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

Substance name: hexamethylene diacrylate (hexane-1,6-diol diacrylate) (HDDA)
CAS number: 13048-33-4
EC number: 235-921-9

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

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

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	Response	
4492
2015/10/02	CEPE,
Industry or trade association,
Belgium	-	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.

The existence of adequate control or risk management measures does not preclude identification as a substance of very high concern.
Sensitization has previously been deemed as an irreversible health effect by the EU court and we believe that the same reasoning should be applied in the assessments of skin sensitization to HDDA. 	
		Attachment: 		
4493
2015/10/05	Sun Chemical,
Company,
Netherlands	Please see the submission from CEPE (our trade association), who have provided consolidated information from member companies on exposures and incidences of skin sensitisation, and also from DUCC and CEFIC, who have provided a commentary as to the significance of the equivalent level of concern proposal; we support these submissions as well.	Please refer to the answer to comment 4492 under general comment to the SVHC proposal
	
4505
2015/10/12	Zeller+Gmelin GmbH&Co KG,
Company,
Germany	
Confidential attachment has been removed	
Please refer to the answer to comment 4492 under general comment to the SVHC proposal 

The classification of HDDA as Skin sens 1 is based on the skin sensitising properties of HDDA itself and not to any impurities. Thus, the skin sensitizing properties of HDDA are attributed to the substance itself. In addition, many of the reports of allergic contact dermatitis to HDDA in humans that we have found were published in 2010 and onwards. This indicates that the problem with occupational allergic contact dermatitis is still relevant although reports from the industry suggest improvements in the purification process (Ido, Kiyohara et al. 2012, Kiec-Swierczynska, Krecisz et al. 2013, Vogel, Christoffers et al. 2014)	
4508
2015/10/12	Germany,
Member State	The German CA would like to add one remark related to an aspect of the dossier:
Chapter 10 (page 33) lists potential alternatives. All of these are skin sensitisers as well. Some of them also score high in the "Cross sectional work place study" (page 17). The usefulness of mentioning these compounds as alternatives is therefore questionable.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4509
2015/10/13	TOYO INK ARETS NV,
Company,
Belgium	-	Please refer to the answer to comment 4492 and 4505 under general comment to the SVHC proposal. 
	
		Attachment: 
		
4513
2015/10/13	Company,
Germany	Please refer to the attachment	The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  
	
		Attachment: 

4515
2015/10/14	Company,
Norway	Since we are encouraged to refer to page number in front of our comments we would welcome page numbers in the document, not only in the content.	Thank you for your comment	
4517
2015/10/14	Roland DG Mid Europe S.R.L. - Acquaviva Picena (AP),
Company,
Italy	If EC 235-921-9 (CAS 13048-33-4) can't be used in ink industry, ink development of the UV-curing type is restrained. As a result it is no longer forced to use a solvent volatilization type of ink, VOC emissions increases, and social environment load will increase.It's expected that environment risk of global warming and air pollution increases. To restrain use of low UV ink of global environment risk, we would like you to quit designation to SVHC.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.
	
4526
2015/10/14	NXP Semiconductors,
Industry or trade association,
Netherlands	
Confidential attachment has been removed	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.
	
4527
2015/10/14	3M Belgium NV/SA,
Company,
Belgium	See part I comments		
4558
2015/10/15	Company,
Sweden	- At our production site we have had two cases over a period of 30 years (1985 and 2005) when a worker exhibited skin rashes. The correlation with acrylates was not proven, and the workers recovered when not handling acrylates. HDDA was not identified as the sensitizing substance.
- HDDA has been used in the manufacture of UV inks on our site for 15-20 years.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.
	
4562
2015/10/15	PARAD Consortium,
Other contributor,
Belgium	-	The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  
	
		Attachment: 
		
4564
2015/10/15	Company,
United Kingdom	
Confidential attachment has been removed	Please refer to the answer to comment 4492 under general comment to the SVHC proposal 	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Response	
4490
2015/09/09	European Trade Union Confederation
Trade union,
Belgium	ETUC supports the identification of hexamethylene diacrylate (hexane-1,6-diol diacrylate)as SVHC. The substance is included in the Trade Union Priority List for REACH Authorisation. See: https://www.etuc.org/trade-union-priority-list 	Thank you for your support and the valuable information	
4492
2015/10/02	CEPE,
Industry or trade association,
Belgium	We are of the opinion that HDDA does not fulfill the conditions of SVHC according to REACH ARt 57(f). It is a know skin sensitizer but its use in our sector is controlled and the number of workers having shown skin reactions during the past 40 years is limited and the observed effects were reversible.See attached document for further information.	Please refer to the answer to comment 4492 under general comment to the SVHC proposal
	
		Attachment: 
		
4493
2015/10/05	Sun Chemical,
Company,
Netherlands	Section 4.5.1.2 It is important to note that the purity of HDDA has changed significantly during the time of its commercialisation.  In the early days of manufacture, HDDA could contain significant levels of residual acrylic acid (1%) and processing solvents (2%).  Since around 2000 the purity specification has improved such that the residual levels of acrylic acid and processing solvent are below 0.1%.  This means that epidemiological studies and historical data generated using the much less pure HDDA is of limited significance in determining the human sensitisation hazard as compared with the relatively pure substance in commercial use today.  Analysis of the epidemiological data should take this into account (in particular the high level of residual solvent in the historical purity grade is considered to have facilitated dermal penetration and induction of sensitisation).

Section 6.3.2  The signs of skin sensitisation are erythema and oedema.  These are the same as exposure to skin irritants (although the mechanism is different).  It may often be difficult to distinguish between simple dermatitis and allergic contact dermatitis for this reason.  The physical manifestation of the exposure disappears when the substance or the individual is removed from the exposure situation.  Although skin sensitisation may be considered as irreversible, the health effects are reversible and can be easily implemented.  This does not make skin sensitisers in general and HDDA in particular, of equivalent concern to CMR substances.  In the few situations where occupational exposure has occurred, due to operator failure to wear appropriate PPE, it is simply remedied by the operator avoiding exposure to HDDA in future by changing task or moving to another part of the factory production.  Unlike CMRs, skin sensitisation from exposure to HDDA is not life-threatening.	Thank you for your comment. Please refer to answer to comment 4505 under general comments. 
The reported cases of allergic contact dermatitis that we refer to in the Annex XV report have all been diagnosed by positive patch tests to HDDA. Those cases are therefore confirmed as skin sensitization and not skin irritation. 

Please refer to the answer to comment 4492 under general comment to the SVHC proposal 	
		-		
4494
2015/10/09	Spain,
Member State	We acknowledge HDDA is a potent skin sensitizer that fulfils the criteria for Skin Sens. 1A. As explained in the report, skin sensitization first needs an induction phase that is irreversible although asymptomatic. However, the adverse effects elicited after subsequent exposure are generally of a reversible nature after cessation of exposure. These adverse effects can be of varying severity (the most severe case described is rare) but we have doubts that they can be considered as serious or equivalent to those effects provoked by CMR substances or even respiratory sensitizers. It also should be noted that in CLP legislation skin sensitization is communicated as a lower level of hazard (Warming and Exclamation pictogram) than CMR and respiratory sensitization (Danger and Health Hazard pictogram).	The Swedish Chemicals Agency thank Spain for the comments on the Annex XV dossier for HDDA, please find our answers below and in the attached document.

Irreversibility:
Allergic contact dermatitis to HDDA is an irreversible adverse health effect commonly manifested as eczematous lesions (i.e. rash, blisters, skin detachment) on the exposed skin that in severe cases can spread outside of the exposed area (Morgan and Fewings 2000, Ido, Kiyohara et al. 2012, Vogel, Christoffers et al. 2014). A person that is sensitized to HDDA can only be free from symptoms if he or she can avoid exposures to HDDA. The sensitized subject may also respond to other acrylates, when cross reactivity has occurred.
A judgement by the EU Court of Justice concluded that the adverse health effects from the respiratory sensitizer HHPA and MHHPA are irreversible . For both skin and respiratory allergy, the sensitization phase is irreversible and the elicitation is in principle reversible. However, prolonged or repeated exposures may lead to chronic health effects, particularly so in highly sensitised individuals or to potent sensitizers. Respiratory sensitizers can lead to chronic inflammation of the lung and skin sensitizers may lead to permanent scarring or persistent dermatitis. Since the development of allergic skin reactions occur according to the same principles as allergic lung reactions, the skin sensitizing effect of HDDA should also be considered irreversible. 

Severity of effects:
In the ECHA discussion paper on identification of substances as SVHC under REACH article 57(f) mild and severe skin damage are described as follows :
“Mild damage e.g. a rash that can heal quickly, when exposure to the sensitising agent is stopped.”
“Severe damage e.g. blistering that can burst. Skin function (integrity) is impaired, possibly leading to infection. Ongoing exposure can lead to chronic inflammation and scar formation. Minimal or a single small focus of scarring does not normally constitute “severe organ damage or major permanent functional change” in the skin as an organ.”
Based on this definition, we believe that the case studies in the Annex XV dossier provide sufficient evidence that HDDA can cause severe effects in humans. The most severe case describes a woman who developed severe allergic contact dermatitis that progressed to the life threatening condition “Toxic epidermal necrolysis” (TEN)(Ido, Kiyohara et al. 2012). We have been in contact with a Professor Anders Vahlqvist, expert in dermatology at Uppsala University who confirmed that the clinical and histopathological signs of the patient described in the report are consistent with TEN. 
 
Conclusion:
With the background on the definition of severe skin reactions in the ECHA discussion document and the judgement on HHPA and MHHPA in the EU court. We believe that the case studies in the Annex XV dossier provide sufficient evidence of that HDDA can cause severe and irreversible effects in humans.	
4495
2015/10/09	Siegwerk Druckfarben AG & Co. KGaA,
Company,
Germany	Generally, Siegwerk thinks that a Classification and Labelling of a substance according to the CLP Regulation No. (EC) 1272/2008 as a skin sensitizer cannot be an adequate basis for a substance with dermal sensitising properties for examination as SVHC due to “equivalent level of concern”.
In the majority of cases, skin sensitization become manifest in allergic contact dermatitis, which is treatable and preventable by avoidance of exposure (e.g. by appropriate personal protective equipment – PPE). An event of allergic contact dermatitis is not life-threatening to the same extent as adverse effects potentially caused by carcinogenic, mutagenic and reprotoxic chemicals.
HDDA is classified as category 1 skin sensitizer according to CLP Regulation (EC) No 1272/2008. Classification itself has not been challenged by the Swedish competent authority. Nevertheless, they state that occupational exposure to HDDA is of societal concern. As HDDA processing downstream user / ink manufacturer we have the practical experience that this is not the case. The main application is UV curing printing inks for industrial use only. The skin sensitizing effect of HDDA depends upon several criteria, most notably the intensity and duration of contact, as well as individual susceptibility. The proposed PPE as referenced in section 8 of the respective product safety data sheets (SDS) is sufficient and effective in order to avoid occupational HDDA exposure levels which are relevant for neither an induction step nor an elicitation step of allergic contact dermatitis.
The risk of skin sensitization is well known. Internal trainings and communication of risk management measures is done on a regular basis. However, unintended exposure can occur due to splashing and spillages or improper use of PPE. Also at Siegwerk five cases of unintended exposure to HDDA are documented. In none of these cases allergic contact dermatitis occurred even to people working with HDDA regularly over years which means they had not been induced due to effective risk management measures (PPE). The exposed worker showed only local irritating effects which were reversible after a couple of days.
HDDA is an important raw material used mainly in UV curing ink production. It has been used in the ink manufacturing industry in thousands of tons over decades of years. Its skin sensitization potential is well known and effective managed and controlled by proper measures (e.g. use of PPE). Siegwerk is convinced that skin sensitizers in general and HDDA in particular do not present an equivalent level of concern and should not be considered as SVHC.	Article 57(f) does not limit the kind of intrinsic properties that a substance can have in order to be of equivalent concern to substances listed in Article 57(a) to (e). Substances can therefore be identified as SVHC under Article 57(f) on the basis of their skin sensitising properties. Indeed,  several MSCAs and the Commission/ECHA have been considering the possibilities for and need to identify substances with sensitising properties as SVHC under the ‘equivalent level of concern’ route set out in Article 57(f) of REACH. To support this work ECHA has prepared a discussion paper which can be used when assessing whether substances with sensitising properties could be identified as SVHC, under the ‘equivalent level of concern’ route set out in Article 57(f) of REACH.

KemI carried out an ELoC assessment for HDDA according to the principles in the ECHA discussion paper. Based on the assessment, we believe that HDDA fulfil the criteria in REACH Article 57(f) and should be identified as an SVHC.

Please also refer to the answer to comment 4492 under general comment to the SVHC proposal
	
		-		
4503
2015/10/12	Norway,
Member State	The Norwegian CA supports that Hexamethylene diacrylate (HDDA) fulfils the criteria as a substance of very high concern (SVHC) in accordance with Article 57(f). HDDA is a skin sensitizer with a strong potency. The sensitization is an irreversible effect and may give rise to severe allergic contact dermatitis in humans (lesions with blisters and skin loss that spread outside the exposed area). The severe reactions may in some cases progress to life threatening conditions. We agree there is scientific evidence of probable serious effects to humans that give rise to "equivalent level of concern", HDDA fulfils the criteria of Article 57 (f).	Thank you for your support.	
4505
2015/10/12	Zeller+Gmelin GmbH&Co KG,
Company,
Germany	
Confidential attachment has been removed	Please refer to the answers to comment 4492 and 4505 under general comment to the SVHC proposal 	
4506
2015/10/12	Finland,
Member State	HDDA is proposed to be identified as a substance of very high concern (SVHC) in accordance with Article 57 (f) of Regulation (EC) 1907/2006 based on its skin sensitisation properties. HDDA has harmonised classification Skin Sens. 1; H317.

The available animal and human data indicate strong potency of skin sensitization for HDDA. SE CA has included a good ELoC assessment in the proposal. Comparison of adverse health effects between HDDA and CMR substances was made using the comparison factors which are described in ECHA's general approach for identification of substances as SVHCs due to equivalent level of concern to CMRs (Article 57 (f)). Based on the available information FI CA supports the conclusion that HDDA should be considered as a substance that is of ELoC with substances that fulfil the criteria in Article 57 (a)-(c).

The RMOA conclusion document on HDDA which has been published on ECHA's website concluded that a revision of the harmonised classification from Skin Sens. 1 to sub-category 1A might be warranted. However, the revised CLH was not considered as the most appropriate RMO for risk reduction. Instead, SVHC identification was considered more appropriate.

As a procedural first step, the Finnish CA would favour a decision (or RAC opinion) on the harmonised classification (possible Skin Sens. 1A) and labelling prior to SVHC identification. We agree with SE CA that the effect of revised classification may not be adequate to reduce the risk, if most of the products actually contain ≥ 0.1 % of HDDA. However, in our view, the sub-categories for skin sensitization, especially 1A, are important for risk communication. In addition, known strong skin sensitisers classified for sub-category 1A would better justify the SVHC identification. A case-by-case assessment is however always necessary.

The Finnish CA considers that after inclusion of the substance in the candidate list (for eventual inclusion in the Annex XIV) it still needs to be further considered which risk management measures would be the most appropriate.	Thank you for your support and valuable comments. The Swedish Chemicals Agency will take your suggestions into consideration.	
		-		
4508
2015/10/12	Germany,
Member State	The German CA supports the identification of hexamethylene diacrylate as substance of very high concern in accordance with article 57 (f) of regulation (EC) No 1907/2006 (REACH).	Thank you for your support	
4509
2015/10/13	TOYO INK ARETS NV,
Company,
Belgium	We believe that HDDA is not a substance that presents an equivalent concern to CMRs Category 1 and it should not be considered an SVHC because:
• We had not one case in our plant of skin sensitization during the past 15 years.
• Where exposure is possible (through splashing and spillages) proper protective equipment is worn in our factory for protection at all times (for all products): gloves (nitrile), safety glasses, goggles, full coverall, apron, long sleeves, respiratory mask, safety boots.
• Where possible, manual handling is avoided (automated pumping, enclosure, ..).
• The risk of skin sensitization of HDDA is well known. We give regular internal training on the risk of chemicals and the use of PPE.
• Tox. data being used in consideration of the SVHC rating is old and was generated at a time when the monomer was quite “dirty” and contained relatively high levels acrylic acid, which was responsible for a lot of the skin contact issues seen with its early use.
• HDDA has very unique properties as a raw material, namely it gives very good adhesion, has low viscosity and a high reactivity.
• The alternative raw materials for HDDA often have SDS ratings that are more severe, i.e. corrosive.

Conclusions:
HDDA is a valuable acrylate for our company in the formulation and manufacturing of UV curing ink and varnishes for various industrial applications. It has been used in hundreds of tons in our company during the past 15 years with zero reported cases of skin sensitization. Its skin sensitization potential is well known and proper measures have been put in place to avoid exposure: training, PPE and engineering measures. For these reasons we believe that HDDA is not a substance that presents an equivalent concern to CMRs Category 1 and it should not be considered an SVHC.	Thank you for your comments. Please refer to answers to comment 4492 and 4505 under general comments to SVHC proposal. 
	
		Attachment: 
		
4512
2015/10/13	Company,
Germany	Skin sensitization in general can not be compared to CMR properties. A well-known source for skin sensitization, for example, is flour. Bakers often suffer such a sensitization. If skin sensitizers are considered to be of equivalent concern like CMR substances, this means that flour is to be considered to be as hazardous as, for example benzene. Skin sensitization, however, is a problem, but it isn't life-threatening.	Thank you for your comment. Please refer to RCOM on comment 4495 under specific comments on the justification.	
4513
2015/10/13	Company,
Germany	-	The Swedish Chemicals Agency would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document. 

		Attachment: 4513_HDDA-PARAD questionnaire to DU final_20150604.pdf
		
4515
2015/10/14	Company,
Norway	p. 15

Top of page says that patient groups at dermatology clinics indicate a high frequency of sensitisation as they report positive diagnostic patch test reactions in more than 2% of the patients.  It is implicit that these patients are elucidated for their skin eczema. What is the cause of the residual 98%..?
Under Case reports one incident of TEN is reported. The last sentence in the first section refers to “The patients was…”. It should be “patient” as it is only one patient. In section two it is said that the incident of TEN is very low, 0.4-1.2 cases per million and year. And that the majority of this is related to adverse drug reactions. This means that getting TEN caused by HDDA is far below one in a million. Normally the acceptable risk of getting cancer is one in a million per year. The report gives the expression that the risk of getting TEN is perceived as even higher than getting cancer. We do not agree with this. The majority cases of TEN are reversible, cancer is not.
By the way, in last section on p. 15 it says that her clothing had become soaked.  This is far beyond exposure expected by normal handling and use and must best be described as an accident.

p. 16

First section describes a man that spilled a bucket of effluent over himself. Again, this can be defined as an accident.

p. 18

A general remark to the information on this page is that we don’t really find the findings in these studies surprising. The report already states that cross-reactivity between HDDA and other acrylates may be expected. Also, the patients included in these studies are already suspected of having allergy to acrylates. We therefore can’t see that these studies justify that HDDA in particular shall be treated as an SVHC.

p. 23

The last sentence under the heading “Delay of health effects” says that it is difficult for workers to take precautionary actions in time to avoid development of sensitisation. We do not agree with this statement as the hazard label will warn about skin allergy and recommend precautions to avoid skin contact.

p. 24

Under “Societal concern” section two relating to “heavy socioeconomic impact” we would like to question the relevance of the Diepgen et al. study regarding the cost-of-illness from occupational chronic hand eczema. As far as we understand the biggest cause of hand eczema is related to water exposure (hair dressers, cleaners etc.). We can’t see that there is any documentation supporting the hypothesis that HDDA may have significant socioeconomic impact in this respect as the cases of HDDA eczema would be only marginal in comparison to other causes of eczema.
Last sentence in the section beginning with “A widespread use in…” says that the highest volume in products is about 30% HDDA, indicating that exposure to these products are associated with a relatively large probability of becoming sensitized. We find this statement a bit vague/ speculative since there is a presumption that there is exposure in an occupational setting where this “30% HDDA” is used.
Under first bullet point: With reference to the very rare incidents of TEN (already described as life threatening) we find the wording “in some severe cases” very strong and that it may be misleading to the reader (ref. comments p. 15) as he may believe that it is more common than it actually is.

p. 25

Section beginning with “Occupational allergic contact…”. We do not agree that ooccupational allergic contact dermatitis is associated with the same impaired quality of life similar to psoriasis and asthma. In fact, the occupational allergic contact dermatitis will be reversed ones the exposure discontinues while psoriasis is a long lasting autoimmune disease. Further, it is known that asthma may be triggered by non-specific factors (e.g. low temperature, perfumes, irritants etc.) while ooccupational allergic contact dermatitis is a caused by a chemical specific reaction e.g. by individual acrylates.	Thank you for your comments. As a general remark please refer to answers to comment 4492 under general comments to SVHC proposal. 
p. 15: The information given in the Annex XV dossier describe that the frequency of sensitization to HDDA exceed the guidance value (2%) for classification as Skin Sens. 1A and should be considered a potent human skin sensitizer. Thus, the information should be interpreted as 2% of the dermatitis patients in the studies are allergic to HDDA and 98% are allergic to another substance. 
The patients included in the studies are tested for contact allergy against a number of selected allergens. The frequency of sensitization to HDDA as well as to other acrylates varied among the patients in the different studies (see section 4.5.1.2 epidemiological studies in the dossier) and patients were often sensitized to more than one acrylate. 
TEN is an idiosyncratic skin reaction which means a very severe, rare and unpredictable hypersensitivity reaction that is mostly associated with exposure to pharmaceuticals. The information in the dossier illustrate that HDDA is a substance that can cause the idiosyncratic reaction TEN. It is not relevant for the SVHC identification to make any comparisons to the risk of developing cancer. 
p. 18: The fact that there is a cross reactivity between different acrylates and that sensitization to HDDA, in some cases, can be caused by exposure to other acrylates is not a reason for not taking regulatory measures. It should be noted that exposure to HDDA may also cause sensitization to other acrylates. The overall problems with occupational skin sensitization to acrylates may therefore improve following a phasing out of HDDA.
24: The study by Diepgen et. al. estimates societal costs from occupational chronic hand eczema. The concept of hand eczema includes several diagnoses, where the most frequently occurring are irritant contact dermatitis and allergic contact dermatitis. Individuals with hand eczema perceive the lesions in a similar way, regardless of origin. 
The case reports in the Annex XV dossier describe patients that develop eczematous lesions on the hands, wrist, face etc. and because they patch test positive to HDDA, the eczema is considered to be of allergic origin. Studies on patient with hand eczema are therefore relevant for the ELoC assessment of HDDA.	
		-		
4516
2015/10/14	Company,
United Kingdom	pg 7 and 14 - The data being used for the consideration of the SVHC rating is quite old.  At the time the data was generated, the monomer contained relatively high amounts of acrylic acid, which may be responsible for many of the skin contact issues seen many yaesr ago.  The monomer is much cleaner today.	Thank you for your comment. Please refer to answer to comment 4505 under general comments. 
	
4517
2015/10/14	Roland DG Mid Europe S.R.L. - Acquaviva Picena (AP),
Company,
Italy	There was the case that substances classified as respiratory sensitization has been the SVHC equivalent concern, but there are no case that substances classified as skin sensitization are equivalent to SVHC in the past.
On the CLP Regulation, H334 is required pictogram "Health hazard mark" and signal word "Danger" by CLP regulation.
On the other hand, H317 is required pictogram "Exclamation mark" and signal word "Warning", it is the low grade compared to H334.
In addition, we recognize that H334 is likely to cause difficulty breathing and the high risk because there is a risk of life-threatening.  On the other hand, the risk of H317 is not relate to life immediately. Therefore, we think that risk of H317 is low compared to H334.	Thank you for your comment. Please refer to RCOM on comment 4495 under specific comments on the justification.	
4526
2015/10/14	NXP Semiconductors,
Industry or trade association,
Netherlands	
Confidential attachment has been removed	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4527
2015/10/14	3M Belgium NV/SA,
Company,
Belgium	3M supports and promotes the fundamental principles of REACH, including but not limited to the goals of life cycle management, product safety, sustainable development, and effective risk communication to employees and customers. 3M appreciates the opportunity to comment on the proposed identification of hexamethylene diacrylate (HDDA in the following) as Candidate List substance according to Article 59.
In the Annex XV dossier “HDDA is 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 skin sensitising properties for which there is scientific evidence of probable serious effects to human health which gives rise to an equivalent level of concern (ELoC) to those substances listed in points (a) to (c) of Article 57 REACH.”

1) 3M recommends not to add HDDA to the Candidate List for eventual inclusion in Annex XIV, as substances having sensitizing properties should not be directly assimilated or listed under the “equivalent level of concern” to substances having CMR Cat1A and 1B properties, but to consider alternative risk management options to protect human health which are more precise and application driven. This could be a restriction according to Article 67 of REACH or a sector specific regulation. The aim should be to reduce the risk of exposure from high risk applications which currently take place under less controlled conditions.
Any regulatory action should be carefully investigated for its counter measures. In any case it should not be forgotten that REACH should ensure a high level of protection of human health and the environment as well as the free movement of substances, on their own, in mixtures and in articles, while enhancing competitiveness and innovation.

2) HDDA is to a large degree used in well controlled industrial production processes of the polymer industry as well as in largely closed professional processes. Industry has taken appropriate measures to protect human health and to minimize the exposure risk. Communication is done via Safety Data Sheets, labelling and safe use guidance information to downstream users to ensure safe handling and safe use of those products containing HDDA.  (Co)polymers made with the multifunctional acrylic monomer HDDA are used in almost any market segment. The resulting polymers do have valuable properties. The chemical industry should not be put at risk and forced to shift manufacturing locations outside the EU. Thus the risk of humans being sensitized by the exposure to HDDA will merely shift to outside the EU.

3) Annex XV report states that HDDA belongs to the group of “multifunctional vinyl monomers” (Chapter 10.1.). It is 3M’s believe that “monomers” are exempt from the authorisation as stated in ECHA’s “Guidance on intermediates” (Version 2, December 2010)1): “Any use of a substance as an on-site isolated intermediate is not subject to authorisation (i.e. Title VII – Authorisation - does not apply) (Article 2 (8)(b)). This is also valid for intermediates used as monomers for the synthesis of polymers).”
This should be also the case for HDDA which is used as “multifunctional vinyl monomer” in many polymerization processes.

4) Replacement of HDDA in those processes is not possible within reasonable time frames to fully match the application specific polymer characterization profiles.
Furthermore, in chapter 10 of the Annex XV report current knowledge on alternatives is given. All of the listed alternative substances either have a harmonized classification as Skin sens. 1 or are Self-classified as Skin Sens. 1.

As a producer, formulator and coater of polymers it is 3M’s believe that an in depth evaluation of safer and technically feasible alternatives should be performed before the decision is taken to include substances on the candidate list for eventual inclusion in Annex XIV. Monomers are necessary for these industrial products that are ultimately reacted and safe for intended use. Replacement of one substance by several substances with similar properties might add higher complexity to the risk assessments.	Thank you for your comments. As a general remark and answer to comment 2) and 4) please refer to answers to comment 4492 under general comments to SVHC proposal. 

1) Identification of respiratory sensitizers as SVHC have previously been deemed not to be a disproportionate measure . 
The judge from the EU general court says that worker protection legislation and restriction in REACH cannot be considered as more appropriate and less burdensome measures  compared to identification as SVHC which solely entails information obligations.

We believe the same reasoning should apply to skin sensitizers of equivalent level of concern to CMR such as HDDA
 
3) The exemption of HDDA from the authorization system covers monomers intended for intermediate uses only. The registration dossier for HDDA includes non-intermediate uses that are covered by the authorisation system (see part II section 8 in Annex XV dossier).  

The mere fact that a substance has an intermediate use cannot exempt it from identification as a SVHC. Art 57 criteria relate to the intrinsic properties of a substance and intermediate does not relate to properties of a substance.
Concerning the definition of intermediate: Art 3(15) an intermediate is a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance (‘synthesis’) 

According to ECHA guidance on intermediates: Where the main aim of the chemical process is not to manufacture another substance but rather to achieve another function, specific property or a chemical reaction as an integrated part of producing articles is not an intermediate use.	
		-		
4533
2015/10/14	Ireland,
Member State	The Irish CA agrees that there may be sufficient evidence to indicate that HDDA is a potent skin sensitiser. However, we consider that the case for equivalent level of concern in accordance with article 57(f) has not yet been proven for the following reasons:

• A number of the points presented in the Annex XV dossier to support identification of HDDA as equivalent level of concern in accordance with article 57(f) are not specific to HDDA and could in fact be applied to all skin sensitisers. For example, the irreversibility of the induction phase of sensitisation, the delay of health effects, quality of life and societal concern.
• While we accept that the induction phase of sensitisation can be considered an irreversible reaction, in the case of skin sensitisers the elicitation reactions are generally reversible upon cessation of exposure to the causative agent. For HDDA, the available information indicates that the skin reactions were reversible following cessation of exposure. Therefore, we consider that case for the “severity” criterion being comparable to CMR effects is not yet proven.
• A number of the case reports presented in the Annex XV dossier did not definitively identify HDDA as the causative agent and during follow up patch testing, positive reactions were also found to other acrylates and/or other substances. While we accept that this indicates a possible concern for the cross reactivity of acrylates as a group, it makes the assessment of the influence of HDDA in the induction of sensitisation difficult.
• We note the argument that the use of high concentrations of HDDA in industrial settings may be associated with higher probability for more people to become sensitised is presented in the Annex XV dossier to support equivalent level of concern (section 6.3.3). We consider this may be a reason to consider other regulatory measures to minimise the concentrations used in certain high risk applications rather than supporting the case for equivalent level of concern.

Therefore, based on the information presented in the Annex XV dossier, the Irish CA considers that it is currently not possible to definitively conclude on whether HDDA should be identified as an SVHC in accordance with Article 57(f).	The Swedish Chemicals Agency thank Ireland for the comments on the Annex XV dossier for HDDA, please find our answers below and in the attached document.

Specificity of the provided evidence:
We believe that the Annex XV dossier provide sufficient evidence that HDDA is of equivalent level of concern to CMR according to the ELoC factors presented in the ECHA discussion paper . For the health related factors; severity of effects, irreversibility and delay of effect, and also for derivation of a safe level of exposure, the dossier provide scientific evidence that are specific for HDDA on each factor. The case reports describe that the patients developed symptoms after weeks to years at the workplace, clearly indicating a delay from initial exposures to manifestation of hazardous effects (Morgan and Fewings 2000, Ido, Kiyohara et al. 2012, Vogel, Christoffers et al. 2014). The reports also state that the patients suffered from recurring symptoms if the exposure continued, clearly indicating the irreversibility of the induction phase (Morgan and Fewings 2000). Delayed effects and recurring allergic reactions are also reported in manicurists that are sensitized to acrylates, including HDDA, but were HDDA has not been confirmed as the culprit allergen (Cravo, Cardoso et al. 2008, Pesonen, Kuuliala et al. 2012, Kiec-Swierczynska, Krecisz et al. 2013). 
For the “other” factors; impact on quality of life (QoL) and societal concern there are less specific evidence to HDDA. However, there is convincing evidence that occupational contact dermatitis decreases the quality of life and entails large costs to the society and also that exposure to HDDA can cause allergic contact dermatitis (se answer to comments above). 
In our experience studies on QoL and societal concern are rarely done on specific substances. Instead, it is more common to carry out such studies based on a specific diagnosis, such as contact dermatitis. Also, it is in general difficult to estimate the true incidence of contact allergy from skin and respiratory sensitizer’s substances in the EU. Thus, if identification of skin- and respiratory sensitizers will require studies on quality of life and societal concern that are specific for the particular substance we think it will be difficult to identify any sensitizing substances as SVHC.

Irreversibility:
Allergic contact dermatitis to HDDA is an irreversible adverse health effect commonly manifested as eczematous lesions (i.e. rash, blisters, skin detachment) on the exposed skin that in severe cases can spread outside of the exposed area. A person that is sensitized to HDDA can only be free from symptoms if he or she can avoid exposures to HDDA. The sensitized subject may also respond to other acrylates, when cross reactivity has occurred.
A judgement by the EU Court of Justice concluded that the adverse health effects from the respiratory sensitizer HHPA and MHHPA are irreversible. For both skin and respiratory allergy, the sensitization phase is irreversible and the elicitation is in principle reversible. However, prolonged or repeated exposures may lead to chronic health effects, particularly so in highly sensitised individuals or to potent sensitizers. Respiratory sensitizers can lead to chronic inflammation of the lung and skin sensitizers may lead to permanent scarring or persistent dermatitis. Since the development of allergic skin reactions occur according to the same principles as allergic lung reactions, the skin sensitizing effect of HDDA should also be considered irreversible.

Cross reactivity:
The fact that there may exist cross reactivity between different acrylates and that reactivity to HDDA, in some cases, possibly is caused by exposure to other acrylates is not a reason for not taking regulatory measures. Cross-reactivity between sensitizing substances is common and should not prevent regulatory measures for specific substances. It should be noted that exposure to HDDA may also cause sensitization to other acrylates. HDDA is a very potent skin sensitizer and the overall problems with occupational skin sensitization to acrylates may improve following a phasing out of the most potent ones, such as HDDA.
Cross-reactivity to acrylates is difficult to prove in humans who generally have been exposed to more than one acrylate, particularly in the case of occupational exposure (Kanerva 2001). Cross-reactivity has been studied in guinea pigs, and the cross reactivity pattern among diacrylates seems to be much more pronounced for TPGDA and NPGDA, than for HDDA (Bjorkner 1984). Reactions due to cross-reactivity are of very high clinical relevance since skin exposure to a cross-reacting substance also may elicit severe allergic reactions.

Other risk management options:
First we would like to point out that considerations of other regulatory options are not relevant for the SVHC identification. The issue on different risk management options was addressed earlier under the RMO phase and a justification on why we consider SCHC identification as the best RMO is included in the RMO document.

In addition, the identification of respiratory sensitizers as SVHC has previously been deemed not to be a disproportionate measure. A judge from the EU general court says that worker protection legislation and restriction in REACH cannot be considered as more appropriate and less burdensome measures compared to SVHC identification which solely entails information obligations as a first step. We believe that the same reasoning should apply to skin sensitizers of equivalent level of concern such as HDDA.	
		-		
4534
2015/10/15	European Trade Union Confederation,
Trade union,
Belgium	ETUC supports the identification of hexamethylene diacrylate.
This substance is included in our Trade Union Priority list for REACH authorisation as a sensitiser and neurotoxicant.
See www.etuc.org/trade-union-priority-list 	Thank you for your support and the additional information.	
4538
2015/10/15	CEPE,
Industry or trade association,
Belgium	CEPE is the voice of the paint and printing ink industry. The substance HDDA is in use in some of our industrial applications. We have collected information on its use and on cases of skin sensitization. On the basis of our experience of handling the substances in industrial settings for many years CEPE does not believe that HDDA should be considered as being of equivalent concern to CMRs Category 1 (Art 57(f) of REACH. More information is submitted in the attached submitted document.	Thank you for your comment. Please refer to answer to comment 4492 under general comments. 
	
4540
2015/10/15	United Kingdom,
Member State	We thank Sweden for their proposal and have the following comments;

Equivalent level of concern having probable serious effects to human health (Article 57 f)

The general concept of whether sensitisers can meet the criteria as SVHC as having an equivalent level of concern (ELoC) has been debated previously (RiME, CARACAL and MSC). It has been agreed that assessment should be made on a case-by-case basis and it should be demonstrated that the impacts caused by these substances on both the health of affected individuals and society as a whole are comparable to the impact of CMRs.  To date some respiratory sensitisers have been listed as SVHC but the case for skin sensitisers being SVHC is considered not to be as strong.

The assessment considers a number of factors to conclude on ELoC:

Type and severity of possible health effects:
In addition to the animal data that clearly show HDDA is a very potent skin sensitiser meeting the CLP criteria for classification as Skin Sens. 1A the dossier submitter has evaluated a cross sectional work place study, eight case studies and seven epidemiological studies (retrospective analysis of patch test data).

Overall we agree that the human data do indicate a high frequency of sensitisation among some exposed individuals, indicating that HDDA is a strong sensitiser in humans. However it is not clear whether the number of cases of sensitisation caused by exposure to HDDA represent a large or small proportion of those working with HDDA.

Regarding the severity of reactions the contention that reactions can be very severe is less well supported by the case studies. The most severe effects were reported following accidental exposure to large amounts of uncured HDDA.

Irreversibility of health effects:
Reference is made to a recent judgement by the Court of Justice of the European Union (JUDGMENT OF THE GENERAL COURT (Fifth Chamber), Case T-135/13, 30 April 2015) where the adverse health effects from sensitizing substances should be considered irreversible. Whilst an individual will always be sensitised, the adverse effects of exposure are reversible.

Delay of health effects:
We agree that generally health effects of skin sensitisation are considered to be delayed. However given the classification of HDDA as a skin sensitiser workers should already be taking precautionary action to avoid becoming sensitised.

Derivation of a safe level of exposure:
We agree it is difficult to establish a safe-level of exposure in general for sensitisers. The use of suitable gloves to prevent exposure to skin sensitisers is the prescribed risk management measure.

Quality of life:
The information presented is a general statement regarding occupational contact dermatitis. Mention is made of “several case reports” specific to HDDA where patients experienced difficulties at work associated with a negative impact on quality of life but little detail is given.

Societal concern:
The data presented relate to the concern of occupational allergic contact dermatitis as a whole and not specific to exposure to HDDA.

In conclusion much of the evidence presented relates to skin sensitisers in general and a case has not been made specific to HDDA.

On a more general level, whilst skin allergy and the consequent dermatitis are not trivial effects, it is difficult to view it as being equivalent to CMR effects. Unlike the CMR effects, skin sensitisation is not generally life threatening nor will it interfere or affect our basic capacity to reproduce.	The Swedish Chemicals Agency thanks the United Kingdom for the comments on the Annex XV dossier fort HDDA, please find our answers in the attached document. 

Severity of health effects 1:
We would first like to point out that the issue about severity of health effects is separate from the issue about frequency of reactions. Discussions on how common a certain condition are more relevant for the discussions on societal concern in the ELoC assessment. However, a high frequency of sensitization is indicative for a strong sensitizer and can be used as supportive evidence to estimate the potency of a substance. We believe that the data showing that HDDA is a potent skin sensitizer together with available reports on severe skin reactions from HDDA (se answer below) is sufficient proof that HDDA should be considered a substance that can cause severe effects.
We found reports on 50 patients in the EU that tested positive to HDDA in clinical patch tests in studies from year 2000 and onward. It is, however, important to emphasize that the number of reported cases of contact allergy to HDDA in the scientific literature does not represent the total number of cases in the EU but reflect the number of patients that were tested and included in scientific reports. Clinicians only publish patient cases under exceptional circumstances and the number of case reports cannot be used as a measure on how common a diagnosis is. Also, since HDDA is not included in the European Baseline Series, patients are rarely patch tested for HDDA, only if they enrol in special clinical trials or are subject to a more thorough clinical examination. The number of reported cases is therefore most likely an underestimation of the true incidence. The only study, to our knowledge, that studied the frequency of sensitization among people working with acrylic compounds reported a 6.2 % frequency of sensitisation to HDDA. This can be considered a high frequency of sensitization that clearly exceed the guidance value for classification of skin sensitizers as Skin Sens. 1A of >1.0 %. 
As stated above there are little available data describing how common occupational contact dermatitis to HDDA is in the EU and also to acrylates in general.  However, the Health Safety Executive (HSE) in the UK has to some extent described the magnitude of the problem with occupational allergic dermatitis to acrylates in a report based on data from EPIDERM. On average 76 new diagnoses of occupational contact dermatitis to acrylates and resins were reported per year in the UK in 2012-2014. Acrylates and resins were estimated to be the ninth most common cause of occupational contact dermatitis in the UK, accounting for just below 5% of the cases. Soaps/cleaners and wet work constitute the most common cause.

Severity of health effects 2:
Regarding the severity of reactions the contention that reactions can be very severe is less well supported by the case studies. The most severe effects were reported following accidental exposure to large amounts of uncured HDDA.
Answer:
In the ECHA discussion paper on identification of substances as SVHC under REACH article 57(f)  describe mild and severe skin damage as follows:
“Mild damage e.g. a rash that can heal quickly, when exposure to the sensitising agent is stopped.”
“Severe damage e.g. blistering that can burst. Skin function (integrity) is impaired, possibly leading to infection. Ongoing exposure can lead to chronic inflammation and scar formation. Minimal or a single small focus of scarring does not normally constitute “severe organ damage or major permanent functional change” in the skin as an organ.”
Based on this definition, we believe that the case studies in the Annex XV dossier provide sufficient evidence that HDDA can cause severe effects in humans. The most severe case describes a woman who developed severe allergic contact dermatitis that progressed to the life threatening condition “Toxic epidermal necrolysis” (TEN). We have been in contact with a Professor Anders Vahlqvist, expert in dermatology at Uppsala University who confirmed that the clinical and histopathological signs of the patient described in the report are consistent with TEN.  
Regarding the comment that the most severe effects to HDDA is caused by accidental exposures. We would like to emphasize that identification of SVHC should not be based on the nature of exposures. However, we do not agree that the reports indicate that the skin reactions were caused by accidental exposures. The reported cases include both accidental and non-accidental  exposures. The worker that suffered the most severe effects state that “Although she had worn goggles, gloves, and protective clothing, her face and arms had come into contact with UV-cured inks, and her clothing had become soaked in the inks”.  This suggests that there are difficulties to establish safe routines for handling HDDA at the workplace.

Irreversibility:
Reference is made to a recent judgement by the Court of Justice of the European Union (JUDGMENT OF THE GENERAL COURT (Fifth Chamber), Case T-135/13, 30 April 2015) where the adverse health effects from sensitizing substances should be considered irreversible. Whilst an individual will always be sensitised, the adverse effects of exposure are reversible.
Answer:
Allergic contact dermatitis to HDDA is an irreversible adverse health effect commonly manifested as eczematous lesions on the exposed skin that in severe cases can spread outside of the exposed area. A person that is sensitized to HDDA can only be free from symptoms if he or she can avoid exposures to HDDA The sensitized subject may also respond to other acrylates, when cross reactivity has occurred.
The judgement by the EU Court of Justice concluded that the adverse health effects from the respiratory sensitizer HHPA and MHHPA are irreversible. For both skin and respiratory allergy, the sensitization phase is irreversible and the elicitation is in principle reversible. However, prolonged or repeated exposures may lead to chronic health effects, particularly so in highly sensitised individuals or to potent sensitizers. Respiratory sensitizers can lead to chronic inflammation of the lung and skin sensitizers may lead to permanent scarring or persistent dermatitis. Since the development of allergic skin reactions occur according to the same principles as allergic lung reactions, the skin sensitizing effect of HDDA should also be considered irreversible. 

Delay of health effects:
The assessment on whether a substance gives rise to delayed health effects should be carried out based on its inherent properties and not take the possibility of risk management measures at the workplace into account. Indeed, in the case of HHPA, the EU Court of Justice considered that, the existence of adequate control or risk management measures does not preclude identification of a substance as SVHC .  We believe that the same reasoning should be applied in the identification of HDDA as SVHC.

Derivation of a safe level of exposure:
Just as for assessment of delayed health effects, the lack of a safe level of exposure for HDDA is relevant for the ELoC assessment regardless of the possibility to use personal protective equipment.  According to ECHA discussion paper on SVHC identification under REACH article 57(f), derivation of a safe concentration does not play a role in identifying a substance as an SVHC. However, in the context of ELoC assessments, an inability to derive a safe concentration may warrant a higher ‘level of concern’ being associated with the substance in question.

Quality of life:
We believe that the overall evidence is sufficient proof of that occupational allergic contact dermatitis to HDDA may have a negative impact on quality of life for the affected individuals. Several studies report that occupational contact dermatitis and occupational hand eczema leads to an impaired quality of life. The Annex XV dossier include several case reports of occupational contact dermatitis to HDDA describing patients suffering from eczematous lesions on the skin of varying severity (Morgan and Fewings 2000, Ido, Kiyohara et al. 2012, Vogel, Christoffers et al. 2014). Thus, contact allergy to HDDA can give rise to health effects that are associated to an impaired quality of life. In addition, the reports also indicate that the affected individuals suffer from an impaired quality of life. One patient quit her job, one had to take extensive protective measures at the work place and one continued to suffer from dermatitis as he continued with the same work tasks. Such consequences of a disease are generally associated with impaired quality of life. There are also reports of manicurists with contact allergy to acrylates, including HDDA, that have been forced to change jobs or that suffer from recurring problems also in their new work tasks (Cravo, Cardoso et al. 2008, Roche, de la Cuadra et al. 2008, Pesonen, Kuuliala et al. 2012, Kiec-Swierczynska, Krecisz et al. 2013). However, the origin of the allergy was not investigated in those cases and HDDA was not confirmed as the causal allergen.

Societal concern:
First, we would like to point out that an identification of SVHC under article 57(f) does not require exact estimations of societal costs or proof of proportionality of the proposed risk management. Information about societal concern is included in the ELoC assessment as one out of six ‘level of concern’ factors that should be considered together in one package.
The available data on frequency of contact dermatitis to HDDA as well as to acrylates in general is limited and does not allow for accurate estimations of societal costs (see answer to comment on Type and severity of possible health effects above). There are, however scientific studies supporting that occupational allergic contact dermatitis and occupational hand eczema should be considered of societal concern (Diepgen, Scheidt et al. 2013, Saetterstrom, Olsen et al. 2014). 
Saetterström et.al studied the cost-of illness of people with contact dermatitis in Denmark from four years before diagnosis to one year after. This study gives a long-term perspective on the societal costs from occupational contact dermatitis. Patients with contact dermatitis that had been seen and patch tested at dermatology clinics and were work was considered a causal or contributing factor were included in the study as cases of occupational contact dermatitis. The results showed that health care costs for people with occupational contact dermatitis were significantly higher than for matched controls. The total attributable health care cost of occupational contact dermatitis for the 5 year period were € 724 per case and the total cost for productivity loss due to sick-leave and rehabilitation was €10 722 per case for the same period. The costs loss attributable to occupational contact dermatitis remained constant for the first three years and increased one year before and one year after the diagnosis period. Health care costs increased from € 58 two years from diagnosis of the diagnosis to € 390 in the year after diagnosis. The productivity costs followed the same pattern but the exact yearly numbers are not revealed in the publication. Thus, this suggests that occupational contact dermatitis is a condition entailing large costs for the society.  
We believe that the information about severity and frequency of contact allergy to HDDA presented above and in the Annex XV dossier together with the estimated societal costs from occupational contact dermatitis is sufficient evidence to indicate a societal concern. Also, data from REACH registrations and the Swedish product register suggest that the use of HDDA is increasing indicating that the societal costs from HDDA may increase if no risk management measures are taken.

General comment 1:
We believe that the Annex XV dossier provide sufficient evidence that HDDA is of equivalent level of concern to CMR according to the ELoC factors presented in the ECHA discussion paper . For the health related factors; severity of effects, irreversibility and delay of effect and also for derivation of safe exposure levels, the dossier provide scientific evidence that are specific for HDDA on each factor. For the “other” factors; impact on quality of life and societal concern there are less evidence specific to HDDA. However, there is convincing evidence that occupational contact dermatitis decreases the quality of life and entails large costs to the society and also that exposure to HDDA can cause allergic contact dermatitis (se answer to comments above). 
In our experience, studies on QoL and societal concern are rarely done on specific substances. Instead, it is more common to carry out such studies based on a specific diagnosis, such as contact dermatitis. Also, it is in general difficult to estimate the true incidence of contact allergy from specific skin and respiratory sensitizing substances in the EU. Thus, if identification of skin and respiratory sensitizers would require studies on quality of life and societal concern that are specific for the particular substance we think it would be difficult to identify any sensitizing substances as SVHC.

General coment 2:
Article 57(f) does not limit the kind of intrinsic properties that a substance can have in order to be of equivalent concern to substances listed in Article 57(a) to (e). Substances can therefore be identified as substances of very concern under Article 57(f) on the basis of their skin sensitising properties. Indeed,  several MSCAs and the Commission/ECHA have been considering the possibilities for and need to identify substances with sensitising properties as SVHC under the ‘equivalent level of concern’ route set out in Article 57(f) of REACH. To support this work ECHA has prepared a discussion paper which can be used when assessing whether substances with sensitising properties could be identified as SVHC, under the ‘equivalent level of concern’ route set out in Article 57(f) of REACH.
KemI carried out an ELoC assessment for HDDA according to the principles in the ECHA discussion paper. Based on the assessment, we believe that HDDA fulfil the criteria in REACH Article 57(f) and should be identified as an SVHC.	
		-		
4548
2015/10/15	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust supports the inclusion of Hexamethylene diacrylate (HDDA) in the candidate list as an SVHC of equivalent concern (article 57f) based on the presented evidence and argumentation. Data from experimental animal studies show that Hexamethylene diacrylate   is an extremely  potent skin sensitizer. Human exposure can lead to irreversible sensitization. Sensitized individuals typically develop allergic skin reactions upon subsequent exposures to HDDA, which can lead to be very severe conditions.	Thank you for your support	
4554
2015/10/15	ChemSec,
International NGO,
Sweden	ChemSec supports the definition of HDDA as an SVHC based on its properties, which the dossier proves to be of Equivalent Level of Concern.	Thank you for your support	
4557
2015/10/15	Company,
Germany	p. 22ff, Equivalent level of concern assessment:
Printing ink manufactures are fully conversant with the skin sensitization potential of HDDA.  The experience over the last years shows that appropriate measures to avoid exposure contribute effectively to safe handling. Therefore, HDDA is not presenting an equivalent level of concern like a CMRs Category 1 substance. HDDA should not be considered as an SVHC.	Thank you for your comment. Please refer to answer to comment 4492 under general comments. 
	
4558
2015/10/15	Company,
Sweden	p. 11 Table 2: The typical concentration appears to be based on old data. Typically the quality of HDDA in use in the industry today has HDDA concentration >99%.

p. 14: The guinea pig tests were done more than 30 years ago when the available HDDA qualities contained a high amount of impurities (older value typically 8.2% according to Table 2 section 1.2 on page 11) compared to the qualities available today.

p. 15: If the woman worked with her clothing soaked with UV-curable inks she did not follow the instructions in the safety data sheet when handling the inks. Further there is no comment on the correct use of PPE. The safety data sheet has a section about first aid measures which should say something like “Take off immediately contaminated clothing. After contact with skin, wash immediately with plenty of water and soap.”

p. 16: The man put on contaminated trousers which caused buttock dermatitis. This had never happened if safety instructions had been followed. The data does not appear to point directly at the HDDA being the sensitiser but a reactor to sensitized skin.

pp. 16-17: Several examples about artificial nails. In none of the cases it has been shown that the products contain HDDA.	Thank you for your comments please find specific answers below:

p.11 and p.14: Thank you for your comment. Please refer to answer to comment 4505 under general comments. 

p. 15 and p.16: Please refer to answer to comment 4492 under general comments and 4540 under specific comments on the justification

pp. 16-17: In the examples of contact allergy to HDDA from exposures to artificial nails, no attempts have been made to identify the culprit allergen. Based on available data, it is not possible to confirm or rule out HDDA as the causative agent. However, all reported cases represent a patient that suffers from contact allergy to HDDA indicating a need for regulatory measures.

		-		
4562
2015/10/15	PARAD Consortium,
Other contributor,
Belgium	Intro to PARAD

The PARAD Consortium includes 7 out of the 10 HDDA registrants:
• BASF SE Carl-Bosch-Str. 38, 67056, Ludwigshafen am Rhein Rheinland-Pfalz, Germany (lead registrant)
• Allnex Belgium NV/SA Anderlechtstraat 33, 1620, Drogenbos, Belgium
• Allnex Belgium NV/SA OR Anderlechtstraat 33, 1620, Drogenbos, Belgium
• ARKEMA France 420 rue d'Estienne d'Orves, 92700, COLOMBES, France
• ARKEMA PHOTOCURES 420 rue d'Estienne d'Orves, 92700, Colombes, France
• ETERNAL CHEMICAL EUROPE B.V. Noordenweg 24, 2984AG, 2984, Ridderkerk Netherland, Netherlands
• KIST Europe Forschungsgesellschaft mbH Universitaet des Saarlandes Campus E 71, D-66123, Saarbruecken, Germany
The PARAD companies are the main and the historical players on the European market for the manufacture and import of HDDA. They have more than 30 years of experience producing/importing and supporting the safe handling and use of HDDA.

Comments on ANNEX XV – IDENTIFICATION OF HEXAMETHYLENE DIACRYLATE - AS SVHC: toxicological arguments

1. Overview of key points:

Hexamethylene diacrylate (HDDA, EC number: 235-921-9, CAS number: 13048-33-4) has been identified for inclusion on the list of substances of very high concern in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because of its skin sensitising properties by the Swedish Authorities (KEMI).
The PARAD Consortium has carefully read the Annex XV dossier and has developed comments on each of the arguments put forward by KEMI. Outlined in bullet points below are the key arguments and conclusions presented in this document. The reasoning is provided in the subsequent sections of this document:
• It is difficult to differentiate between irritation and sensitisation unless a patch test is done. Because HDDA is a skin irritant it is usually known that dermal contact took place. As a consequence it is easy to identify the source of sensitisation and the measures to be taken to ensure the worker exhibiting a reaction to sensitisation are no longer exposed to that source.
• All skin reactions related to HDDA exposure were completely reversible within 2 weeks. No scarring or permanent damage occurred. This is also true for the single case of TEN (toxic epidermal necrolysis) identified, which resulted from an accident in Japan and is not related with certainty to HDDA.
• Since potential exposure to HDDA does not occur in private life and exposure to the substance can be well controlled in industrial and professional settings, impairment to the quality of a worker’s life is not an expected consequence of exposure to HDDA and no evidence can be found to support arguments in favour of impairment to quality of life.
• Positive patch test reactions may not be due to prior HDDA exposure but due to cross reactions against other methacrylates or acrylates.
• In the published literature (from 1977 to date) only 35 positive patch test reactions to HDDA have been reported in workers for whom there was only a chance that they had previously been exposed to HDDA.
• A very low frequency of positive patch test reactions toward HDDA was reported in two epidemiological surveys not included in the Annex XV dossier (see section 4.1 of this document). A higher frequency (though lower than that of several other (meth) acrylates) of positive patch test reactions was only observed for one study with patients already preselected for (meth)acrylate allergies.
• The personal protective equipment and handling procedures are the same for non-sensitised and for sensitised individuals, i.e., all dermal contact must be avoided. Since the irritation and sensitising properties are known and efficient risk management measures are properly communicated in SDSs and already applied, the argument concerning possible delay between sensitisation and expression of effects is not relevant. Nonetheless, it should be noted that literature data for HDDA report a delay of a few weeks rather than a delay of years.
• With the exception of a single case, no reports mention sick leave. Lost productivity is an exception and only potentially related to HDDA. This matches the observations of short treatment times, no chronic diseases, and efficient dermal protection. Also considering the low overall number of cases, societal costs are of very limited concern, as is discussed in more detail in this document.
• In general, care should be taken to differentiate between chronic diseases and the relatively short episodes of acute allergic dermatitis reactions when evaluating literature data on treatment costs and personal impairment. Only short episodes of acute allergic dermatitis reaction may be relevant for the assessment of HDDA.

2. Introduction

REACH Article 57(f) provides a clause for inclusion on Annex XIV of substances that present serious risks to human health and the environment, which are not defined in Article 57 (ac).  However, as hazardous substances of potential relevance are governed by a number of existing regulatory requirements, inclusion of a substance to the SVHC process under Art. 57(f) is appropriate only where other risk management options have been considered and authorisation has been found to be the best way to manage the risks identified.
Hexamethylene diacrylate (HDDA, EC number: 235-921-9, CAS number: 13048-33-4) has been identified for inclusion on the list of substances of very high concern in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because of its skin sensitising properties by the Swedish Authorities (KEMI). The PARAD Consortium has carefully read the Swedish Annex XV dossier and developed comments on each of the arguments proposed by KEMI.
Formal conclusion that SVHC criteria set out in REACH Article 57 are met, is in the remit of the Member State Committee (MSC), or the European Commission in cases where the MSC does not reach unanimous agreement.  As will be detailed in this document, PARAD believe that the scientific arguments in the Annex XV dossier do not provide the evidence required for inclusion of HDDA in the Candidate List as a skin sensitiser of equivalent level of concern (ELoC) to CMRs (Carcinogenic, mutagenic or reprotoxic substances).
For substances classified with a Human Health (HH) endpoint, ELoC can only be considered upon demonstration of relevant health impacts of equivalent strength and seriousness to CMR Category 1 substances; possible examples including death, major permanent functional changes in organ systems, severe organ damage or other irreversible effects.
Skin sensitisation by dermal exposure to HDDA may result in contact dermatitis. Characterised by itching papules or vesicles, small fissures, extensive redness, swelling and oozing, contact dermatitis can be defined as an eczematous skin reaction caused by direct repeat exposure to allergens.  Histopathologically, biopsies of acute dermatitis have shown acute inflammation in the outmost layers of the dermis, with involvement of the epidermis. As only superficial parts of the skin are involved, healing is usually complete, leaving no residual scar.  With this definition in mind, it is important to note that appropriate risk mitigation measures should sufficiently protect industrial and professional workers and these effects of contact dermatitis are usually reversible. However, as an acquired contact allergy, the induction phase is irreversible.
Whether skin sensitisation can be considered as of equivalent level of concern to that of CMRs (Art. 57 (a-c), the discussion presented here focusses on the quality of evidence for ELoC and attribution to HDDA (i.e. proof of causality).

Considerations on skin sensitizers as Equivalent Level of Concern:

Article 57 of REACH provides that Category 1A and B CMRs and PBT/vPvB substances may be included in REACH Annex XIV (authorisation list). These endpoints represent serious, irreversible and life-threatening impacts on human health and/or serious long-term environmental impact.  Sensitisers by contrast, differ in the severity of response in that this varies from individual to individual. In many cases the potential clinical manifestation after sensitisation can be a transient and comparatively minor condition, although in others this can be of longer duration and more severe.

Managing sensitisers in the same manner as CMRs fails to take into account the clinical evidence that, for sensitised individuals, limitation or avoidance of exposure to a sensitising substance is the primary strategy for the reversal of any existing disease symptoms and the prevention of new disease. The key difference between CMRs and sensitisers is the reversibility of the response. It is important to note that although the induction phase is irreversible, the allergic response, will go away if the sensitiser is avoided.

When it is important to consider the potential risks of a particular substance with harmonized classification, an initial probabilistic risk assessment can be conducted to inform a Risk Management Option Analysis (RMOA). The RMOA should be performed with industry contribution before any decision is taken to add any sensitisers to the Candidate List. For those sensitising substances for which the risk to health is of concern and requires regulatory intervention, other risk management option routes should be considered such as substance evaluation, restriction, or compliance with existing community legislation.

Once the potential risk to health is managed effectively, as it can be for most cases, considerations such as health effects, quality of life and societal impact will not be relevant anymore.

3. General remarks on the assessment of HDDA
HDDA is used in industrial UV/EB-cured applications, like for example in inks and coatings. Professional applications are limited to the use of ink cartridges. This can be considered as a closed system that results in negligible exposure. It is acknowledged by the Swedish authorities’ Annex XV dossier that no consumer uses have been registered under REACH for HDDA.  However, several publications cited in the Annex XV dossier report positive patch tests to HDDA resulting from the use of artificial nails (Kiec- Swierczynska et al. (2013), Pesonen et al. (2012), Cravo et al. (2008), Roche et al. (2008) and dental products (Goon et al. (2006)). The PARAD Consortium believes that these results are cross-reactions against the methacrylates commonly used in these applications (Aalto-Korte et al.  2007, Escobar et al. 2005, Bjorkner (1984), Clemmensen (1984), Aalto-Korte et al. (2008), Vogel et al. (2014)).
Cases of allergic dermatitis attributed to HDDA are typically identified on the basis of positive patch test reactions. In all publications (except one – Morgan et al. (2000)) identified by KEMI, information on exposure was limited to job description and speculative identification of the product most likely to be responsible for the allergic reaction.  A positive patch test reaction does not necessarily identify the initiator of hypersensitivity or suggest previous exposure.  For example, a patient sensitised to p-phenylene diamine present in hair dye, may experience ‘flare up’ up eczema as a result of exposure to p-aminobenzoic acid, present in sunscreens.  Thus, “it is important to carefully consider the relevance of all positive patch tests, since some of them may constitute immunological residues from eczematous episodes earlier in life” . Note that HDDA is part of a screening series to diagnose allergic contact dermatitis caused by methacrylates or acrylates.  No convincing evidence has been provided by KEMI that HDDA is present in consumer products (page 29 of the annex XV dossier). Indications for its use in nail applications are limited to the availability of UV-cured “do it yourself” gel nail products available on ebay.com (the international ebay site, not a European site – products coming from Honk Kong), however, whilst methacrylates are most frequently used for these applications, HDDA is not mentioned as an ingredient. Only one single sentence refers to HDDA in the description of the patch test sold by Chemotechnique. The latter provides no source for this statement. All linked webpages do not list HDDA as a possible component in these applications. Again, it should be noted that the PARAD Consortium registrations do not support consumer use and that registration dossiers are being update to specifically indicate consumer uses as uses advised against.
With regard to dental applications, the argumentation is based on the presence of patents containing “dental” and “HDDA” in their abstract. Aside from the fact that it is not clear if the patents state that HDDA can/must be/are used for the dental application, the sole presence of a patent does not equate to a marketed product. It should also be noted that the steep increase mentioned in the Annex XV dossier is from one to ten patents.
In conclusion, it is considered unlikely that people using EU artificial nail or dental products are exposed to HDDA and that HDDA is the cause for their allergic dermatitis. Studies with these cohorts should thus not be used to evaluate the sensitising potential of HDDA in the context of an EU listing as a Substance of Very High Concern. Additionally, these applications are not supported in the joint submission dossier for REACH.
A summary of the evaluation of HDDA as a substance of equivalent level of concern to CMRs, based on the ECHA 2014 Guidance on Annex XV dossiers and on the information presented by PARAD in this response to the public consultation, is presented in Table 1-1.

Table 1-1: Evaluation of HDDA as SVHC in Consideration of ECHA Guidance on ‘Equivalent Level of Concern’ comparison between CMRs and skin sensitisers
Carcinogenicity & Mutagenicity Reproductive Toxicity (developmental) Skin Sensitisation Swedish arguments Consortium Response

Possible serious health effects?
YES
• Serious & permanent organ dysfunction
• Inheritable defects
• Could lead to death
YES
• Serious & permanent organ dysfunction
• Malformations or death in (unborn) children
POSSIBLY YES
• If response is severe

NORMALLY NO
• As organ dysfunction is reversible
YES
• Potent skin sensitiser that can give rise to severe allergic contact dermatitis
• Severe cases involve blistering and skin loss on large areas that require hospital care and may be life threatening
NO
• The skin reaction is limited to exposed area
• Healing is achieved within one to two weeks with no or standard medication
• No permanent dysfunction of the skin

Irreversibility of health effects?
YES
• Irreversible effects
YES
• Irreversible effects
NORMALLY NO
• Induction phase of sensitisation is irreversible

HOWEVER
• The effects on skin (elicitation phase) is   reversible
YES
• Skin sensitisation to HDDA is an irreversible adverse effect.
• Recurring symptoms if the exposure to acrylic based products continues
• Severe cases can lead to scarring and permanent skin damage
NO
• All skin reactions were completely reversible within 2 weeks
• No scarring or permanent damage occurred, even in the single case of toxic epidermal necrolysis

Delay of health effects?
YES
• Long delay until effects manifest
YES
• Medium delay until effects manifest
YES
• Long/medium delay between start of the induction phase and appearance of clinical symptoms
YES
• Can take years form the initial exposure to HDDA until the symptoms develop
• By the time symptoms appear and the patient has been diagnosed with contact allergy, the irreversible state of sensitisation is already established
NOT RELEVANT
• All dermal contact is avoided by industrial and professional workers
• Since the irritating and sensitising properties are known, efficient risk mitigation measures are in place for workers occupationally exposed.
• Nevertheless, literature supports a delay of a few weeks rather than years

Quality of life impaired?
YES
• Long term illness limiting possibility of living a normal working and private life
• Possible mental / psychological impacts
YES
• Children with developmental effects may need life-long medication / support in their daily life
• Life of parents also affected (emotional investment, care financial costs)
POSSIBLY YES
• Possibility of long term illness limiting the possibility of living a normal working and private life
• Re-training of allergic staff
• Possible mental/psychological impacts
YES
• Allergic contact dermatitis is associated with impaired quality of life due to physical and social problems at the workplace
• May need to change occupation
• Re-training of sensitised staff
NO
• Since exposure to HDDA does not occur in EU consumers and exposure to the substance can be well controlled in industrial and professional settings, there is no impairment on the quality of life

Societal concern?
YES
• Widespread concern about cancer
• Cost implications for society in terms of healthcare
YES
• Widespread concern about adverse effects in children
• Cost implications for society in terms of healthcare
• Disability
YES
• Cost implications for society in terms of healthcare and retraining
YES
• Widespread occupational exposures to HDDA
• Cost implications for society in terms of healthcare
• Cost of reduced productivity at work and sick leave
NO
• Potential reduction in productivity may not be related to HDDA.  This matches the observation of short treatment times, no chronic diseases and efficient dermal protection.
• Considering the low overall number of cases, societal costs are of very limited concern
• Cost is overestimated because it is based on hand eczema which is a chronic skin disease that requires a long term treatment

Is derivation of a ‘Safe concentration possible’
NORMALLY NO
• ‘Zero risk’ only possible where no exposure
NORMALLY YES
• Possible to determine a safe concentration
NO
• Difficult to establish the threshold dose for induction and elicitation
• Derivation of safe concentration is not routinely possible
NO
• No available dose-response data from studies in animals or humans that support determination of a quantitative DNEL for HDDA
• Susceptible individuals may become sensitised following exposure to low concentrations
CURRENTLY NO
• HDDA is part of a standard patch test screening series (at the concentration of 0.1%). This level is presumably safe but not proven.
ECHA Guidance on ‘Identification of substances as SVHCs due to equivalent level of concern to CMRs (Article 57(f)) – sensitisers as an example’. Available at: http://echa.europa.eu/documents/10162/13657/svhc_art_57f_sensitisers_en.pdf (Accessed 8.10.15)

4. Type and severity of possible health effects

The statement that HDDA is a potent sensitiser is not sufficiently justified based on human data, due to the low frequency of skin sensitisation related with certainty to HDDA in humans. The cross-reaction of acrylates for skin sensitisation is well known and doesn’t allow the attribution or assignment of a sensitising effect to a particular acrylate. The actual cases related to HDDA do not show any severe cases of skin sensitisation, moreover the dermal effects were reversible within two weeks in absence of new exposure.  More arguments to support this statement are developed below.

4.1. Cross-reactions for acrylates and patch tests

The Consortium would respectfully like to re-iterate that cross-reactions are well known for acrylates and methacrylates (Bjorkner (1984), Clemmensen (1984), Aalto-Korte et al. (2008), Vogel et al. (2014)). Moreover the Annex XV document acknowledges this phenomenon (on pages 7, 13, 14, 16, 20, 23).  Cross reactivity with other acrylates (1,4-butandioldiacrylate (BUDA), diethyleneglycoldiacrylate (DEGDA), tetraethyleneglycoldiacrylate (TEGDA), tripropyleneglycoldiacrylate (TPGDA) and neopentylglycoldiacrylate (NPGDA)) was demonstrated in guinea pig maximisation test (GPMT) (Bjorkner, 1984; Clemmensen, 1984). In humans, due to these cross-reactions, the multi-exposure to acrylates, and the usually multiple positive patch test reactions in a single subject, it is difficult to find evidence to attribute the symptoms of contact dermatitis to only one acrylate based on the result of a positive patch test.

4.2. Low frequency / unclear previous exposure
Several references listed in the Annex XV dossier are used to demonstrate high frequency of sensitisation due to HDDA exposure. However the Consortium considers that a high frequency of sensitisation was not established. Looking at each of these references:

Cross sectional work place study (p. 14, 17)
One cross-sectional work-place study as described by Kiec-Swierczynska, Krecisz et al. (2005) shows that 5 out of 81 workers (6.2 %) who had been exposed to an acrylic glue were sensitised and suffered from allergic contact dermatitis. It is agreed that the requirement of frequency (>2% according to the ECHA Guidance) of exposure to an acrylic glue is fulfilled. However, HDDA was not listed as a component of the glue and therefore the effects of the positive patch test are likely due to cross reactions between acrylates. No detailed data on the previous exposure situation are provided by the authors, but judging by the fact that 9 or 10 out of 80 workers reacted to diethyleneglycol diacrylate and triethyleneglycol diacrylate, respectively, and no worker reacted solely to HDDA, it is more likely that original exposure was to these acrylates. The relationship between HDDA exposure and these cases of sensitisation is therefore not substantiated, meaning this study should not be used to define a subcategory sensitisation for HDDA.
Critique of epidemiological studies mentioned in the Annex XV dossier (p.18)
Again, in several studies listed in the Annex XV proposal (Constandt et al. (2005), Goon et al. (2006), Aalto-Korte et al. (2008)), the people with positive patch tests reactions were unlikely to have been previously exposed to HDDA. The observed reactions are therefore probably due to cross sensitisation.
For the publication by Christoffers et al. (2013), it is impossible to know if previous HDDA exposure occurred, however, it is interesting to note that HDDA did not cause the most positive reactions.  Ramos, Cabral et al. (2014) reported a single case where the induction of the allergic reaction might be due to HDDA, for all others a previous exposure is highly unlikely.  All the publications detailed above failed to provide evidence that HDDA was responsible for a high percentage of positive patch test reactions - they only underline that cross sensitisation between acrylates is frequently observed.
The publication by Teik-Jin Goon et al. (2007) reports 4 cases with potential prior HDDA exposure. The remaining 6 patients only had contact to nail products (and thus most likely to methacrylates), but not to HDDA. As it was the goal to define effective screening antigens for future patch testing, the cohort was selected based on allergic potential to acrylates or methacrylates. In this study, a high frequency of positive reactions to acrylates was thus expected and indeed required by the research objective. It should be noted however that the frequency of 48% as stated in the annex XV dossier on page 18 is not correct, because patch tests with the acrylic series were not performed on only 21 patients, but on 90. Rather, 21 is the number of patients that were tested for HDDA and reacted to at least one (meth) acrylate. Though it is known that HDDA was not tested on three patients, patch testing with this substance can be assumed for the vast majority of the remaining 87 subjects. Moreover, the frequency of sensitisation for substances with known cross-reaction mechanisms will always overestimate true incidences for one substance.

Additional epidemiological case studies
A few further publications found by the Consortium are considered relevant to assess the frequency and severity of allergic reactions against acrylates in addition to those cited in the Annex XV dossier:
In the report from The National Institute for Occupational Safety and Health (NIOSH, 1997), 13 plants representative for the multifunctional acrylate/methacrylate radiation-cured applications were examined for any skin reactions related to the use of this technology. 18 skin lesions were reported in 4 of the plants. No cases occurred in the remaining 9 factories. 14 cases were classified as chemical burns and not as allergic reactions. This report describes the sum of skin reactions to all acrylates in use. The authors also state that most cases occurred during the early experience of the plants with acrylates / methacrylates and were due to improper handling of Personal Protective Equipment (PPE). In summary, over a 5 year period 585 workers in 13 relevant plants were exposed to multifunctional acrylates. Only 4 plants reported skin lesions with a total of 18 reported incidents. Only 4 were allergic reactions to any of the acrylates in use and this was related to improper handling due to inexperience.

The following five studies were conducted between 21 and 38 years ago. It can reasonably be assumed that operating conditions and risk management measures have improved considerably since then. Nevertheless, these data are provided for completeness as they do refer to HDDA.
Fischer et al. (1994) assessed all workers in contact with UV curable acrylates from 38 (out of 48) Swedish plants working with UV curable wood coatings. Of these 659 workers, 144 were selected for a more detailed assessment based on current or previous episodes of allergic contact dermatitis. Most skin reactions were diagnosed as irritant dermatitis. Regarding allergic reactions, 49 positive patch test reactions were observed in 31 individuals. Only one single worker of the 144 identified in an occupation cohort (n=659) as likely to be exposed, reacted to HDDA. The same individual also tested positive for 5 further allergens from the acrylate series.
Of 58 workers using UV-cured inks in the same plant, 8 developed allergic contact dermatitis (Emmet et al. (1977)). These were patch tested with three multifunctional acrylates. Trimethylolpropane triacrylate caused 7, HDDA 6, and penterythritol triacrylate 4 positive patch test reactions. Since no data on previous exposure is available, it is unclear which substance induced the allergic reaction. The causative agent could also be different from the tested allergens.
Malten et al. (1979) monitored 20 workers in the electron beam coating department for 4 years for skin lesions. No positive patch test reactions in these workers or an additional volunteer were obtained.
Nethercott et al. (1978) assessed the skin reactions of 26 workers who produced or handled UV-curable printing inks in Canada. None of these patients reacted positive to a patch test performed with HDDA.
The same result was obtained by Guerra et al. (1993) for 82 workers in Italy who were suspected to have developed allergic dermatitis due to occupational exposure to acrylates. However, based on the job description, prior HDDA exposure was only possible for one subject.
The Consortium has found 35 published case reports of occupational allergic dermatitis mentioning HDDA in the EU, US and Canada since 1977 (see Annex I). Non-supported uses such as gel nails and dental applications were not taken into account (see introduction). Moreover, the frequency of sensitisation for substances with known cross-reaction mechanisms will always overestimate true incidence for one substance.
Both EUPIA (the European Printing Ink Association) and PARAD Consortium have conducted new surveys in the past months. According to the survey made by EUPIA, only 7 cases of sensitisation were reported in 39 plants from 21 companies handling acrylates. 85 responses were obtained from the survey among PARAD Consortium downstream users. 21 people showing skin reactions were identified in the past 30 years in this second survey of which not all were allergic reactions. Even in the worst case scenario, assuming that HDDA caused the sensitisation in all cases and that no cases were counted twice (e.g. both by the hospitals and the companies), that results in less than 100 cases of occupational allergic dermatitis in more than 30 years. This cannot be considered a sensitiser of high frequency.
4.3. Skin sensitising potency of HDDA

The Annex XV report mentions there is enough information to classify HDDA as a Skin Sens. 1A based on the high frequency of skin sensitisation and the severity of the effects observed in humans (pages 9, 14, 15, 17, 19, 22, 24).
According to the ECHA Guidance (2015), the frequency of occurrence of skin sensitisation based on human diagnostic patch test data in association with the level of exposure can be used to define a sub-category of the skin sensitisation classification. However, this assumption should not be applied to substances for which cross-reactions are known (e.g. acrylates). Most publications describe either single accidents or report patch testing results with no established relation with previous exposure to HDDA. Cross sectional studies with a better link with acrylate exposure such as the one of NIOSH (1987) and Fischer et al. (1994) showed low incidences, which is confirmed by the recent survey conducted among our customers (See separate report on this survey in Annex II).
In the absence of reliable epidemiological patch test data, the ECHA Guidance (2015) states that a substance could potentially be classified as Skin Sens.1A based on a high severity of skin reactions observed in humans. In the Annex XV dossier, the Swedish authorities refer to a single case of TEN (toxic epidermal necrolysis) which they considered to be related to HDDA (Ido et al. (2012)). Note that this case was the result of an accident without permanent skin lesions following a treatment of only two weeks. The Japanese clinical report relayed severe diffuse erythema and blistering of a 33-year old women working in the ultraviolent (UV)-cured ink industry that had become “soaked” in inks. A provisional diagnosis of TEN-like contact dermatitis, due to UV-cured inks was made, which was later confirmed according to the authors by skin biopsies. Figure 1 presents the patch test results.

Figure 1 Patch Testing of Japanese Toxic Epidermal Necrolysis Case (Ido et al., 2012)
Firstly, positive results were identified for a number of other allergens, including Nickel sulphate and Propoxylated neopentyl glycol diacrylate. Secondly, as TEN is a very rare drug hypersensitivity reaction, the effects described in this publication are not related with certainty to HDDA, very few acrylates were tested and the worker was likely exposed to a range of acrylates.
TEN is a rare cutaneous drug reaction as it has been admitted in the Annex XV dossier (page 15). According to House et al. (1992), the frequency of TEN is 0.5 - 1.2 cases per million per year in developed countries where the data is available. Thereof, most cases of TEN (80%) are drug related and many co-factors are known to be a possible causative agent (e.g. genetic factors). Few details on the history of woman are provided in the Ido’s publication (precedent job, precedent exposure to acrylates, genetic pre-disposition...). It was stated the woman was already sensitised to nickel, which may have played a role in the progress from contact dermatitis into TEN.
The first symptoms occurred after one week but woman continued to work for another 9 days with presumable intimate and repeated contact with the ink. Abnormally high exposure is deduced based on the soaked clothing. No further details on exposure conditions were given, but continuous allergen exposure will worsen the dermal reaction. According to a dermatologist, diagnosis of TEN is based on the presence of necrotic cells and subepidermal blisters. However, both symptoms may also be seen for severe cases of allergic dermatitis. It might thus clinically look very similar to TEN. Presumably Ido et al. (2012) called it a TEN-like reaction, because it was not a typical TEN case: there were some histopathology matches with TEN but the mucosa were not affected. Moreover, the affected body parts do not match the expected area in case of real TEN (back and intertriginous areas). The report mentions the abdomen, the extremities and the face. These areas match with those body parts that were in contact with the ink, especially with soaked clothes. Furthermore, in this patient all skin lesions healed completely within approximately 2 weeks.
No further severe case of skin lesion potentially related to HDDA has been found which can provide evidence to justify the Skin Sensitisation sub-categorisation of 1A.

4.4. Severity of health effects

On page 7 of the Annex XV dossier, it is stated that "The symptoms are most often located to the exposed area, usually hands and arms and sometimes the face, but may also spread to other parts of the body". In the literature (Klimisch rating 2) provided, skin reactions occurred at the point of contact, mostly hands or wrists, but also legs or abdomen if the clothes were accidentally soaked with the substance (Morgan and Fewings (2000), Vogel et al. (2014), Higgins et al. (2012), Botella-Estrada et al. (1992)).
No examples of symptoms of contact dermatitis at non–exposed parts of the body have been shown in the bibliographic research (full literature research including the Annex XV references) on skin sensitisation cases related to HDDA. One reference used in the Annex XV dossier (p16) describes a patient who was patch tested and who developed a skin reaction on the back and a serious crust on the forehead during this test. The latter was interpreted as a recall reaction. It should be noted that no other parts of the body – parts that were clearly exposed recently – gave the same recall effect. A dermatologist contacted by the Consortium stated that recall phenomena should normally occur on skin areas that were affected before the new exposure. There is no real reason why this did not occur on hands and wrists that had been exposed before. The reliability of this assessment cited in the Annex XV dossier is therefore considered questionable.
On page 9 of the Annex XV dossier it states that “In some severe cases the condition involve blistering and skin loss on large areas of the body that require hospital care and may even be life threatening" and “[…] severe cases of contact dermatitis involving symptoms such as blistering and skin detachment can lead to scarring and permanent skin damage". It is assumed that both sentences refer to the single case of TEN (toxic epidermal necrolysis) reported by Ido et al. (2012), which describes an accident in Japan and which is discussed in Section 4.3. Despite this accident resulting in an exceptional allergic reaction, it did not involve scarring and permanent skin damage.
Since only one single report on TEN exists, which is the result of an accident, with no established link with HDDA or other acrylates, there is no indication that HDDA shows a special risk of equivalent concern to CMRs.

5. Irreversibility of health effects

Page 9 of the Annex XV dossier states that "Skin sensitisation to HDDA is an irreversible adverse effect. Reports show that people that are sensitised to HDDA experience recurring symptoms, if the exposure to acrylic based products continues. Furthermore, severe cases of allergic contact dermatitis involving symptoms such as blistering and skin detachment can lead to scarring and permanent skin damage". Both statements are generally true for every skin sensitiser, however they fail to refer to the reversibility of the effects of sensitisation to HDDA. Moreover, no scarring or permanent skin damage was observed in all cases presented, many of which cannot be (clearly) attributed to HDDA.
In an article of Basketter and Kimber (2014) with regard to the levels of equivalent concern for including skin sensitisers on the SVHC list, it is indeed considered that the induction phase of sensitisation is irreversible, even if this phase is symptom free. However the elicitation phase of a skin sensitisation is reversible, as long as no permanent skin damage occurs. We found no case of irreversible skin damage even only possibly associated with HDDA, neither in the literature nor in our own companies’ or our customers’ data.
In all publications about allergic dermatitis reactions that might be related to HDDA and that provide information on treatment, the skin reactions could be completely resolved within one to two weeks either by simple avoidance of the allergen or with the help of standard medications, e.g., antihistamines, steroids, betamethasone dipropionate cream (Botella-Estrada et al. (1992), Emmet et al. (1977), Morgan and Fewings (2000), Higgins and Collins (2012), Fischer et al. (1994), Vogel et al. (2014)).
Without going into details on the articles already mentioned in the comments, the one of Botella-Estrada is an interesting case. This describes an accident in which a container of pure HDDA was spilled over the right thigh of the patient, soaking his trousers. Erythematous plaques developed. Treatment with 0.1% of betamethasone diproprionate cream led to complete resolution after 10 days. Even in such a case of high accidental exposure, the effects were fully reversible within a short timeframe.
Higgins (2012) describes the case of a 17 year old printer, who developed a florid erythematous rash on his trunk and limbs. Two weeks previously, he commenced work as a printer and reported contact with ink from posters, through his clothes onto his abdomen. After cessation of exposure and superficial treatment with 0.05% clobetasol diproprionate the rash completely disappeared within a week. Patch testing revealed positive reactions towards all acrylates and methacrylates of the standard series, including HDDA. Since the composition of the ink is unknown, no conclusions can be drawn about the cause of the allergic dermatitis.
Even for the severe case of TEN described by Ido et al. (2012), which resulted from an accident in Japan, all effects disappeared after 2 weeks without scar formation (remark: the relationship with HDDA was not confirmed in this case).
The Annex XV dossier refers to a judgment by the Court of Justice of the European Union with regard to irreversible health effects induced by the respiratory sensitiser Hexahydro¬methyl¬phthalic anhydride (pages 7 and 23). In this case of respiratory sensitisation and in contrast to skin sensitisation, both phases of sensitisation were considered by the Court to be irreversible. Different to what is stated in the Annex XV dossier, the final ruling of the Court of Justice of the European Union explicitly focused on the fact that permanent damage to the lungs in the elicitation phase could not be excluded. As HDDA is not a respiratory sensitiser and as it does not induce permanent damage to the lungs and other organs, the final ruling for Hexahydro¬methyl¬phthalic anhydride cannot be applied.

6. Delay of health effects

Generally, it takes approximately two weeks for the immune system to become capable to elicit a dermal (T-cell dependent) reaction towards an antigen. This is supported by the 3 references originally provided in the Annex XV report on page 24 to illustrate delay of health effects:
In the first publication by Morgan and Fewings (2000) (page 16 of Annex XV dossier), two case reports are described. In the first case symptoms developed weeks after the person started working with the substance, in the second case, a reaction occurred 10 days after first contact.
The second publication by Ido, Kiyohara et al. (2012) (page 15 of Annex XV dossier) reported a time interval of 16 days between the first use of the substance and the development of skin effects.
In the third publication of Vogel, Christoffers et al. (2014) (pages 16 and 23 of Annex XV dossier) the person might have been exposed for a maximum of 3 years, but no further details are provided. He already experienced 2 episodes of an allergic reaction. So this report mainly stresses the importance of early and correct diagnosis of skin lesions, but does not prove a long delay of effects.
The delay of effects does not affect the seriousness of the effect. It is only relevant in combination with the following question: can appropriate risk management measures be applied in time to prevent any effect? The Swedish Authorities state that it is “difficult for workers to take precautionary actions in time to avoid development of sensitisation" (pages 8 and 23). However, this is not applicable as the skin irritating and sensitising properties of HDDA are well known. HDDA is classified accordingly by all registrants under REACH, and it has a harmonized classification as a skin sensitiser in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation) and before this in the Annex I to Council Directive 67/548 (by its 19th Adaptation to technical progress from September 1st 1993 (Commission Directive 93/72/EEC)). There is therefore long-term knowledge of the potential skin sensitisation properties of HDDA and long-term experience in handling it appropriately in the work place. The sensitisation risk is identified in the safety data sheet, and the appropriate risk management measures are advised. To prevent both irritation and sensitisation, also non-sensitised individuals must avoid all dermal contact. The protective measures thus do not change after sensitisation occurs, and this knowledge does not affect how the substance is handled.
Additionally, in the case of HDDA, the uses are limited to industrial and professional conditions and ink cartridges applications. Good surveillance minimises the delay to diagnose the cause of a skin reaction in these settings.
Kiec-Swierczynska et al. (2005) have done investigations into the most suitable type of gloves and  recommend 4H® gloves marketed by Safety 4 A/S, Lyngby, Denmark for handling acrylates. All information is on hand to allow the implementation of the right operational conditions (OC) and risk management measures (RMM) in order to avoid exposure. It should be stressed, that most cases, occur either after accidental exposure or are triggered by absence inappropriate use of personal protective equipment (breakthrough time, type, nature, thickness,...  of gloves - Sasseville, D. (2012)).
Our data indicate that the use of right Personal Protective Equipment (PPE) is sufficient not only to prevent sensitisation, but also that symptoms can be avoided in already sensitised individuals, if acrylate-based products are handled correctly.

7. Derivation of a safe level of exposure
As mentioned on pages 8 and 23 of the Annex XV dossier, we indeed agree that no relevant data are available to support the determination of a quantitative DNEL for HDDA.

8. Quality of life
The references to link HDDA to an impaired quality of life is missing in the annex XV dossier.  All citations of pages 8 and 24 (Skoet et al. 2003, Benyamini et al. 2012, Boehm et al. 2012) of impaired quality of life describe general properties of allergic contact dermatitis. Chronic allergic reactions and chronic hand eczema are included as well and chronic effects are so far not described for HDDA.  No differentiation is made between allergic contact dermatitis and chronic hand eczema, even though they have largely different causes, treatments, and consequences. Chronic hand eczema usually starts as skin irritation, which must be ignored for years to manifest as a chronic condition. This is not caused by a single allergic reaction, but has multiple causes. Breakdown of the barrier function of the skin because of continuous wet environment is one of the major causes (DGUV.de - 1). Though it is acknowledged that an allergic reaction can worsen a pre-existing skin condition to become chronic, they are usually localised at different parts of the body. While the chronic hand eczema affects the hands, allergic contact dermatitis most often occurs at the wrists and arms, where the gloves no longer provide protection.
On page 9 of the annex XV report, it is written that “Occupational allergic contact dermatitis is associated with an impaired quality of life similar to psoriasis and asthma due to the physical and social problem at the work place”.
To our knowledge, no long-term illness has been reported. There is minimum influence on the private life, because HDDA and other (meth)acrylates should not be used in consumer products. We clearly advise against the use of HDDA in consumer applications, however we are aware of the use of other (meth)acrylates in some specific applications like nails and dental. Avoiding such specific activities / products is not expected to have a major impact on the quality of life. In the vast majority of cases, workers continued their job (appropriate PPE and handling procedures must prevent skin contact also prior to accidental sensitisation). In conclusion, there is no indication of an impaired quality of life due to HDDA allergy.
9. Societal concern

Page 24 of the Annex XV report costs of 8799€ for illness from occupational chronic hand eczema in Germany, based on a publication of Diepgen et al. (2013). It should be pointed out that this refers to treatment of chronic hand eczema, which require continuous treatment for years and lost productivity. In contrast, the treatment of the allergic dermatitis reactions described for HDDA lasted for 1-2 weeks. No chronic cases have been reported.
As stated above, no information is available about costs and retraining needs specifically associated with HDDA. A German database (DGUV.de – 2) reports all types of skin diseases in Germany caused by occupational exposure. Most cases are hand eczemas caused mainly by repeated contact with water, cleaning agents, or other liquids leading to a frequently or permanently wet skin. Generally, allergic reactions are not the main cause for occupational skin reactions, though no further details are provided. Moreover, the data show that preventive strategies and protective measures at the workplace are effective to prevent retraining of workers. Out of the approximately 20,000 confirmed occupational related cases reported each year, only app. 580 workers (2.9%) cannot continue in their job (DGUV.de – 3).
For the purposes of this public consultation, calculations have been done to estimate the Social costs of occupational dermatitis:
In 2014, a study carried out for ECHA by the Charles University in Prague and VU University Amsterdam  was published which provides willingness to pay estimates for the avoidance of a case of dermatitis. The primary objective of the study was two-fold: (1) to estimate willingness to pay to avoid selected adverse human health outcomes due to exposure to chemicals in the EU, and (2) to derive representative EU-wide benefit estimates that could act as reference values that ECHA and other bodies can use when carrying out socio-economic analyses within the context of REACH.
One of the reports focuses on skin sensitisation and elicits Willingness-to-Pay values (WTP) for health outcomes related to skin sensitisation. These WTP values were elicited from an adult population sample in four EU Member States: the Czech Republic, the United Kingdom, the Netherlands and Italy to provide an estimate of the economic value of avoiding a case of dermatitis associated with each of the above health outcomes. Although the authors identify some issues surrounding the resulting estimates, including the fact that the WTP values for avoiding acute dermatitis appear high compared to other similar morbidity symptoms, the estimates are the most recent and the most directly relevant figures currently available.  The resulting estimates are as follows:
• acute mild dermatitis:     €227 per case
• episodes of mild acute dermatitis (4 over 1 year):  €329 per case
• episodes of mild acute dermatitis (1/yr. over 5 years): €352 per case
• episodes of mild acute dermatitis (4/yr. over 10 years): €615 per case

It is of note that WTP decreases with increases in episodes over time (from €227 per episode to less than €20 per episode for the 4/year over 10 years example), with the first figure associated with the avoidance of a single episode of acute mild dermatitis being much higher. Nevertheless for the purposes of this exercise, we adopt the figure of €227 as the WTP to avoid a case of mild dermatitis from occupational exposures.
When we add all reported cases within the last 30 years together (35 cases from the literature, 21 cases in the PARAD survey and 7 cases from the EUPIA survey), we come to a rough estimate of an average of 2 cases per year. Even assuming very conservatively that only about 10 to 20% of the workers were covered by the surveys and that again the same number of cases were not reported, we end up with a maximum of 40 cases per year. Multiplying this number with the estimated treatment costs per case, we end up with yearly cost of 9 080 Euro.

10. PARAD Conclusions on Inclusion of HDDA as a SVHC

Hexamethylene diacrylate (HDDA, EC number: 235-921-9, CAS number: 13048-33-4) has been identified for inclusion on the list of substances of very high concern in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because of its skin sensitising properties by the Swedish Authorities (KEMI).
The PARAD Consortium has not found sufficient evidence to support the inclusion in the list of substances of very high concern.
HDDA has no properties that distinguish it from other skin sensitizing substances. Especially, no chronic or difficult to treat skin effects were described. In all reported cases the skin reactions completely resolved within two weeks, leaving no scars or permanent damage. We found a total of 35 positive patch test reactions in the literature since 1977 for which previous exposure to HDDA could not be excluded. This number, though already low, overestimates the number of cases really caused by HDDA due to the fact that HDDA is part of a patch test screening series to detect allergies caused by any acrylate or methacrylate and some of them are due to the cross reaction mechanisms. Part of the reason that not many new cases of potentially HDDA related contact dermatitis are found, is the efficient use of personal protective equipment. Since the sensitising properties of the substance have been known for long, operational procedures and protective clothing have been established to prevent all dermal contact. All cases were related to misuse (including absence) of PPE and/or accidents. As a consequence, working procedures do not have to be changed after a worker has been sensitized to HDDA. An allergy against HDDA does not justify that a worker needs to switch jobs. Additionally, there is no use of HDDA outside the industrial / professional environment and very limited uses of other (meth)acrylates, so that an occupational contact dermatitis against HDDA does not affect a person’s private life. The overall impairment in the quality of life is thus minimal. The relevant societal concern is low because of short treatment times, efficient mechanism to prevent dermal contact at work and thus no need to switch jobs, and a low overall number of cases.

 
References

Aalto-Korte, K., Alando, K., Kuuliala, O., Jolanki, R. (2007): Methacrylate and acrylate allergy in dental personnel. Contact Dermatitis 57, 324-330.
Aalto-Korte, K., K. Alanko, O. Kuuliala and R. Jolanki (2008): Occupational methacrylate and acrylate allergy from glues. Contact Dermatitis, 58(6): 340-346
Acrylic fingernail – Raw Materials - http://www.madehow.com/Volume-3/Acrylic-Fingernail.html
Basketter, D. and I. Kimber (2014): Consideration of criteria required for assignment of a (skin) sensitiser a substance of very high concern (SVHC) under the REACH regulation. Regul Toxicol Pharmacol, 69(3): 524-528
Benyamini, Y., D. Goner-Shilo and A. Lazarov (2012): Illness perception and quality of life in patients with contact dermatitis. Contact Dermatitis, 67(4): 193-199
Bjorkner, B. (1984): The sensitising capacity of multifunctional acrylates in the guinea pig. Contact Dermatitis, 11(4): 236-246
Boehm, D., G. Schmid-Ott, F. Finkeldey, S.M. John, C. Dwinger, T. Werfel, T.L. Diepgen and K. Breuer (2012): Anxiety, depression and impaired health-related quality of life in patients with occupational hand eczema. Contact Dermatitis, 67(4): 184-192
Botella-Estrada R., Mora E and de la Cuadra J. (1992): Hexanediol diacrylate sensitisation after accidental occupational exposure. Contact Dermatitis, 26: 50 – 51
Christoffers, W.A., P.J. Coenraads and M.L. Schuttelaar (2013): Two decades of occupational (meth)acrylate patch test results and focus on isobornyl acrylate. Contact Dermatitis, 69(2): 86-92
Clemmensen, S. (1984): Cross-reaction patterns in guinea pigs sensitised to acrylic monomers. Drug Chem Toxicol, 7(6): 527-540
Constandt, L., E.V. Hecke, J.M. Naeyaert and A. Goossens (2005): Screening for contact allergy to artificial nails. Contact Dermatitis, 52(2): 73-77
Cravo, M., J.C. Cardoso, M. Goncalo and A. Figueiredo (2008): Allergic contact dermatitis from photobonded acrylic gel nails: a review of four cases. Contact Dermatitis, 59(4): 250- 251
Diepgen, T.L., R. Scheidt, E. Weisshaar, S.M. John and K. Hieke (2013): Cost of illness from occupational hand eczema in Germany. Contact Dermatitis, 69(2): 99-106
DGUV.de – 1: http://www.dguv.de/de/Versicherung/Berufskrankheiten/Hauterkrankungen/index.jsp
DGUV.de – 2: http://www.dguv.de/de/Zahlen-und-Fakten/BK-Geschehen/Best%C3%A4tigte-BK-F%C3%A4lle/index.jsp
DGUV.de – 3: http://www.dguv.de/de/Zahlen-und-Fakten/BK-Geschehen/Anerkannte-BKen/index.jsp
ECHA (2013): Guidance on information requirements and chemical safety assessment Chapter R.8: Appendix 8-10
ECHA (2015): Guidance on the Application of the CLP Criteria. 333-345
Emmett E.A., Kominsky M.B, Kominsky J.R. (1977): Allergic Contact Dermatitis From Ultraviolet Cured Inks. Journal of Occupational Medicine 19 (2): 113-115
Emmett, E.A., Taphorn, B.R. and Kominsky, J.R. (1977): Phototoxicity Occurring During the Manufacture of Ultraviolet-Cured Ink. Arch Dermatol, 113(6):770-775.
Escobar, A., Yamarik T.A., Andersen F.A. (2005): Final report of the safety assessment of methacrylate ester monomers used in nail enhancement products. Int J Toxicol. 24 (5):53-100.
European Society of Contact Dermatitis (2015) What is contact dermatitis.  http://www.escd.org/aims/contact_dermatitis/ (accessed 8.10.15)
Fischer T, Nylander-French L. and Rosén G (1994): Dermatological Risk to Workers in the Ultraviolet Radiation Wood Surface Coating Industry, Dermatitis, 5(4):
Geukens, S. and A. Goossens (2001): Occupational contact allergy to (meth)acrylates. Contact Dermatitis, 44(3): 153-159
Goon, A.T., M. Isaksson, E. Zimerson, C.L. Goh and M. Bruze (2006): Contact allergy (to meth)acrylates in the dental series in southern Sweden: simultaneous positive patch test reaction patterns and possible screening allergens. Contact Dermatitis, 55(4): 219- 226
Guerra L, Vincenzi C, Peluso AM, Tosti A (1993): Prevalence and sources of occupational contact sensitisation to acrylates in Italy. Contact Dermatitis 28: 101-103
Higgins E. and Collins P. (2012): Urticarial allergic contact dermatitis caused by UV-cured printing ink. Contact Dermatitis, 66(6): 340-355
House, R.A., H. Jakubovic, L. Wong and D.L. Holness (1992): Work-related toxic epidermal necrolysis? J Occup Med, 34(2): 135-139
Ido, T., T. Kiyohara, H. Takahashi, Y. Yamaguchi, D. Tani and M. Kumakiri (2012): Toxic epidermal necrolysis following allergic contact dermatitis caused by occupational exposure to ultraviolet-cured inks. Acta Derm Venereol, 92(3): 313-315
Kiec-Swierczynska, M., B. Krecisz and D. Chomiczewska-Skora (2013): Occupational contact dermatitis to acrylates in a manicurist. Occup Med (Lond), 63(5): 380-382

Kiec-Swierczynska, M., B. Krecisz, D. Swierczynska-Machura and J. Zaremba (2005): An epidemic of occupational contact dermatitis from an acrylic glue. Contact Dermatitis, 52(3): 121-125

Malten KE, den Arend JACJ, Wiggers RE (1979): Delayed irritation: Hexanediol diacrylate and butanediol diacrylate. Contact Dermatitis 5: 178-184
Morgan, V.A. and J.M. Fewings (2000): 1,6-hexanediol diacrylate: a rapid and potent sensitiser in the printing industry. Australas J Dermatol, 41(3): 190-192
Nethercott JR (1978): Skin problems associated with multifunctional acrylic monomers in ultraviolet curing inks. British Journal of Dermatology 98: 541-552
Ramos, L., R. Cabral and M. Goncalo (2014): Allergic contact dermatitis caused by acrylates and methacrylates--a 7-year study. Contact Dermatitis, 71(2): 102-107
Roche, E., J. de la Cuadra and V. Alegre (2008): [Sensitisation to acrylates caused by artificial acrylic nails: review of 15 cases]. Actas Dermosifiliogr, 99(10): 788-794
Pesonen, M., O. Kuuliala, M.L. Henriks-Eckerman and K. Aalto-Korte (2012): Occupational allergic contact dermatitis caused by eyelash extension glues. Contact Dermatitis, 67(5): 307-308
Sasseville, D. (2012): Acrylates in contact dermatitis. Dermatitis, 23(1): 6-16
Skoet, R., R. Zachariae and T. Agner (2003): Contact dermatitis and quality of life: a structured review of the literature. Br J Dermatol, 149(3): 452-456
Teik-Jin Goon, A., M. Bruze, E. Zimerson, C.L. Goh and M. Isaksson (2007): Contact allergy to acrylates/methacrylates in the acrylate and nail acrylics series in southern Sweden: simultaneous positive patch test reaction patterns and possible screening allergens. Contact Dermatitis, 57(1): 21-27
The National Institute for Occupational Safety and Health (NIOSH, 1987): Exposure Assessment of acrylate/methacrylate in radiation-cured applications, http://www.cdc.gov/niosh/nioshtic-2/00175433.html
Vogel, T.A., W.A. Christoffers, M. Engfeldt, M. Bruze, P.J. Coenraads and M.L. Schuttelaar (2014): Severe bullous allergic contact dermatitis caused by glycidyl methacrylate and other acrylates. Contact Dermatitis, 71(4): 247-249	
The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  

  

The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  

The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.

The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.

	
		Attachment: 
		
4564
2015/10/15	Company,
United Kingdom	
Confidential attachment has been removed	Thank you for your comment. Please refer to answer to comment 4492 under general comments. 	
4568
2015/10/15	Health and Environment Alliance (HEAL),
International NGO,
Belgium	We support the nomination of Hexamethylene diacrylate to the Candidate List	Thank you for your support.	

PART II: Comments and responses to comments on uses, exposures, alternatives and risks

Specific comments on use, exposure, alternatives and risks
Number / Date	Submitted by (name, submitter type, country)	Comment	Response	
4492
2015/10/02	CEPE,
Industry or trade association,
Belgium	We are of the opinion that HDDA does not fulfill the conditions of SVHC for the reasons explained in the attached document.	Thank you for your comment. Please refer to answer to comment 4492 under general comments on SVHC proposal	
		Attachment: 
		
4493
2015/10/05	Sun Chemical,
Company,
Netherlands	Section 8.1.1.1 Industrial uses are well controlled, and exposures to HDDA are minimal.  Within my Company, several sites have used HDDA in many tonnes in formulating printin Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.g inks for many years.  Whilst there were some issues with exposures to acrylates generally in the 1980s and early 1990s, since 2000, the higher purity production processes have played an important part in worker safety.  In addition, there has been a steady improvement in guidance, understanding and communication, together with good advice on suitable handling and PPE / risk management, such that there have been remarkably few (one) instances of skin sensitisation to any acrylates (including where HDDA is in common use).  The normal solution to this issue is to remove the affected employee from the immediate vicinity and reassign their work tasks (e.g. from formulation / mixing to warehouse activities, or from UV products to water-based or solvent-based production).
Section 9.3.1  It is important to specify appropriate material for dermal protection to UV curing printing inks.  In the past, workers have used thin disposable gloves, made from inappropriate materials such as polyethylene, which may seem to offer protection, but in fact are no barrier to penetration, and even exacerbate the exposure due to the occlusive effect.  RadTech, the trade association of acrylate suppliers, recommend the use of thick nitrile gloves, and these recommendations are included in the SDS information and guidance passed along the supply chain to downstream users.
Section 10.1  There are very limited alternatives to HDDA.  When formulating, it is necessary to achieve adequate cure speed at the appropriate (low) viscosity and surface tension.  In this regard, most of the alternative multifunctional acrylates listed are not suitable as alternatives.  The next useful low viscosity, low surface tension, reactive diacrylate would be dipropylene glycol diacrylate, or butanediol diacrylate (but BUDA is corrosive and of greater concern regarding dermal exposure).	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.

Please also refer to answer on comment 4505 under general comments on SVHC proposal	
		-		
4505
2015/10/12	Zeller+Gmelin GmbH&Co KG,
Company,
Germany	
Confidential attachment has been removed	Please refer to answer to comment 4505 under general comments on SVHC proposal	
4509
2015/10/13	TOYO INK ARETS NV,
Company,
Belgium	We believe that HDDA is not a substance that presents an equivalent concern to CMRs Category 1 and it should not be considered an SVHC because:
• We had not one case in our plant of skin sensitization during the past 15 years.
• Where exposure is possible (through splashing and spillages) proper protective equipment is worn in our factory for protection at all times (for all products): gloves (nitrile), safety glasses, goggles, full coverall, apron, long sleeves, respiratory mask, safety boots.
• Where possible, manual handling is avoided (automated pumping, enclosure, ..).
• The risk of skin sensitization of HDDA is well known. We give regular internal training on the risk of chemicals and the use of PPE.
• Tox. data being used in consideration of the SVHC rating is old and was generated at a time when the monomer was quite “dirty” and contained relatively high levels acrylic acid, which was responsible for a lot of the skin contact issues seen with its early use.
• HDDA has very unique properties as a raw material, namely it gives very good adhesion, has low viscosity and a high reactivity.
• The alternative raw materials for HDDA often have SDS ratings that are more severe, i.e. corrosive.

Conclusions:
HDDA is a valuable acrylate for our company in the formulation and manufacturing of UV curing ink and varnishes for various industrial applications. It has been used in hundreds of tons in our company during the past 15 years with zero reported cases of skin sensitization. Its skin sensitization potential is well known and proper measures have been put in place to avoid exposure: training, PPE and engineering measures. For these reasons we believe that HDDA is not a substance that presents an equivalent concern to CMRs Category 1 and it should not be considered an SVHC.	Thank you for your comments. Please refer to answer to comment 4505 under general comments to SVHC proposal. 
	
		Attachment: 
		
4512
2015/10/13	Company,
Germany	HDDA is normally not used in public products, but only in industrial uses. As we are a manufacturer of printing inks, we use HDDA in the manufacture of UV-curing inks. Within our company exposure to HDDA can occur in our research and development laboratory as well as in our production area. The inks and auxiliaries manufacuted with HDDA are handled in our quality assurance laboratory and by our technical stuff when they load the printing machines for test printings. Our customers using the inks can be exposed when mixing the wet inks, or when loading their printing machines. The HDDA content in the inks and auxiliaries varies between 0,1 to 50%. Concerning the printed products, however, no HDDA exposure will occur, as the monomers are chemically bond into the ink film during the UV curing process. To avoid such exposure, within our company protective equipment is worn: Gloves,safety goggles and safety boots are used in the laboratory when handling UV curing products. As much higher quantities are handled in the production area, stuff wears full coverall, apron and safety boot  Same equipment is recommended to our customers in the safety data sheets. Thanks to all these measures, we had one single case of skin sensitization related to HDDA in our company, and this was back in 1993 and related to an accident.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4513
2015/10/13	Company,
Germany	-	
 The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  
	
		Attachment: 
		
4516
2015/10/14	Company,
United Kingdom	pg 27: We have had no incidences of exposure to HDDA, but PPE precautions are followed rigorously.  For inkjet printing, HDDA's properties are unique as it is low viscoaity, gives high adhesion and high reactivity.  In addition, the alternatives for inkjet printing tend to have more severe SDS ratings, typically being rated as corrosive or causing environmental hazards	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4517
2015/10/14	Roland DG Mid Europe S.R.L. - Acquaviva Picena (AP),
Company,
Italy	Healthy risk seems to the product a consuming public uses, therefore we propose that the sensitization chemical should be restricted by the EU orders and the standards which are category to Cosmetic, Toy and Medical, instead of SVHC.

UV ink will be used primarily for industry, and EC 235-921-9 (CAS 13048-33-4) contained in UV ink is polymerized by UV curing in the printing process. As the result, the risk including the skin sensitization eliminates almost.
The uncured EC 235-921-9 (CAS 13048-33-4) are exposed to human is the limited scene that are ink manufacturing and disposal, and the risks should be reduced in normal use if it is a control of preventing exposure.
It should be noted that it is often dealing with high hazardous substances such as volatile solvent in the ink manufacturing, therefore exposure risk to humans  is considered low by exposure measures.
Also in the waste, putting on impermeable protective laminated gloves made of polyvinyl alcohol etc. instead of nitrile gloves (as written in Sweden report, page 16), wear protective clothing, face protection and protection mask,  exposure risk will be reduced substantially.
It should be noted that the vapor pressure of the substance is about 0.06Pa (at 20 ℃) and the volatile is low at room temperature, the risk of exposure to vaper in short time work.

About 1000 substances are relevant to H317 only by the substance listed in CLP ANNEX6 Table3.1. If H317 is judged to be subject to SVHC, a lot of substances will be subject to SVHC, it is concerned with the socio-economic impact is very large.
In CLPANNEX6 Tabel3.1, there Hazard code is attached substance of further CMR in H317 is more than 180 substances, it should be considered with priority for these dangerous substances.

There is many substances which relevant to CMR in addition to H317 more than 180 substances in CLPANNEX6 Tabel3.1, however only the part among these substances is designated as SVHC. It should be considered with priority for these dangerous substances to SVHC.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4526
2015/10/14	NXP Semiconductors,
Industry or trade association,
Netherlands	USE
The substance hexamethylene diacrylate with CAS number 13048-33-4 is present as an essential constituent in a special glue used by NXP Semiconductors to assemble dedicated semiconductor devices into their final package. The devices have a specific use in the identification domain.
Hexamethylene diacrylate is present in the glue at a concentration in the range of 1-5 % w/w.
The hexamethylene diacrylate containing glue is manufactured in Europe and currently available on the European market. NXP perform the assembly 100% in the Far East.
On a yearly basis NXP use less than 2 kg of the glue in their Far East assembly sites. This corresponds with a use of 50-100 gram of hexamethyl diacrylate.
PROCESS AND EXPOSURE TO EMPLOYEES
During chemical handling and maintenance workers wear proper gloves to avoid skin contact.
The glue is dispensed via conventional DAP (pneumatic) method from syringes. The glue is then cured in an oven at 200⁰C. LEV is applied to extract potentially released fumes. There is no release of hexamethylene diacrylate to wastewater. Empty syringes are sent for incineration.
During glue curing the hexamethylene diacrylate present in the glue (co-)polymerizes and is no longer found in the final device, which means that there is no exposure to the actual user of the device.
The process descriptors are as follows:
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 RISK FOR CUSTOMERS
Hexamethylene diacrylate is no longer present in the final device, so there is no exposure to customers. At the end of life these devices are disposed of following the WEEE Directive.
BUSINESS RISK AND ECONOMICAL IMPACT
The hexamethylene diacrylate containing glue is manufactured in Europe and currently available on the European market. NXP semiconductors perform their assembly activities in facilities located in the Far East. A European ban would therefore comprise a supply-chain interruption for NXP Semiconductors worldwide.

The market value of the products manufactured with this glue is given in a separate, confidential document.
There may be hexamethylene diacrylate-free glue substitutes, but their performance is still to be proven. Substitution would entail relatively high cost, qualification effort, and time, since every application requires thorough qualification. A ban on hexamethylene diacrylate based glues would be disproportionate in view of the negligible risks to workers, the environment and customers.	Thank you for your comments and the information provided.
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
		
4527
2015/10/14	3M Belgium NV/SA,
Company,
Belgium	See part I comments		
4532
2015/10/14	Company,
Ireland	HDDA (Hexamethylene diacrylate) is used in the manufacturing process of a specific membrane type used in a variety of venting applications where sterility must be maintained, including for example bioreactors in protein therapeutics for cancer and other treatments.

Manufacture of these membranes is carried out in a tightly controlled GMP environment as well as ISO 9001 and ISO 13485 standards.

Alternative chemicals for our manufacturing process are not available and it will require considerable resources to trial and validate alternatives, if at all possible.   The replacement of HDDA in the process with an alternative chemical may not be technically feasible, and if a suitable alternative is identified, process re-development and qualification using this alternative will require significant investment in time and resources in a multi-year program.

In addition, our required efforts to change the manufacturing processes to find an alternative will impact our customers in the pharmaceutical industry who have validated their use of our membranes through governmental agencies such as the European Medicines Agency (EMEA) or the United States Food and Drug Administration (FDA) and they also will be forced to undergo a lengthy revalidation process to continue the therapeutics they produce.

Exposure of workers:
The risk of exposure of the operator, whilst handling HDDA is low, due to appropriate engineering controls (including containment and local extraction) and correct PPE.

Exposure to the environment/public:
Low quantities of HDDA are used in the process and consumed within the product.  Any residue material after curing is extracted through the manufacturing process.  Trace amounts of HDDA in waste solvent is sent for hazardous waste disposal and incineration in accordance with the site IPPC licence.  Areas of use are equipped with spill barriers (bunded) and containment programmes are in place.

Exposure to the customer:
The vast majority of our customers are in the pharmaceutical industry, so validation is often required, including approval by government agencies such as the EMEA or FDA.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
		-		
4537
2015/10/15	Coates Screen Inks GmbH,
Company,
Germany	Wir setzen das Monomer HDDA in unserem Betrieb seit ca. 40 Jahren ein.
Uns ist kein Fall bekannt, dass im Umgang mit diesem Monomer, bei konsequenter und vorgeschriebener Verwendung der PSA, ein Mitarbeiter verletzt bzw. geschädigt wurde.
Der Umgang mit HDDA kann in unserem Betrieb als „sicher“ betrachtet werden, solange die Arbeitsanweisungen von den Mitarbeiter befolgt werden. Um dies sicherzustellen, gibt es regelmäßige Schulungen.

HDDA ist ein Rohstoff in der Farbenindustrie, der für uns unverzichtbar ist. Insbesondere bei Farben für die Kunststoffbeschichtung sind uns keine Alternativen bekannt.
Die uns bekannten Monomere, die ebenfalls eine gute Haftung auf Kunststoffoberflächen ermöglichen, haben sogar ein höheres Reiz- und Gefährdungspotenzial als HDDA.
Diese wurden größtenteils bereits  durch HDDA substituiert.
Eine Einstufung von HDDA als SVHC-Substanz würde bedeuten, dass viele technische Verfahren in der Kunststoffbeschichtung nicht mehr praxistauglich wären, und den Produktionsstandort Deutschland bzw. Europas schaden.	??? Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4538
2015/10/15	CEPE,
Industry or trade association,
Belgium	CEPE is the voice of the paint and printing ink industry. The substance HDDA is in use in some of our industrial applications. We have collected information on its use and on cases of skin sensitization. On the basis of our experience of handling the substances in industrial settings for many years CEPE does not believe that HDDA should be considered as being of equivalent concern to CMRs Category 1 (Art 57(f) of REACH. More information is submitted in the attached submitted document.	
Thank you for your comment. Please refer to answer to comment 4492 under general comments on SVHC proposal	
4543
2015/10/15	Industry or trade association,
Belgium	The substance hexamethylene diacrylate with CAS number 13048-33-4 is present as an essential constituent in special glues used in the semiconductor sector to assemble dedicated semiconductor devices into their final package. The devices have a specific use in the identification domain.
Hexamethylene diacrylate is present in these glues at a concentration in the range of 1-5 % w/w.
The hexamethylene diacrylate containing glues are manufactured in Europe and currently available on the European market. The assembly uses by the semiconductor industry are all in the Far East.
The total quantity of hexamethylene diacrylate containing glues used is less than 2 kg per year which corresponds with a use of 50-100 gram hexamethylene diacrylate per year.

PROCESS AND EXPOSURE TO EMPLOYEES

The glue is dispensed via conventional DAP (pneumatic) method. The glue is then cured in an oven at 200⁰C. LEV is applied to extract potentially released fumes. There is no release of hexamethylene diacrylate to wastewater.
During glue curing the hexamethylene diacrylate present in the glue (co-)polymerizes and is no longer found in the final device, which means that there is no exposure to the actual user of the device.

FINAL PRODUCT AND RISK FOR CUSTOMERS

Hexamethylene diacrylate is no longer present in the final device, so there is no exposure to customers. At the end of life these devices are disposed of following the WEEE Directive.

BUSINESS RISK AND ECONOMICAL IMPACT
The hexamethylene diacrylate containing glues are manufactured in Europe and currently available on the European market. The semiconductor industry performs their assembly activities in facilities located in the Far East. A European ban would therefore comprise a supply-chain interruption for the industry.
The market value of the devices manufactured with these hexamethylene diacrylate containing glues is considerable. There may be hexamethylene diacrylate-free glue substitutes, but their performance is still to be proven. Substitution would entail relatively high cost, qualification effort, and time, since every application requires thorough qualification. A future ban on hexamethylene diacrylate based glues would be disproportionate in view of the negligible risks to workers, the environment and customers.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
		-		
4557
2015/10/15	Company,
Germany	P. 31, 9.3.1. Human exposure: On the basis of past experience, risk management measures like proper protective equipment have allowed a safe handling  of HDDA over more than a decade.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4558
2015/10/15	Company,
Sweden	HDDA as a raw material contributes with unique properties in inks and varnishes for the graphic industry. It gives good adhesion, has low viscosity and high reactivity. The alternative raw materials usually have been accused of causing more severe detrimental health effects.	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4559
2015/10/15	Netherlands,
Member State	NL agrees that some of the effects reported for workers and induced by dermal exposure to HDDA may be severe warranting the identification as SVHC. NL agrees that if these severe effects are representative for the general worker population and can also be expected for consumers getting in contact with, for example, nail-glues this would support the identification of HDDA as SVHC. However, from the present Annex XV dossier, in the opinion of NL, remains unclear if the severe effects observed in a limited number of workers are the result of representative working conditions, or if these effects should rather be considered as incident cases. Further elaboration on this topic would be appreciated. Further, regarding candidate listing and authorization, NL questions why not restrictions is proposed as an appropriate RMO allowing a more target approach for those uses that are of concern, including also import of articles. As this option was not further elaborated in the RMOA, NL would appreciate some further discussion on this topic. However, NL agrees that the substance meets the SVHC criteria, the Netherlands would prefer a restriction rather than authorisation for this substance.	First we would like to point out that considerations of other regulatory options are not relevant for the SVHC identification. The issue on different risk management options was addressed earlier under the RMO phase and a justification on why we consider SCHC identification as the best RMO is included in the RMO document.
In addition, the identification of respiratory sensitizers as SVHC have previously been deemed not to be a disproportionate measure. A judge from the EU general court says that worker protection legislation and restriction in REACH cannot be considered as more appropriate and less burdensome measures compared to SVHC identification which solely entails information obligations as a first step. We believe that the same reasoning should apply to skin sensitizers of equivalent level of concern such as HDDA.

Please also refer to the answer on comment 4527 under specific comments on the justification.	
4562
2015/10/15	PARAD Consortium,
Other contributor,
Belgium	1. Overview of key points:

This response to the public consultation is Part II of the PARAD Consortium response and should be read in conjunction with Part I, which is being submitted the same time as this report. This Part II deals with Part II of the Annex XV dossier.
Hexamethylene diacrylate (HDDA, EC number: 235-921-9, CAS number: 13048-33-4) has been identified by the Swedish Authorities (KEMI) for inclusion on the list of substances of very high concern in accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because of its skin sensitising properties.
The PARAD Consortium has carefully read the Annex XV dossier and has developed comments on each of the arguments put forward by KEMI. Outlined in bullet points below are the key arguments on Part II of the Annex XV dossier presented in this document. The reasoning is provided in the subsequent sections of this document:
• The RMOA analysis conducted by Sweden did not include industry participation. Data mentioned by the Swedish authorities as being missing in the RMOA analysis, such as the incidence of HDDA-specific allergy reactions and estimates of the societal costs, are included in the PARAD response to this public consultation.
• PARAD provides consolidated EU manufacture and import volume data over the period 2007-2014. These do not support any increasing trend in the EU market of HDDA.
• HDDA is primarily used in industrial UV curable coatings (rather than “paints” or “curable paints”). These coating have significant environmental benefits compared to solvent-based coatings for example.
• HDDA is fully consumed in the curing process, so there is no exposure of users of the coated products.
• HDDA is also used as a monomer or cross-linking in the polymer industry. These uses as an intermediate are exempt from authorisation.
• In both the industrial coatings and the polymer industries, worker exposure is low.
• Professional uses are limited to very small volumes and are supported by PARAD only in highly controlled processes. Consumer uses are uses advised against by PARAD.
• Most, if not all, reported cases of HDDA exposure are the result of accidents, no PPE or misuse of PPE.
• SDSs of HDDA suppliers specify clear recommendations on the correct gloves to be used as required by REACH.
• All alternatives listed in the HDDA Annex XV dossier are skin sensitising (meth)acrylates. The substitution of 1 specific acrylate like HDDA will not decrease the risk of sensitisation in the supply chain. This is not a sustainable approach and questions the relevance of the RMOA conclusion.
• The HDDA lead registrant has updated his registration dossier. PARAD co-registrants of HDDA will do so by end-October 2015. These updates indicate as uses advised against all consumer uses as well as professional uses in dental and nail applications.
 
2. Introduction

2.1. Industry was not consulted in RMOA Process

The RMOA was announced on the PACT site on February 6th, 2015 and the final RMOA conclusion document was published on April 15th, 2015. The Lead Registrant (LR) contacted the Swedish Authorities per e-mail on February, 18th, 2015, but did not receive any reply. For information, in the meantime, the substance with CAS # 42978-66-5 (TPGDA) has also been included on the PACT list on March 6th, 2015. The LR (the same as for HDDA) contacted again Kemi per e-mail on March 16th, 2015. The LR received a reply per e-mail on May 6th, 2015, where Kemi stated that they will contact the LR if needed but no further contact took place so far.
After the publication of the RMOA conclusion document on HDDA, the LR managed to get in contact with Kemi on June 11th, 2015. The Swedish Authorities came back to the LR on June 15th but proposed to have a meeting only in the second half of August, which is the time when the Annex XV dossier was ready for submission to ECHA.
The RMOA carries the following disclaimer: “Please note that this RMOA conclusion was compiled on the basis of available information and may change in the light of new information or further assessment.” The RMOA was done without the involvement of industry and does not include any industry data, making it clear that there is additional information available and that there is a possibility that further assessment with industry involvement could have resulted in a different conclusion.
The conclusion of the RMOA is that SVHC listing and ultimately authorisation is the most appropriate route. However, the authors concede that restriction is in fact one possible risk management option, and state the following: « We believe that restriction of HDDA under REACH is one possible option, and also that restriction of skin sensitizing acrylates as a group may be an alternative. However, we do not believe that restriction is the preferable way forward since it will be difficult to assess societal costs. » On this point, the PARAD Consortium would note that a high level estimate of societal costs has been done and can be found in Comments to Part I, section 9.
The RMOA goes on to say: « The severe health effects from HDDA (allergic contact dermatitis), the economic impact of such effects and the wide-spread occupational exposure indicate a societal concern. There is, however, a lack of information regarding the incidence of occupational allergic contact dermatitis from HDDA which makes difficult to estimate the total societal costs with accuracy [our emphasis]. Detailed assessments of societal costs are from our experiences necessary to prove proportionality and get approval of the restriction proposal in ECHAs socioeconomic committee, SEAC. In addition, assessment of proportionality require knowledge about substitution to safer alternatives (substances and/or techniques). It is difficult for authorities to retrieve information about possible alternatives and to assess if substitution is possible. It can be assumed that such knowledge is much higher among producers and users of HDDA. Therefore, we are of the opinion that the issue of alternatives should be addressed under the authorisation process where the applicant is responsible to produce such information. At the moment the Swedish Chemicals Agency has no intention to further investigate the possibilities for restriction. »
We would note that PARAD has provided information regarding the incidence of HDDA related contact dermatitis in Part I of our response to the public consultation.
Finally, we note that, as ECHA points out, the RMOA « is an important step, agreed in the SVHC Roadmap, but it is voluntary (i.e. not part of the processes as defined in the legislation). For authorities, documenting the RMOA allows information to be shared. This promotes early discussion, which helps create a common understanding on the appropriate action to be taken. »
In the RMOA process, creating a common understanding on the appropriate action to be taken requires the active involvement of industry in providing information to the Member State undertaking the RMOA.  This is the only way to ensure that all relevant and available information is taken into account, making the process efficient and effective and ensuring that all possible control routes to ensure safe use are considered, such as substance evaluation, restriction, or compliance with existing community legislation including on occupational health and safety.

2.2. Update on PARAD’s current downstream user and registration dossier activities

PARAD companies have learnt through the surveys and discussions about HDDA that the use of PPE is not yet optimal at all downstream users, despite clear improvements over time for most of the users of HDDA.  For instance, issues with the use of wrong types of gloves and with the management of contaminated PPE may still persist here and there.  Therefore, new information campaigns about the safe use of HDDA and other acrylates will be initiated in the coming months under the umbrella of Cefic UV/EB.
In addition, the Consortium intends to further deepen its Downstream User survey as part of the campaign to provide education and training on the safe use of HDDA.
PARAD registrants’ REACH dossier updates:
The Lead Registrant has already updated its REACH dossier for HDDA to include the following information:
- Joint dossier:
• Updated information in the sensitisation chapters for both animals and humans
• Guidance on Safe Use with revised/detailed recommendations on gloves, submitted by the Lead on behalf of all registrants;
- Each member dossier:
• Deletion of the Guidance on Safe Use in the member dossier;
• Qualitative risk assessment (CSR chapter 9) with revised/detailed recommendations on collective and individual OC/RMMs;
• Revised list of supported uses, with harmonized/more explicit titles, revised lists of PROCs/ERCs and clarification of which precise professional use is covered;
• Identification of any consumer uses and professional uses in dental and nail applications as a “Use advised against”
The other PARAD members will update their dossier by the end of October 2015 accordingly. PARAD will approach the other 3 HDDA co-registrants outside PARAD to encourage them to implement the same changes.
 
3. General comment on Part II of the Annex XV Report by Sweden

We noted that the word “paints” or "curable paints" are used several times in part II to define the use of HDDA. We would like to clarify that HDDA is mainly used in industrial curable coatings, not in classical paints (so-called architectural coatings or decorative paints) like the ones used by the general public or professional painters to coat buildings and homes. UV curable inks and coatings were first developed in Europe as an alternative to solvent-based products to improve productivity and environmental releases. Conventional heat- and air-drying works by solvent evaporation and results in the loss of 50% of the coating weight, released as environmental pollutants. In UV curing, there is no solvent to evaporate, no environmental pollutants, no loss of coating thickness, and no loss of volume. This results in higher productivity in less time, with a reduction in waste, energy use and pollutant emissions .
In Europe, the total market for energy curing (formulated) products is approximately 150.000 tons (of which HDDA is ~6000 tons) in 2014, shared between the following sectors :
1.        Printing Inks & Varnishes: 50%*
2.        Industrial Coatings on wood (mainly), plastics and metal: 43% (with ~38% for wood coatings)**
3.        Opto electronics (resists, optical fiber, liq. displays): 3%**
4.       Industrial adhesives (structural, laminating, pressure sensitive adhesives): 4%*
* mainly industrial, max. 1% professional
** all industrial

For more information on uses, see Section 4.2 below.
 
4. Specific comments on Part II of the Annex XV Report by Sweden

4.1. Annex XV dossier Section 7: Manufacture, Import and export (page 26)

The members of PARAD consortium (which represent 7 of the 10 registrants) gathered the volumes of HDDA produced and imported in EEA since 2007 via ReachCentrum as a third party.  The aggregated information is reflected in the graph below. It can be seen that the HDDA volumes manufactured/imported in EEA over the period of 2007-2014 are rather flat, with some yearly fluctuations linked to the general economy.
The members of PARAD are the main producers and importers of HDDA, so we expect the trend observed in the volumes compiled by PARAD to be representative of the whole European market.

Figure 1. Consolidated HDDA volumes produced and imported in EEA, based on PARAD Consortium data.

The increase in volumes of HDDA observed in Sweden and presented in point 7.2 of the annex XV dossier is not representative of the situation in other European countries or of the entire EEA.  The increase of the volumes in Sweden may also be due a better and/or multiple reporting of downstream users rather than a real increase of HDDA volumes.
As an illustration of the difference between the countries, we refer to the same SPIN database cited in point 7.2 of the Annex XV dossier. Indeed, in addition to the Swedish data, the SPIN database also provides data about the use of HDDA in Denmark, Finland and Norway.   We can see that Norway and Finland have low and stable volumes of HDDA while the trend in Denmark shows a significant decline in the volumes of HDDA.   Therefore, the focus on the Swedish data which shows around 25% growth in the use of HDDA in the 2007 – 2012 timeframe is not representative of the evolution of HDDA volumes used in entire EEA in the same period.

Figure 2: Trends of HDDA in chemical preparations on the Swedish, Danish, Finnish and Norwegian markets based on reported data to the SPIN database (SPIN database 2015).

4.2. Annex XV dossier Section 8: Information on the Uses of the substance (page 26-30)

4.2.1. Overview of Uses

HDDA is a reactive monomer used in inks and coating which are cured (polymerized) upon exposure to UV-light or electron beam (EB). Under UV light with the help of a photoinitiator or under EB, the 2 reactive acrylic groups of HDDA will immediately cross-link with other acrylic groups to form a three-dimensional polymeric coating or ink. The curing process is designed to completely consume HDDA.
HDDA is manufactured and formulated in industrial settings only. The final end use of the coating/ink also happens very largely in industrial settings as it requires a special installation with UV lamps, see below an illustration of a UV printing installation.
Professional uses are limited to very small volumes (~1%) and PARAD companies only support professional uses in very controlled processes like ink cartridges. High exposure in professional applications like artificial nails and dental are not supported by PARAD co-registrants and is advised against in the updated dossier submitted in October 2015, in order to make it even clearer to the downstream users.
The PARAD registrants do not support the use of HDDA in consumer products and therefore did not register any consumer use in the REACH dossier. In the October 2015 updated dossier, the use of HDDA into any consumer applications is advised against in order to make it even clearer to the downstream users.

Figure 3. Industrial printing installation (left) and UV-curing unit (right)

4.2.2. Uses according to the REACH registration

The uses disseminated on ECHA website date from 2010 and need updating based on the registrants’ registration dossier updates.
The PARAD consortium collected information on uses of the substances to be registered under REACH for the 2010 deadline. Back then, this use description was done to the best of the registrants’ and DUs’ knowledge. However, this collection of uses has been revised to reflect updated guidance, tools and the experience gathered since 2010.
Indeed, some of the original disseminated uses or use descriptors provide an inaccurate depiction of the actual use processes and the corresponding level of exposure. In particular the uses in the professional sector have been over-represented due to the use of Generic Exposure Scenarios. Today, the end uses of HDDA supported by its REACH registrants may be split in two main categories: the Coatings and Inks industry and the Polymer industry, with worker exposure in both industries being low. The uses supported by PARAD companies have been updated.  The new common uses are provided in an attachment to this report.

The main use of HDDA is as a reactive component of formulations in the Coating and Ink industry, in line with the market trends for the entire energy curing market (see 4.1.).
In all cases, HDDA finally reacts during a curing process  leading to polymerisation or reticulation (as opposed to non-reactive components of these formulations, such as solvents, pigments, fillers): thus, the chemical function of HDDA as a cross-linking agent is equivalent to that of an intermediate in the Coatings and Inks industries, with no HDDA in the coated and printed articles produced.
Another use of HDDA is its use as an intermediate in the polymer industry.
It is to be noted that this use is out of scope of Authorisation as HDDA is then an intermediate chemically transformed into another valuable substance (polymer).
This interpretation has been explicitly confirmed by ECHA for monomers (“Any use of a substance as an […] intermediate is not subject to authorisation […] This is also valid for intermediates used as monomers for the synthesis of polymers »),  and also implicitly for cross-linking agents (ECHA has listed ERC 6d among the ERC codes compatible with intermediate dossiers).

Speculative uses of HDDA are out of scope:
The Annex XV report suggests that HDDA may be used in artificial nail applications, based on the availability of UV curable formulation for nails on the market. However, as indicated in section 8.1.3 of the Annex XV dossier, there is no proof that HDDA is used in this application. PARAD companies are also not aware of any such use.
In order to address potential concern about the use of HDDA in nail uses, the Cosmetic Product Regulation (No 1223/2009) seem much more appropriate than the REACH Regulation (No 1907/2006) as it require an assessment and a minimization of the risk for human health.

5. Annex XV Section 9: Release and exposure from Uses (page 30)

5.1. Human exposure

As already mentioned in the comments about part I of the annex XV dossier, most reported cases of allergic response cannot be specifically linked to HDDA.  The focus should be on those studies where the effects are clearly caused by HDDA.
Industrial uses are mainly in closed systems with negligible exposure. HDDA is not present in the final coatings/inks as it is converted into a polymeric matrix during the curing step. Therefore, the discussion about exposure should focus on potential exposure during the pre-curing steps. The vast majority of the application techniques are mainly enclosed and/or automated, therefore minimizing potential exposure of the workers.
As mentioned earlier in this document, the following applications represent by far the major consumption (>90%) of radiation curing products in Western Europe:
• Industrial wood finishes, including coatings of parquet, furniture, door skins, dashboards and decorative panels.
• Graphic arts, including printing inks, overprint varnishes and inkjet inks
• Industrial plastics coatings, including vinyl flooring, automotive parts, and so-called consumer electronics (housing of computers, TVs, mobile phones, small electrical equipment,…).
• Industrial metal coatings, including coatings for metal packaging, tubes and piping,…
For almost all these applications, the machines that are used to apply these formulated products, e.g. the coating application lines for wood (panels and parquet), for plastics (vinyl flooring, plastic foils) and for metal coatings, as well as the printing presses and varnishing machines are either closed or semi-closed (smaller industrial printing workshops). The first reason is the protection of the workers from all the moving parts, but also from the product present on the application system. The coatings, inks and varnishes are usually pumped into the printing/varnishing/roller-coating application system, out of a container, a drum or a pail, depending on the size of the installation.

5.2. Industrial uses

All reported cases are accidental, no PPE or misuse of PPE . The conclusion in the Annex XV dossier that “Inks containing HDDA used in the printing industry have been shown to cause critical dermal exposures of hands, arms and face during normal work despite use of protective gloves and clothes” is misleading. It is well known in industry that contaminated clothes should be destroyed or cleaned in a special laundry and not at home. This is stated clearly in safe handling guidelines. Re-using contaminated clothes with no or insufficient cleaning is not considered as a correct use of PPE. See attached safe handling guidelines. The survey of ReachCentrum (attached) also reaches the same conclusion that the reported cases for skin reactions for which the link to HDDA was demonstrated are all due to accidental uses (splashing) and/or absence/misuse of PPE.

Figure 4. Extract from safe handling guidelines “Ink mixing and cleaning up” from the Health and Safety Executive

http://www.cefic.org/Documents/Industry%20sectors/UVEB/Guide-to-the-Classification-and-Labelling-of-UV-EB-Acrylates.pdf

https://www.youtube.com/watch?v=dL4HsPXQLNw

Glove types
Specific information on the correct types of gloves was missing in the safety data sheets of several suppliers in the past.  However, this has been corrected in the last years and the safety data sheets of the HDDA suppliers now provided clear recommendations on the gloves as required by REACH.  Despite clear recommendations on the supplier safety data sheets and in the Cefic UV/EB Guide to the Classification and Labelling of UV/EB Acrylates , PARAD companies have learnt through the surveys and discussions about HDDA that the use of PPE may not be optimal yet at all downstream users.  For instance, issues with the use of wrong types of gloves and with the management of contaminated PPE may still persist here and there.  Therefore, new information campaigns about the safe use of HDDA and other acrylates will be initiated in the coming months under the umbrella of Cefic UV/EB.
Our guidance on safe use actually states the following, as far hand protection is concerned. For prolonged handling of HDDA, i.e. more than 1 hour, the recommendation is to use multilayer laminated gloves, e.g. "Barrier(R)" from Ansell, "Silver Shield / 4H (R)" from North. Alternatively, thick (~0.7mm) Butyl rubber gloves and "Dupont Viton (R)" gloves can also be used.  For brief handling time of HDDA, i.e. up to 1/2 hr. maximum, medium (~0.45mm) and thick (>0.55mm) nitrile rubber gloves may be used. Due to many conditions (e.g. temperature, presence of solvents) it must be considered, that the practical usage of a chemical-protective glove in practice may be much shorter than the determined permeation time. Manufacturer's directions for use should be observed because of great diversity of types. Replace gloves immediately when torn or any change in appearance (dimension, color, flexibility, ...) is noticed.

5.3. Professional exposure

As is clearly stated in the Annex XV report, there is no evidence that HDDA is present in the artificial nails. Other acrylates and methacrylates such as 2-hydroxyethylmethacrylate (HEMA; 868-77-9) or ethyl cyanoacrylate (7085-85-0) are commonly used for such nail applications . The cross-reaction of acrylates for skin sensitisation is well known and does not allow the attribution of a positive patch test result to only one specific acrylate.

5.4. Consumer uses: speculative (patch test does not prove exposure to HDDA)

No real convincing evidence has been provided that HDDA is present in consumer products (page 29 of the Annex XV dossier). Indications for its use in nail applications are limited to the availability of UV-cured “do it yourself” gel nail products on international ebay website, though methacrylates are usually used for these applications and HDDA is not mentioned as an ingredient.
Due to these cross-reactions, the multi-exposure to acrylates, and the usually multiple positive patch test reaction in a single subject, it is difficult to attribute the symptoms of contact dermatitis to only one acrylate based on the result of a positive patch test. Many positive patch test reactions are not due to prior HDDA exposure but due to cross reactions against other methacrylates or acrylates. 
6. Annex XV dossier Section 10. Alternatives (page 33)

Industry’s view is that HDDA can be handled safely in its registered applications in the polymer, coatings and inks industries. This is evidenced by the low incidence of reported allergic reactions clearly related to the use of HDDA, which in addition were almost exclusively the result of accidents or misuse of PPE.
As shown in the table in point 10.1 of the Annex XV dossier, the (meth)acrylates mentioned as possible alternatives to HDDA are also skin sensitizing substances. Replacing HDDA with another sensitiser would not decrease the risk of sensitisation in the supply chain. It would have been more relevant to focus on those specific end-uses leading to allergy cases with (meth)acrylates, which seems to be the professional dental, nail and glue applications.  For such specific applications, other risk management options exist such as restrictions, control under specific end-use Regulation such as the Cosmetic Product Regulation (No 1223/2009), which have not been explored.
Although authorisation may not be the right risk management option to address concerns related to specific end uses of (meth)acrylates, please find below a few comments on the substitution candidates listed by the Swedish authorities:
The table below recaps, for HDDA and each of the substances listed in the annex XV dossier:
- the registration status and registered tonnage, which indicates:
• whether the substance may be able to replace HDDA volumes in the supply chain;
• the level of reliability of its classification (based on the level of toxicological information required in the Annexes VII to X);
- its registered classification, which indicates whether the substance may be considered as safer than HDDA.
Table 1:  Registration status, volume and hazard statement codes for substances listed as possible alternatives to HDDA in the Annex XV dossier
Name CAS Number Registered tonnage band Harmonized classification (specific entry hazard statement code) Registered classification (hazard statement code) RMOA
Hexamethylene diacrylate 13048-33-4 1000-10,000 tonnes per annum H315
H317
H319 H315
H317
H319
H412
H400 Yes
Trimethylolpropane triacrylate 15625-89-5 1,000-10,000 tonnes per annum H315
H317
H319 H315
H317
H319
H411
H302
H335
Pentaerythritol triacrylate 3524-68-3 1,000-10,000 tonnes per annum

(under CAS 1245638-61-2) H315
H317
H319 H302
H315
H318
H317
H411

Pentaerythritol tetraacrylate 4986-89-4  H315
H317
H319
Tetraethylene glycol diacrylate 17831-71-9 not registered   not registered
Dipropylene glycol diacrylate 57472-68-1
1,000-10,000 tonnes per annum   H315
H317
H318
Tripropylene glycol diacrylate 42978-66-5 100,000-1,000,000 tonnes per annum H315
H317
H319
H335
H411 H315
H317
H319
H335
H411 Yes
Under development – sensitiser
Sweden

Neopentylglycol diacrylate 2223-82-7 not registered H311
H315
H317
H319 not registered
1,4-Butanediol diacrylate 1070-70-8 not registered H312
H314
H317
not registered
1,4-Butanediol dimethacrylate 2082-81-7 1000-10,000 tonnes per annum   H317
Urethane dimethacrylate 72869-86-4 0-10 tonnes per annum   H317
Triethyleneglycol dimethacrylate 109-16-0 1000-10,000 tonnes per annum   H317
1,3-Butylene glycol dimethacrylate 1189-08-8 100-1000 tonnes per annum   H317
Diethylene glycol dimethacrylate 2358-84-1
not registered   not registered
Glycerol dimethacrylate 1830-78-0 not registered   not registered
Source:
2 Registered substances database. Available:  http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances

A brief overlook at this table evidences that, out of 14 potential alternative substances listed in the annex XV dossier:
- All 8 registered substances are classified as skin sensitisers (H317)
- Only 7 (in bold) are registered for >100 tpa and may therefore be considered as:
• potentially contributing to a replacement of HDDA volumes,
• reliably classified based on the large amount of data required for this tonnage band;
- 4 of these 7 have additional hazard statements compared to HDDA (in red, see cumulated list below):
H302 – Harmful if swallowed    (no additional risk: no oral exposure)
H318 – Causes serious eye damage   (additional risk to human health)
H335 – May cause respiratory irritation   (additional risk to human health)
H411 – Toxic to aquatic life with long lasting effects (higher long-term risk in environment)
From the above table, it appears that methacrylates seem less irritant than acrylates.  However, they are also much less reactive and do not represent a suitable alternative for the classical industrial coating and ink applications based on the technical performance.

The question is whether there are alternatives to acrylates in the main sectors in which HDDA is used?
A literature review has revealed possible alternatives to acrylates in radiation cured coatings. Husar et al (2013), Huser & Liska (2012) and Mautner et al (2012), have suggested vinyl esters and vinyl carbonates as alternatives to acrylates.  However, the hazard profile of these substances is mainly unknown. Common registered vinyl esters such as vinyl acetate or vinyl 2-ethylhexanoate are pretty hazardous substances (vinyl acetate is Acute Tox. 4, H332; STOT Single 3, H335; Carcinogenicity category 2, H351, Aquatic Chronic 3 H412; vinyl 2-ethylhexanoate is Skin Sens. 1B H317, Repr. 2 H361, Aquatic Acute 1 H400 Aquatic Chronic 1 H410 ). So, it cannot be concluded at this stage that the suggested vinyl esters or vinyl carbonates are less hazardous than HDDA and that they represent a suitable alternative to HDDA.
A review of alternatives databases did not return any results for alternatives to acrylates. The databases reviewed are:
Table 2:

Database Web address
OECD Substitution and Alternatives Assessment Tool Selector http://www.oecdsaatoolbox.org/Home/Tools

Subs Port http://www.subsport.eu/

KEMI - PRIO http://www2.kemi.se/templates/PRIOEngframes____4144.aspx

SciVera http://www.scivera.com/index.php

Swerea - Chemicall http://extra.ivf.se/chemicall

GESTIS substance database http://gestis-en.itrust.de/nxt/gateway.dll/gestis_en/000000.xml?f=templates$fn=default.htm$vid=gestiseng:sdbeng$3.0

GreenScreen® List Translator http://www.greenscreenchemicals.org/method/greenscreen-list-translator

GreenWERCS http://www.thewercs.com/products-and-services/greenwercs

Material IQ http://www.materialiq.com/

Pharos Project https://www.pharosproject.net/

Safer Choice (US EPA) http://www2.epa.gov/saferchoice

Chemsec SIN List http://sinlist.chemsec.org/
Risctox http://www.istas.net/risctox/en/

CAMEO chemicals http://cameochemicals.noaa.gov/

ChEBI https://www.ebi.ac.uk/chebi/

INCHEM http://www.inchem.org/
 
7. Conclusion
The PARAD Consortium has carefully read the Annex XV dossier and has developed comments on each of the arguments put forward by KEMI. Outlined in bullet points below are the key arguments on Part II of the Annex XV dossier presented in this document. The reasoning is provided in the subsequent sections of this document:
• The RMOA analysis conducted by Sweden did not include industry participation. Data mentioned by the Swedish authorities as being missing in the RMOA analysis, such as the incidence of HDDA-specific allergy reactions and estimates of the societal costs, are included in the PARAD response to this public consultation.
• PARAD provides consolidated EU manufacture and import volume data over the period 2007-2014. These do not support any increasing trend in the EU market of HDDA.
• HDDA is primarily used in industrial UV curable coatings (rather than “paints” or “curable paints”). These coating have significant environmental benefits compared to solvent-based coatings for example.
• HDDA is fully consumed in the curing process, so there is no exposure of users of the coated products.
• HDDA is also used as a monomer or cross-linking in the polymer industry. These uses as an intermediate are exempt from authorisation.
• In both the industrial coatings and the polymer industries, worker exposure is low.
• Professional uses are limited to very small volumes and are supported by PARAD only in highly controlled processes. Consumer uses are uses advised against by PARAD.
• Most, if not all, reported cases of HDDA exposure are the result of accidents, no PPE or misuse of PPE.
• SDSs of HDDA suppliers specify clear recommendations on the correct gloves to be used as required by REACH.
• All alternatives listed in the HDDA Annex XV dossier are skin sensitising (meth)acrylates. The substitution of 1 specific acrylate like HDDA will not decrease the risk of sensitisation in the supply chain. This is not a sustainable approach and questions the relevance of the RMOA conclusion.
• The HDDA lead registrant has updated his registration dossier. PARAD co-registrants of HDDA will do so by end-October 2015. These updates indicate as uses advised against all consumer uses as well as professional uses in dental and nail applications.	  
The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.  

The Swedish Chemicals Agency (KemI) would like to thank the companies in the consortium PARAD for the comments and the information provided. 
Please find our responses in the attached document.

	
		Attachment: 
		
4564
2015/10/15	Company,
United Kingdom	
Confidential attachment has been removed	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.