COMMISSION IMPLEMENTING DECISION
of 16.10.2019
on the compliance check of a registration of dimethyl ether, referred by the European Chemicals Agency to the Commission pursuant to Article 51(7) of Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
(Only the English text is authentic)
THE EUROPEAN COMMISSION,
Having regard to the Treaty on the Functioning of the European Union,
Having regard to Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC 1 , and in particular Article 51(7) thereof,
Whereas:
(1)The European Chemicals Agency ('the Agency') carried out a compliance check pursuant to Article 41(1) of Regulation (EC) No 1907/2006 of a joint registration submitted by Nouryon Industrial Chemicals B.V. ('the lead registrant') on behalf of a number of co-registrants, for the substance dimethyl ether, CAS number 115-10-6, EC number 204-065-8 ('DME').
(2)The Agency concluded that the registration dossier submitted for the tonnage band of 1 000 tonnes or more per year, including all relevant information that had been added to the registration by 5 of October 2018, did not comply with the standard information requirement regarding pre-natal developmental toxicity in a second species, as laid down in section 8.7.2 of Annex IX and section 8.7.2 of Annex X to Regulation (EC) No 1907/2006, because the dossier did not contain any information on a second species, and regarding reproductive toxicity as laid down in section 8.7.3 of Annex X to Regulation (EC) No 1907/2006 because the proposed adaptation could not be accepted.
(3)The Agency prepared a draft decision in accordance with Article 41(3) of Regulation (EC) No 1907/2006 requiring the registrants to submit information from a pre-natal developmental toxicity study (PNDT, test method: EU B.31/OECD TG 414) in rabbits via the inhalation route in order to address the non-compliance regarding pre-natal developmental toxicity in a second species and to conduct an extended one-generation reproductive toxicity study ('EOGRTS') in rats via the inhalation route (test method: EU B.56/OECD TG 443) in the basic study design, as required by column 1 of section 8.7.3 of Annex X to Regulation (EC) No 1907/2006 in order to address the non-compliance regarding reproductive toxicity and to submit the results of those studies to the Agency.
(4)Following the examination of the proposals for amendments, the Agency referred its draft decision together with the amendments proposed to the Member State Committee of the Agency ('the MSC') on 19 January 2017. While the MSC agreed that information concerning the two standard information requirements should be requested, it failed to reach unanimous agreement on the draft decision because of diverging opinions on the design of the EOGRTS. Eight members expressed a minority position by voting against the draft decision, as they were of the opinion that the EOGRTS should include cohorts 2A/2B to address developmental neurotoxicity (DNT) concerns pursuant to the second paragraph of column 2 of section 8.7.3. of Annex X to Regulation (EC) No 1907/2006. The eight members were of the view that the concern for developmental neurotoxicity is justified by narcotic effects observed in a 2-weeks repeated dose inhalation toxicity study and in a rat pre-natal developmental toxicity study on the substance. They further justified the request with human exposure data available on TOXNET 2 , which reports narcotic effects at high doses. In relation to the narcotic effects, they argued that the substance can be expected to act on an organism in the same way as its structural analogue diethyl ether ('DEE') which was previously used as an anaesthetic. As the MSC failed to reach unanimous agreement, the Agency referred the draft decision together with all relevant information to the Commission on 13 July 2017 in order for it to take a decision pursuant to Article 51(7) of Regulation (EC) No 1907/2006.
(5)The Commission examined the draft decision of the Agency, the amendments proposed by Member States concerning the design of the EOGRTS, the comments submitted by the lead registrant on behalf the co-registrants on the draft decision of the Agency and the reasons why the MSC could not reach unanimous agreement. After the Agency had carried out the compliance check, other registrants which had registered their substance at any of the tonnage levels covered by Annexes VII to X of Regulation (EC) No 1907/2006 joined the joint registration. Upon request of the Commission, the Agency checked all available information in the dossiers for DME again and informed the Commission that information from a PNDT study in a second species and an EOGRTS was still missing. The Agency also concluded that, based on the available information on the substance, conditions were not met to request those studies at Annex IX level. Consequently, the Agency considered that information from those two studies should be requested to fulfil the standard information requirements for the registrants of this joint registration that are at Annex X level. Therefore, those registrants should provide the missing information and they are the addressees of this Decision.
(6)The registrants concerned have submitted comments on the draft decision of the Agency and the draft decision of the Commission arguing that the PNDT study in a second species and the EOGRTS do not need to be conducted on DME in accordance with the specific rules for adaptation provided for in the third indent of the first paragraph of column 2 of section 8.7. of Annex X to Regulation (EC) No 1907/2006. The registrants concerned argue that the conditions for applying the adaptation are met. However, the Commission considers that none of the three conditions provided for in the third indent of the first paragraph of column 2 of Annex X to Regulation (EC) No 1907/2006, which have to be met cumulatively, are met and therefore adaptation from column 1 of section 8.7. of that Annex is not justified.
(7)Firstly, DME induced narcotic effects after repeated administration and caused death in an acute inhalation toxicity study at concentrations higher than 12,1 % (121 000 ppm). In a rat PNDT study, lower body weight gain, reduced foetal body weight and increase in skeletal variations were observed at a concentration of approximately 4% (40 000 ppm). Even though those effects have been observed at high doses, the Agency and the Commission consider that the criterion ‘low toxicological activity (no evidence of toxicity seen in any of the tests available)’ is not met.
(8)Secondly, toxicokinetic information in the dossier and comments of the registrants concerned on the Agency’s draft decision support the conclusion that an equilibrium between the concentration of the substance in the organism and in the air is reached through exposure via the inhalation route. In particular, toxicokinetic investigations provided evidence of distribution of the substance within the organism, indicating a rapid increase in concentrations of DME in blood, heart, lung, liver, spleen and kidneys, reaching a steady state after 30 minutes of exposure via the inhalation route before rapidly decreasing. The Agency and the Commission therefore consider that the criterion of no systemic absorption via relevant routes of exposure is not met.
(9)Thirdly, DME is used as propellant in many consumer daily-use products like deodorants, hairspray etc., hence there is clearly some human exposure. In its comments to the draft decision of the Agency and to the draft decision of the Commission, the registrants concerned claimed that the criterion of no significant exposure is met, as in its view the risk characterisation ratio (RCR) 0,7 for the industrial or professional use by workers and the RCR of 09 for aggregated inhalation exposure of workers additionally using DME-containing consumer products reported in the registration dossier are overly conservative since they represent peak exposures rather than average daily exposure values. However, the Commission considers that aggregated exposure levels for workers and consumers indicate significant exposure. In addition, maximum possible exposure levels have to be considered for acute effects because even short-term, peak exposure concentrations could cause acute effects. Hence based on the information in the dossier the criterion ‘no or no significant human exposure’ is not met.
(10)Consequently, the criteria for adaptation laid down in the third indent of the first paragraph of column 2 of section 8.7. of Annex X to Regulation (EC) No 1907/2006 are not met and therefore the registration is non-compliant, as also concluded by the Agency.
(11)Given that DME is a gas with explosive properties, it must be considered whether it is technically feasible to conduct the required studies without risk of explosion. The registrants concerned have indicated in their comments on the Agency’s draft decision that testing would be feasible up to a concentration of 1,65%, which has been derived from the Lower Explosive Limit (3,3%) based on OECD Guidance Document on Acute Inhalation Toxicity Testing No 39. In addition, in a 2-year chronic inhalation study in rats the highest concentration tested was 2,5%, and concentrations of up to 4% were reached in a PNDT study and up to 5% in a 2-weeks repeated dose study. The available data therefore indicate a possibility to test at concentrations that could produce effects while being safe in relation to the explosive properties.
