Abstract
The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of d-α-tocopheryl polyethylene glycol-1000 succinate (Vitamin E TPGS) as a new food additive to be used in several food categories as emulsifier. In 2007, the EFSA AFC Panel assessed TPGS as a source of tocopherol intended to be used in foods for particular nutritional uses. The Panel considered the AFC Panel assessment relevant for the present new food additive. Compositional data showed that the proposed food additive is composed of Vitamin E TPGS monoesters (> 82% w/w of the whole preparation) and diesters (< 20% w/w of the whole preparation). Data on the hydrolysis of Vitamin E TPGS showed that the ester bond between d-α-tocopherol and succinic acid is stable under the tested conditions, as no increase in free d-α-tocopherol was observed. Vitamin E TPGS is poorly absorbed and does not represent a source of Vitamin E in the healthy population. Vitamin E TPGS does not raise a concern with respect to genotoxicity and no adverse effects on reproductive and developmental parameters were observed up to 1000 mg TPGS/kg bw per day, the highest dose tested and identified as a reference point. Due to the limitations in the available data (e.g. in reporting), the Panel decided to use an MOE approach instead of deriving an ADI. The Panel considered the calculated MOEs sufficient. Based on the available data, the Panel concluded that the use of Vitamin E TPGS as a new food additive does not raise a safety concern at the proposed use and use levels.
Summary
The European Commission requests the European Food Safety Authority to perform a risk assessment to provide a scientific opinion on the safety in use of d-α-tocopheryl polyethylene glycol-1000 succinate and then add in brackets (Vitamin E TPGS) Vitamin E TPGS as a food additive in different FCs, in accordance with Regulation (EC) No 1331/2008 establishing a common authorisation procedure for food additives, food enzymes and food flavourings. The proposed food additive is marketed as a waxy solid intended to be used in several FCs as emulsifier. The manufacturing involves a reaction between d- α- tocopheryl acid succinate and PEG 1000, followed by a solvent- mediated purification, crystallisation and filtration.
The applicant provided analytical data on five batches of the proposed food additive, showing that Vitamin E TPGS is produced according to the proposed specifications. The Panel considered the specifications provided by the applicant sufficient to properly characterise the proposed food additive but suggested some revisions. d
Compositional data showed that the proposed food additive is composed of Vitamin E TPGS monoesters (> 82% w/w of the whole preparation) and diesters (< 20% w/w of the whole preparation), although the content of diesters is not reflected in the specifications as proposed by the applicant. Unreacted PEG 1000, unreacted d- α tocopheryl acid succinate and free – α- tocopherol may be present. Analytical data on the levels of arsenic (As), lead (Pb), cadmium (Cd) and mercury (Hg) were provided by the applicant for five samples of the proposed food additive. The Panel assessed the risk that would result if these toxic elements were present in Vitamin E TPGS at two concentration scenarios: (i) at the proposed specification limits, and (ii) at the reported limits of quantification (LOQs). The Panel recommended to lower the specification limits proposed by the applicant for all four toxic elements (Pb, Cd, Hg, As), taking into account the fact that the proposed food additive is not the only potential dietary source of these toxic elements, and that the maximum limits should be established based on actual levels in the commercial food additive. The Panel assessed also the safety of calculating the margin of safety (MOE) from the exposure at its maximum residual level according to the specifications provided by the applicant, based on the different exposure assessment scenarios and taking the no observed adverse effect level (NOAEL) of 1000 mg/kg bw per day as the reference point. The resulting MOE in all scenarios was well above the default MOE of 100 (Table 10), thus indicating no concern.
The Panel noted that the proposed maximum limits for solvent and catalyst residues are higher than the actual concentrations quantified in the five batches of Vitamin E TPGS analysed by the applicant. The Panel considered the maximum limits proposed for residual solvents to be adequate, while the proposed limit for was not supported by the analytical data; accordingly, the Panel recommended to lower the specification limit proposed by the applicant. The applicant provided solubility data showing complete dissolution of 1 g of Vitamin E TPGS in 10 mL of water. Although the test does not fully meet the requirements of the EFSA Guidance on particle TR, the Panel concluded that Vitamin E TPGS would be fully solubilised at the intended use levels and conventional risk assessment can be carried out following the EFSA Guidance for submission for food additive evaluations (EFSA ANS Panel, 2012).
The applicant demonstrated a 4- year shelf life from the date of manufacturing for Vitamin E TPGS, when stored and sealed in the original container (parameters considered in the stability study were free d- α- tocopherol, colour and acid value). Additional literature data on the hydrolysis of Vitamin E TPGS were provided. Christiansen et al. (2011) reported that, under gastric conditions (pH 1.0 and 37°C), 3.4% (± 0.4%) of Vitamin E TPGS degraded into d- α- tocopheryl acid succinate and the associated PEG chain within 8 hours. Results showed that the ester bond between d- α- tocopherol and succinic acid is stable under the tested conditions, as no increase in free d- α- tocopherol was observed. Dietary exposure to Vitamin E TPGS was estimated according to three exposure scenarios that addressed the exposure deriving from the proposed uses for (i) the general population, (ii) consumers of food supplements and (iii) the adult population consuming foods for special medical purposes (FSMPs; FCs 13.2 and 13.2). For this last population, the Panel used a daily high consumption of FSMPs in adults as reported by the applicant as the consumption data in the Comprehensive Database do not allow such an assessment. The highest P95 exposure to Vitamin E TPGS in the general population was 5.7 mg/kg bw per day in adults and 8.5 mg/kg bw per day in adolescent consumers of food supplements. In adults, the exposure to Vitamin E TPGS deriving from FSMP was 17.9 mg/kg bw per day at the proposed maximum use level and 8.9mg/kg bw per day at the proposed typical use level. The Panel considered that TPGS as described in EFSA AFC Panel (2007a) is similar to the new proposed food additive Vitamin E TPGS object of this opinion, and therefore the assessment performed in 2007 was considered relevant for the present application. The Panel considered that the proposed food additive Vitamin E TPGS is poorly absorbed and does not represent a source of Vitamin E in the healthy population. Vitamin E TPGS does not raise a concern with respect to genotoxicity. No adverse effects on reproductive and developmental parameters were observed up to 1000 mg TPGS/kg bw per day in a one generation reproductive toxicity study in rats and developmental toxicity studies in rats and rabbits.
Subchronic studies in rats and dogs demonstrated no treatment- related adverse effects of TPGS. The Panel confirmed the NOAEL of 1000 mg TPGS/kg bw per day, the highest dose tested, as a reference point. Due to the limitations in the available data (e.g. in reporting), the Panel decided to use an MOE approach instead of deriving an acceptable daily intake (ADI). The reference point would result in an MOE of 175 for the general population for the highest P95 exposure of 5.7 mg/kg bw per day in adults, and an MOE of 118 for the highest P95 exposure of 8.5 mg/kg bw per day in adolescent consumers of food supplements. Considering the FSMP scenario adult only, the highest estimated exposure of 17.9 mg/kg bw per day would result in an MOE of 56.
The Panel considered these MOEs sufficient, given that (i) Vitamin E TPGS is poorly absorbed and has low bioavailability, (ii) 1000 mg TPGS/kg bw per day was the highest dose tested without adverse effects, (iii) higher doses could not be tested due to animal welfare considerations, (iv) Vitamin E TPGS does not represent a relevant source of Vitamin E in the healthy population, while it could be a nutrient source of Vitamin E in individuals with fat malabsorption and Vitamin E deficiency and (v) the exposure to Vitamin E TPGS through the consumption of FSMPs is expected to be for a limited period of time, not long- term. The Panel estimated the exposure to PEG 1000, d- α- tocopheryl acid succinate and d- α- tocopherol, based on their concentrations reported in the proposed specifications and the P95 exposure estimates for the three scenarios. The resulting exposure to the three components was well below the respective health- based guidance values or reference point.
Therefore, the Panel concluded that there is no safety concern for the exposure to PEG 1000, d- α- tocopheryl acid succinate and D- α- tocopherol from the uses and use levels of the proposed food additive. Based on the available data, the Panel concluded that the use of Vitamin E TPGS as a new food additive does not raise a
safety concern at the proposed use and use levels.
Download the full article as PDF here Safety evaluation of d-α-tocopheryl polyethylene glycol-1000 succinate (Vitamin E TPGS) as a food additive
or read it here
EFSA Panel on Food Additives and Flavourings (FAF), Laurence Castle, Monica Andreassen, Gabriele Aquilina, Maria Lourdes Bastos, Polly Boon, Biagio Fallico, Reginald FitzGerald, Maria Jose Frutos Fernandez, Bettina Grasl-Kraupp, Ursula Gundert-Remy, Rainer Gürtler, Eric Houdeau, Marcin Kurek, Henriqueta Louro, Patricia Morales, Sabina Passamonti, José Manuel Barat Baviera, Gisela Degen, David Gott, Jean-Charles Leblanc, Peter Moldeus, Ine Waalkens-Berendsen, Detlef Wölfle, Civitella Consuelo, Agnieszka Mech, Concepción Medrano-Padial, Ana Maria Rincon, Camilla Smeraldi, Alexandra Tard, Laura Ruggeri, First published: 11 August 2025 https://doi.org/10.2903/j.efsa.2025.9605, Adopted: 11 July 2025, The declarations of interest of all scientific experts active in EFSA’s work are available at https://open.efsa.europa.eu/experts
Read more on Vitamins & Minerals here:
