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

Substance name: Dicyclohexyl phthalate (DCHP)
CAS number: 84-61-7
EC number: 201-545-9

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 57 c); Equivalent level of concern having probable serious effects to human health and the environment (Article 57 f)

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

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

General comments on the SVHC proposal
Number/ Date	Submitted by (name, submitter type, country)	Comment	Responses	
4574
2016/03/15	Germany,
Member State	Chapter 4.1. Toxicokinetics:
The 4th paragraph of this section states that the metabolic pathway follows at least two steps, one being phase I hydrolysis followed by phase II conjugation. However, for other transitional phthalates such as DEHP (CAS 117-81-7), phase I hydrolysis is followed by formation of oxygenated metabolites. This should be addressed.

Chapter 4.3.3:
When discussing human relevance of the in vitro and in vivo findings, available epidemiological studies (obtained from other reproductive phthalates as e.g. DEHP) should be considered and human relevance should be discussed in the context of these studies. In Annex II, 2 epidemiological studies are cited. However, more studies seem to be available and they should be presented in a balanced way.

Chapter 6.2.1:
In the conclusion of the Substances of equivalent level of concern assessment it is stated: “… (DCHP) is proposed to be identified as a substance of very high concern in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because it is a substance with endocrine disrupting properties for which there is scientific evidence of probable serious effects to human health and the environment which give rise to an equivalent level of concern to those of other substances listed in points (a) to (e) of Article 57 of REACH.
With respect to human health it is our understanding that an appropriate ELoC assessment cannot be replaced by or mutated into matching whether elements of the WHO/IPCS definition are met. Further, the human relevance is only globally elaborated in the document and in its Annex II. It should be checked whether in addition to the 2 epidemiological studies mentioned in Annex II further epidemiological studies are available. If so, these studies should in addition be considered when discussing human relevance.

Presentation of physico-chemical data in the dossier:
The pressure stated for the melting point measurement is given as 11 atm. However, it should be changed to 1 atm as stated in the respective reference (ECHA dissemination site)	Section 4.1: To our knowledge there are no data on the formation of oxygenated metabolites of DCHP. A sentence has been added stating this. Since the monoester is believed to be the cause of the adverse effects, knowledge of formation of other phase I metabolites is not considered necessary for evaluating the reprotoxic effects of DCHP, including the mode of action.

Section 4.3: Epidemiological studies on other phthalates are considered in the Mode of action framework described in Annex II.  Inclusion of even more studies on other phthalates is not considered relevant, as the conclusions on the ED properties of DCHP, including the ultimate reprotoxic effects, are mainly based on studies of this particular phthalate. Epidemioloigcal studies on other phthalates are used as supporting evidence only. There are no epidemiological studies on DCHP.

Further, although data exists showing exposure of the general population to DCHP, exposure considerations are not relevant for hazard identification.

Section 6.2.1
Similar to eg. DEHP, the RAC opinion on CLH for DCHP indicates that data are consistent with an anti-androgenic action of DCHP.  Since the ultimate effect of relevance for 57c and 57f is identical in this case an elaborate ELoC assessment is neither necessary nor meaningful.

Physico-chem: This was already changed in the current version of the Annex XV report.

		-		
4577
2016/04/01	Company,
Netherlands	

Confidential attachment has been removed.	Thank you for this information. Please note that the current SVHC proposal is not a ban, but a hazard identification covering DCHP´s effects as toxic for reproduction and endocrine disrupting properties.	
4579
2016/04/08	Industry or trade association,
Switzerland	Confidential attachment has been removed.
	Thank you for this information. Please note that the current SVHC proposal is not a ban, but a hazard identification covering DCHP´s effects as toxic for reproduction and endocrine disrupting properties.	
4587
2016/04/13	ECPI - European Council for Plasticisers and Intermediates,
Industry or trade association,
Belgium	Cf attached file	Please find responses in the attached Word document.

				
4593
2016/04/14	Netherlands
Member State	NL supports the proposal to include DCHP in the candidate list of SVHC in accordance with Article 57 (c, f) of REACH for its reprotoxic and ED effects.	Thank you for your support.	
4609
2016/04/14	Health and Environment Alliance (HEAL),
International NGO,
Belgium	The Health and Environment Alliance strongly supports the nomination of DCHP as an SVHC, particularly as one of equivalent concern for its endocrine disrupting properties.  According to the analysis of our expert participating in the Endocrine Disruptor Expert Group of ECHA, the in vitro and in vivo data indicate an anti-androgenic mode of action; there is biological plausibility between the mode of action and the observed adverse effects and changes in biomarkers; and there is Existence of adverse effects, and these are relevant to humans.  The equivalency of the concern is also fulfilled because of the severity, irreversibility, latency of onset, large effects on society and individual quality of life.  In short we concur with the argumentation of the dossier submitter, and thank them for their work.	Thank you for your support.	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
4574
2016/03/15	Germany,
Member State	The German CA supports the proposal for identification of dicyclohexyl phthalate as a substance of very high concern in accordance with Article 57(c) of Regulation (EC) 1907/2006 (REACH) because it meets the classification criteria for reproductive toxicity, category 1 B. However, the proposal for identification in accordance with article 57(f) is not fully supported in its entirety as explained in the following:

This proposal is in line with the aim to identify all reprotoxic phthalates as SVHC. In accordance with Article 37(4) of the Regulation (EC) No 1272/2008, the Committee for Risk Assessment (RAC) has adopted an opinion for harmonised classification and labelling of dicyclohexyl phthalate. At RAC-31 (December 2014) the RAC adopted the opinion that dicyclohexyl phthalate meets the criteria for classification as toxic for reproduction Repr. 1B, H360D (“May damage the unborn child.”). Therefore the requirements for SVHC identification are fulfilled.
Dicyclohexylphthalate has a harmonised classification as Repr. 1B on the evidence of adverse effects on the reproductive organs in experimental animals. It has been confirmed by RAC that these effects are attributed to an anti-androgenic mode of action (MoA).Therefore the German CA agrees that Dicyclohexylphthalate has an endocrine activity. However, we do not support SVHC identification based on a MoA alone as no equivalent level of concern has been established. It is rather considered the same concern (i.e. effect) which has already been taken into account for the proposal for harmonised classification and labelling as Repr. 1B.

Conclusion regarding human health:
The German CA does not support the additional identification of DCHP as a substance of very high concern for human health in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) as an endocrine disruptor due to the reasons stated above.
Conclusion regarding the environment:
The identification as a substance of very high concern for the environment in accordance with Article 57(f) is supported by the German CA as the presented data allows the identification of the substance as an endocrine disruptor for the environment in fish and mammalian wildlife species according to the WHO/IPCS definition of endocrine disrupting substances.
Thus, disregarding the question how to deal with reprotoxic effects that might be evoked by an endocrine disruption pathway or another mode of action for human health (identification according 57(c) vs. 57 (f)) as mentioned above, identification of DCHP as a 57 (f) substance for the environment seems adequate since a new concern would be addressed by this option.	Thank you for supporting the 57c proposal and your recognition of the endocrine activity of DCHP.

Regarding 57f (ED-human health), we agree that it is the same ultimate toxic effect, but not necessarily the same concern since there are some differences in other parts of the authorization process depending on identification as ED or not. 

Thank you for your support for the Article 57(f) proposal on identifying DCHP as an endocrine disrupter for the environment.

4576
2016/04/01	United Kingdom,
Member State	We thank Sweden for their proposal and have the following comments;

Toxic for Reproduction (Art 57c)
We agree that Dicyclohexyl phthalate (DCHP) meets the criteria according to Article 57(c).

Equivalent level of concern having probable serious effects to human health and the environment – Endocrine disruption  (Article 57 f)

As an opening remark, until an EU regulatory definition of endocrine disrupters (EDs) has been endorsed by CARACAL, the UK believes that it is premature to propose substances for identification as endocrine disrupting chemicals (EDCs) under REACH. We also do not accept an interpretation of Article 57(f) which proposes that EDs automatically meet the definition of equivalent concern.  The requirement for “scientific evidence of probable serious effects to human or the environment which give rise to an equivalent level of concern” must still be demonstrated case-by-case.

The proposal is that Dicyclohexyl phthalate (DCHP) meets the criteria of Article 57(f) on both human health and environmental grounds. UK does not support this proposal.

Considering the human health and environmental aspects separately we have the following comments;

Human Health

Although there is evidence that DCHP may have endocrine disrupting properties, the causality of the adverse reproductive effects in relation to the endocrine activity/pathway has not been clearly demonstrated, and a clear endocrine MoA has not been established.

Although adverse effects on reproduction have been observed following exposure to various other transitional phthalates and are thought to be mediated by an anti-androgenic or estrogenic MoA, the adverse effects observed in studies conducted on DCHP were not as extensive as other phthalates and the potency of DCHP was considered to be low.

In studies conducted on DCHP, reproductive organs in adult male animals were not affected and there were no observed effects on fertility. Furthermore, the relevance of the observed evidence of endocrine effects to humans cannot be fully determined and there are some inconsistencies between the available studies.

Based on the data available, there is no clear evidence of equivalent level of concern of having probable serious effects to human health, relating to the potential for endocrine disruption, sufficient to identify DCHP as SVHC.

In addition, if it is considered that the reproductive toxicity of DCHP is mediated by an anti-androgenic or estrogenic mode of action, resulting in classification for Repr. 1B, then these adverse effects on human health support the identification as a SVHC under article 57(c). It is not necessary further identification under article 57(f), for the same effect.

In conclusion we do not consider that identification of DCHP as SVHC under Article 57(f) is appropriate. Classification of DCHP as Repr. 1B will result in identification under Article 57(c) and the evidence of endocrine disruption is not sufficient for identification under Article 57(f). Equally there is no justification for further identification under Article 57(f) for a mechanism which drives the classification for Repr. 1B and subsequent identification of DCHP as SVHC under Article 57(c).

Environment

In our opinion, the dossier submitter has not presented a convincing argument that DCHP can cause adverse effects in the environment via endocrine disruption sufficient to be considered of “equivalent concern” (p.7).  We therefore do not support the proposal on environmental grounds.

Further comments on the Annex XV dossier;

• Environmental fate properties
p. 12, Section 3.1 (Degradation): A ready test giving between 68.5 and 91% degradation would appear to show rapid degradation. Although no reference is given, we presume from other sources that this is a Japanese regulatory test, so has the dossier submitter contacted the Japanese government for additional details? Would BIOWIN predictions help to provide more confidence in this result?

p. 12, Section 3.3 (Bioaccumulation): It would be helpful to indicate what the calculated BCF values are using the measured log Kow value (the text just says they will be ‘lower’ – by how much?), and to confirm that the substance is within the model domain(s). We have also found another Kow prediction of 5.4 quoted on the INERIS portal (accessed via the OECD eChemporal), citing “JRC (2009)”, but have not reviewed this information.

Whilst we agree that the Kow values imply a high bioaccumulation potential, we note that the substance is metabolized in mammals (Section 4.1). We therefore think that experimental evidence (or a much more convincing weight of evidence analysis based on non-test information, including relevant read-across) is required to confirm the actual level of bioaccumulation before this information can be used to identify an SVHC.

• Environmental hazard assessment

p. 20-21, Section 5 (Environmental hazard assessment): The logic presented in the dossier is that any substance causing reproductive effects via endocrine disruption in mammals can automatically be considered to pose a sufficiently high concern to identify it as an SVHC for the environment. We do not agree as a matter of principle. Instead, we consider that it depends on the environmental fate and behaviour properties of the substance as well as the potency of the effect.

In our opinion, DCHP appears to be rapidly degradable, the actual level of bioaccumulation is unknown and the NOAELs for the mammalian effects are in the range 10-50 mg/kg bw/day. The dossier submitter has not assessed the likelihood of relevant secondary poisoning potential (“exposure”) in this context.

Based on the comments on the mammalian studies above, the evidence for a consistent and significant adverse effect with a clear endocrine mode of action is weak, and there is no discussion about whether the level of “effect” is considered to be of high potency.

A high level of concern on the basis of the mammalian studies has therefore not been demonstrated.

In addition, the lack of dose response and limited findings in the fish partial life-cycle test mean that the data are not sufficiently robust to use as supporting evidence (contrary to the statement made in the dossier).

In conclusion, we do not believe that the dossier submitter has made a convincing argument that DCHP can cause adverse effects in the environment via endocrine disruption.	Thank you for the support to nominate DCHP according to the Article 57(c) criteria.

We agree that it would be good to have criteria for endocrine disruptors, but unfortunately these are not available. The REACH text does neither refer to, nor require, criteria for inclusion of endocrine disruptors in the candidate list on a case-by-case basis. 

This process has already been applied for other substances (nonylphenol + ethoxylates + 4-tert-octylohenol + ethoxylates + DEHP) identified as endocrine disruptors fulfilling REACH art. 57f with relevance for the environment. 
The same process can be applied for endocrine disrupters with relevance for human health.

Human health:

We do not share your view that the data are insufficient to conclude on the endocrine MoA of the developmental toxicity. In our view the data reviewed and discussed in detail in Annex I and II of the SVHC proposal show that the WHO/IPCS definition of an endocrine disruptor is fulfilled. This view was shared by the majority of the members in the ECHA ED expert group, when assessing these data. Further, RAC in their opinion on the harmonized classification of DCHP for developmental effects concluded that “mechanistic studies indicate an antiandrogenic mode of action that is considered relevant for humans”. 

Please note that potency is not a criterion when assessing reprotoxic effects.

More information/detailed responses can be found in the response to comment #4587 (from EPCI). 

Regarding 57f (ED-human health), we agree that it is the same ultimate toxic effect, but not necessarily the same concern since there are some differences in other parts of the authorization process depending on identification as ED or not. 

Environment:

We agree that DCHP appears to be readily biodegradable in screening tests. This is also in concordance with results for other similar phthalate esters such as DEHP. Biowin estimates have been included in the annex XV report. We have furthermore included a table that compares environmental fate properties between different phthalates. The Japanese government has not been contacted to get access to the study report.

BCF values estimated with the experimentally derived log Kow of 4.82 have been included in the Annex XV report. And it has been noted that predictions are within the applicability domain.

Phthalate esters are known to be metabolized in mammals (and in fish) and hence BCF values for phthalates are lower than expected from log Kow alone. Experimental BCF values are available for the “neighbouring” C4/C6 phthalate BBP (Highest BCF: 188) and the C8/C8 phthalate DEHP (highest BCF: 1380). The BCF for DCHP (C6/C6) is expected to be somewhere in between that of BBP and DEHP.   

The logic behind the proposal is, amongst others, that rodents are environmental relevant species (besides being used as models for effects in humans) and that adverse effects on development and reproduction are normally considered relevant at population level. 

Article 57(f) does neither refer to environmental fate related properties nor to exposure, but rather to the likelihood of serious effects of EloC as CMRs/vPvB/PBTs due to endocrine disruptive properties of the substance.

In summary, we do not agree that the evidence for a consistent and significant adverse effect with a clear endocrine mode of action is weak. This view was shared by the majority of the members in the ECHA ED expert group, when assessing these data. Potency is not mentioned in neither the WHO definition nor in Article 57f (both texts refer to “effects”). Neither is potency used for classification for reproductive toxicity. It is very difficult to compare “potency” between rodent studies and fish studies due to the different exposure routes (dietary compared to uptake via gills). The effects observed in the partial life cycle test with Medaka (VTG induction at 4.39 µg/L, sex ratio at 1.41 µg/L) could indicate effects at low concentrations. However, due to the lack of dose response it is difficult to interpret the results. 
	
		-		
4577
2016/04/01	Company,
Netherlands	See attachments under General comments:
4577_NXP Submission_DCHP_ CAS number 84-61-7_20160401.doc
Confidential attachment has been removed.	Thank you for this information. Please note that the current SVHC proposal is not a ban, but a hazard identification covering DCHP´s effects as toxic for reproduction and endocrine disrupting properties.	
4578
2016/04/07	Belgium,
Member State	Belgium wants to thank Sweden and Denmark for the work done. Overall, the annex XV report on DCHP is very clear. The use of the “Mode of action framework analysis” helps to have a clear understanding of the available data on ED properties (MoA and adverse effects) of DCHP. This also helps to clarify the plausible relationship between the different identified key events.

Based on the data available, Belgium supports the identification of DCHP as SVHC (according to art.57(c) and art.57(f)).
The scarce data on fish don’t allow to draw a firm conclusion for fish, but the available rodent data indicate a concern for human health and for wildlife species with a natural low reproductive output. So we support the identification of DCHP as an endocrine disruptor for both human health and the environment.
The assessment of the equivalent level of concern is supported by Belgium.	Thank you for your support.	
4579
2016/04/08	Industry or trade association,
Switzerland	Confidential attachment has been removed.	Thank you for this information. Please note that the current SVHC proposal is not a ban, but a hazard identification covering DCHP´s effects as toxic for reproduction and endocrine disrupting properties	
4583
2016/04/12	Norway,
Member State	The Norwegian CA supports that Dicyclohexyl phthalate (DCHP) should be identified as a substance of very high concern (SVHC) and should be included in the Candidate List. We support that DCHP should be identified as a SVHC in accordance with Article 57 (c) of the REACH Regulation, as the Committee for Risk Assessment (RAC) has concluded that the substance meets the criteria for classification as toxic for reproduction Repr. 1B, H360D (“May damage the unborn child”). Concerning the proposal to identify DCHP as a SVHC in accordance with Article 57 (f) of the REACH Regulation, the ECHA Endocrine Disruptor Expert Group (EDEG) has concluded that the substance can be regarded as an endocrine disrupting substance for human health in accordance with the WHO/IPCS definition of an endocrine disruptor. The Norwegian CA supports this approach. According to the Annex XV report, the information on endocrine disrupting effects of DCHP in the environment is scarce. The reproductive effects of DCHP in mammals (rats), in combination with the absence of clear adverse effects related to an endocrine mode of action in partial life-cycle test in fish, makes it plausible that DCHP can cause adverse effects in the environment via an endocrine mode of action. We agree that due to the conservation of the steroid hormone system it is very likely that a wide range of wildlife species with different functions in the ecosystems could be affected. However, more data on fish and other wildlife species would be desirable to make the conclusions regarding endocrine effects.
DCHP was tentatively identified in several biota types in
non-target screening in Norway in 2014, see: http://www.miljodirektoratet.no/no/Publikasjoner/2016/Februar-2016/Screening-program-2014/
DCHP was also tentatively found in sewage sludge in non-target screening in Norway in 2013, see: http://www.miljodirektoratet.no/Documents/publikasjoner/M27/M27.pdf	Thank you for the support.

Thank you for the screening information on DCHP occurring in biota and sewage sludge. However, since there is no quantification of concentration levels we have not included the information in the dossier. 
	
4586
2016/04/13	Company,
Italy	According to the RAC report (Feb 2015), the DCHP Category 1B classification for development is based on observations of reduced anogenital distance and mammae/nipple retention in males; and recorded effects on male reproductive organs (testicular atrophy, reduced testicular spermatid head count and decreased weight of the prostate and of the levator ani/bulbocavernosus). When considered in the light of the entire database, the significance of these findings is low and therefore does not warrant classification.
While effects on reproductive organs were noted in some studies for DCHP, the toxicological significance of these reported findings is questionable as they are not dose responsive, consistently observed, and/or reliably reported in the database.
o For example, it cannot be agreed that observations of testicular atrophy are reliable in a study (Ayodogan Ahbab, 2013) the dossier submitter described as „not so well reported‟.
 This study failed to report several important parameters which are key for understanding if the observed effects are chemical specific (e.g. clinical signs, litter size, sex ratio, live birth index etc.).
 The study also had gross errors in the reporting of organ weight outcomes where, for example, the testes are reported to weigh more than the entire animal; and questionable statistics (e.g. small standard errors were calculated for endpoints with large variation in reported values).
o Deficiencies in study design impact the quality and reliability of the evidence and should not be overlooked in assessments. The CLP refers to this aspect of study quality consideration as follows: “if deficiencies in the study make the quality of the evidence less convincing, Category 2 classification could be the more appropriate classification.”
o The reported occurrence of reduced testicular spermatid head counts (Hoshino et al. 2005) is also of questionable significance.
 This observation was found in only one of the two generations of animals examined; was not accompanied by a change in sperm motility morphology, or number; and did not lead to any deficit in the ability of these males to reproduce.
 This finding was also not reported in other studies examining DCHP effects on sperm (Ahbab Ayodogan, 2013). The identified decreased weight of the prostate and levator ani/bulbocavernosus were also not dose dependent nor consistently reproduced in the database as they were only reported in one study (Yamasaki et al. 2009).
Consistency and toxicological significance of observations impacts the weight of the evidence and should be considered in a classification determination. For DCHP, the above observations are of low toxicological significance and therefore do not provide clear and sufficiently convincing evidence to warrant classification as category 1B.	The harmonized classification of DCHP as Repr.1B (H360D) has been agreed and will thus not be discussed further in the context of the present SVHC proposal.
	
4587
2016/04/13	ECPI - European Council for Plasticisers and Intermediates,
Industry or trade association,
Belgium	Cf attached file	Please see attachment under General comments.	
		See attachment under General comments: 
4587_DCHP Annex XV dossier_ECPI_comments_ April_13_2016_Final.pdf		
4590
2016/04/14	ChemSec,
International NGO,
Sweden	DCHP
ChemSec supports the identification of DCHP as an SVHC based on its endocrine disrupting properties. It is clear that the identification should cover both human health and the environment. We already in 2011 identified it as an EDC for the SIN List. In 2012 the Danish EPA again evaluated the substance in the context of their proposed EDC critera, and concluded it to be a Category 1 EDC. We are impressed by the report, which is thorough and takes the relevant scientific studies into account.

RAC having agreed that the substance fulfils classification as a reprotoxic compound further strengthens the case.

Recently published study further strengthens the case:
Mathieu-Denoncourt J et al. 2016. Lethal and sublethal effects of phthalate diesters in Silurana tropicalis larvae. Accepted manuscript online: 29 February 2016. Environmental Toxicology	Thank you for the support and the additional information on ecotoxicity.

The Mathieu-Denoncourt et al. (2016) study investigates acute effects (lethality and sub-lethality) on tadpoles combined with measurements of gene expression of certain genes related to drug metabolism and transport, liver metabolism, xenobiotic clearance, and xenobiotic metabolism. As such, the results are not directly useful for identification of endocrine disrupting effects and we have therefore not included this information in the Annex XV dossier.  	
4600
2016/04/14	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust particularly supports inclusion of Dicyclohexyl phthalate in the REACH candidate list under article 57 (f) due to its endocrine disrupting properties. Based on the convincing evidence presented in the Annex XV dossier we concur with the conclusion that DCHP should be considered an endocrine disruptor for both the environment and for human health.  In addition, CHEM Trust supports the proposal to include DCHP on the candidate list based on it meeting the classification criteria for reproductive toxicity, category 1 B (RAC opinion December 2014). Therefore the inclusion in the candidate list should indeed be based on both articles 57(f) and (c).	Thank you for your support.	
4608
2016/04/14	Academic institution,
France	ANSES supports identification of  DCHP as SVHC 57(c) on the basis of its classification Repr 1B pending on adoption of the 9th ATP.

In relation to identification of DCHP as SVHC 57(f) for endocrine disruptive properties on human health , ANSES notes:
- The adverse effect on male reproductive tract is well established as acknowledged by the corresponding classification
- ANSES welcomes the detailed assessment by SW/DK using the MoA/Human relevance Framework. The proposed general MoA is highly supported by the whole database. Although ANSES notes that there is no experimental evidence of causal relationship in between the various observations and key events, (in particular, it is unclear from the dossier what are the identified early alterations of Leydig and Sertoli cells functions and how it is expected to impact testosterone levels -may also be secondary?), ANSES considers that the biological plausibility, temporal association and dose-response relationship strongly support that male reproductive tract damages observed are linked with alteration of steroidogenesis in fetal life. In particular specific effects such as decreased AGD are considered to be good indicator of an anti-androgenic effect. The overall consistency in the pattern of effects is therefore considered as convincing and sufficient by ANSES to show an antiandrogenic endocrine MoA relevant for identification as SVHC 57(f).
- On the basis of the different steps identified in the MoA, ANSES agrees that there is no reason to exclude human relevance. In addition, testosterone is essential for male reproductive tract differentiation in mammalian species. We however note that all experimental data for DCHP (except some toxicokinetics data) are performed on rat. The effect of DCHP on male reproductive tract is similar to effects observed with other medium chain phthalates, which provides strong support to the adverse effects observed but thus it would be relevant to also consider the DCHP discussion of human relevance in the light of data for medium chain phthalates (or justify why it is not relevant).
In particular experiments performed on marmosets as well as in animals with xenographs of human fetal testis raise some uncertainties on whether the anti-androgenic pathway is predominant in humans or has a different expression or whether additional MoA may operate. It is however recognized that available data may not cover (all) the appropriate critical windows for exposure and the anti-androgenic MoA identified in rats does not preclude that additional MoA (in particular involving effects on germ cells) may operate in primates/humans. Overall, ANSES support that human relevance of the antiandrogenic MoA should be assumed but welcome a more transparent description of the uncertainties in the dossier in order to provide a scientifically complete dossier.
In relation to endocrine disruptive properties on environment, ANSES completely agrees to consider data on effects in rats as relevant for mammalian wildlife species, especially as environmental data in fish don’t allow concluding alone. Moreover a significant exposure of DCHP for environmental organisms and a potential bioaccumulation cannot be ruled out as there is a lack of characterization of the environmental exposure and on the PBT status. No scientifically robust conclusion on the readily biodegradable criteria and the bioaccumulation criteria is given.

ANSES is therefore generally in support to the proposed identification as SVHC 57(f) due to endocrine disrupting properties through an antiandrogenic MoA relevant for humans and environment.	Thank you for your support. The 9th ATP was agreed in February 2016.

Thank you for the support to identify DCHP as SVHC 57(f) due to endocrine disrupting properties through an antiandrogenic MoA relevant for humans and environment.	
		-		
4616
2016/04/25	Finland,
Member State	In the Annex XV report DCHP is proposed to be identified as a substance of very high concern (SVHC) in accordance with both Article 57 (c) and Article 57 (f) of REACH Regulation (EC) 1907/2006. The presented justifications for identification according to Article 57 (c) are based on the adopted opinion of the Committee for Risk Assessment (RAC-31, December 2014) that the substance meets the criteria for classification as Repr. 1B; H360D (May damage the unborn child). DCHP is included in the 9th ATP to CLP. The identification according to Article 57 (f) is based on identified endocrine disrupting effects both on human health and the environment.

Human health:

The Finnish CA agrees that DCHP meets the criteria as SVHC according to Article 57 (c) because of its Repr. 1B classification and according to Article 57 (f) as giving rise to an equivalent level of concern because of its endocrine disrupting properties and scientific evidence of probable serious effects to human health.

However, the added value of this approach in relation to human health risk management is not evident to us. The identification of DCHP as a SVHC in accordance with article 57 (c)  appears to cover to some extent endocrine disrupting properties because an anti-androgenic mode of action seems to be one of the mechanistic backgrounds for the reproductive toxic effects which are the basis for Repr. 1B classification. The Finnish CA considers that it could be evaluated further whether a candidate list entry based on Article 57 (c) and the following authorization process would cover sufficiently the concerns of endocrine disrupting effects from the human health point of view.

Environment:

In general, The Finnish CA acknowledges the added value of the proposed approach to apply two parallel criteria (Article 57 (c) and 57 (f)) for the entry to the candidate list from the environmental risk management point of view.

It is concluded in the proposal that the effects observed in rats are of particular concern for wildlife species, and justify the identification of DCHP as an endocrine disruptor for the environment. While the Finnish CA acknowledges the relevance of the effects detected with rats for mammalian wildlife, we have some concern about the scarce information of other relevant environmental impacts of DCHP as a whole.

The general approach for identification is presented in the proposal: 'For considering endocrine disrupting effects in the environment, data from both terrestrial and aquatic species should be analyzed'. In agreement to that approach, the available fish tests with ED relevant endpoints, although showing some inconsistencies in dose responses, should be reconsidered in the identification to get a more complete picture of the environmental ED properties of DCHP. Additionally, given that DCHP indicates potential ready biodegradation and potential fast biotransformation, the impact of these properties on environmental ED identification should be further evaluated.

The Finnish CA notes that in the Risk Management Option Analysis (RMOA) Conclusion Document (March 2015) it was concluded that the identification as SVHC according to Article 57 (c) and/or 57 (f) would be appropriate.

The Finnish CA considers that after a potential inclusion of the substance in the candidate list (for eventual inclusion in the Annex XIV) it can still be further explored which risk management measures would be the most appropriate.
	Thank you for your comments and general support. 

Regarding 57f (ED-human health), we agree that it is the same ultimate toxic effect, but not necessarily the same concern since there are some differences in other parts of the authorization process depending on identification as ED or not. 

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	
4573
2016/02/29	Individual,
Belgium	Clearly DCHP is an endocrine disruptor.  I did no serious literature search, but a fast review on PubMed for:
dicyclohexyl phthalate (toxic* OR hazar* OR risk* )

reveals several experiments clearly establishing this.  I hope you also searched Web of Science; together the two best sources for finding financially independent academia's studies.

I strongly support SE & K's proposal (and note how the conclusion differs from SE's (KEMI) ridiculous Substance Evaluation of Thiram; deciding its published studies indicating EDCness were invalid based on illogical and industry junk science arguments, such as systemic toxicity at lowish doses in industry studies somehow invalidates its EDC findings at similar dose (and only a single dose!)).	Thank you for supporting our proposal.	
4575
2016/03/29	Industry or trade association
Belgium	The substance DCHP with CAS number 84-61-7 is present as a minor, but essential constituent in special glues used in the semiconductor sector to assemble dedicated semiconductor devices into their final package.

The use of glues with minor levels of DCHP is essential for the functionality of several specific semiconductor components in the identification, medical and security domain. DCHP is present in these glues at a concentration < 0.3 % w/w.

The DCHP containing glues are manufactured in Europe and currently available on the European market. Part of the semiconductor assembly production is located in Europe, whereas the major part of assembly by Europe based semiconductor companies is performed in their Asian Pacific assembly facilities. A European ban on DCHP would therefore chiefly imply a supply-chain interruption for the European semiconductor industry with assembly sites in other continents.
The total quantity of DCHP used is < 5 kg/y (< 2.5 kg/y in Europe) in chemicals @ concentration < 0.3 % w/w. The total quantity of the chemical consumed is < 100 kg/y, around 50 kg/y in Europe.

Due to the low concentration in glue and the low glue quantity consumed for each semiconductor device product the nominal DCHP concentration in the assembled semiconductor device – the article - is < 0.1.

During glue curing the DCHP present in the glue (co-)polymerizes and it is no longer present in the final device as pure, free DCHP. No exposure will arise to the public because material is cured and immobilized in the semiconductor assembly inside a package, which is sealed with an epoxy compound. Those components are used in the electronics of several appliances. During semiconductor manufacturing, there is no potential exposure of employees, thanks to the strict requirements on air borne contaminants in semiconductor clean rooms. The glue is dispensed in closed syringes and LEV is applied at the dispensing area, and in and close to the polymerization oven, to extract potentially released fumes.
Empty syringes are managed as hazardous waste and sent for incineration. There is no expected release to water.
Like all electronic components embedded in electronic equipment these devices are managed at the end of their life according to the WEEE Directive in Europe.

The value of the semiconductor devices manufactured in Europe with these DCHP based glues is very significant.  Whereas the value of devices manufactured with DCHP based glues in Asia Pacific is a few orders of magnitude higher. The business impact in Europe and Worldwide of a future legislative measure would be very substantial. Substitution of DCHP in the glue is difficult in view of the high user requirements and would require disproportionate, high investment costs and qualification resources. In some cases the replacements identified may contain suspected CMR substances that do not improve the nature of hazardous composition. It is not likely that complete substitution and phasing out can be achieved within 40 months.	Thank you for this information. 

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
		-		
4577
2016/04/01	Company,
Netherlands	USE
The substance dicyclohexyl phthalate (DCHP) with CAS number 84-61-7 is present as a minor, but essential constituent in a special glue used by NXP Semiconductors to assemble dedicated semiconductor devices in their package. The concentration of DCHP in the glue is < 0.3 wt percent.
NXP applies this DCHP based glue in the manufacture of devices used in the identification, and security domain. Application of this glue with minor levels of DCHP ensures the functionality of these devices. Besides, the high requirements of these specific semiconductor devices can be met.
The glue is produced by a European supplier. Currently, NXP perform the assembly 100% in the Far East.
On a yearly basis NXP use approximately 20 kg of the glue in their Far East assembly sites. The corresponding DCHP use is less than 100 gram per year.

PROCESS AND EXPOSURE TO EMPLOYEES
The glue is dispensed in closed syringes. The glue is cured at 150⁰C in an oven. Upon curing the DCHP co-polymerizes and is no longer present as pure, free DCHP.
The exposure to workers is minimal thanks to the measures applied: the glue is dispensed in syringes, and LEV is applied at the dispensing and oven areas to extract potentially released fumes.
There is no release to wastewater. Empty syringes are treated as hazardous waste and are sent for incineration.
The process descriptors are indicated in the table.

Sector  Identified use  Life cycle stage  Sector of use  Chemical product Process Category  Article Category  Environmental  Release Category
Semiconductor  Use of adhesive Manufacturing  SU 16 PC 1 PROC 2  AC 2 ERC 5

FINAL PRODUCT AND POTENTIAL RISK TO CUSTOMERS
The nominal DCHP concentration in the final semiconductor device – the article – is < 0.1%. Due to the curing the DCHP is co-polymerized and immobilized, and no longer present as free DCHP. Therefore, there is no exposure to the customer. At the end of life these devices are disposed of following the WEEE Directive in Europe.

BUSINESS RISK AND ECONOMICAL IMPACT
The DCHP containing glue is currently available on the European market. NXP Semiconductors perform their assembly activities in facilities located in the Far East. A European ban on DCHP would comprise a supply-chain interruption for NXP Semiconductors worldwide. Besides, a ban in Europe would be a blockade for potential future NXP assembly activities with DCHP in Europe.

The market value of the devices that NXP manufactures with this DCHP containing glue is very high. The exact value is given in the confidential attachment.
There may be DCHP-free glue substitutes, but their performance is questionable and is still to be proven. Substitution would entail high cost, qualification effort, and much time. Every application requires thorough qualification. Complete phasing out is expected to take more than 40 months. All in all, a ban on DCHP based glues would be disproportionate in view of the negligible and well controlled risks.	Thank you for this information. 

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
		See attachments under General comments:
4577_NXP Submission_DCHP_ CAS number 84-61-7_20160401.doc
Confidential attachment has been removed.		
4579
2016/04/08	Industry or trade association,
Switzerland	The substance DCHP with CAS number 84-61-7 is present as a minor, but essential constituent in special glues used in the semiconductor sector to assemble dedicated semiconductor devices into their final package.
The use of glues with minor levels of DCHP is essential for the functionality of several specific semiconductor components in the identification, medical and security domain.
DCHP is present in these glues at a concentration < 0.3 % w/w.
The DCHP containing glues are manufactured in Europe and currently available on the European market. Part of the semiconductor assembly production is located in Europe, whereas the major part of assembly by Europe based semiconductor companies is performed in their Asian Pacific assembly facilities. A European ban on DCHP would therefore chiefly imply a supply-chain interruption for the European semiconductor industry with assembly sites in other continents.
The total quantity of DCHP used is < 5 kg/y (< 2.5 kg/y in Europe) in chemicals @ concentration < 0.3 % w/w. The total quantity of the chemical consumed is < 100 kg/y, around 50 kg/y in Europe.
Due to the low concentration in glue and low quantity consumed for each semiconductor device product the nominal DCHP concentration in the assembled semiconductor device – the article - is < 0.1 %.
During glue curing the DCHP present in the glue (co-)polymerizes and it is no longer present in the final device as pure, free DCHP.
No exposure will arise to the public because material is cured and immobilized in the semiconductor assembly inside a package, which is sealed with an epoxy compound. Those components are used in the electronics of several appliances.
During semiconductor manufacturing, there is no potential exposure of employees, thanks to the strict requirement on air borne contaminants in semiconductor clean rooms.
The glue is dispensed in closed syringes and LEV is applied at the dispensing area, and in and close to the polymerization oven, to extract potentially released fumes.
Empty syringes are managed as hazardous waste and sent for incineration. There is no expected release to water.
Use = semiconductor sector
Identified Use = adhesive
Life Cycle Stage= Manufacturing
Sector = SU 16
Chemical Product = PC 1
Process Category = PROC 2
Article Category = AC 2
Environmental Category Release = ERC 5
Like all electronic components embedded in electronic equipment these devices are managed at the end of their life according to the WEEE Directive in Europe.
The value of the semiconductor devices manufactured with these DCHP based glues is 80M$ per year. Substitution of DCHP in the glue is difficult in view of the high user requirements and would require disproportionate, high investment costs and qualification resources. Moreover In some cases the replacements identified may contain suspected CMR substances that do not improve the nature of hazardous composition.  It is not likely that complete substitution and phasing out can be achieved within 40 months.	Thank you for this information. 

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
		Confidential attachment has been removed.		
4586
2016/04/13	Company,
Italy	Dicyclohexylphthalate is used as phlegmatizer for organic peroxides to be used by professionals and industry, and, as such, is not expected to be in contact with general public	Thank you for this information. 

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4587
2016/04/13	ECPI - European Council for Plasticisers and IntermediatesIndustry or trade association, Belgium	Cf attached file	Please see attachment under General comments.	
		See attachment under General comments: 
4587_DCHP Annex XV dossier_ECPI_comments_ April_13_2016_Final.pdf