EFSA Journal 2015;13(2):4021 SCIENTIFIC OPINION Scientific Opinion on the safety assessment of the substance fatty acids, C16 18 saturated, hexaesters with dipentaerythritol for use in food contact materials 1 ABSTRACT EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) 2,3 European Food Safety Authority (EFSA), Parma, Italy This scientific opinion of the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) deals with the safety assessment of fatty acids, C16 18 saturated, hexaesters with dipentaerythritol (FADP), FCM substance No 01053, for use as a processing agent at up to 1.5 % in various types of plastics. Based on the modelled specific migration calculation results, it cannot be ruled out that the overall migration limit may be exceeded. No toxicological data were provided for the assessed substance. Toxicological data from similar pentaerythritol fatty acids were submitted for read across. Based on the genotoxicity data provided, the CEF Panel considered that there is no indication of mutagenic potential of the substance. The CEF Panel concluded that the substance FADP is not of safety concern for the consumer if used in polymers intended for contact with all types of foodstuffs at all time temperature conditions, provided that the fatty acid precursors are obtained from edible fats or oils and that any impurities in the dipentaerythritol are under the control of the producer. European Food Safety Authority, 2015 KEY WORDS fatty acids, C16 18 saturated, hexaesters with dipentaerythritol, FADP, FCM substance No 01053, food contact materials, safety assessment 1 On request from the Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, Question No EFSA-Q-2014-00494. Adopted on 28 January 2015. 2 Panel members: Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Karl-Heinz Engel, Paul Fowler, Roland Franz, Konrad Grob, Rainer Gürtler, Trine Husøy, Wim Mennes, Maria Rosaria Milana, André Penninks, Vittorio Silano, Andrew Smith, Maria de Fátima Tavares Poças, Christina Tlustos, Fidel Toldrá, Detlef Wölfle and Holger Zorn. Correspondence: fip@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on Food Contact Materials, Mona-Lise Binderup, Laurence Castle, Riccardo Crebelli, Alessandro Di Domenico, Nathalie Gontard, Ragna Bogen Hetland, Martine Kolf-Clauw, Eugenia Lampi, Maria Rosaria Milana, Maria de Fatima Poças, Philippe Saillard, Kettil Svensson and Detlef Wölfle for the preparatory work on this scientific opinion and EFSA staff, Marisa Escudero Hernandez, for the support provided to this scientific opinion. Suggested citation: EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2015. Scientific Opinion on the safety assessment of the substance, fatty acids, C16-18 saturated, hexaesters with dipentaerythritol, for use in food contact materials. EFSA Journal 2015;13(2):4021, 8 pp. doi:10.2903/j.efsa.2015.4021 Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2015
SUMMARY Within the general task of evaluating substances intended for use in materials in contact with food in accordance with 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 foodstuffs, the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) received a request from the Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, for safety assessment of the substance fatty acids, C16 18 saturated, hexaesters with dipentaerythritol (FADP), following a corresponding application submitted by the applicant, Emery Oleochemicals GmbH, Düsseldorf, Germany. The safety assessment of FADP, FCM substance No 01053, was requested for use as a processing aid at concentrations of up to 1.5 % in various types of plastics. Specific migration of the small molecule pentaerythritol C16/C18 diester was determined using various simulants in polyethylene glycol terephthalate glycol-modified (PETG) plates containing 1 % FADP. However, this does not represent the worst case because of low diffusion in polyethylene terephthalate (PET)-type materials compared with other plastics. Specific migration from other polymers was calculated by conservative modelling. Since the level of FADP used can be higher, it cannot be ruled out that the overall migration limit may be exceeded. However, the CEF Panel noted that, in accordance with Regulation (EU) No 10/2011 (Article 11.2), migration of the substance would be limited by the generic specific migration limit of 60 mg/kg food and has to be controlled by the user. No toxicological data were provided for the substance FADP. However, toxicological data from other similar pentaerythritol fatty acid esters were submitted for read across. The CEF Panel considered that, based on structural similarities and toxicokinetic considerations of the metabolism of fatty acid esters, the read across is acceptable. Bacterial gene mutation tests were submitted for structurally similar substances. Based on read across, the CEF Panel considered that there is no indication of mutagenic potential of the substance FADP. Repeated-dose toxicity literature data were provided for pentaerythritol esters homologues of FADP. The No Observed Adverse Effect Level (NOAEL) was 2 500 ppm. A similar NOAEL is expected for FADP. It is noted that highly lipophilic compounds, such as pentaerythritol esters with long-chain fatty acids, could be of concern if they have the potential to bioaccumulate. However, considering the low exposure and the fact that polyethylene esters are cleaved by esterases, including lipases, the CEF Panel has no concern with respect to the accumulation potential of this substance. The CEF Panel concluded that the substance FADP is not of safety concern for the consumer if used in polymers intended for contact with all types of foodstuffs at all time temperature conditions, provided that the fatty acid precursors are obtained from edible fats or oils using conventionally applied procedures, and that any impurities in the dipentaerythritol are under the control of the producer. EFSA Journal 2015;13(2):4021 2
TABLE OF CONTENTS Abstract... 1 Summary... 2 1. Introduction... 4 1.1. Background and Terms of Reference as provided by the legislation... 4 2. Assessment... 4 2.1. Introduction... 4 2.2. General information... 4 2.3. Data available in the dossier used for this evaluation... 5 2.4. Evaluation... 5 2.4.1. Non-toxicological data... 5 2.4.2. Toxicological data... 6 3. Conclusions... 7 Documentation provided to EFSA... 7 References... 7 Abbreviations... 8 EFSA Journal 2015;13(2):4021 3
1. Introduction 1.1. Background and Terms of Reference as provided by the legislation Before a substance is authorised to be used in food contact materials and is included in a positive list EFSA s opinion on its safety is required. This procedure has been established in Articles 8 and 9 of the 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. 4 According to this procedure the industry submits applications to the Member States competent Authorities which in their turn transmit the applications to the EFSA for their evaluation. The application is supported by a technical dossier submitted by the industry following the SCF guidelines for the presentation of an application for safety assessment of a substance to be used in food contact materials prior to its authorisation (EC, 2001). In this case, EFSA received an application from Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, requesting the evaluation of the processing agent fatty acids, C16 18 saturated, hexaesters with dipentaerythritol (FADP) with the FCM substance No 01053. 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 on the risks related to the indented use of the substance and to deliver a scientific opinion. 2. Assessment 2.1. Introduction The European Food Safety Authority (EFSA) was asked by the Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, to evaluate the safety of fatty acids, C16 18 saturated, hexaesters with dipentaerythritol (FADP), FCM substance No 01053. The request was registered in the EFSA s register of received questions under the number EFSA-Q-2014-00494. The dossier was submitted by the applicant, Emery Oleochemicals GmbH. 2.2. General information According to the applicant, the substance FADP is intended to be used as a processing aid for various types of plastics, acting as a lubricant to improve injection moulding and to improve the distribution of additives in the polymer melt. The amount used varies from 0.5 to 1.5 % w/w, depending on the polymer type and the application. The polymers listed for application are polyvinyl chloride, polyethylene terephthalate (PET), polyamide, polycarbonate, polyolefins (polyethylene and polypropylene), polyoxymethylene, polylactic acid and styrene butadiene rubber. Materials and articles containing the substance are intended for use in contact with all types of food without restrictions on temperature and duration. The substance itself has not been evaluated by the Scientific Committee on Food (SCF) or EFSA previously, but the two substances used to make FADP, namely dipentaerythritol (PM Reference Nos 16480 and 51200) and fatty acids from animal and vegetable food fats and oils (PM Reference No 31328), have been evaluated by the SCF and are listed in Regulation (EC) No 2011/10 without specific restrictions. Furthermore, the related polyester of adipic acid with glycerol or pentaerythritol, esters with even numbered unbranched C12 22 fatty acids, including pentaerythritol tetrastearate and pentaerythritol distearate (PM Reference No 76815), is listed along with numerous other esters with an total specific migration limit (SML(T)) of 60 mg/kg. 4 This Regulation replaces Directive 89/109/EEC of 21 December 1988, OJ L 40, 11.2.1989, p. 38. EFSA Journal 2015;13(2):4021 4
2.3. Data available in the dossier used for this evaluation Dipentaerythritol stearate The studies submitted for evaluation followed the SCF guidelines for the presentation of an application for safety assessment of a substance to be used in food contact materials prior to its authorisation (EC, 2001). Non-toxicity data: data on identity and composition data on physical and chemical properties data on thermal stability of the substance data on measured migration of the substance from glycol-modified PET (PETG) information on migration from other polymers, calculated by migration modelling. Toxicity data obtained from the European Chemicals Agency database: bacterial gene mutation test in vitro mammalian cell gene mutation test in vitro mammalian chromosome aberration test in vivo mammalian chromosomal aberration test bacterial gene mutation test on the major decomposition product in vitro micronucleus test on the major decomposition product. 2.4. Evaluation 2.4.1. Non-toxicological data Chemical formula of the substance: C 106 H 216 O 20 C 118 H 240 O 20 ; molecular mass: ca. 1 808 1 976 Da Chemical structure of the substance: where R = (CH 2 ) 14 CH 3 and (CH 2 ) 16 CH 3 EFSA Journal 2015;13(2):4021 5
FADP is a dipentaerythritol hexaester with a molecular weight that ranges from 1 808 to 1 976 Da depending on the fatty acids in the esters. It is produced using dipentaerythritol and fatty acids (C16 18) obtained from animal and vegetable food fats and oils. FADP has a melting point of 75 80 C and has a calculated log P o/w of > 6. No decomposition was observed by thermogravimetry up to 220 C. Above 220 C, a slow weight loss was observed which was not explained by the applicant. The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) noted that the temperature during the processing of some polymers might be substantially higher. The CEF Panel assumed that, in analogy to heating saturated edible fats, no products of concern were formed. There were no detectable impurities, except the starting substances dipentaerythritol and fatty acids, since, after hydrolysis and methylation, no impurities were detected by gas chromatography mass spectrometry with a detection limit of approximately 1 %. If the fatty acids used are obtained from edible oils or fats using conventionally applied procedures, no impurities of concern are expected. No information about impurities introduced by the dipentaerythritol is provided. As these would depend on the process used to produce the dipentaerythritol, controls must be implemented by the producer in accordance with good manufacturing practice (GMP). Because of the high molecular weight of the substance, specific migration of FADP was estimated by using the smaller molecule, pentaerythritol C16 18 diester, as a model. This diester was incorporated at 0.7 % w/w into sheets made of PETG. After 10 days at 40 C and with a surface area to mass ratio of 6 dm 2 /kg, migration into 10 % ethanol and iso-octane was < 0.04 and 0.3 mg/kg, respectively. After 10 days at 60 C, migration into iso-octane was 1.2 mg/kg. As this diester has a molecular weight of 668 Da, its migration is expected to be higher than that of FADP and, therefore, it was proposed by the applicant as a worst case for the migration of the hexaester from the PETG sample. However, migration from PETG is not considered as a worst case for all intended polymer applications, since diffusion in PET-type materials is extremely slow. Specific migration from other polymers (including low-density polyethylene and polypropylene) was estimated by conservative migration modelling using a range of pentaerythritol esters (from C8 diester to C22 tetraester) added at various concentrations to the polymer (0.1 to 1 %). However, the CEF Panel noted that migration of the substance would be limited under Regulation (EC) No 10/2011 (Article 11.2) by the generic specific migration limit of 60 mg/kg food and has to be controlled by the user. 2.4.2. Toxicological data No toxicological data were provided by the applicant for the substance FADP. Instead, toxicological data from other similar pentaerythritol fatty acid esters were submitted for read across. The CEF Panel considered that, based on structural similarities and toxicokinetic considerations of the metabolism of fatty acid esters, the read across is acceptable. Data on bacterial mutagenicity (Ames test) are available for five pentaerythritol esters and one dipentaerythritol ester that are structural homologues of FADP. These esters are fatty acids, C16 18, esters with pentaerythritol (CAS No 85116-93-4); decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No 68441-68-9); pentaerythritol ester of pentanoic, isopentanoic and isononanoic acids (CAS Nos 900017-19-8 and 173011-03-5); fatty acids, C16 18, mixed esters with citric acid, pentaerythritol and stearyl alcohol (CAS No 130328-22-2); fatty acids, C6 12, mixed esters with C18 unsaturated fatty acid dimers and dipentaerythritol and isononanoic acid (CAS No 146832-04-4); and fatty acids, C16 18, polymers with adipic acid and pentaerythritol (CAS No 118577-81-4). These substances did not induce gene mutations in bacteria (Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 for the first five substances and TA97, TA98, TA100 and TA102 for fatty acids, C16 18, polymers with adipic acid and pentaerythritol) either with or without metabolic activation by the S9 fraction. Another pentaerythritol ester, pentaerythritol dioleate (CAS No 25151-96-6), has already been evaluated by the SCF and was considered not mutagenic on the basis of three mutagenicity tests. Furthermore, the potential of fatty EFSA Journal 2015;13(2):4021 6
acids, C12 18, mixed esters with citric acid, pentaerythritol and stearyl alcohol (CAS No 130328-22- 2), to induce micronuclei in vivo was investigated in mice in accordance with OECD Guideline 474. There was no evidence of mutagenic effects with this substance. It is not clear whether or not the target tissue (bone marrow) was exposed. However, these in vitro and in vivo data did not provide any indication of mutagenicity with any of the test systems applied, with any of the substances tested or regardless of the metabolic activation of the pentaerythritol esters. Based on read across from these data, the CEF Panel considered that there is no indication of mutagenic potential of the substance FADP. Available data or data from the literature on repeated-dose toxicity were provided for five pentaerythritol esters that are structural homologues of FADP. The lowest NOAELs were derived from two 90-day experiments in rats with the test substances pentaerythritol and adipic acid, polyester with oleic acid (CAS No 68130-33-6) and fatty acids, C16 18, polymers with adipic acid and pentaerythritol (CAS No 118577-81-4). In both cases, the NOAEL was found to be 2 500 ppm, corresponding to approximately 170 mg/kg bw/day in males and 200 mg/kg bw/day in females. Therefore, a similar NOAEL is expected for FADP. It is noted that highly lipophilic compounds, such as pentaerythritol esters with long-chain fatty acids, could be of concern if they have the potential to bioaccumulate. However, because polyethylene-esters are cleaved by esterases including lipases (EFSA, 2009), the CEF Panel has no concern with respect to the accumulation potential of this substance. Similarly, because of hydrolysis in vivo, any content of lower esters (e.g. penta-, tetra-, etc.) in the substance used would not be of safety concern. 3. Conclusions Having considered the above-mentioned data, the CEF Panel concluded that the substance fatty acids, C16 18 saturated, esters with dipentaerythritol (FADP) is not of safety concern for the consumer if used in polymers intended for contact with all types of foodstuffs at all time temperature conditions, provided that the fatty acid precursors are obtained from edible fats or oils using conventionally applied procedures and that any impurities in the dipentaerythritol are under the control of the producer. DOCUMENTATION PROVIDED TO EFSA 1. Dossier: dipentaerythritol stearate. June 2014. Submitted by the applicant Emery Oleochemicals GmbH. REFERENCES EC (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 to its authorisation. Available online: http://ec.europa.eu/food/fs/sc/scf/out82_en.pdf EFSA (European Food Safety Authority), 2009. Scientific Opinion of the Panel on food contact materials, enzymes, flavourings and processing aids (CEF) on 24th list of substances for food contact materials. The EFSA Journal 2009, 1157 1163, 1 27. doi:10.2903/j.efsa.2009.1157 EFSA Journal 2015;13(2):4021 7
ABBREVIATIONS bw body weight CAS CEF EC EFSA EU FADP FCM NOAEL OECD PET PETG PM P o/w SCF SML(T) Chemical Abstract Service Food Contact Materials, Enzymes, Flavourings and Processing Aids European Commission European Food Safety Authority European Union fatty acids, C16 18 saturated, hexaesters with dipentaerythritol food contact material No Observed Adverse Effect Level Organisation for Economic Co-operation and Development polyethylene terephthalate glycol-modified polyethylene terephthalate packaging material partition coefficient in octanol water Scientific Committee on Food total specific migration limit EFSA Journal 2015;13(2):4021 8