an intermediate in the manufacture of other substances and polymers. Therefore exposure is extremely low due to the risk management measures in place throughout the life cycle of the substance and its extremely low volatility in water and low solubility. Experimental data on exposure from manufacture and use of PDDP-containing additives confirms this.	According to the Court ruling in Case T-636/17 (§207), the ‚identification of a substance as a substance meeting the criteria in Article 57 of Regulation No 1907/2006 is based chiefly on the intrinsic properties of that substance and therefore irrespective of the question of which uses are to be taken into account at the stage of the inclusion on Annex XIV to that regulation, or at the stage of the granting of an authorisation pursuant to Article 60(2) or (4) of that regulation.‘	
		There is insufficient evidence to identify PDDP as an endocrine disruptor for either human health or the environment. Article 57(f) requires both probable serious effects on human health and/or the environment and that those effects give rise to an equivalent level of concern to be demonstrated.

It has been established in the European Court (Cases C-323/15 P and C-324-15 P) that Article 57(f) of REACH requires two cumulative conditions for SVHC identification: (i) probable serious effects on human health and/or the environment; and (ii) that those effects givef rise to an “equivalent level of concern”. Since these conditions are cumulative, the identification of a substance as an SVHC must be rejected if either of those conditions is not met. In should be noted that both of these conditions are not met for PDDP.	Your disagreement is noted. We commented on the detailed arguments in the below section ‚Specific comments on the justification‘.
For PDDP highly diagnostic parameters for oestrogenicity were seen in in vivo mammalian data (increase in uterus weight and accelerated vaginal opening; furthermore, reduced ovary weight, decreased corpora lutea and prolongation of the oestrus cycle and the number of implantations was decreased). 
Adversity is proven by significant effects on fecundity and fertility in mammals (such as reduction in number of corpora lutea, reduced number of implantation sites, reduced fertility index, reduced number of pups, reduced litter size) leading to a reduced number of offspring. These effects are of population relevance and hence sufficient to conclude on the environmental ED properties of PDDP as well. 
The diagnostic and adverse effects are linked by a causal relationship as described in the Annex XV dossier and therefore PDDP fulfills the WHO/IPCS definition of an endocrine disruptor. 
	
		The Annex XV report does not address potency to any meaningful extent.	ED identification does not require consideration of potency (see for example the ECHA/EFSA ED guidance (https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5311) 
	
5501
2021/04/22	Health and Environment Alliance (HEAL),
International NGO,
Belgium		Thank you for your support.	
		Attachment: 5501_2021.04.HEAL_Comments_SVHC identification_PDDP Group.pdf
		
5537
2021/04/23	The Lubrizol Corporation,
Company,
France	Please see attached document	Thank you for your comment. Specific parts of the comment are responded to below.	
		Attachment: 5537_Lubrizol response to PDDP SVHC consultation 23 April 2021-FINAL.pdf
		
		The proposal fails to recognize that endocrine disruption is a mode of action (MoA) and not necessarily an adverse effect endpoint. Both ECHA and the Commission have been clear in their views that evidence should include an adverse effect, an endocrine MoA, and a link between both the adverse effect and MoA. The Annex XV report does not provide the necessary strong link.	Your disagreement is noted. We commented on the detailed arguments in the section ‚Specific comments on the justification‘. 	
		Furthermore, if the proposal that PDDP is an endocrine disruptor leading to adverse reproductive toxicity is accepted, then the substance would be double-categorized by adding SVHC for endocrine disrupting properties. In addition, the European Commission has begun discussions with member states to classify endocrine disruptors into hazard classes under CLP ((EC) No 1272/2008). To endorse the current proposal that PDDP should be identified as an SVHC of equivalent concern would ultimately double categorize PDDP for the same endpoint.	See answers above to comments by Additives Technical Committee (ATC) Consortium, Task Force 33C. We commented on the detailed arguments in the below section ‚Specific comments on the justification‘. 	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5479
2021/04/22	CHEM Trust Europe ,
National NGO,
Germany	CHEM Trust supports the inclusion of the group of alkylated phenols (C12) (PDDP) in the REACH candidate list as proposed by Germany based on its identification as reprotoxic substance meeting the criteria of article 57(c) and as substances of equivalent concern under article 57(f) due to their  endocrine disrupting properties.
The harmonised classification for reproduction toxicity for any substance which predominantly contains C12 (branched) alkyl-substituted phenols has already been confirmed by RAC in 2013.
There is further a strong evidence that the reprotoxic effects on fertility and sexual function leading to the classification are plausibly linked to estrogenic activity, and PDDP has shown estrogenic activity both in vitro and in vivo. The overall observed effect pattern of PDDP from several OECD level 4 and 5 reproductive toxicity studies is considered EATS mediated/sensitive to EATS modalities, and is also in line with that of known estrogens.
These effects are also relevant for mammals in the environment, and the effects on the environment is further supported by the fact that other phenol alkylation products (4-nonylphenol, branched and linear, 4-tert-octylphenol, 4-tert-pentylphenol, 4-tert-butylphenol, as well as phenol, heptyl derivs. have already been identified as SVHC based on endocrine disrupting properties for the environment.
As for the other phenol alkylation products, PDDP can be regarded of equivalent level of concern due to the potential for serious and irreversible effects on organisms and populations that may have long term consequences, the large variety of species that may be adversely affected and the difficulties to determine a safe level of exposure with regard to the endocrine mediated effects, as well as the impacts on future generations.	Thank you for your support.	
5488
2021/04/22	ANSES,
National Authority,
France	FR agrees with the conclusions of the proposal for identification of substance of very high concern on the basis of the criteria for Article 57 (f) and 57 (c).

Identity of the substances
It is unclear whether the definition of the entry is specific enough so that there is no confusion in its application. In particular, the term “C12-rich” is defined to our knowledge neither in the SVHC identification proposal nor in the ECHA guidance for identification of substances. To ensure applicability and enforcement of the SVHC identification, the word “rich” should be defined.
With regard to the UVCB nature of many of these substances, the possibility to define the entry as substance having a C12-alkyl phenol as constituent should also be considered.

Editorial remarks on the identity of the substance:
Phenol (tetrapropenyl) derivatives (PTPD, EC 616-100-8, CAS 74499-35-7) is mentioned in the list of test substances and in the list of substances with harmonised classification (although without its EC number listed in the CLH entry) but it is not present in the non-exhaustive list of group members (table 2). This substance should be added in the table 2.

ED relevant for human health
There is strong evidence that this substance have endocrine disrupting properties relevant for human health. The data are clear and consistent across studies, especially in relation to an alteration of female reproductive function plausibly linked to its estrogenic activity. This is demonstrated with a sufficient level of evidence to fulfil the WHO definition of an endocrine disruptor relevant for human health.
Mechanistic in silico data and in vitro studies demonstrate estrogen receptor (ER) binding and activation by PDDP (OECD level 2), but the data also indicate interaction with antiandrogenic receptor and components of the thyroid hormone system (Interaction with T systems, inhibition of DIO 1, 2 and 3). Despite these results, all the argumentation of the endocrine disrupting properties of PDDP focus on the estrogenic effects. The effects of PDDP on AR and thyroid should not be totally excluded from the ED conclusion in view of the results (particularly in parts 4.11.5 and 4.11.8). They may be considered as potential additional modes of action that may superimpose to estrogenicity and as supportive argument to the identification of PDDP as an ED.

ED relevant for environment and ELoC
- We are of the opinion that the justification for ED effects on ENV and ELOC could be further strengthen, especially as there is no data for the substance above OECD level screening assays. We suggest the use of read-across and literature data    to give additional information and solid arguments on the effects linked to the conservation of the reproductive endocrine system among different taxa. For example, read-across data on substances 4-Nonylphenol and 4-tert-Octylphenol on fish and rodents, could lead to a better understanding of how the endocrine system is well conserved across vertebrate taxa with respect to hormone structure, receptors, synthesis pathways, hormonal axes and degradation pathways. It will reinforce the main argument and make a clearer link to substances already classified for their ED effects on the environment.

- Data on synergistic effects (increased sensitivity of the assay when co-exposed to E2) were mentioned in the “in vitro information indicative of endocrine activity” section. This information could have been mentioned to support the argument for additive or synergistic effects. However, it was not discussed further in the document.
. Finally, equivalent level of concern assessment for human health could be benefit from a shared discussion with environment part as many arguments apply to both aspects. In particular, the difficulties to derive and quantify a safe level of exposure also applies to human health protection with regard to sensitive life stage and lack of appropriate characterization of the multiple endpoints that can be affected by ED.

Editorial comments:
- Please harmonised the abbreviation for 4-tert-octylphenol (both 4-tOP or OP are mentioned in the document)
- p.20 3.1.2.1.2. Screening tests, paragraph 2: Please correct CONCAWE instead of CONCAVE.
- p.20 3.1.2.1.2. Screening tests: Please review text format for the title
- p.22 3.4.1. Bioaccumulation in aquatic organisms (pelagic and sediment organisms): Please correct “Uncerteinties”.
- p.29 In the Hershberger assay (Yamasaki et al., 2003), which turns out to be negative, the route of administration is not described (part. 4.11.4).
- p.56 paragraph 2: Abbreviation of Molecular Initiating Event (MIE), the letter E is missing.
- p.57 4.11.9: Please correct “ostrogenic “
- p.57 last paragraph: please correct “( and ())”
- p.62 5.1.1. Fish: Please define and precise the use of LL50 instead of LC50.
- p.63 5.1.3. Algae and aquatic plants: Please precise for which substance the ErC50= 0.36 mg/L was obtained (PDB or PTPD?).
- p.65 Second to last paragraph: Please define 4-NP. This abbreviation is not introduced above in the text.
- p.65 5.2.4.2. In vitro information indicative of endocrine activity: Can you please clarify or precise the statement “It is assumed” for the use of 4-DP and 4-DPM.
- p.69 Table 23, line AO: please precise on which specie (Medaka).
- p. 76 References: Please use justified format for this section.	Thank you for your support.

We agree that the term “rich” is not defined, like the term “predominately” which was used in the RAC opinion, too. A clarifying sentence was added to the draft support document.

The substance was already included in table 2 (line 2).

Thank you for the comments. We amended the text accordingly. Interaction with the thyroid hormone system is put forward as an additional concern in the ELOC assessment for HH.

Thank you for this valuable comment. First of all, we would like to mention that ED ENV identification here is based on the population relevant adverse effects derived from the available mammalian data. The effects of structurally related long chain alkylphenols on fish are used as additional evidence to show that there is also a concern for other non-mammalian species in the environment. We think that a further general discussion on the state of the science of the transferability of ED effects between species is not necessary here. However, we included now a supporting table to compare in vitro effects of the substances 4-t-Octylphenol, 4-Nonylphenol and PDDP, and to show in vivo effects in fish of 4-t-OP and 4-NP to strengthen the supporting read-across.

Synergistic effects from in vitro information are added to the summary on page 9.
However, we prefer to keep the ELOC assessment for HH and ENV mostly separated.

Thank you for the editorial comments. The text was amended accordingly.	
5495
2021/04/22	Norway,
Member State	The Norwegian Environment Agency thanks the German Competent Authority for preparing the SVHC proposal for PDDP due to the criteria set out in REACH Article 57 (c) and (f), based on reproductive toxicity and endocrine disrupter for human health and the environment.

SVHC according to REACH Article 57 (c)
We support that PDDP is identified as a SVHC according to REACH Article 57 (c). One of the substances included in the group proposal is phenol, dodecyl-, branched (PDB, EC 310-154-3, CAS 121158-58-5), and we agree that the SVHC proposal is mainly based on data from this substance. PDB has a harmonised classification according to CLP Annex I as Repr. 1B for effects on fertility and sexual function. In the opinion of the Risk Assessment Committee (RAC) it was included that “the harmonised classification will apply to any substance which predominantly contains C12 (branched) alkyl-substituted phenols”. We therefore support that PDDP meets the criteria of REACH Article 57 (c) due to its classification as Repr. 1B; H360F.

SVHC according to REACH Article 57 (f)
The regulation of endocrine disrupters for human health and the environment is of high priority in Norway. PDDP has been discussed in the ECHA Expert Group for Endocrine Disruptors and the group agreed that PDDP fulfils the WHO criteria as an endocrine disrupter for human health and the environment.
We support that for PDDP there is strong evidence that the adverse effects on fertility and sexual function (PDB has a harmonised classification as Repr. 1B) particularly in females, are due to the estrogenic activity of PDDP. Therefore, we support that PDDP is identified as substances of very high concern in accordance with Article 57(f) of REACH for human health.
Further, we support that the assessment of the endocrine disrupting properties of PDDP for the environment is based on mammalian data and supported by fish in vitro tests and adverse outcome pathways. The observed endocrine mediated adverse effects in mammals are considered to be of population relevance. Further, PDDP has a similar structure as 4-t-octylphenol and 4-nonylphenol that are already identified as a SVHC for their endocrine disrupting properties in the environment. Therefore, in a weight of evidence assessment we support that PDDP is identified as a substance of very high concern in accordance with Article 57(f) of REACH for the environment.

We support the equivalent level of concern assessment performed by Germany. The effects on fertility reported in mammals are considered to be relevant and serious for human health and the environment.	Thank you for your support.	
				
5499
2021/04/22	Calicio Limited (Additives Technical Committee (ATC) Consortium, Task Force 33C),
Industry or trade association,
United Kingdom	Please see the comments in the attachment submitted in Section IV.	
Thank you for your comments. Specific parts are responded to below. Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process of the SVHC dossier.
	
		See the corresponding embedded attachment in table 1 of Part I: 5499_ATC TF33c Response to PDDP SVHC consultation_April 2021_Final.pdf

Confidential attachment removed
		
		Comment by Calcio on p8: “It is proposed to identify the substances as substances of equivalent level of concern…”

and p9: “... it is concluded based on the weight of evidence that PDDP is an endocrine disrupter with regard to human health”
and
“… it is concluded based on the weight of evidence that PDDP is an endocrine disrupter environment”

It has been established in the European Court (Cases C-323/15 P and C-324-15 P) that Article 57(f) of REACH requires two cumulative conditions for SVHC identification: (i) probable serious effects on human health and/or the environment; and (ii) that those effects give rise to an “equivalent level of concern”. Since these conditions are cumulative, the identification of a substance as an SVHC must be rejected if either of those conditions is not met. In should be noted that both of these conditions are not met for PDDP. PDDP has been shown to cause adverse effects characteristic of endocrine disruptor-like properties in rodents only at high doses in several in vitro or in vivo assays alongside other signs of systemic toxicity but not when non-specific systemic toxicity was absent. Careful comparison of these effects with those of other known endocrine disruptors shows however that PDDP has a potency that is almost 1000 times less than the known endocrine-disruptor beta-estradiol and equivalent to that of several phytoestrogens found in dietary supplements. Additionally, no clear mode of action (MoA) can be determined from the available data. We would argue therefore that adverse effects often associated with endocrine-disrupting properties that were seen at high doses together with other signs of non-specific systemic toxicity would not meet any subjective, critical comparison of ‘equivalent concern’ with a Category 1 CMR, PBT or vPvB. Therefore, PDDP would also not meet the requirements for probable serious effects to human health or the environment.

According to ECHA Guidance, an assessment of EDs under Article 57(f) of REACH requires a weight of evidence approach considering factors such as positive and negative responses observed in both in vivo and vitro assays, potency, as well as human and environmental exposure. The Annex XV report does not address potency to any meaningful extent.
The Annex XV report fails to recognize that substances can be classified as reproductive toxicants but not be significant endocrine disruptors. It is reasonable to conclude that while some compounds are reproductive toxicants they are not necessarily endocrine disruptors” (Cooke et al. 2002).
	The adverse effects of PDDP on reproductive function and fertility are both, serious and specific, and are not a consequence of non-specific systemic toxicity. This is reflected by classification of the substance as Repr. 1B. Furthermore, PDDP clearly displays oestrogenic activity in a number of in vitro and in vivo studies. In our opinion, this oestrogenic activity plausibly explains the adverse effects on apical reproductive endpoints. The presence of other systemic toxicity is not pronounced enough to negate the findings of oestrogenic activity or the specificity of the adversity. PDDP in vivo displays endocrine activity as well as adversity within the limit dose for in vivo toxicity testing. Therefore, the findings are relevant for SVHC identification (which is based on hazard).

Potency is not a relevant factor when identifying substances as ED. The presence of other systemic toxicity is not pronounced enough to negate the findings of oestrogenic activity or the specificity of the adversity. 
A substance can be identified as endocrine disruptor without fulfilling PBT or vPvB criteria. Art. 57(f) of REACH states that the effects have to be of an equivalent level of concern, i.e. the type of effect msut be considered here, e.g. with respect to irreversibility, decoupling of exposure and effect.

	
		Comment by Calcio on p22: “…bioavailability issues that could have resulted in a decreased BCF”:

The Annex XV report’s language regarding surface activity in the fish bioconcentration study is speculative. These data clearly indicate that PDDP has a low potential for bioconcentration in the food chain and does not meet the EU vPvB or PBT criteria.
To clarify, the BCF measurement was not normalized to lipid content. However, the lipid content of 9 fish were measured at the end of the study period, resulting in an average lipid content (whole fish) of 7.3%. This results in a 5% lipid normalized BCF value of 561.5 (using the BCFs value of 823).
Furthermore, the rapid elimination of PDDP during the depuration stage indicates metabolism is playing a critical role, especially as the log Kow of PDDP is 7.14. This is a critical part of the weight of evidence that is not considered in the Annex XV report.
	Though it is unclear whether or not surface activity will influence bioaccumulation it is possible that it does. This issue contributes to the uncertainty and should thus not be neglected. We cannot retrace your statement that the average lipid content for whole fish was 7.3 % as there is no such value to be found in the IUCLID data nor is the original report available. In addition, important information on the bioconcentration study is missing, e.g. it remains unknown whether or not the kinetic BCF that is reported was growth corrected. A further example is that data lacks the renewal rate. PDDP consists of components of different chain length that have different log KOW. You are referring to the component with the longest chain length. While the shorter chain components of PDDP showed a rapid elimination with a clearance half-life (ct50) less than three days, the longest chain component does not but showed a delayed elimination. We would also like to draw your attention to the fact that log KOW is not a good metric for an elimination estimate. Hence, the uncertainty concerning the bioaccumulation of PDDP remains.
However, it is reiterated here that it is not required that a substance identified as endocrine disrupter also fulfills the critera for PBT or vPvB. In case it does, this of course increases the overall environmental concern related to the substance.	
		Comment by Calcio on p55: “This classification implies adverse effects on apical toxicity endpoints concerning fertility and sexual function which are not considered to be secondary non-specific consequences or other toxic effects”:

For a substance to be identified as an endocrine disruptor several conditions must be met in addition to adverse changes in reproductive parameters. The legal text of the endocrine disruptor criteria (Commission 2018) requires that all elements are met. These scientific criteria include showing: an adverse effect, an endocrine mode of action, an adverse effect that is a consequence of the endocrine mode of action, a weight of evidence approach, and an adverse effect that is neither non-specific nor a secondary consequence of other toxic effects. Therefore, where any one of these ED criteria are not met, the only conclusion can be that the substance is not an ED. The Annex XV report has not recognized that the weight of evidence of the in vivo studies show secondary effects.
In 2013 RAC concluded, on PDDP, that alterations in male reproductive parameters occurred with significant effects on general health. The RAC experts also stated that the effects on fertility were not of high severity and might be mediated by weak estrogen activity but did raise the point that the effects occurred concurrently with general toxicity. Reproduction effects occurred at dose levels that also caused systemic toxicity. This systemic toxicity cannot be simply explained away by potential food restriction, but rather the adverse effects are a symptom of the underlying systemic toxicity of PDDP and not directly the cause of the toxicity. The systemic toxicity caused, among other effects, the reduction in absolute body weight, body weight gain and retarded growth that, combined, had a significant impact on the reproduction parameters in treated animals above a particular point of departure based on route of administration and dose.
	Among the general toxicity observed, effects on body weight associated with reduced food consumption were the most relevant findings which can have an unspecific impact on reproductive function, if of sufficient effect size. General toxicity in males was higher than in females, but as noted by RAC, the classification is nonetheless also based on reduced epididymal sperm count.
Together, the effects on fertility and reproductive function particularly in females were severe and specific enough for classification.
In addition, body weight effects are consistently reported for model oestrogens. Therefore, the body weight effects of PDDP can also be explained, at least in part, by its oestrogenic activity.

		Comment by Calcio to p55 “The RBA of PDDP to the ER was higher than to the AR”:
The interpretation is misleading and incorrect. If PDDP were an ER agonist, the AR binding should be positive (Marty et al. 2015) not negative as it was for PDDP. Further, the rat ER binding in vitro was very weak and at same level of common natural dietary phytoestrogens that have no known adverse ED properties.
It is also important to note that the in vitro ER binding study used concentrations in the uM range, whereas physiologic exposure to endogenous estrogens approaches a maximum at 1 nM (Miller et al. 2017). Hence, the use of excessively high concentrations of chemicals for the in vitro study is an unrealistic worst case. Significantly, even under these worst-case dosing conditions, the ER showed very weak relative binding affinity for PDDP.
	The binding test of PDDP to AR contained in the registration dossier was considered positive by Thomas (2002a) with an IC50 of 92 µM and a relative binding activity (RBA) of 0.0016 % (relative to R1881). The study you cited in your attachment (we guess you refer to Fang et al., 2003, Chem Res Toxicol 16: 1338-58; this study is now included in the SVHC dossier for completeness) determined for 4-dodecylphenol (CAS 104-43-8) an IC50 of 20 µM and a RBA of 0.0153% (relative to R1881). The authors considered the substance as a weak AR binder.	
		Comment by Calcio to p55: “There are clear and consistent estrogenic responses in uterotrophic assays”:
The interpretation of the data is incorrect. A critical review of the uterotrophic assays demonstrates no estrogenic responses at doses absent of systemic toxicity/stress; and uterine weight increases only at systemically toxic doses (i.e,. 250 mg/kg) and the responses at these high doses was still ~2,500 fold less potent compared to positive control.
	There are four uterotrophic assays consistently demonstrating increased uterine weight starting from doses of 40 or 75 mg/kg bw/day. This increase in uterine weight cannot be explained by the general toxicity observed (lower body weight).
Furthermore, for example in the uterotrophic assay contained in the registration dossier (Edwards, 2010a), the positive control group receiving 17α-ethinylestradiol (EE2) had a 10.7% lower body weight compared to controls. This is comparable to the body weight effect of PDDP in the high dose group (11.1% lower). Thus, by the implication of your comment, also the effect of EE2 on uterine weight would not indicate oestrogenic activity.	
		
And to p55 “There are clear and consistent estrogenic responses in … female pubertal assays”:
The interpretation of the female pubertal data is incorrect. Endocrine disruptor consistent effects were not observed at non-systemically toxic doses. Furthermore there was no change in estradiol, TSH, T4, LH; no significant decreased body weight at vaginal opening; no change in estrous cycle length; decreased uterine weight; no persistent estrous. The Annex XV report does not present a balanced view of the weight of evidence.
Regarding the other higher tier studies such as the one gen and two gen, there is evidence that most observations of potential adversity were confounded by some evidence of non-endocrine systemic toxicity/stress at the higher dose levels examined.

	Accelerated time to vaginal opening (VO) at a lower body weight compared to controls was observed in four pubertal assays and in the 2-generation study. In the pubertal assays, a significant effect on VO was already detected at doses of 50 or 60 mg/kg bw/d with minimal signs of other toxicity. Time to vaginal opening is highly diagnostic for oestrogenic activity. General toxicity and lower body weight usually lead to a delay in vaginal opening. Thus, despite some body weight effects at high doses, PDDP still accelerated vaginal opening, clearly displaying oestrogenic activity. Regarding E2 and LH in the pubertal assays: In order to detect substance-induced changes, a high number of animals needs to be investigated and comparison should be done between animals at the same oestrous stage. Since hormone levels were not grouped according to oestrous stage, the data regarding LH (and E2) are not informative. Thus, the absence of any effects on LH does not contradict an oestrogenic mode of action of PDDP. Regarding oestrous cycles: More animals were in permanent dioestrus or oestrus. Cycle length was determined only for a limited number of animals in the pubertal assays. However, in the higher tier studies, cycle length was increased. Regarding the decreased uterus weights in cycling females: This parameter is highly dependent on oestrous stage, and uterus weights in studies with cycling females were not correlated to oestrous stage at termination. Regarding the adverse reproductive toxicity findings in higher tier studies: As already commented above, the presence of general toxicity is not pronounced enough to negate the findings of oestrogenic activity or the specificity of the adversity.
	
		Comment by Calcio to p57 “There is no reason to assume that the observed adverse effects on fertility by disruption of estrogen signaling in rats have no human relevance”:
The Annex XV report fails to describe the scientific literature on this topic and presents a biased view. A comparison of plasma 17beta-estradiol levels reveal that mouse, rat and dog regulate their normal cycle at comparatively low levels of estrogen, whereas estrogen levels in humans are 1 to 2 orders of magnitude higher (Gunzel et al. 1989). Hence, higher exposure levels of exogenous estrogens will be required to elicit changes in the endocrine regulation of humans compared to rats and dogs.	An Annex XV report is not a risk assessment. Potential quantitative differences in sensitivity between species do not change the outcome of the present SVHC identification based on hazard.	
		Comment by Calcio to p57 “The lack of effects in the single dog study …gives no reason to question the human relevance of the proposed mode of action and AO”

The Annex XV report does not present a balanced weight of evidence. At a minimum the 90-day study in dogs – which showed no treatment related changes observed, including in liver, spleen, kidneys, heart, brain, lungs, testes, adrenals, thyroid, pituitary, and ovaries, with a NOEL at the highest dose tested – provides a line of evidence indicating lack of consistency across species. Hence raising doubts about their read across to humans and from mammalian to environment.
	In section 4.11.6 it is mentioned that this finding might indicate a species-specific sensitivity of rat towards the substance. However, in this study, no analytical verification of the concentrations was performed, and it used only three animals/sex/dose. Since no other data on further mammalian species are available, this study gives no reason to question the general relevance of the whole data set for mammals including humans.
	
		Comment by Calcio to p68 “For the various KEs [key events] no data for PDDP itself are available but data on structurally similar compounds 4-nonylphenol and 4-tert-octylphenol show that these Kes can be triggered by long chain alkylphenols”:

The Annex XV report selectively uses data from different substances than PDDP itself to put together its arguments, and provides no robust read across argument other than saying they are alklyphenols. Reading from lower chain alkylphenols to PDDP is not scientifically sound and it is not consistent with robust read across practices required by ECHA. PDDP should be evaluated based on its own weight of evidence.
PDDP is a UVCB and it is extremely difficult to reliably compare analogs to UVCBs. For example, there is a wide range in water solubilities:
• PDDP (C12 fraction) = 0.031 mg/L
• PDDP (UVCB) = 1.54 mg/L
• 4-nonylphenol (branched; CAS 84852-15-3) = 5.7 mg/L
Undoubtedly, the water solubility will influence bioavailability and the potential to exert any adverse effects. However, these aspects were not considered in the Annex XV report.
There is, therefore, no credible scientific justification for considering the ED potential of other structurally-similar substances as part of any weight of evidence determination.
Regulators have a very high bar for accepting read across justifications from registrants, so they should use the same approach when doing read across themselves. The Annex XV report provides no robust read across or category assessment framework and is not scientifically justified.	The ED ENV identification of PDDP according to Art. 57(f) is based on the mammalian data since they show adverse and population relevant effects that can biologically plausible be linked to an endocrine mode of action. The read-across to other long chain alkylphenols is used only as supporting information in the dossier. We amended this part of the dossier to further strengthen the evidence that PDDP acts via the same ED mode of action as other long chain alkylphenols. Hence, it is very likely that PDDP shows the same adverse effects in fish as the alkylphenols which have already been identified as SVHC due to their ED properties for the environment. These supporting data fit into the overall picture regarding the ED ENV properties of PDDP as derived from the mammalian assays.
Water solubility and bioavailability issues do not principally change that picture since PDDP can be ingested by fish and amphibians via the food.	
		Comment by Calcio to p72 “The reproductive endocrine system is highly conserved not only between mammals but also between mammals and oviparous vertebrates such as fish….it is highly likely that PDDP also leads to adverse effects such as reproductive dysfunction and skewed sex ratios in oviparous vertebrates”:

For PDDP, there are no specific studies relating to hormonal and biomarker measurements responsive for estrogen receptor agonists in aquatic species
A hypothesis of an estrogenic mode of action is furthermore put into question by the fact that daphnia seems to be more susceptible to toxicity of PDDP than fish when comparing the acute study results. Given that crustaceans have a lesser developed estrogen mediated system and mammalian estrogen receptor agonists and antagonist do not act through the ecdysone receptor (Clubbs and Brooke, 2007) one would expect fish to demonstrate higher toxicity with a substance demonstrating a specific mode of action
Sufficient data from high tier studies covering part or full reproduction cycle including apical endpoints that are considered indicative of an endocrine mediated effects are required to draw any relevant conclusion. There is insufficient evidence provided either in the report or available to call PDDP an ED for environment.
	As explained above, standard acute fish and Daphnia studies cannot give any indication for an endocrine MoA on the HPG axis. 

Effects on mammals like rats and mice are also relevant for the environment, as these organisms are also environmental organisms. For rats and mice meaningful studies are available (see also the answer above).	
		Comment of Calcio to p73 “It is difficult to derive a safe level of exposure”:

The Annex XV report does not address thresholds to any meaningful extent. Brescia 2020 justified a threshold for endocrine disruption. The article states, “Biology predicts that thresholds of adversity exist and are the rule for all endpoints, including those arising from endocrine disruption. A threshold approach to the risk assessment of endocrine disrupting chemicals is scientifically justified.”
ECHA Guidance on SVHCs emphasizes that the uncertainties over whether effects could occur at very low doses must be considered. An endocrine MoA past the human response threshold for natural botanicals in the diet has not been demonstrated by the dossier submitter, and the weight of evidence does not support it.
Specifically for PDDP, its binding is over 3 orders of magnitude weaker than 17beta-estradiol and shows no clear evidence of ER mediated estrogenic activity in definitive studies. By comparison, soy isoflavones are also 3 orders of magnitude less potent than 17beta-estradiol and they have shown no clear evidence of ER mediated estrogenic activity at high dietary levels of exposure (Borgert et al. 2018).
If PDDP had an endocrine disrupting MoA that could lead to a significant endocrine disrupting related adverse effect, its mechanistic potency (i.e., affinity for the functional components that comprise the MoA, and its ability/activity to alter the functional state of those components) would have to be stronger than the human relevant potency threshold (HRPT) for ER agonism (Borgert et al. 2018)
	The substance induces adverse effects on fertility by its endocrine activity at doses relevant for classification in animal studies. A risk assessment is not part of an Annex XV dossier. Furthermore, neither ‘risk’ nor ‘potency’ are part of the ED definition according to OECD/WHO.	
		
• The available data on PDDP does not provide clear evidence of probable serious effects to human health and environment.

• The review of the Weight of Evidence by the dossier submitter has not considered potency, that the in vivo studies show secondary effects, and overall indicates a lack of strength of plausible causal relationship between activity and adverse effects.

For PDDP highly diagnostic parameters for estrogenicity were seen in in vivo mammalian data (increase in uterus weight and accelerated vaginal opening; furthermore, reduced ovary weight, decreased corpora lutea and prolongation of the oestrus cycle and the number of implantations was decreased). 
Adversity is proven by significant effects on fecundity and fertility in mammals (such as reduction in number of corpora lutea, reduced number of implantation sites, reduced fertility index, reduced number of pups, reduced litter size) leading to a reduced number of offspring. These effects are of population relevance and hence sufficient to conclude on the environmental ED properties of PDDP as well. 
The diagnostic and adverse effects are linked by a causal relationship as described in the Annex XV dossier and therefore PDDP fulfills the WHO/IPCS definition of an endocrine disruptor. 

Regarding potency: 
Potency is not a relevant factor when identifying substances as ED. The presence of other systemic toxicity is not pronounced enough to negate the findings of oestrogenic activity or the specificity of the adversity. 

		• Specifically, for human health:
o RAC stated in 2013 that the effects on fertility were not of high severity and that effects occurred concurrently with general toxicity
o No clear or consistent adverse outcome pathways for endocrine disruptor properties
	Please see the above responses in this section, where detailed answers for our reasoning are given.	
		• Specifically, for the environment:
o The substance is not PBT/vPvB
o Chronic daphnia study involved apical endpoints which are responsive to endocrine but as well to non-endocrine mediated pathways so no firm conclusion can be drawn
o Fish have a more sensitive system to endocrine modulators than daphnids, but daphnids shown to be more sensitive in acute studies
o Modelling of baseline toxicity effect concentrations indicative that apical effects are not related to specific mode of action but rather of polar narcosis
o Acute to chronic aquatic toxicity ratio is approximately 10; not supportive of specific mode of action (>10,000 for endocrine substances such as estradiol and trenbolone)
o Read-across to structurally similar substances not sufficiently robust to draw any further conclusions for PDDP as outside of boundaries
o The mammalian data should not be used as a surrogate to conclude on the environment.	- A substance can be identified as endocrine disruptor without fulfilling PBT or vPvB criteria. Art. 57(f) of REACH states that the effects have to be of an equivalent level of concern, e.g. with respect to irreversibility, decoupling of exposure and effect.
- A long term fish study is not available. It is not possible to draw any conclusions from standard acute aquatic studies for endocrine disruption, therefore it is irrelevant here that Daphnia are more sensitive than fish in acute aquatic toxicity assays. 
- Endocrine disruption occurs independently from polar narcosis. 
The presence of other systemic toxicity is not pronounced enough to negate the findings of oestrogenic activity or the specificity of the adversity (e.g. on fertility and fecundity).
- Acute to chronic aquatic toxicity ratio:  for fish no chronic studies are available, therefore an acute chronic ratio for fish cannot be derived here. 
- Read-across: The read-across to other long chain alkylphenols is used only as supporting information in the dossier. We amended this part of the dossier to further strengthen the applied read-across and to show how these data fit into the overall picture.
- Mammalian data can and must explicitly be used to conclude on effects in the environment if they are of population relevance. Please refer also to the Revised OECD Guidance Document 150 (OECD, 2018) and to the ECHA/EFSA ED Guidance relating to the Biocidal Products Regulation and the Plant Protection Products Regulation (ECHA et al., 2018). 
	
5501
2021/04/22	Health and Environment Alliance (HEAL),
International NGO,
Belgium	The Health and Environment Alliance (HEAL) thanks the German Competent Authority for its proposal to identify the group of substances Phenol, alkylation products with C12-rich branched or linear alkyl chains from oligomerisation, covering any individual isomers and/ or combinations thereof (PDDP) as substances of very high concern, under REACH article 57(c) as meeting the criteria for classification in the hazard class reproductive toxicity category 1B, and under article 57(f) due to their endocrine disrupting properties relevant for human health and the environment.
We fully support this proposal and our full comments can be found in the attachment.	Thank you for your support.	
		See the corresponding embedded attachment in table 1 of Part I: 5501_2021.04.HEAL_Comments_SVHC identification_PDDP Group.pdf		
5509
2021/04/22	Netherlands,
Member State	NL supports the proposal to include PDDP in the candidate list of SVHC in accordance with Article 57 (c) and Article 57 (f) of Regulation (EC) 1907/2006 (REACH) given the reprotoxic and endocrine disrupting properties.	Thank you for your support.	
				
5515
2021/04/23	Sweden,
Member State	We thank Germany for this proposal. We support the proposal to identify the substances as SVHC, meeting the criteria of Article 57 (c) and 57 (f). We agree, based on the provided data in the dossier, that these substances have endocrine disrupting properties for which there is scientific evidence of probable serious effects to human health and the environment which gives rise to an equivalent level of concern, according to the criteria of article 57(f) in REACH, to those of other substances listed in points (a) to (e) of Article 57 REACH.

We have following specific comments:

Page 8 and Sections 1 and 2, Concerning the description of the substance identity:
We interpret that the intended scope for the SID is to cover substances with both branched and linear alkyl chains, as indicated in the dossier by "Phenol, alkylation products (mainly in para position) with C12-rich branched or linear alkylchains from oligomerisation, covering any individual isomers and/or combinations thereof” (e.g. page 8 and section 1.2 page 12).
However, at the same time we note that the identification for 57c, based on the harmonized classification repro 1B refers to the CLH dossier and RAC opinion that covers only substances with branched alkyl chains, as indicated in the dossier by "Risk Assessment Committee (RAC) states that "the harmonised classification will apply to any substance which predominantly contains C12 (branched) alkyl-substituted phenols" (e.g. page 8 and section 2 page 18).
We interpret that substances with linear alkyl chains do not have harmonized classification and we are concerned that including them in the scope of SID for identification as 57c could be seen as an error for this "formal" reason.
As for the identification under 57f we note that there is data, presented in the dossier, for both type of substances, substituted with "branched" or "linear" alkyl chains. We consider that harmonized classification is not necessary for 57f entry, so the SID scope for this SVHC entry seems to be more flexible and it could cover branched (with harmonized classification) and linear (without harmonized classification).

Page 9 and Section 5, Concerning data for identification as ED for the environment.
We support the approach to use the rodent studies showing reproductive adverse effects to support identification as ED for the environment. (e.g. page 9 and sections 5.2.1-5.2.3).	Thank you for your support.

Thank you for your comment. We removed the reference to linear alkyl chains from the scope of this dossier accordingly. However, to strengthen the identifcation under 57f for the environmental part, we added a paragraph justifying the read-across between substances with linear and branched alkyl chains.

Thank you for your support.

5520
2021/04/23	European Environmental Bureau (EEB),
International NGO,
Belgium	The EEB supports the proposal by Germany to identify phenol, dodecyl-, branched (PDB) and all other group members (PDDP) as SVHCs based on their reproductive toxicity (REACH art 57(c)) and  endocrine effects on human health and the environment (REACH Article 57(f)).

The group of PDDP meets the criteria of Article 57 (c) of Regulation (EC) No 1907/2006 (REACH) owing to the classification of PDB in the hazard class toxic for reproduction category 1B, based on the RAC opinion adopted in 2013.

In addition PDDP should be identified as SVHC in accordance with Article 57 (f) of the REACH regulation because of their endocrine disrupting properties for which there is scientific evidence of probable serious effects to human health and the environment which gives rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 of the REACH Regulation.

The Annex XV dossier provides strong evidence for a causal link between the estrogenic activity of PDDP and adverse effects on fertility and sexual function. This supports the conclusion that PDDP are endocrine disruptors for human health according to the WHO/IPCS definition. In vitro data suggest also interaction with the androgen receptor and thyroid system. PDDP can be identified as endocrine disruptors for the environment as well based on the observed effects on fecundity and fertility, leading to a reduced number of offspring. The observed effects are relevant for terrestrial and marine mammalian wildlife because negative effects on reproduction and development will lead to serious effects at the population level, especially in case of wildlife species with low reproductive output. This supports the conclusion that PDDP are endocrine disruptors for the environment according to the WHO/IPCS definition. Due to the serious, irreversible effects at the population level in combination with the difficulty to derive safe effect levels for EDCs acting by estrogen activity, PDDP can be considered of equivalent level of concern to PBT and vPvB substances in the environment. In conclusion, the EEB agrees to the identification of PDDP as SVHC according to article 57(c) and 57(f) of REACH.	Thank you for your support.	
				
5530
2021/04/23	ChemSec,
International NGO,
Sweden	ChemSec supports the identification of this group of phenols as Substances of Very High Concern. While the classification as toxic to reproduction alone justifies Candidate listing the scientific data shows clearly the endocrine disruptive properties for both human health and the environment.	Thank you for your support.	
				
5537
2021/04/23	The Lubrizol Corporation,
Company,
France	Please see attached document.	See answers above to comments by Additives Technical Committee (ATC) Consortium, Task Force 33C.	
		See the corresponding embedded attachment in table 1 of Part I: 5537_Lubrizol response to PDDP SVHC consultation 23 April 2021-FINAL.pdf		
5538
2021/04/23	Finland,
Member State	We thank Germany for this proposal. We have the following comments on the Annex XV report:

page 9: “Furthermore, the organisms in the environment are exposed to a mixture of substances. Hence there can be additive or synergistic effects that might enhance the impact."
comment: Please consider adding a reference to other alkylphenols to make it more concrete statement about mixture effects.

page 20, 3.1.2.1.2. Screening tests
comment: Regarding the OECD TG 301B study, the results suggest a potential concentration effect. Did the study include toxicity controls or is other information on microbial toxicity available? We were not able to access these data from ECHA’s web pages.

page 70, 5.2.6. Summary and discussion of endocrine environmental effects
comment: We propose to restructure the text so that the main evidence used for environmental ED effects is presented first, and supportive data/lack of data are presented thereafter. Currently the text indicates that the mammalian data is used for the assessment of environmental ED effects because there is no data available for aquatic organisms. This can be understood so that if aquatic in vivo data was present, indicating ED effects, the mammalian data would then be less relevant. This is in contradiction with the text elsewhere in the document (also referred to in the same paragraph) that ED effects observed in mammalian studies conducted for human health assessment are relevant for environmental ED assessment if they are relevant at population level. For example, in the summary it is stated that “The evaluation of PDDP for the environment is based on mammalian data and supported by available fish in vitro tests and adverse outcome pathways.”.	Thank you for your comments. The document was amended accordingly.

Page 9: examples and 3 references are included in summary on page 9 included.

Thank you for bringing this to our attention. We reviewed the data and found that the authors report a toxicity control. Unfortunately, it did not comply with the usual provisions of the test guideline because it showed 57 % mineralisation at day 56 instead of giving details on mineralisation at day 14. Thus, it is not possible to compare with the usual specifications given for screening tests on ready biodegradability. However, we conclude that degradation was not hampered by toxicity because inoculum was pre-exposed and thus probably adapted prior to use. Inoculum should have at least developed some tolerance against the substance. A test on microbial toxicity in which the EC50 was found to be > 1000 mg/L (nominal) after 3 h seems to confirm this conclusion. 

Thank you for bringing this to our attention. The text is restructured, showing that the mammalian health data are of same importance as the environmental data for evaluation of the environment. 

	

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	
5499
2021/04/22	Calicio Limited (Additives Technical Committee (ATC) Consortium, Task Force 33C),
Industry or trade association,
United Kingdom	Please see the comments in the attachment submitted in Section IV.	Thank you for your comment and the information provided, that relate to the use of PDDP. 

Comments regarding use, exposure, alternatives and risks may, when relevant, be considered at later stages of the risk management process of the SVHC dossier.
	
		See the corresponding embedded attachment in table 1 of Part I: 5499_ATC TF33c Response to PDDP SVHC consultation_April 2021_Final.pdf

Confidential attachment removed		
5501
2021/04/22	Health and Environment Alliance (HEAL),
International NGO,
Belgium		Thank you for comment.	
		See the corresponding embedded attachment in table 1 of Part I: 5501_2021.04.HEAL_Comments_SVHC identification_PDDP Group.pdf		
5537
2021/04/23	The Lubrizol Corporation,
Company,
France	Please see attached document	Thank you for providing additional information on the use, exposure, alternatives and risks of PDDP, especially to the manufacture and application of calcium phenate detergents, as well as your comments (Annex XV report Part II; p. 83-89). However, the current focus in the proceeding is on the issue of SVHC identification of PDDP, so we will address this at a later step (see our responses in Part II of the comment table).	
		See the corresponding embedded attachment in table 1 of Part I: 5537_Lubrizol response to PDDP SVHC consultation 23 April 2021-FINAL.pdf