Safety of a change of specifications of phytosterols/phytostanols as a novel food pursuant to Regulation (EU)2015/2283

EFSA Journal. 2025;23:e9162. efsa.onlinelibrary.wiley.com/journal/1831-4732 | 1 of 11 https://doi.org/10.2903/j.efsa.2025.9162 SCIENTIFIC OPINION Safety of a change of specifications of phytosterols/ phytostanols as a novel food pursuant to Regulation (EU) 2015/2283 EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) | Dominique Turck | Torsten Bohn | Montaña Cámara | Jacqueline Castenmiller | Stefaan DeHenauw | Karen Ildico HirschErnst | Ángeles Jos | Alexandre Maciuk | Inge Mangelsdorf | Breige McNulty | Androniki Naska | Kristina Pentieva | Alfonso Siani | Frank Thies | Margarita AguileraGómez | Francesco Cubadda | Thomas Frenzel | Marina Heinonen | Monika NeuhäuserBerthold | Helle Katrine Knutsen | Morten Poulsen | Miguel Prieto Maradona | Josef Rudolf Schlatter | Alexandros Siskos | Henk van Loveren | Wolfgang Gelbmann | Harry J. McArdle Approved: 28 November 2024 DOI: 10.2903/j.efsa.2025.9162 Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to provide an opinion on the safety of a change of the specifications of the authorised NF ‘phytosterols/phytostanols’ as a novel food (NF) pursuant to Regulation (EU) 2015/2283. This authorised NF concerns phytosterols extracted from plants and which may be presented as free sterols and stanols or esterified with food grade fatty acids. It has to contain less than 81% βsitosterol, less than 35% βsitostanol, less than 40% campesterol, less than 15% campestanol, less than 30% stigmasterol and less than 3% brassicasterol. Regarding the maximum limit of the specification parameter ‘other sterols/stanols’, the applicant asks for an increase from currently less than 3% to less than 7% to better reflect and cover the natural composition and proportions of sunflowerbased phytosterols/phytostanols, noting that the existing specifications have been established largely based on the NF when sourced from soy. No evidence was found from the literature for the genotoxicity, subchronic toxicity, chronic toxicity and carcinogenicity, and reproductive toxicity of four phytosterols which have been identified by the applicant in the NF when produced from sunflower oil. These four phytosterols, albeit at lower concentrations, are also found in the NF if produced from soy. The Panel also notes the history of multiple safety assessments of phytosterols performed by Member States and EFSA, in addition to the group ADI established by JECFA. The Panel also considers that an increase from less than 3 to less than 7% for the maximum specification limit for ‘other phytosterols’ is of no relevance regarding nutritional considerations. The Panel concludes that the NF is safe under the proposed change of the specifications. KEYWORDS delta7stigmastenol, novel foods, phytostanol esters, phytostanols, phytosterol esters, phytosterols, sunflower oil The declarations of interest of all scientific experts active in EFSA's work are available at https:// open. efsa. europa. eu/ experts 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. © 2025 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority. Correspondence: [email protected] 2 of 11 | A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 CONTENTS Abstract................................................................................................................................................................................................................................1 1. Introduction ..............................................................................................................................................................................................................3 1.1. Background and Terms of Reference as provided by the requestor .........................................................................................3 1.2. Additional information ..............................................................................................................................................................................3 2. Data and Methodologies ......................................................................................................................................................................................4 2.1. Data ...................................................................................................................................................................................................................4 2.2. Methodologies..............................................................................................................................................................................................4 3. Assessment ................................................................................................................................................................................................................4 3.1. Introduction ...................................................................................................................................................................................................4 3.2. Production process .....................................................................................................................................................................................5 3.3. Compositional data .....................................................................................................................................................................................5 3.4. Specifications ................................................................................................................................................................................................7 3.5. The safety of the fraction ‘other phytosterols’ ..................................................................................................................................7 4. Discussion...................................................................................................................................................................................................................8 5. Conclusions ................................................................................................................................................................................................................8 5.1. Protection of Proprietary data in accordance with Article 26 of Regulation (EU) 2015/2283 ...........................................8 6. Steps taken by EFSA ................................................................................................................................................................................................8 Abbreviations ....................................................................................................................................................................................................................8 Requestor ............................................................................................................................................................................................................................9 Question number .............................................................................................................................................................................................................9 Panel members .................................................................................................................................................................................................................9 References...........................................................................................................................................................................................................................9 Appendix A ......................................................................................................................................................................................................................10 Annex A .............................................................................................................................................................................................................................11 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 3 of 11 A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 1 | INTRODUCTION 1.1 | Background and Terms of Reference as provided by the requestor On 29 June 2023, the company Advanced Organic Materials SA. submitted an application to the European Commission in accordance with Article 10 of Regulation (EU) 2015/2283 for a change of the specifications of the authorised novel food (NF) ‘phytosterols/phytostanols’. The applicant has requested data protection under Article 26 of Regulation (EU) 2015/2283 for data in support of this request. In accordance with Article 10(3) of Regulation (EU) 2015/2283, the European Commission asks the European Food Safety Authority to provide a scientific opinion on the safety of a change of the specifications of the authorised NF ‘phytosterols/ phytostanols’. In this opinion on a change of the specifications of the authorised NF ‘phytosterols/phytostanols’, the European Food Safety Authority should also document whether and to what extent the requirements of Article 26(2)(c) of Regulation (EU) 2015/2283 are fulfilled regarding the data for which the applicant is requesting data protection. 1.2 | Additional information In 2000, the Scientific Committee on Food (SCF) assessed the safety of phytosterol esters (PSE) in yellow fat spreads under Regulation (EU) No 258/97 (SCF,2000). That assessment concerned phytosterols isolated from conventional edible oils (soya, maize, sunflower, rapeseed) esterified with fatty acids from sunflower oil. The SCF concluded that PSE in yellow fat spreads at a maximum level corresponding to 8% free PS are safe for human use. Consequently, in 2000, the European Commission adopted the Decision 2000/500/EC authorising the placing on the market of ‘yellow fat spreads with added PSE’ as a novel food or novel food ingredient under Regulation (EC) No 258/97. In 2002, the SCF was asked to assess potential longterm effects of the intake of elevated levels of PS from multiple dietary sources, with particular attention to the effects on βcarotene (SCF,2002). Considering that intakes of PS above 3 g per person per day do not provide additional benefits on blood cholesterol and that the consequences of a persistent decrease in βcarotene blood concentrations on human health are largely unknown, the SCF deemed it prudent to avoid PS intakes exceeding 3 g/day. In 2004, an extension of this marketing authorisation was authorised for the uses of PSE in milkand yoghurt typeproducts by Commission Decision 2004/335/EC.1 Also in 2004, Commission Regulation (EC) No 608/20042 concerning the labelling of foods and food ingredients with added free phytosterols, phytosterol esters, phytostanols and/or phytostanol esters, laid down labelling requirements and limiting the consumption of added PS to a maximum of 3 g per person per day. In 2005, the EFSA NDA Panel published their opinion on certain aspects of serum levels of phytosterols (EFSA NDA Panel,2005); in the following years, on the safety of rice drinks with added phytosterols (EFSA NDA Panel,2006) and in 2007 on the safety of fruit juices and nectars with added phytosterols (EFSA NDA Panel,2007a). In another opinion from 2007, the NDA Panel assessed the production process of phytosterols when sourced from soybean (EFSA NDA Panel,2007b). At their 69th meeting, JECFA noted that phytosterol and phytostanol esters and mixtures of phytosterols and phytostanols generally show similar effect profiles and established a group acceptable daily intake (ADI) of 0 to 40 mg PS/kg body weight for free phytosterols and – stanols and their esters. This corresponds to a daily intake of 2.8 g PS/day for a 70 kg individual (JECFA, 2009). This conclusion was based on an overall NOAEL derived from several subchronic (90 days) studies, supported by studies on reproductive toxicity. The JECFA Panel also noted that there is no evidence for genotoxicity of phytosterols or phytostanols and their esters and no indication of potential for carcinogenicity. In 2013, the applicant submitted a notification pursuant to Article 5 (‘substantial equivalence’) of Regulation (EC) No 258/973 for their phytosterols and phytosterol esters derived from edible oils, mainly from soybean, supported by a statement of the competent authority of Finland (Evira,2013; unpublished) to the European Commission. Free phytosterols, − stanols, and their esters have been multiple times subject of such notifications (European Commission, 20184). In 2017, existing applicantspecific authorisations granted under Regulation (EU) 1997/258 for free and esterified phytosterols and stanols extracted from plants were transferred into the EU Union list for NF (Commission Implementing Regulation (EU) 2017/2470)5 and are now covered there by the entry ‘phytosterols/phytostanols’. The marketing authorisation lays down labelling requirements in accordance with Annex III of Regulation (EU) No 1169/2011,6 including the need to indicate (1) the target population, i.e. ‘people who want to lower their cholesterol levels’, (2) that patients on cholesterol 1https:// eurlex. europa. eu/ legalconte nt/ EN/ TXT/ HTML/? uri= CELEX: 32004 D0335 . 2https:// eurlex. europa. eu/ LexUr iServ/ LexUr iServ. do? uri= OJ:L: 2004: 097: 0044: 0045: EN: PDF#: ~: text= It% 20sets% 20out% 20spe cific% 20lab ellin g,lower% 20the ir% 20blo od% 20cho leste rol% 20lev els. & text= This% 20Reg ulati on% 20sha ll% 20app ly% 20to,phyto stano ls% 20or% 20phy tos% 2D% 20tan ol% 20esters. 3https:// eurlex. europa. eu/ legalconte nt/ EN/ TXT/ HTML/? uri= CELEX: 31997 R0258 . 4https:// food. ec. europa. eu/ system/ files/ 201806/ novelfood_ notif icati ons_ en. pdf. 5https:// eurlex. europa. eu/ legalconte nt/ EN/ TXT/ HTML/? uri= CELEX: 32017 R2470 . 6https:// eurlex. europa. eu/ legalconte nt/ EN/ TXT/ HTML/? uri= CELEX: 32011 R1169# ntr10-L_ 20113 04EN. 01001 801E0010 . 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 11 | A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 lowering medication should only consume the product under medical supervision, (3) that the product may not be nutritionally appropriate for pregnant and breastfeeding women and children under the age of 5 years, (4) that the product should be used as part of a healthy diet, including regular consumption of fruit and vegetables to help maintain carotenoid levels and (5) to avoid consumption of more than 3 g per day. The EFSA NDA Panel's most recent safety assessment of phytosterols concerned an extension of use of phytosterol esters added to vegetable fat spreads and to liquid vegetable fatbased emulsions for cooking and baking purposes, which could not establish the safety for these purposes (EFSA NDA Panel,2020). 2 | DATA AND METHODOLOGIES 2.1 | Data The safety assessment of this NF is based on data supplied in the application and additional data identified by the Panel. Administrative and scientific requirements for NF applications referred to in Article 10 of Regulation (EU) 2015/2283 are listed in Commission Implementing Regulation (EU) 2017/2469.7 A common and structured format on the presentation of NF applications is described in the EFSA guidance on the preparation and presentation of a NF application (EFSA NDA Panel,2021). As indicated in this guidance, it is the duty of the applicant to provide all available (proprietary, confidential and published) scientific data, (including both data in favour and not in favour) that are pertinent to the safety of the NF. The applicant has submitted a confidential and a nonconfidential version of a dossier following the EFSA guidelines on the preparation and presentation of a NF application (EFSA NDA Panel,2021) and the administrative guidance for the preparation of applications on novel foods pursuant to Article 10 of Regulation (EU) 2015/2283 (EFSA, 2024). In accordance with Art. 38 of Regulation (EC) No 178/20028 and taking into account the protection of confidential information and of personal data in accordance with Articles 39 to 39e of the same Regulation, and the Decision of EFSA's Executive Director laying down practical arrangements concerning transparency and confidentiality,9 the nonconfidential version of the dossier has been published on Open.EFSA.10 According to Art. 32c(2) of Regulation (EC) No 178/2002 and to the Decision of EFSA's Executive Director laying down the practical arrangements on presubmission phase and public consultations,2 EFSA carried out a public consultation on the nonconfidential version of the technical dossier from 1/8 to 22/8/2024. The comment received has been carefully evaluated and considered during the current assessment (Annex A). This NF application includes a request for protection of proprietary data in accordance with Article 26 of Regulation (EU) 2015/2283. The data requested by the applicant to be protected are listed in Appendix A. 2.2 | Methodologies The assessment follows the methodology set out in the EFSA guidance on NF applications (EFSA NDA Panel,2021) and the principles described in the relevant existing guidance documents from the EFSA Scientific Committee. The legal provisions for the assessment are laid down in Article 11 of Regulation (EU) 2015/2283 and in Article 7 of Commission Implementing Regulation (EU) 2017/2469. This assessment concerns only the risks that might be associated with consumption of the NF under the proposed conditions of use and is not an assessment of the efficacy of the NF with regards to any claimed benefit. 3 | ASSESSMENT 3.1 | Introduction The NF ‘phytosterols/phytostanols’ falls under the category defined in article 3.2 (a) (iv) of Regulation (EU) 2015/2283, i.e. food consisting of, isolated from or produced from plants or their parts. According to Table1 of the Annex of the EU Union list,11 the NF subject of the application, is phytosterols and phytostanols extracted from plants and may be presented as free sterols and stanols or esterified with food grade fatty acids. It shall 7Commission Implementing Regulation (EU) 2017/2469 of 20 December 2017 laying down administrative and scientific requirements for applications referred to in Article 10 of Regulation (EU) 2015/2283 of the European Parliament and of the Council on novel foods. OJ L 351, 30.12.2017, pp. 64–71. 8Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. OJ L 31, 1.2.2002, p. 1–48. 9Decision available at: https://www.efsa.europa.eu/en/corporatepubs/transparencyregulationpracticalarrangements. 10The nonconfidential version of the dossier has been published on Open.EFSA and is available at the following link: https:// open. efsa. europa. eu/ consu ltati ons/ a0cTk 00000 4rWHX IA2? search= EFSA-Q202300497 . 11https:// eurlex. europa. eu/ legalconte nt/ EN/ TXT/ HTML/? uri= CELEX: 32017 R2470 . 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 5 of 11 A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 contain less than 81% βsitosterol, less than 35% βsitostanol, less than 40% campesterol, less than 15% campestanol, less than 30% stigmasterol, less than 3% brassicasterol and less than 3% other sterols/stanols. The applicant notes that the first safety assessment of the NF by the SCF in 2000, which led to the marketing authorisation of the NF, covered ‘conventional edible oils (soya, maize, sunflower, rapeseed)’. The applicant also noted that the main source of phytosterols for most of the manufacturers, including the applicant himself, so far had been soybean. According to the applicant, the phytosterol fractions in sunflower oil is however slightly different compared with the phytosterols/ phytostanols defined in the EU Union list for NF (Commission Implementing Regulation (EU) 2017/2470). The applicant therefore asks to increase the maximum limit of the specification parameter ‘other sterols/stanols’ from less than 3% to less than 7% to better reflect and cover the natural composition and proportions of sunflowerbased phytosterols/phytostanols. The application is supported by data on two phytosterol products produced by the applicant from refined sunflower oil, one concerns free phytosterols and the other one phytosterol esters. 3.2 | Production process According to the applicant, the phytosterols are extracted from edible sunflower oil produced from sunflower crops grown and harvested according to normal agricultural practices. For their ester product, fatty acids from soybean, rapeseed or sunflower are used. According to the information provided by the applicant, their phytosterol ingredients, one composed largely of free phytosterols, the other one of phytosterol esters, are produced in line with Good Manufacturing Practice (GMP) and Hazard Analysis Critical Control Points (HACCP) principles. 3.3 | Compositional data The applicant provided compositional analytical data on five batches each of their free phytosterol (Table1) and phytosterol ester (Table2) ingredients derived from sunflower. TABLE 1 Batch to batch analysis of the NF composed largely by free phytosterols produced from sunflower. Parameter (g/100 g NF) Batch 1 Batch 2 Batch 3 Batch 4 Batch 5 Total plant sterols + stanols 92.76 92.15 94.31 94.16 94.01 βSitosterol 57.58 56.45 58.14 58.10 58.53 Campesterol 11.56 11.88 11.99 11.97 12.00 Campestanol 0.17 0.20 0.15 0.15 0.15 Stigmasterol 14.64 14.70 15.30 15.28 14.79 Brassicasterol 0.97 1.02 1.12 1.11 1.04 βSitostanol + delta5avenasterol 1.80 1.78 1.74 1.75 1.76 βSitostanola1.73 1.69 1.74 1.74 1.76 Delta5avenasterolb0.07 0.09 0.00 0.01 0.00 Delta7avenasterol 0.45 0.45 0.43 0.43 0.43 Delta7stigmastenol 3.16 3.25 3.06 3.05 2.94 Delta5,24stigmastadienol 0.63 0.61 0.65 0.59 0.61 Unidentified sterols 1.81 1.81 1.74 1.75 1.75 Sum of other sterols/stanolsc6.12 6.21 5.88 5.83 5.73 aCalculated by using the formula of 0.03 × βsitosterol content. bCalculated by subtracting the βsitostanol content from βsitostanol + delta5avenasterol content. cSum of delta5avenasterol, delta7avenasterol, delta7stigmastenol, delta5,24stigmastadienol and unidentified sterols. TABLE 2 Batch to batch analysis of the NF composed largely by phytosterol esters. Parameter (g/100 g NF) Batch 1 Batch 2 Batch 3 Batch 4 Batch 5 Total plant sterols + stanols 58.51 58.47 57.83 58.42 58.12 βSitosterol 36.36 36.48 36.35 35.60 35.80 Campesterol 7.27 7.05 7.03 7.67 7.34 Campestanol 0.05 0.05 0.06 0.12 0.09 Stigmasterol 10.09 9.62 9.29 9.51 9.54 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 11 | A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 The phytosterols/phytostanols of both products were analysed by accredited laboratories with validated gas chromatography–flame ionisation detection (GC–FID) based methods in compliance with the requirement (i.e. GC–FID or equivalent method) specified in the EU Union list. The applicant notes that the composition of all tested batches presented in Tables1, 2 complies with the specification limits of the NF as laid down by the EU Union list, except for the parameter ‘Other sterols/stanols’ which exceeds the maximum permitted limit of ‘below 3 %’. According to Tables1, 2, four phytosterols were identified representing at least 2/3 of the fraction ‘other phytosterols’. One of the identified phytosterols, delta7stigmastenol, represents about half of the fraction ‘other phytosterols’ in both products, while the other identified phytosterols, i.e. delta5avenasterol, delta7avenasterol, delta5,24stigmastadienol represent about 10% or less of that fraction or less than 0.7% of the NF. According to the applicant, the exceedance for ‘other phytosterols’ is due to the slightly different phytosterol profile, i.e. higher proportion of delta7avenasterol, delta7stigmastenol and delta5,24stigmastadienol of sunflower oil compared to soybean oil for which the current specification limits have been mainly established. To support this claim, the applicant provided a comparison of the phytosterol profile of the NF when produced from soybean oil and from sunflower oil (two batches of each type; Table3). The Panel notes that the main differences between the NFs of the applicant when produced from soybeans or sunflowers concern the proportion of ‘other phytosterols’, which appears to be about double when produced from sunflower and with regards to the four identified phytosterols comprised by the fraction of ‘other phytosterols’, the main differences were found for delta7stigmastenol (about five times higher in sunflowerderived phytosterols) and delta7avenasterol TABLE 3 Comparison of the sterol composition of the NF (free phytosterols/stanols) when sourced from soybean oil and sunflower oil, both manufactured by the applicant. Parameter (g/100 g NF) NF sourced from soybean NF sourced from sunflower Batch 1 Batch 2 Batch 1 Batch 2 βSitosterol 43.49 42.20 55.96 53.30 Stigmasterol 24.89 26.50 16.28 16.14 Campesterol 21.51 22.40 11.68 13.53 Brassicasterol 0.20 0.21 0.22 0.23 Campestanol 0.34 0.39 0.20 0.25 βSitostanol + delta5avenasterol 1.68 1.67 1.73 1.80 βSitostanola1.30 1.27 1.68 1.60 Delta5avenasterolb0.38 0.40 0.05 0.20 Delta7avenasterol 0.17 0.19 0.45 0.43 Delta7stigmastenol 0.64 0.68 3.19 3.16 Delta5,24stigmastadienol 0.45 0.35 0.54 0.59 Unidentified sterols 1.40 1.26 1.74 1.86 Total plant sterols + stanols 94.76 95.84 91.97 91.28 Sum of other sterols/stanolsc3.04 2.88 5.97 6.24 aCalculated by using the formula of 0.03 x βsitosterol content. bCalculated by subtracting the βsitostanol content from βsitostanol + delta5avenasterol content. cSum of delta5avenasterol, delta7avenasterol, delta7stigmastenol, delta5,24stigmastadienol and unidentified sterols. Parameter (g/100 g NF) Batch 1 Batch 2 Batch 3 Batch 4 Batch 5 Brassicasterol 0.33 0.28 0.35 0.18 0.22 βSitostanol + delta5avenasterol 1.17 1.15 1.09 1.11 1.09 βSitostanola1.09 1.09 1.09 1.07 1.07 Delta5avenasterolb0.08 0.06 0.00 0.04 0.02 Delta7avenasterol 0.22 0.28 0.26 0.28 0.27 Delta7stigmastenol 1.48 2.06 1.90 2.24 2.13 Delta5,24stigmastadienol 0.46 0.37 0.43 0.36 0.36 Unidentified sterols 1.09 1.13 1.09 1.36 1.26 Sum of other sterols/stanolsc3.33 3.90 3.68 4.28 4.04 aCalculated by using the formula of 0.03 x βsitosterol content. bCalculated by subtracting the βsitostanol content from βsitostanol + delta5avenasterol content. cSum of delta5avenasterol, delta7avenasterol, delta7stigmastenol, delta5,24stigmastadienol and unidentified sterols. TABLE 2 (Continued) 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 7 of 11 A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 (about two to three times higher in sunflowerderived phytosterols). However, the Panel considers that quantitatively, the differences observed between soybean and sunflower NFs for these compounds are also small. In addition, aiming to provide additional evidence that the fraction of ‘other phytosterols’ differs slightly between phytosterols sourced from sunflower as compared to other sources, in particularly soya, the applicant provided two published references from the literature (Phillips etal.,2005; Zhang etal.,2006). Zhang etal.(2006) noted about five times higher amounts of delta7phytosterols in sunflower oil as compared to soya oil. Phillips etal.(2005) reported amounts of total phytosterols in three different sunflower seed kernels (265–289 mg/100 g) and for delta7stigmastenol (17.5–22 g/100 g), which corresponds to approximately 7% of phytosterols represented by delta7stigmastenol in these samples. In addition, EFSA found additional references which reported a proportion of about 8–10% for delta7stigmastenol of the total phytosterol fraction in two Brasilian sunflower seed samples (Rosa etal., 2009). Choong etal.(1999), who analysed the free and total phytosterol composition of various animal and vegetable fats and oils, reported 213 μg (3.2%) delta7stigmastenol among 6587 μg total phytosterols for their sunflower oil sample, similar to the proportion of that phytosterol in the NF of the applicant when sourced from sunflower. In addition to the analytical data on the phytosterol and phytostanol composition, microbiological analyses (total aerobic bacteria, yeast and moulds, coliforms, E. coli, Salmonella and Staphylococcus) and on contaminants (heavy metals, PAHs, dioxins and furans, polychlorinated biphenyls (PCBs), aflatoxins, sulphated ash and pesticide residues) are provided to demonstrate the purity of the applicant's products. Also, analytical data on the solvent residues were provided. The Panel considers that the analytical testing of both applicant's products indicates that they can be reproducibly manufactured. The batches of both products show a consistent phytosterol/phytostanol profile with small differences between the batches. 3.4 | Specifications The applicant is requesting a change of the specifications of the NF phytosterols/phytostanols in Commission Implementing Regulation (EU) 2017/2470 (‘EU Union list’). The request concerns to increase the specification parameter for ‘other sterols/ stanols’ from less than 3 to less than 7% as indicated below in Table4. The underlying reason for this request is to better reflect and cover the natural composition and proportions of phytosterols/phytostanols if sourced from sunflower oil, which is already a permitted source for the NF. 3.5 | The safety of the fraction ‘other phytosterols’ No new data have been generated by the applicant regarding absorption, digestion, metabolism and excretion, nutritional information, toxicity and allergenicity. Because the biggest differences between the phytosterols sourced from soybean and sunflower concerned delta7stigmastenol and delta7avenasterol, the applicant conducted an extensive literature search for toxicity studies targeting these two compounds. The literature search was designed to detect invitro and invivo toxicity studies investigating the safety of phytosterol preparations containing a similar proportion of delta7stigmastenol and delta7avenasterol as the sunflowerbased phytosterol produced by the applicant. In addition, invitro and invivo toxicity studies especially on delta7stigmastenol and delta7avenasterol individually, were searched for. No new invitro or invivo data related to genotoxicity, subchronic toxicity, chronic toxicity and carcinogenicity, and reproductive toxicity were identified. Nevertheless, the applicant abstained from performing new toxicological studies, considering that sunflower oil is not only an already authorised source, but has also an extensive history of human consumption, that their production process (albeit using mainly soy as a source) has been already assessed by the Finnish competent authority in 2013, and that ‘phytosterols/phytostanols’ from different plant sources have been already assessed multiple times by EFSA and by Member States. The applicant also refers to JECFA who has established a group ADI for free phytosterols, − stanols and their esters. The applicant further considered that the identified four phytosterols which comprise about 2/3 of the TABLE 4 Specifications of the NF. Description as defined by Commission Implementing Regulation (EU) 2017/2470: Phytosterols and phytostanols are sterols and stanols that are extracted from plants and may be presented as free sterols and stanols or esterified with food grade fatty acids. Parameter Limits as currently authorised under Commission Implementing Regulation (EU) 2017/2470 (‘EU Union list’) Change as proposed by the applicant βsitosterol < 81% – βsitostanol < 35% – Campesterol < 40% – Campestanol < 15% – Stigmasterol < 30% – Brassicasterol < 3% – Other sterols/stanols < 3% < 7% 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 11 | A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 fraction of ‘other phytosterols’ are also, albeit in lower quantities, present in phytosterol preparations when produced from soy. The applicant also considered that the ability of toxicity tests to detect or discriminate effects of such a small concentration difference in the ‘other sterol fraction’ is most likely to be insufficient. 4 | DISCUSSION The NF, which is the subject of the application, concerns the authorised NF phytosterols and – stanols extracted from plants and which may be presented as free sterols and stanols or esterified with food grade fatty acids. The applicant has requested to increase the maximum specification limit for ‘other phytosterols’ from < 3% to < 7%. According to the applicant, and supported by published references, such a higher maximum specification limit would better reflect the natural composition and proportions of sunflowerbased phytosterols/phytostanols, noting that the existing specifications have been established largely on the basis of the NF when sourced from soy. No evidence was identified for the genotoxicity, subchronic toxicity, chronic toxicity and carcinogenicity, and reproductive toxicity of four phytosterols (delta5avenasterol, delta7avenasterol, delta7stigmastenol, delta5,24stigmastadienol) which have been identified by the applicant in the NF when produced from sunflower oil. These four phytosterols, albeit at lower concentrations, are also found in the NF if produced from soy. The applicant provided arguments why he considered that the small differences of the fraction ‘other phytosterols’ of the NF when sourced from soyor sunflower oil, do not warrant to perform new toxicological studies. Considering these arguments and noting the history of multiple safety assessments of phytosterols performed by Member States and EFSA, in addition to the group ADI established by JECFA, the Panel concurs with that view. The Panel also considers that an increase from < 3% to < 7% for the maximum specification limit for ‘other phytosterols’ is of no relevance regarding nutritional considerations. 5 | CONCLUSIONS The Panel concludes that the NF is safe under the proposed change of the specifications. 5.1 | Protection of Proprietary data in accordance with Article 26 of Regulation (EU) 2015/2283 The Panel could not have reached the conclusion on the safety of the NF under the proposed conditions of use without the data claimed as proprietary by the applicant (each five batches of the applicant's free phytosterol product and their phytosterol ester product manufactured from sunflower oil; Annexes 11a and 12a) and validation data of their inhouse method for the determination of phytosterol content using gas chromatography (Annex 17e). 6 | STEPS TAKEN BY EFSA 1. On 04/01/24, EFSA received a letter from the European Commission with the request for a scientific opinion on the safety of a change of specifications of the authorised novel food NF ‘phytosterols/phytostanols’ Ref. Ares(2024)39029–04/01/2024. 2. On 04/01/24, a valid application on a change of specifications of phytosterols/phytostanols, which was submitted by Advanced Organic Materials SA., was made available to EFSA by the European Commission through the Commission esubmission portal (NF 2022–12,290) and the scientific evaluation procedure was initiated. 3. During its meeting on 28 November 2024 the NDA Panel, having evaluated the data, adopted a scientific opinion on the safety of a change of specifications and phytosterols/phytostanols as a NF pursuant to Regulation (EU) 2015/2283. ABBREVIATIONS ADI acceptable daily intake FAO Food and Agriculture Organisation GCFID Gas chromatography flame ionisation detector GMP Good Manufacturing Practice HACCP Hazard Analysis Critical Control Points JECFA Joint FAO/WHO Expert Committee on Food Additives NDA EFSA Panel on Nutrition, Novel Foods and Food Allergens NOAEL no observed adverse effect level NF novel food PAHs polycyclic aromatic hydrocarbons PCBs polychlorinated biphenyls PS phytosterols 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 9 of 11 A NOVEL FOOD PURSUANT TO REGULATION (EU) 2015/2283 PSE phytosterol esters SCF Scientific Committee on Food WHO World Health Organization REQUESTOR European Commission QUESTION NUMBER EFSAQ202300497 PANEL MEMBERS Dominique Turck, Torsten Bohn, Montaña Cámara, Jacqueline Castenmiller, Stefaan de Henauw, KarenIldico HirschErnst, Ángeles Jos, Alexandre Maciuk, Inge Mangelsdorf, Breige McNulty, Androniki Naska, Kristina Pentieva, Alfonso Siani, and Frank Thies. REFERENCES Choong, Y.- M., Lin, H.- J., Chen, C.- W., & Wang, M.- L. (1999). A rapid gas chromatographic method for direct determination of free sterols in animal and vegetable fats and oils. Journal of Food and Drug Analysis, 7(4), 2859. https:// doi. org/ 10. 38212/ 22246614. 2859 European Commission. (2018). 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How to cite this article: EFSA NDA Panel (EFSA Panel on Nutrition, Novel Foods and Food Allergens), Turck, D., Bohn, T., Cámara, M., Castenmiller, J., De Henauw, S., HirschErnst, K. I., Jos, Á., Maciuk, A., Mangelsdorf, I., McNulty, B., Naska, A., Pentieva, K., Siani, A., Thies, F., AguileraGómez, M., Cubadda, F., Frenzel, T., Heinonen, M., … McArdle, H. J. (2025). Safety of a change of specifications of phytosterols/phytostanols as a novel food pursuant to Regulation (EU) 2015/2283. EFSA Journal, 23(1), e9162. https://doi.org/10.2903/j.efsa.2025.9162 18314732, 2025, 1, Downloaded from https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9162 by Readcube (Labtiva Inc.), Wiley Online Library on [10/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License