Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the safety of “methyl vinyl ether-maleic anhydride copolymer” (Gantrez SF, chewing gum base ingredient) as a novel food ingredient in the context of Regulation (EC) No 258/97, taking into account the comments and objections of a scientific nature raised by Member States.
The novel food ingredient, Gantrez SF, is an anhydrous copolymer formed by the reaction of methyl vinyl ether (MVE) and maleic anhydride (MAN) under appropriate conditions. Dilauroyl peroxide (LP) is used to initiate the reaction. Depending on the reaction conditions, the process results in one of two end product types, referred to as type A or type B polymers. The two variants differ in their molecular weights and therefore viscosities. As with many high molecular weight polymers that may be subject to oxidation damage in storage or in use, butyl hydroxytoluene (BHT) is added to type B polymers as an antioxidant. The Panel considers that the information provided on the specifications, stability and production process do not raise safety concerns.
An estimated daily intake (EDI) for Gantrez SF associated with its use in chewing gum may be calculated based on its maximum concentration (2 %) in chewing gum and an estimated intake of 14 g chewing gum per day for high consumers. No data have been provided on the amount of Gantrez SF that may be released from the chewing gum upon consumption. In the absence of such data, it is assumed that Gantrez SF would be fully ingested. The applicant used chewing gum consumption data from the United States National Association of Chewing Gum Manufacturers, which indicate a mean chewing gum consumption level among all individuals who chew gum of 0.7 grams per day, and of 1.3 grams of gum per day for consumers at the 90th percentile. This covers long-term consumption (i.e. taken from three- or four-week food consumption diaries. Based on this information, the estimated daily intake for Gantrez SF, when present at levels up to 2 % in finished chewing gum, is calculated to be 26 mg per person per day for high consumers. However, in a previous EFSA opinion a value of 14 g per day was calculated for European high consumers of chewing gum, which was based on the 95th percentile of United Kingdom adolescent consumers. This would correspond to an intake of 280 mg Gantrez SF per day.
Taking into account the negative results from an Ames test and a mouse micronucleus assay (although both tests were not fully in accordance with the respective current OECD Guidelines), and the chemical structure of copolymer, the Panel has no concerns related to genotoxicity.
The applicant provided two 90-day rat studies. One study was not performed according to the current standard and it was unclear whether the test material ‘Gantrez Resin Salt’ corresponds to the novel food ingredient. Therefore, the Panel considers that this study is of limited value for the risk assessment. Another 90-day rat study was performed with the novel food ingredient and in compliance with GLP standards and OECD Guideline 408. Gantrez SF was administered to groups of 20 male and 20 female CRL:CD(SD) rats at dietary concentrations of 1, 2.5 or 5 %. The NDA Panel noted a higher incidence of skeletal muscle degeneration (minimal grade) and thymus epithelial hyperplasia (minimal grade) in male animals of the high dose group, when compared with the control group. On request of the Panel, the applicant provided additional histopathological examinations of skeletal muscle tissue and thymus for all rats of the mid and low dose groups.
Skeletal muscle degeneration was identified in male and female animals of all groups with a similar incidence rate (i.e. max. 20 %), except for high-dose males (i.e. 60 %), where the incidence was considerably higher than the percentage observed in historical controls (i.e. 21.8 %). Thymus epithelial hyperplasia was identified in male and female animals of all groups, including the control group, with a higher incidence than usually observed in historical controls. Considering the high background incidence of thymus epithelial hyperplasia in this study, the Panel is of the opinion that the higher incidence observed in high dose males was not test material-related. On the basis of the results, the NDA Panel concludes that the mid dose administered, i.e. 2.5 % Gantrez SF in the diet, equivalent to approximately 1.8 and 2.1 g/kg bw per day for male and female rats, respectively, represents the NOAEL in this study.
The Panel notes that the NOAEL of the 90-day rat study is about 500-fold more than the conservatively estimated intake of Gantrez SF of 280 mg/day for high consumers of chewing gum.
urthermore, the Panel notes that the novel ingredient would usually not, but may rarely, be swallowed.
The maximum consumption of 14 g chewing gum per day also forms the basis for calculations of the amount of low molecular weight components (less than 1000 Da), which are potentially released from the gum during the act of chewing. Since there are no data on the release of low molecular weight compounds during chewing the Panel must assume that all such materials, e.g. residual MAN, MVE, methanol, acetaldehyde, LP and BHT, are released at the maximum values indicated in the specification. The estimated maximum intake of 70 µg/day of MAN is considered negligible in relation to the tolerable daily intake of 0.5 mg/kg bw. Regarding the other monomer, MVE, the Panel considers that there is no safety concern with respect to genotoxicity. In accordance with relevant EFSA Guidance for the evaluation of monomers used in the production of high-molecular weight polymers to be used in food contact materials, no additional toxicological data are required considering the estimated maximum intake of 42 µg/day MVE.
The Threshold of Toxicological Concern (TTC) concept has been applied in the safety evaluation of residual levels of LP, which is used as a synthesis initiator in the production process of Gantrez SF. There is no concern with regard to genotoxicity of this substance. The estimated maximum intake of LP of 4.2 µg/day is well below the threshold value for Cramer class I substances, and thus does not raise safety concerns. The estimated maximum intakes of methanol of 140 µg/day and acetaldehyde of 140 µg/day are considered low in relation to the intake from natural sources, and do not pose a health risk at the levels set in the specification.
Addition of the antioxidant BHT to Gantrez SF, as indicated in the specification, is in accordance with EU legislation on food additives.
The Panel concludes that the novel food ingredient “Methyl Vinyl Ether-Maleic Anhydride Copolymer” (Gantrez SF, chewing gum base ingredient) is safe under the proposed uses and use levels.