Call for technical and toxicological data on citric acid esters of mono- and diglycerides of fatty acids (E 472c) for uses as a food additive in foods for all population groups including infants below 16 weeks of age

EFSA-Q-number: EFSA-Q-2021-00674

Published: 01/12/2021

Deadline for registering interest:11/01/2022

Deadline for submission of data: 31/08/2022

New deadline for submission of data: 30/06/2023

Background

Pursuant to Article 32(1) of Regulation (EC) No 1333/2008^[1], food additives which were permitted for use in the European Union before 20 January 2009 need to be re-evaluated by the European Food Safety Authority (EFSA). The programme for this re-evaluation is established by Commission Regulation (EU) No 257/2010^[2].

In accordance with the above legal framework, the EFSA Panel on Food Additives and Flavourings (FAF) issued a scientific opinion on the safety of acetic acid, lactic acid, citric acid, tartaric acid, mono- and diacetyltartaric acid, mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids (E 472a-f) from their uses as food additives^[3] in food categories currently specified in Annex II to Regulation (EC) No 1333/2008.

In its opinion the FAF Panel noted that in Annex II of Regulation (EC) No 1333/2008 use levels of citric acid esters of mono- and diglycerides of fatty acids (E 472c) in food for infants below the age of 12 weeks are included in category 13.1.1 and 13.1.5.1. The Panel considered that these uses for infants below the age of 12 weeks would require a specific risk assessment. Therefore, the re-evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c) as a food additive is not applicable for infants below the age of 12 weeks. The reason was that the risk assessment approach followed at the time by the EFSA’s Scientific Panels in the re-evaluation of food additives did not apply to this age group^[4].

On 31 May 2017, EFSA’s Scientific Committee (SC) published a guidance document^[5] on the risk assessment of substances present in food intended for infants below 16 weeks of age, enabling the assessment of the safe use of citric acid esters of mono- and diglycerides of fatty acids (E 472c) and of other food additives for the population group below that age.

Following the latest advice from the EFSA’s Scientific Committee (SC) published guidance document^[5], the risk assessment to be performed will address the safety of uses of citric acid esters of mono- and diglycerides of fatty acids (E 472c) in foods for infants below 16 weeks of age.

In addition, the FAF Panel identified in the conclusions and recommendations of its published opinions on citric acid esters of mono- and diglycerides of fatty acids (E 472c) data gaps in the risk assessment, relevant for all population groups.

For the sake of efficiency, the European Commission asked EFSA to address the above lack of data (data gaps) during its risk assessment of food additives for uses in food for young infants. Therefore, specific data requirements for all uses of citric acid esters of mono- and diglycerides of fatty acids (E 472c) are included in this call for data.

EFSA will consider the relevance of the information provided for the risk assessment of citric acid esters of mono- and diglycerides of fatty acids (E 472c). The submission of the requested information is without prejudice to the final opinion of the Panel.

According to Article 6(5) of Regulation (EU) No 257/2010 where the requested information has not been submitted to EFSA within the set deadlines, the food additive may be removed from the Union list in accordance with the procedure laid down in Article 10.3 of Regulation (EC) No 1333/2008.

Overall objective

The purpose of this call for data is to offer interested parties and/or stakeholders the opportunity to submit documented information (published, unpublished or newly generated) relevant to the re-evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c) to be used in foods for infants below 16 weeks of age, as well as to address the data gaps that have been identified for all population groups in the already published EFSA opinions on this food additive.  

It is noted that the present call for data is targeted to citric acid esters of mono- and diglycerides of fatty acids (E 472c). A call for data has been launched by the European Commission on acetic acid esters of mono- and diglycerides of fatty acids (E 472a), lactic acid esters of mono- and diglycerides of fatty acids (E 472b), tartaric acid esters of mono- and diglycerides of fatty acids (E 472d), mono- and diacetyltartaric acid esters of mono- and diglycerides of fatty acids (E 472e) and mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids (E 472f)^[6]. The interested parties and/or stakeholders are invited to also consult these calls for data and coordinate the data submission as necessary.

Deadlines for submission of data and disclosure of contact details

Interested parties and stakeholders should provide earlier or at the latest by the new updated deadline of 30/06/2023 the information described below.

Within 6 weeks from the publication of this call, please communicate in writing by e-mail to: RAL [at] efsa.europa.eu (RAL[at]efsa[dot]europa[dot]eu), your availability to submit the requested information by the timeline specified above or any proposal for a new deadline providing justified reasons. Depending on the replies received the final deadline will be communicated to you through e-mail and by updating the current call.

In accordance with Article 6(4) of the Regulation (EU) No 257/2010 the information not submitted within the final deadline will only exceptionally be considered and EFSA can finalise its opinions on the basis of the information already provided.

In order to facilitate the collaboration of all interested business operators and interested parties to provide the data needed, we are seeking your consent to disclose contact details to the other parties that have expressed an interest to provide the requested information. If you do not wish to make these contact details available, clearly indicate it in your first communication.

Information sought

EFSA invites business operators and other interested parties (governments, interested organisations, universities, research institutions, companies) to submit information on the following food additive:

 This information will be used:

• for the follow-up on issues that have been expressed in the conclusions and recommendations of the EFSA FAF Panel Scientific Opinion on the re-evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c)^[3].
• for the risk assessment of citric acid esters of mono- and diglycerides of fatty acids (E 472c) in food for infants below 16 weeks of age in the food categories 13.1.1 and 13.1.5.1. It should be in accordance with the EFSA Guidance of the Scientific Committee on the risk assessment of substances present in food intended for infants below 16 weeks of age^[5].

A. Information regarding the follow up of the conclusions and the recommendations for the food additive citric acid esters of mono- and diglycerides of fatty acids (E 472c) for all uses

With reference to the conclusions and recommendations in the Scientific Opinion on the re-evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c) as a food additive, information is sought on:

1. Technical data

• Information on the manufacturing process(es) used for the production of E 472c. The list of potential impurities outlined below is based on the information provided for the re-evaluation of E 472a‐f as food additives^[3]. In case changes have been implemented in the manufacturing process(es) for E 472c in comparison to that information^[3], then other impurities may arise. Depending on the information provided on the manufacturing process(es) used, analytical data on any other additional impurities of toxicological concern should be provided too. 
• Analytical data on current levels of toxic elements such as arsenic, lead, cadmium and mercury in commercial samples of the food additive E 472c.
• Analytical data on current levels of any impurities of toxicological concern identified in the EU specifications for the food additive glycerol (E 422) (e.g. butanetriols, acrolein, chlorinated compounds, 3-monochloropropane-1,2-diol) as well as those mentioned in the call for data for E 422^[7] because glycerol (E 422) can be used in the manufacturing process of E 472c.
• Analytical data on the current levels of trans fatty acids in commercial samples of the food additive E 472c.
• Analytical data on current levels of glycidyl esters/glycidol and free and bound 3-MCPD in commercial samples of the food additive E 472c.
• Analytical data on current levels of erucic acid in commercial samples of the food additive E 472c.
• Analytical data on current levels of oxalates in commercial samples of the food additive E 472c.
• The lowest technologically achievable level for any potential impurities mentioned above, including any potential impurities resulting from changes in manufacturing process(es), in order to adequately define maximum limits in the EU specifications for the food additive E 472c.

The analyses should be performed on at least five independently produced batches of the food additive (as recommended in the Guidance for submission for food additive evaluations^[8]), with appropriate analytical methods applying state of the art techniques. The results of the analysis should be supported by certificates of analysis. In addition, information on the representativeness of the tested batches should be provided. Specific information on the methods of analysis used should be provided. This includes, but is not limited to, e.g. the principle of the method, the scope of the method (i.e. the range of sample types that the method is used for), the concentration units used to express the analytical result(s), validation of the method (in particular limit of detection (LOD) and quantitation (LOQ)).

2.  Toxicological data

• Available toxicological information should be provided to support the risk characterisation at the lowest technologically achievable level of any impurities of toxicological concern.

3. Literature searches

• Literature searches, from 01/01/2020 up to the date of the data submission, should be conducted relevant for the safety evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c) for all uses in foods for all population groups, as described in the Guidance for submission for food additive evaluations (section 5.3)^[8]

B.  Information required for the risk assessment of citric acid esters of mono- and diglycerides of fatty acids (E 472c) for uses as food additive in foods for infants below 16 weeks of age

1. Technical data
   For the uses of citric acid esters of mono- and diglycerides of fatty acids (E 472c), in foods for infants below 16 weeks (food categories 13.1.1 and 13.1.5.1) EFSA seeks:

• Information on the levels of citric acid esters of mono- and diglycerides of fatty acids (E 472c) alone or in combination with the food additives E 322, E 471 and E 473. In the case of use in combination, the name and levels of the food additive(s) used together with E 472c should be provided.
• Information on the fate and the reaction products of citric acid esters of mono- and diglycerides of fatty acids (E 472c) in these foods.
• Proposals for particular EU specification requirements for identity and purity of citric acid esters of mono- and diglycerides of fatty acids (E 472c) when used in these food categories.

2. Toxicological data
   Within the frame of the EFSA Guidance of the Scientific Committee on the risk assessment of substances present in food intended for infants below 16 weeks of age^[5] the following information on the toxicological properties of citric acid esters of mono- and diglycerides of fatty acids (E 472c) and its adverse effects relevant for its use in food categories for infants below 16 weeks of age (13.1.1 and 13.1.5.1.) is required:

• Information to demonstrate that the metabolism of E 472c in infants below 16 weeks of age is comparable to the metabolism in adult i.e. it can be expected that E 472c is extensively hydrolysed in the infants’ gastrointestinal tract and/or (pre)systemically after absorption into its individual hydrolysis products which are all normal dietary constituents and are metabolised or excreted intact, see also EFSA FAF Panel (2020)^[3].
• Comparative data to demonstrate that the exposure in infants to fatty acids through infant formulae containing E 472c is comparable to the exposure to fatty acids through breast milk.  
  
  If it cannot be demonstrated that the metabolism of E 472c in infants is comparable to the metabolism in adults and that the exposure to fatty acids in infants from breast milk and infant formulae are comparable, additional toxicological data should be provided i.e. a repeated dose study with direct oral administration of E 472c to neonatal animals. The study shall be performed in piglets unless justification for the relevance of a study in another species is given.
  
  Additionally, the following information is required:
• Any available clinical data to assess the safety of citric acid esters of mono- and diglycerides of fatty acids (E 472c) in the relevant age group.
• Post-marketing surveillance reports on undesired and adverse reactions, indicating the ages and other relevant data of the exposed infants and young children and the use levels in the marketed products.
• Published and unpublished case reports (e.g. available nutrivigilance data) on undesired and adverse effects, associated with the oral administration of citric acid esters of mono- and diglycerides of fatty acids (E 472c) to infants and young children.

3. Literature searches

• Literature searches relevant for the safety evaluation of citric acid esters of mono- and diglycerides of fatty acids (E 472c) when used in foods for infants below 16 weeks of age, should be conducted as described in the Guidance for submission for food additive evaluations (section 5.3)^[8].

Confidentiality

In accordance with Article 8 of Regulation (EU) No 257/2010 setting up a re-evaluation programme of approved food additives, confidential treatment may be given to information the disclosure of which might significantly harm the competitive position of business operators or other interested parties.

Therefore, data providers should indicate any information they wish to be treated as confidential and provide verifiable justification supporting this request. Please also note that the information described in Article 8(2) of Regulation (EU) No 257/2010 cannot be regarded as confidential in any circumstances.

In application of Article 8(4) of Regulation (EU) 257/2010, following a proposal from EFSA, the Commission will decide after consulting the interested business operator and/or the other interested parties, which information may remain confidential.

Submission of information

Interested business operators and/or interested parties should submit the information to EFSA through their chosen internet-based software (submission by email is not allowed) with

• a cover letter that should contain:
  • Reference to the specific call and the specific EFSA question number indicated (EFSA-Q-2021-00674);
  • Reference to the substance concerned and its E number;
  • The contact details^[9] (name of contact person, name of company/organisation, e-mail address and telephone number) of the person responsible for the data submission and, if applicable, the list of interested business operators and/or interested parties represented and their contact details;
• a statement of the submitter that they hold all the necessary rights to grant EFSA per-mission to use and, where appropriate, to disclose the submitted information, data, document, paper or study for the purposes better defined in this call. In case the submitter does not enjoy such rights for the submitted subject matter, they should share the contact details of the respective owner(s) of data and/or the holder(s) of any relevant intellectual property rights, so that EFSA may seek their approval directly.
• separate folders with the confidential and with the non-confidential parts.

Possibility for EFSA to use the data for the safety assessment of the same or other substance under the same or other legal or regulatory frameworks.

In case future mutual interests arise in exchanging any relevant information (i.e. technical or toxicological data) with the Joint WHO – FAO Expert Committee on Food Additives (JECFA) for the re-evaluation of food additives, we would appreciate your written consent for data sharing between EFSA and JECFA on this additive.

Please note that EFSA may, where legally possible, use or re-use relevant information or data (i.e. technical, toxicological data) for the evaluation of the same or another substance under the same or a different legal or regulatory framework from the one mentioned above.

Correspondence

Once internet-based software chosen please kindly send the link and login to RAL [at] efsa.europa.eu (RAL[at]efsa[dot]europa[dot]eu). If a password is needed, kindly send it to the same email address in a separate email.