SCIENTIFIC OPINION ADOPTED: 14 September 2016 doi: 10.2903/j.efsa.2016.4582 Safety assessment of the substance 2,3,3,4,4,5,5- heptafluoro-1-pentene, for use in food contact materials EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) Abstract This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety assessment of 2,3,3,4,4,5,5-heptafluoro-1-pentene (Chemical Abstracts Service (CAS) No 1547-26-8, Food Contact Materials (FCM) substance No 1063) for use as a comonomer in different combination with the comonomers, ethylene and tetrafluoroethylene, to manufacture fluoropolymers. The fluoropolymer is intended to be used as a polymeric processing agent in a wide range of plastics. Finished articles made with those plastics are intended for contact with all kind of foodstuffs at room temperature or below with no time limit or at high temperatures. Worst-case migration of the substance, of the sum of its impurities and of fluoropolymer low molecular weight oligomers below 1,500 Da from finished articles were estimated to be 0.02 lg/kg food, below 0.02 lg/kg food and 1.5 lg/kg food, respectively. Based on negative results in a bacterial mutation assay and in an in vivo combined micronucleus/comet assay, the Panel considers that the substance does not give rise to concern for genotoxicity. In view of the worst-case migration calculations for the impurities and the oligomers, the lack of genotoxicity of the substance and the mechanism of polymerisation, no additional data are requested on impurities or oligomers. The CEF Panel concluded that 2,3,3,4,4,5, 5-heptafluoro-1-pentene does not raise a safety concern for the consumer if used as comonomer together with tetrafluoroethylene and/or ethylene comonomers to manufacture fluorocopolymers for application as a polymer processing aid at up to 0.2% w/w of the FCM. For this application, the low molecular weight fraction below 1,500 Da in the fluorocopolymer should be no greater than 30 mg/kg. 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. Keywords: heptafluoropentene, CAS No 1547-26-8, FCM substance No 1063, monomer, processing aid, food contact materials, safety assessment Requestor: Food Standards Agency, United Kingdom Question number: EFSA-Q-2015-00050 Correspondence: fip@efsa.europa.eu www.efsa.europa.eu/efsajournal EFSA Journal 2016;14(10):4582
Panel members: Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Karl-Heinz Engel, Paul Fowler, Roland Franz, Konrad Grob, Rainer G urtler, Trine Husøy, Sirpa K arenlampi, Wim Mennes, Maria Rosaria Milana, Andre Penninks, Vittorio Silano, Andrew Smith, Maria de Fatima Tavares Pocßas, Christina Tlustos, Detlef W olfle, Holger Zorn and Corina-Aurelia Zugravu Acknowledgements: The Panel wishes to thank the members of the Working Group on Food Contact Materials: Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Roland Franz, Konrad Grob, Martine Kolf-Clauw, Eugenia Lampi, Maria Rosaria Milana, Maria de Fatima Tavares Pocßas, Kettil Svensson and Detlef W olfle for the preparatory work on this scientific opinion and EFSA staff member: Eric Barthelemy for the support provided to this scientific opinion. Note: The full opinion will be published in accordance with Article 10(6) of Regulation (EC) No 1935/2004 once the decision on confidentiality, in line with Article 20(3) of the Regulation, will be received from the European Commission. The following information has been provided under the confidentiality framework and has been redacted awaiting the decision of the Commission: the level of impurities in heptafluoropentene; the maximum amount of heptafluoropentene intended to be used to manufacture fluorocopolymers; the residual amount of heptafluoropentene in fluorocopolymers; methods of analysis of extractable amount of oligomers in fluorocopolymers; the level of the oligomeric faction below 1,500 Da in fluorocopolymers; the maximum amount of the fluorocopolymer intended to be used as processing aid to manufacture plastics; and the migration potential of impurities from plastics Suggested citation: EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2016. Scientific opinion on the safety assessment of the substance 2,3,3,4,4,5, 5-heptafluoro-1-pentene, for use in food contact materials. EFSA Journal 2016;14(10):4582, 7 pp. doi:10.2903/j.efsa.2016.4582. ISSN: 1831-4732 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. www.efsa.europa.eu/efsajournal 2 EFSA Journal 2016;14(10):4582
Table of contents Abstract... 1 1. Introduction... 4 1.1. Background and Terms of Reference as provided by the requestor... 4 2. Data and methodologies... 4 2.1. Data... 4 2.2. Methodologies... 4 3. Assessment... 5 3.1. Non-toxicological data... 5 3.2. Toxicological data... 6 4. Conclusions... 6 Documentation provided to EFSA... 7 References... 7 Abbreviations... 7 www.efsa.europa.eu/efsajournal 3 EFSA Journal 2016;14(10):4582
1. Introduction 1.1. Background and Terms of Reference as provided by the requestor Before a substance is authorised to be used in food contact materials (FCMs) and is included in a positive list, EFSA 0 s opinion on its safety is required. This procedure has been established in Articles 8 and 9 of the Regulation (EC) No 1935/2004 1 of the European Parliament and of the Council of 27 October 2004 on materials and articles intended to come into contact with food. According to this procedure, the industry submits applications to the Member States Competent Authorities which transmit the applications to the European Food Safety Authority (EFSA) for their evaluation. In this case, EFSA received an application from the Food Standards Agency, United Kingdom, requesting the evaluation of the substance 2,3,3,4,4,5,5-heptafluoro-1-pentene, with the CAS No 1547-26-8, and the FCM substance No 1063. The dossier was submitted on behalf of Daikin Industries Ltd. According to Regulation (EC) No 1935/2004 of the European Parliament and of the Council on materials and articles intended to come into contact with food, EFSA is asked to carry out an assessment of the risks related to the intended use of the substance and to deliver a scientific opinion. 2. Data and methodologies 2.1. Data The applicant has submitted a dossier in support of their application for the authorisation of 2,3,3,4,4,5,5-heptafluoro-1-pentene, to be used in FCMs. Data submitted and used for the evaluation are: Non-toxicological data and information Data on identity Data on physical and chemical properties Data on intended use and authorisation Data on impurities Data on migration of the substance Data on residual content of the substance Data on oligomers Toxicological data Bacterial gene mutation test In vitro mammalian chromosome aberration test Combined micronucleus test and comet assay in rats 2.2. Methodologies The assessment was conducted in line with the principles laid down in Regulation (EC) No 1935/2004 on materials and articles intended to come into contact with food. This Regulation underlines that applicants may consult the Guidelines of the Scientific Committee on Food (SCF) for the presentation of an application for safety assessment of a substance to be used in FCMs prior to its authorisation (European Commission, 2001), including the corresponding data requirements. The dossier that the applicant submitted for evaluation was in line with the SCF guidelines (European Commission, 2001). The methodology is based on the characterization of the substance(s) object of the request for safety assessment prior to authorisation, its impurities and reaction and degradation products, the evaluation of the exposure to those substances through migration, and the definition of minimum sets of toxicity data required for safety assessment. To establish the safety from ingestion of migrating substances, the toxicological data indicating the potential hazard and the likely human exposure data need to be combined. Exposure is estimated from 1 Regulation (EC) No 1935/2004 of the European parliament and of the council of 27 October 2004 on materials and articles intended to come into contact with food and repealing Directives 80/590/EEC and 89/109/EEC. OJ L 338, 13.11.2004, p. 4 17. www.efsa.europa.eu/efsajournal 4 EFSA Journal 2016;14(10):4582
studies on migration into food or food simulants and considering that a person may consume daily up to 1 kg of food in contact with the relevant FCM. As a general rule, the greater the exposure through migration, the more toxicological data is required for the safety assessment of a substance. Currently, there are three tiers with different thresholds triggering the need for more toxicological information as follows: a) In case of high migration (i.e. 5 60 mg/kg food), an extensive data set is needed. b) In case of migration between 0.05 and 5 mg/kg food, a reduced data set may suffice. c) In case of low migration (i.e. < 0.05 mg/kg food), only a limited data set is needed. More detailed information on the required data is available in the SCF guidelines (European Commission, 2001). The assessment was conducted in line with the principles described in the EFSA Guidance on transparency in the scientific aspects of risk assessment (EFSA, 2009) and considering the relevant existing Guidance from the EFSA Scientific Committee. 3. Assessment The substance, 2,3,3,4,4,5,5-heptafluoro-1-pentene (called here heptafluoropentene), is intended to be used as comonomer in different combinations with the comonomers tetrafluoroethylene and ethylene to manufacture fluorocopolymers. Tetrafluoroethylene is authorised with a specific migration limit (SML) of 0.05 mg/kg food (FCM substance No 281) and ethylene without any specific restriction (FCM substance No 125) (Regulation (EU) No 10/2011 2 ). The fluorocopolymers are intended to be used as polymeric processing agents at up to 0.2% w/w in a wide range of plastics. Finished articles made with the above various plastics are intended for contact with all kinds of foodstuffs at room temperature or below with no time limit, or at high temperatures (e.g. microwave) for up to 30 min. Examples of finished articles are tubes and pipes for carrying liquid foods (e.g. soup), films for packing meats and vegetables and bottles for water and juice. 3.1. Non-toxicological data Chemical formula: C 5 F 7 H 3 Chemical structure: The substance has a molecular weight of 196 Da. Its boiling point is 58 C. It has a log P o/w of 3.18. It is slightly soluble in water and soluble in organic solvents. A representative fluorocopolymer made with the substance was shown to be thermally stable under the maximum processing temperature that, according to the applicant, may be applied for manufacturing the range of plastics in which it is intended to be used. Seventeen compounds are reported (under confidentiality) as impurities of the substance among which 12 are unknown. Two of the five that were identified were alkenes closely structurally related to the substance. The other three were similar in structure but saturated. Altogether, these five constitute the major part of the impurities. The alkenes are expected to be incorporated in the copolymer chain and the non-reacting impurities (identified and non-identified) are volatile and so are expected to evaporate under the processing conditions. Specific migration of the substance was not determined. Instead, migration from a representative fluorocopolymer made using the maximum comonomer content of the substance was calculated based on the assumption of total mass transfer of the residual amount in the finished product as follows: the residual heptafluoropentene in samples of the fluorocopolymer itself was 2 Commission Regulation (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food. Text with EEA relevance. OJ L 12, 15.1.2011, p. 1 89. www.efsa.europa.eu/efsajournal 5 EFSA Journal 2016;14(10):4582
. When the fluorocopolymer is used at the maximum level of 0.2% w/w, the worst-case migration (total mass transfer) was calculated to be 0.02 lg/kg food. Similar to the substance, the migration of its impurities was estimated by assuming they behave like the substance itself and may remain as residues in the finished FCM in fixed proportion to their percentage as an impurity in the starting substance. This estimate for the sum of all impurities was below 0.02 lg/kg food and covers uncertainties in the assumptions made. The migration of oligomers from the fluorocopolymer was estimated based on the assumption of total mass transfer of solvent-extractable amounts. The ground fluorocopolymer was extracted by solvent reflux for 4 h with isooctane, 95% ethanol, 10% ethanol and 3% acetic acid, respectively. These extracts were analysed using different techniques. The 4 h reflux with isooctane gave the highest amount of extractables. The use of isooctane at this time and temperature (the boiling point (bp) of isooctane is 99 C) is intermediate between a severe migration test and exhaustive extraction of the fluorocopolymer and the test is therefore suitable to determine the migratable low molecular weight fraction (LMWF). Analysis of the isooctane extraction residue by two different laboratories each using different methods gave similar results of ca. 27 mg of oligomeric fraction below 1,500 Da per kg of fluorocopolymer. Similar to the scenario and calculations above, the worst-case migration of oligomers < 1,500 Da from finished articles was calculated to be in total 1.5 lg/kg food. Being comprised of combinations of heptafluoropentene and/or tetrafluoroethylene and/or ethylene, not all constituents of this migrate will be strictly poly- or perfluoro in character, but the exact nature is unknown and will in any case be variable depending of the relative proportions of the three comonomers used. 3.2. Toxicological data The substance was adequately tested for gene mutation with the Ames test in Salmonella Typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA in the presence and absence of metabolic activation up to 5,000 lg/plate. The Panel considered that the substance does not induce mutagenicity in this study. An increase in structural chromosomal aberrations in Chinese Hamster Lung cell line was reported, but the study was considered inadequate due to methodological limitations. To address this concern, an in vivo combined micronucleus/comet assay was conducted in rats. The substance was administrated by gavage at 0, 250, 500 and 1,000 mg/kg body weight (bw) (maximum tolerated dose based on the results of a range-finding test) three times at 48, 24 and 3 h before the specimen preparation. A statistically significant and dose-related increase in the immature to mature erythrocyte ratio was observed in the treatment groups, providing the evidence of the bone-marrow exposure to heptafluoropentene. The substance was not clastogenic/aneugenic in the bone marrow and did not induce DNA damage in liver, kidney and at the site of first contact (glandular stomach). Based on the results in the bacterial mutation assay and the in vivo combined micronucleus/comet assay, the Panel considered that the substance does not give rise to concern for genotoxicity. Seventeen compounds are reported as impurities of the starting substance among which 12 are unknown. No data are available on the toxicity of the identified substances. Taking into account that the total mass transfer of the sum of the residual impurities from finished articles (considering similar behaviour as the substance itself) is below 0.02 lg/kg food, no additional data are requested on the impurities. Considering that the substance itself is not genotoxic and considering the polyaddition mechanism of polymerisation which eliminates the double bounds, the oligomers do not give rise to concern for genotoxicity. But being a mixture that contains a fraction of per- and polyfluorinated substances, the question of accumulation arises. Taking into account that the total mass transfer of the fluoropolymer oligomeric fraction below 1,500 Da from finished articles (based on extractable amounts of 27 mg/kg fluorocopolymer) was calculated to be 1.5 lg/kg food, the concern for accumulation (if any) is low and no additional data are requested. 4. Conclusions Having considered the above-mentioned data, the CEF Panel concluded that 2,3,3,4,4,5,5- heptafluoro-1-pentene does not raise a safety concern for the consumer if used as comonomer www.efsa.europa.eu/efsajournal 6 EFSA Journal 2016;14(10):4582
together with tetrafluoroethylene and/or ethylene comonomers to manufacture fluorocopolymers for application as a polymer processing aid at up to 0.2% w/w of the FCM. For this application, the low molecular weight fraction below 1,500 Da in the fluorocopolymer should be no greater than 30 mg/kg. Documentation provided to EFSA 1) Initial dossier. January 2015. Submitted on behalf of Daikin Industries Ltd. 2) Additional data. June 2016. Submitted on behalf of Daikin Industries Ltd. References EFSA (European Food Safety Authority), 2009. Guidance of the Scientific Committee on transparency in the scientific aspects of risk assessments carried out by EFSA. Part 2: general principles. EFSA Journal 2009;7 (5):1051, 22 pp. doi:10.2903/j.efsa.2009.1051 European Commission, 2001. Guidelines of the Scientific Committee on Food for the presentation of an application for safety assessment of a substance to be used in food contact materials prior its authorisation. Available online: http://ec.europa.eu/food/fs/sc/scf/out82_en.pdf Abbreviations bp bw CAS CEF FCM GC-MS LC-TOF-MS LMWF P o/w SCF SEC SML boiling point body weight Chemical Abstracts Service EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids food contact materials gas chromatography coupled with a mass spectrometry detector liquid chromatography with a time of flight mass spectrometry detector low molecular weight fraction octanol/water partition coefficient Scientific Committee on Food size exclusion chromatography specific migration limit www.efsa.europa.eu/efsajournal 7 EFSA Journal 2016;14(10):4582