SCIENTIFIC OPINION Scientific Opinion on the safety assessment of the substance ethylene glycol dipalmitate, CAS No 624-03-3, 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 ethylene glycol dipalmitate (EGDP), CAS No 624-03-3, FCM substance No 01048, for use as a processing aid at concentrations of up to 2 % in various types of plastics, acting as a lubricant to improve injection moulding and to improve the distribution of additives in the polymer melt. Based on the modelled specific migration results, it cannot be ruled out that the overall migration limit may be exceeded. No toxicological data were provided for the substance EGDP. Toxicological data from similar ethylene and propylene glycol fatty acid esters were submitted for read across. Based on the genotoxicity data provided, the CEF Panel considered that there is no indication of genotoxic potential for the substance EGDP. Based on two 90-day oral toxicity studies on structural homologues, no sub-chronic toxicity of EGDP is expected at relevant doses (< 1 000 mg/kg bw/day). The CEF Panel concluded that the substance EGDP is not of safety concern for consumers if it is used in plastics intended for contact with all types of foodstuffs under all contact conditions, provided that the fatty acid precursor is obtained from edible fats or oils using conventionally applied procedures, and that any impurities in the ethylene glycol are under the control of the producer. The substance should be included in the group total specific migration limit (SML(T)) of 30 mg/kg expressed as ethylene glycol. European Food Safety Authority, 2015 KEY WORDS ethylene glycol dipalmitate, 1,2-dipalmitoyl ethylene glycol, ethane-1,2-diyl palmitate, EGDP, CAS No 624-03- 3, food contact materials, safety assessment 1 On request from the Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, Question No EFSA-Q-2014-00434. 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 (2014-2017): Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Riccardo Crebelli, Roland Franz, Konrad Grob, 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 member, Marisa Escudero Hernandez for the support provided to this scientific opinion. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2015. Scientific Opinion on the safety assessment of the substance, ethylene glycol dipalmitate, CAS No 624-03-3, for use in food contact materials., 8 pp. doi:10.2903/j.efsa.2015.4019 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 ethylene glycol dipalmitate (EGDP), following a corresponding application submitted by the applicant, Emery Oleochemicals GmbH, Düsseldorf, Germany. The safety assessment of EGDP, CAS No 624-03-3, FCM substance No 01048, was requested for its use as a processing aid at concentrations of up to 2 % in various types of plastics, acting as a lubricant to improve injection moulding and to improve the distribution of additives in the polymer melt. Specific migration of the substance was determined using various simulants in non-plasticised polyvinyl chloride (PVC) containing 1 % EGDP. However, this does not represent the worst case because of low diffusion in PVC compared with other plastics. The specific migration from other polymers was calculated by conservative modelling. The migration was 26 mg/kg for 0.1 % EGDP in low-density polyethylene, the same value as that obtained for total mass transfer. Since the level of EGDP 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) 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 EGDP. However, such data were submitted for similar ethylene and propylene glycol fatty acid esters for read across. Based on the structural similarities and toxicokinetic considerations the Panel accepted this read across. Three limited bacterial gene mutation tests and a mammalian gene mutation test were carried out. Based on read across from these data, the CEF Panel considered that there is no indication of genotoxic potential of the substance EGDP. Two 90-day oral toxicity studies on similar substances using rats showed no adverse effects; therefore, based on read across from these structural homologues, no sub-chronic toxicity of EGDP is expected at relevant doses (i.e. < 1 000 mg/kg bw/day). In a prenatal development toxicity study in rats dosed with 900 mg/kg bw/day of fatty acids, C16 18, esters with ethylene glycol, no adverse effects were observed. Therefore, the Panel concluded, based on read across from these structural homologues, that no developmental toxicity of EGDP is expected. No accumulation of EGDP is expected because of its hydrolysis. The CEF Panel concluded that the substance EGDP is not of safety concern for the consumer if it is used in plastics intended for contact with all types of foodstuffs under all contact conditions, provided that the fatty acid precursor is obtained from edible fats or oils using conventionally applied procedures, and that any impurities in the ethylene glycol are under the control of the producer. The substance should be included in the group total specific migration limit (SML(T)) of 30 mg/kg expressed as ethylene glycol. 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 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 the Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany, requesting the evaluation of the processing aid ethylene glycol dipalmitate (EGDP), CAS No 624-03-3 and FCM substance No 01048. 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 ethylene glycol dipalmitate (EGDP), CAS No 624-03-3 and FCM substance No 01048. The request was registered in the EFSA s register of received questions under the number EFSA-Q-2014-00434. The dossier was submitted by the applicant, Emery Oleochemicals GmbH. 2.2. General information According to the applicant, the substance EGDP 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 concentration of EGDP used varies from 0.1 to 2 % w/w, depending on the polymer type. The polymers listed for application are polyvinyl chloride (PVC), polyethylene terephthalate, polyamide, polycarbonate, polyolefins (polyethylene, polypropylene), polyoxymethylene, polylactic acid and styrene butadiene rubber. Materials and articles containing the substance are intended to be used in contact with all types of food without restrictions on temperature or duration. The substance itself has not been evaluated by the Scientific Committee on Food (SCF) or EFSA, but palmitic acid and ethylene glycol, which are used in the production of EGDP, are listed in Regulation (EU) 10/2011. Palmitic acid (FCM substance No 00105) is listed without a specific migration limit (SML). Ethylene glycol (FCM substance No 00227) has a total specific migration limit (SML(T)), together with ethylene glycol distearate (FCM substance No 00089) and diethylene glycol (FCM substance No 00263), of 30 mg/kg (expressed as ethylene glycol). 4 This Regulation replaces Directive 89/109/EEC of 21 December 1988, OJ L 40, 11.2.1989, p. 38. 4
2.3. Data available in the dossier used for this evaluation Ethylene glycol dipalmitate 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 intended use method for analysis of the substance in polymers and simulants data on migration of the substance from non-plasticised PVC data on migration from other polymers, obtained by migration modelling. Toxicity data obtained from the European Chemicals Agency database: limited bacterial gene mutation tests ( read across from CAS 627-83-8, CAS 91031-31-1 and CAS 68583-51-7) in vitro mammalian cell gene mutation test ( read across from CAS 91031-31-1) in vivo mammalian micronucleus erythrocyte test ( read across from CAS 151661-88-0) sub-chronic 90-day oral toxicity studies in rats ( read across from CAS 68583-51-7 and CAS 151661-88-0) prenatal developmental oral toxicity study in rats ( read across from CAS 91031-31-1). 2.4. Evaluation 2.4.1. Non-toxicological data Chemical formula of main constituent: C 34 H 66 O 4 ; molecular mass: 538 Da. Chemical structure of the main constituent: 5
The substance consists of 94 95 % EGDP, 1 2 % ethylene glycol monopalmitate and 1 2 % of the mixed palmitic/steric diester (monopalmitate monostearate). EGDP is produced from palmitic acid (> 95 %) and ethylene glycol (> 95 %). The water formed during esterification and the unreacted glycol are removed from the product. EGDP melts at 74 C. It is poorly soluble in aqueous media with a calculated log P o/w of 14.1. Solubility in 50 % ethanol is < 0.7 g/l. No changes in weight of the substance were detected by thermogravimetry below 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) assumed that, by analogy with heating edible saturated fats, no products of concern were formed. No upper temperature limit during use is specified, but the processing temperature of some polymers containing the substance is likely to exceed 220 C. If the palmitic acid is obtained from edible oils or fats using conventionally applied procedures, no impurities of concern are expected. No information about impurities introduced by the ethylene glycol was provided. As these depend on the process used to produce the ethylene glycol, controls must be implemented by the producer in accordance with good manufacturing practice. An adequate method for determining EGDP in plastics and simulants was provided. Specific migration of EGDP was measured from 1 mm plates made of non-plasticised PVC containing 1 % EGDP into the food simulants 3 % acetic acid, 50 % ethanol and iso-octane. After 10 days at 40 C and with a surface area to mass ratio of 6 dm 2 /kg, the migration was < 6, 19 and 27 µg/kg, respectively. However, neither the addition of 1 % of the substance nor the use of non-plasticised PVC in the migration test represents the worst case, as diffusion in PVC is lower than in other plastics, such as polyolefins. Therefore, this test was considered informative but not representative. Specific migration from other polymers was calculated by conservative modelling and amounted to, for example, 26 mg/kg for 0.1 % EGDP in low-density polyethylene of 0.5 mm thickness. This migration value is the same as that obtained when calculating total mass transfer, so migration can be extensive. As higher addition levels are requested, it cannot be ruled out that the overall migration limit may be exceeded. However, the Panel noted that migration of the substance would be limited under Regulation (EU) No 10/2011 (Article 11.2) by the generic SML 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 EGDP. Instead, toxicological data from other similar ethylene and propylene glycol 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, e.g. ethylene glycol distearate, the read across is acceptable. Three limited bacterial gene mutation tests were carried out with ethylene glycol distearate, decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and fatty acids, C16 18, esters with ethylene glycol. These substances did not induce gene mutations in bacteria: Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 for the two first substances and strains TA98, TA100, TA1535, TA 1537 and TA1538 for the third substance, with and without metabolic activation. In a mammalian gene mutation assay with mouse lymphoma L5187 cells, no mutations were induced by the substance fatty acids, C16 18, esters with ethylene glycol. Likewise, no clastogenic/aneugenic effects were induced in a micronucleus erythrocyte test using mice administered by gavage 5 000 mg/kg bw of the substance fatty acids, C18 and C18 unsaturated epoxidised, ester with ethylene glycol (CAS 151661-88-0). In summary, the reported in vitro/in vivo genotoxicity data for different members of the glycol ester category show that these substances do not have any genotoxic properties. Based on read across from 6
these data, the Panel considered that there is no indication of genotoxic potential of the substance EGDP. No systemic toxicity or toxicity in bone marrow was observed. Thus, it was not clear whether or not the target tissue was exposed. In two 90-day oral toxicity studies with rats, the substances decanoic acids, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and fatty acids, C18 and C18 unsaturated epoxidised, ester with ethylene glycol (CAS 151661-88-0) did not give rise to any adverse effects up to the highest tested dose of 1 000 mg/kg bw/day. Based on read across from these results of studies using structural homologues, no sub-chronic toxicity of EGDP is expected at relevant doses, i.e. below 1 000 mg/kg bw/day. In a prenatal developmental toxicity study, rats were orally dosed up to 900 mg/kg bw/day with fatty acids, C16 18, esters with ethylene glycol by gavage from day 6 to day 15 of gestation. In conclusion, there were no adverse effects at any dose level. With regard to the present study, the No Observed Adverse Effect Level (NOAEL) for maternal toxicity and offspring toxicity was 900 mg/kg bw/day. Based on this result from a structural homologue, no developmental toxicity is expected for EGDP. No accumulation of the substance is expected because glycol esters are readily hydrolysed, in this case to palmitic acid and ethylene glycol. 3. Conclusions Having considered the above-mentioned data, the CEF Panel concluded that the substance ethylene glycol dipalmitate (EGDP) is not of safety concern for the consumer if it is used in plastics intended for contact with all types of foodstuffs under all contact conditions, provided that the fatty acid precursor is obtained from edible fats or oils using conventionally applied procedures, and that any impurities in the ethylene glycol are under the control of the producer. The substance should be included in the group SML(T) of 30 mg/kg expressed as ethylene glycol. DOCUMENTATION PROVIDED TO EFSA 1. Dossier: ethylene glycol dipalmitate (EGDP). 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 7
ABBREVIATIONS bw body weight CAS CEF EC EFSA EGDP EU FCM P o/w PVC SCF SML SML(T) Chemical Abstract Service Food Contact Materials, Enzymes, Flavourings and Processing Aids European Commission European Food Safety Authority ethylene glycol dipalmitate European Union Food Contact Materials partition coefficient in an octanol water system polyvinyl chloride Scientific Committee on Food specific migration limit specific migration limit (total, for a group of substances) 8