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

Substance name:	bis(2-methoxyethyl) ether	
CAS number:	111-96-6	
EC number:	203-924-4	

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: 

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, Organisation/MSCA)	Comment	Response	
13	2011/10/13	National Authority
Rivm
Netherlands	NL supports the proposal to include bis(2-methoxyethyl) ether in the candidate list of substances of very high concern	Thank you for the support.	
11	2011/10/13	Member State
Sweden	The Swedish CA agrees that bis(2-methoxyethyl) ether, being classified as Repr. 1B, meets the criteria according to Article 57(c) in REACH and is thus eligible for identification as a substance of very high concern.	Thank you for the support.	
10	2011/10/13	Company
Sweden	Page 16, Part II, section 1.2. Use of the substance and page 25, section 2. Current knowledge on alternatives.

Confidential comment submitted. 

The purpose in submitting these comments is to ensure that ECHA is familiar with certain critical uses of diglyme. Although our uses of this substance are in small volumes, the uses are critical in the manufacture of sensors for protein interaction analysis and for the manufacture of fine chemicals used for purification of active pharmaceutical ingredients. Please note that our uses are NOT as medicinal products. However, inability to use diglyme in the manufacturing processes of the fine chemicals and the sensors will adversely impact drug discovery and development, the pharmaceutical industry and the food industry. There are currently no known substitutes for these uses. In the comments uploaded confidentially we describe our uses in more detail together with the controls used to protect the health and safety of employees in accordance with EU directives. 
	Information on uses, exposure, release and alternatives will be forwarded for discussion on prioritisation and if applicable on exemption of uses for the preparation of the entry in Annex XIV.	
					
9	2011/10/12	Member State
Belgium	Belgium supports the identification of bis(2-methoxyethyl) ether (DEGDME) as SVHC according to article 57 (c) 	Thank you for the support.	
8	2011/10/12	International NGO
Health and Environment Alliance
Belgium	HEAL supports the nomination of DIGLYME to the Candidate List based on the information in the Annex XV dossier, and commends Austria, Belgium and Poland for their collaboration on this dossier.	Thank you for the support.	
7	2011/10/12	National Authority
Allgemeine Unfallversicherungsanstalt
Austria	We strongly support Diglyme to enter the list of candidates. This will be a consecutive step in regulating this chemical that is already regulated on European and to some extent MS level.	Thank you for the support.	
6	2011/10/12	Member State
Germany	The German-CA supports the identification of Diglyme (bis(2-methoxyethyl)ether as a possible SVHC candidate.
-Because of its ReproTox 1B classification, the substance undoubtedly fulfils the condition to be identified as SVHC. However, the arguments that should prove existing risks are not very well communicated. Examples in this context are given as follows:
- Some data are listed in the confidential Annex. This is also true for the PROCs, etc of the identified uses. However, these data are to a large extent present in the public data on the ECHA website. There should be a more clear discrimination between what is really confidential (and belongs in the confidential Annex) and what is known from other sources and can be included in the public version.
	Thank you for the support.

Annex III, Chapter 3 includes partly also non confidential information. Due to readability and comparability of data the whole chapter has been put into the confidential part of the dossier. 

See also responses in the attached confidential document.	
					
5	2011/10/10	Trade union
European Trade Union Confederation
Belgium	ETUC supports the identification of bis(2-methoxyethyl) ether as SVHC.	Thank you for the support.	
4	2011/10/07	International NGO
ChemSec
Sweden	We fully support the inclusion of this substance into the candidate list.	Thank you for the support.	
3	2011/10/07	International NGO
WWF European Policy Office
Belgium	WWF supports the inclusion of this substance in the candidate list owing to its classification as toxic for reproduction category 1B.	Thank you for the support.	
1	2011/10/06	Member State
Norway	The Norwegian CA supports that bis(2-methoxyethyl) ether should be identified as a substance of very high concern and should be included in the Candidate List.	Thank you for the support.	

Specific comments on the justification
Number	Date	Submitted by (name, Organisation/MSCA)	Comment	Response	
12	2011/10/13	Member State
Ireland	Bis(2-methoxyethyl) ether is classified as Repr. 1B according to Regulation EC No. 1272/2008, and therefore the Irish CA agrees that the substance meets the criteria for identification as an SVHC in accordance with Article 57 (c) of REACH.	Thank you for the support.	
6	2011/10/12	Member State
Germany	Page 20: It is stated that diglyme is listed in Annex XVII, group 30, as a substance which shall not be placed on the market “in mixtures above the generic concentration limit of 0.3 %.” To our knowledge the relevant concentration limit is 0.1 % according to Directive 1999/45/EC, Article 3(3). (A concentration limit of 0.3% would be relevant for the classification of mixtures as “Repr. 1B” according to Regulation (EC) No 1272/2008, Annex I, Part 3, Table 3.7.2). 	The SVHC dossier reads as follows (page 20): Diglyme is listed in Annex XVII, Group 30, of the REACH regulation and shall not be placed on the market, or used for supply to the general public as substance or in preparations. Suppliers shall ensure before the placing on the market that the packaging of such substances and mixtures is marked visibly, legibly and indelibly as follows: “Restricted to professional users”. This restriction was introduced in 2003 (Directive 2003/36/EC amending, for the 25th time, Council Directive 76/769/EEC).
No information on concentration limits was given in the SVHC dossier. According to Directive 1999/45/EC a limit of 0.5% for substances toxic for reproduction is given. 
From June 2015 a concentration limit of 0.3% will be relevant according to Regulation (EC) No 1272/2008.

5	2011/10/10	Trade union
European Trade Union Confederation
Belgium	bis(2-methoxyethyl) ether is included in the Trade Union Priority List for REACH authorisation.
see : http://www.etuc.org/a/6023	Thank you for this information.	

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, Organisation/MSCA)	Comment	Response	
14	2011/10/13	Industry or trade association
AIA
United States	The Aerospace Industries Association of America (AIA) is pleased to provide comments on the proposal to add Bis (2-methoxyethyl) ether to Annex XIV.  Founded in 1919, AIA is the premier trade association representing over 280 major aerospace and defense manufacturers and suppliers and approximately 844,000 aerospace and defense workers.  Our members represent the United States of America’s leading manufacturers and suppliers of civil, military, and business aircraft, helicopters, unmanned aerial systems, missiles, space systems, aircraft engines, materiel, and related components, equipment services, and information technology.  

Our comments, presented in the attached table address the accuracy and completeness of information regarding the use of Bis (2-methoxyethyl) ether. This substance is found in materials that are common to aerospace manufacturing product applications.  Bis (2-methoxyethyl) ether is used in the following applications: as a PTFE Etchant, in rain erosion coatings, syntactic foam, specialty thinner for electronic coatings, and rubber and adhesives articles.  There are at least 7 company proprietary specifications that require the use of Bis (2-methoxyethyl) ether. AIA is not aware of any alternative substances that are currently available.

The members of AIA are committed and actively working towards reducing the use Bis (2-methoxyethyl) ether throughout the aerospace industry.   While progress has occurred in some applications, the industry is unable to eliminate the use of this substance before alternatives are identified and qualified for all applications.   We appreciate your consideration of these comments.  If you have any questions or need additional information, please do not hesitate to contact me at lisa.goldberg@aia-aerospace.org or by phone at 703-358-1050.
Sincerely,
 
Lisa Goldberg
Director, Environment, Health and Safety
	From your comment it is unclear whether all these uses are relevant for Europe or for the United States only.

Information on (relevant) uses, exposure, release and alternatives will be forwarded for discussion on prioritisation and if applicable on exemption of uses for the preparation of the entry in Annex XIV.	
			See also:
Comment 14 attachment (October 13 Consultation Bis (2-methoxyethyl) ether.docx).docx		
10	2011/10/13	Company
Sweden	Page 16, Part II, section 1.2. Use of the substance and page 25, section 2. Current knowledge on alternatives.

Diglyme – Input for ECHA. Confidential comment submitted.

Diglyme is used as a solvent in the manufacture of sensors for protein interaction analysis and for the manufacture of fine chemicals used for purification of active pharmaceutical ingredients.  Diglyme is not part of the final products.

Use descriptors for use of diglyme:
•	SU3 Industrial uses: Uses of substances as such or in preparations at industrial sites
•	SU9 Manufacture of fine chemicals - C20.5.9 Manufacture of other chemical products n.e.c.
•	PC0 Other – UCN code O15000 Solvents
•	PROC4 Use in batch and other process (synthesis) where opportunity for exposure arises.
•	ERC4 Industrial use of processing aids in processes and products, not becoming part of articles. No release of the substance to water, air or soil. 100 % of the substance is handled as hazardous waste and treated by authorized waste vendor.
	Information on uses, exposure and release will be forwarded for discussion on prioritisation and if applicable on exemption of uses for the preparation of the entry in Annex XIV.	
					
7	2011/10/12	National Authority
Allgemeine Unfallversicherungsanstalt
Austria	P22, 1.3.2.1 Workplace exposure
The dossier demonstrates that nevertheless Diglyme is an HPV-chemical there is little exposure data. Using ecetoc-tra results in exposure levels above national OELs and furthermore similar solvents with less concerning properties are at the market. 
	Thank you for that comment.	
6	2011/10/12	Member State
Germany	 Page 15: It is doubtful how an outdated list of Producers/importers from 2000 is still relevant for identification of risks in 2011. A number of the companies mentioned no longer exist as such. Moreover, the cited link that would allow further inspection of the data does not work.	We agree that the registration data is the most important information source.(see also next response below) 

The link to ESIS has changed to: http://esis.jrc.ec.europa.eu/ 	
					
2	2011/10/07	Company
Germany	VOLUMES (pages 15-16): The estimate of imported/manufactured volume described in the Annex XV dossier (10.000 – 50.000 tonnes based on IUCLID Chemical data set (2000)) is excessive and outdated. We expect the notified volume to be considerably lower than even the lower limit. Accurate figures on volumes are available to ECHA since November 30th, 2010 when all manufacturers/importers have registered their respective volumes. (Substances classified as toxic to reproduction and manufactured in the European Community or imported, had to be registered in quantities reaching one tonne or more per year per manufacturer already before the first registration deadline).

USES (pages 16-21): The information on uses presented in the Annex XV dossier is rather historic and does not give enough consideration to the fact that Diglyme is listed in Annex XVII of REACH regulation (entry 30). According to this restriction Diglyme shall not be used in substances and preparations placed on the market for sale to the general public above the concentration limit of 0.3%. Therefore, exposure of consumers through the use of sealants and adhesives, automotive care products and paints or coatings is expected to be negligible.

Comments on the DNELs provided in the Annex XV dossier:
The DNELs proposed in the Annex XV dossier comprise the use of the “remaining factor“ of 2.5 for interspecies extrapolation.
The use of the “remaining factor” is not justified in view of followings: 
- Generally, the current scientific knowledge does not support the use of the “remaining factor” (argumentations summarized as in chapter 3.2.2 of ECETOC Technical Report No. 110). 
- The POD is selected among the data set comprising three species (rats, rabbits, mice), thus the interspecies variability is already considered to a certain degree. 
- The PBPK models, developed and validated for 2-methoxyethanol, predicts comparable internal burden of 2-methoxyacetic acid for pregnant rodents and pregnant women (i.e. Welsch, 2005; Gargas et al, 2000). Being the fact that 2-methoxyacetic acid is the metabolite responsible for the toxic effects of diglyme, it is questionable whether any assessment factor should be applied when extrapolating the animal data to human. The use of allometric scaling factor is considered to be sufficiently conservative. 

References: 
(1) ECETOC. 2010. Guidence on Assessment Factors to Derive DNEL. Technical Report 110. European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium. 
(2) Welsch F. 2005. The mechanism of ethylene glycol ether reproductive and developmental toxicity and evidence for adverse effects in humans. Toxicol Lett. 156(1):13-28. 
(3) Gargas ML, Tyler TR, Sweeney LM, Corley RA, Weitz KK, Mast TJ, Paustenbach DJ, Hays SM. 2000. A toxicokinetic study of inhaled ethylene glycol monomethyl ether (2-ME) and validation of a physiologically based pharmacokinetic model for the pregnant rat and human. Toxicol Appl Pharmacol 165(1):53-62.
	The information from IUCLID should only help to identify a trend (declining or increasing) in the use of the substance. 
Actual volumes according to the registration data are given in the confidential Annex III, Chapter 2 

The restriction according Annex XVII, Group 30 is cited in the dossier. Present uses according to the registration data are given in Annex III.

Risk considerations are not decisive for the selection of a substance for authorization as the ultimate goal is the phase out of substances with SVHC properties.

According to Gargas et al, 2000 the human model described is only partly validated. 
A single human data set consisting of only seven male volunteers was used for comparison to model prediction.
When used for risk assessment purposes, confidence in PBPK models should be high.

Therefore a default value of 2.5 for remaining differences seems to be more appropriate as recommended in the REACH guidance R.8. 

Attachments

Comment number	Public attachment	
14	
Comment 14 attachment (October 13 Consultation Bis (2-methoxyethyl) ether.docx).docx