Call for data relevant to the genotoxicity assessment of the flavouring substance acetaldehyde [FL No. 05.001]

EFSA -Q-NUMBER: EFSA-Q-2025-00509
DEADLINE FOR SUBMISSION OF DATA: 31 DECEMBER 2027

Background

The use of flavourings in food is regulated under Regulation (EC) No 1334/2008 of the European Parliament and of the Council of 16 December 2008¹ on flavourings and certain food ingredients with flavouring properties for use in and on foods.

Acetaldehyde [FL No. 05.001] is an authorised flavouring substance in the European Union (EU). 
It was evaluated as a flavouring substance by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1997 (JECFA, 1999)². The Committee concluded that there were no health concerns regarding the use of acetaldehyde as a flavouring substance, but genotoxicity data were not assessed at that time. In line with the provision of Commission Regulation (EC) No 1565/2000³, on the basis of the conclusions of the JECFA evaluation, the substance was included in the Union list of flavourings, i.e. Annex I of Regulation (EC) 1334/2008.

In 2023, in the context of the EFSA’s renewal opinions on smoke flavouring primary products SF-002, SF-005 and SF-006, concerns were raised about the genotoxic potential of several components present in the primary products assessed, including acetaldehyde (EFSA FAF Panel, 2023a⁴, EFSA FAF Panel, 2023b⁵, EFSA FAF Panel, 2023c⁶). With respect to acetaldehyde, in its assessment, EFSA noted that experimental genotoxicity data had been already evaluated by ECHA (ECHA, 2016)⁷, leading to an EU harmonized classification of the substance under Regulation (EC) No 1272/2008, as ‘Muta 2’ (i.e., substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans) and ‘Carc 1B’ (i.e. presumed to have carcinogenic potential for humans , largely based on animal evidence). Based on these data, EFSA considered that there was the potential for direct genotoxicity in vivo of acetaldehyde at the site of contact tissues and concluded that:

“…based on the experimental data acetaldehyde is genotoxic in vitro and in vivo following its intraperitoneal (ip) administration. These findings would require in vivo genotoxicity studies following oral administration. These studies should address gene mutations and structural and numerical chromosomal aberrations in particular at the site of contact, (…)”.

In view of this conclusion and considering that acetaldehyde is an authorised flavouring substance in the EU, in September 2025 the European Commission requested the European Food Safety Authority (EFSA) to carry out an evaluation of the flavouring substance acetaldehyde, [FL No. 05.001] in relation to genotoxicity (EFSA-Q-2025-00509)⁸.

In particular, the European Commission asked EFSA:

• to issue a call for the relevant required data 
• taking into account the data submitted, to evaluate the substance acetaldehyde [FL No. 05.001] in relation to genotoxicity and advise on its safety when used as flavouring substance.

This mandate has been assigned to the EFSA Panel on Food Additive and Flavourings (FAF) supported by its Working Group (WG) on Flavourings and by the cross-cutting Scientific Committee Working Group on Genotoxicity and the evaluation process is ongoing.

As part of EFSA’s commitment to transparency and stakeholder engagement, on 6 February 2026, EFSA organised a public stakeholder meeting on acetaldehyde⁹ to share preliminary considerations of the FAF Panel on the existing information related to the genotoxicity of acetaldehyde, explore availability of additional information, and clarify timelines for data availability in relation to the assessment schedule.

During the stakeholder meeting, the International Organisation of the Flavour Industry (IOFI) delivered a presentation¹⁰ outlining an industry study plan intended to generate data that may support the genotoxicity assessment of acetaldehyde when used as a flavouring substance.

Overall objective

The purpose of this call for data is to offer interested parties (e.g. food business operators, national food authorities, research institutions, academia) and/or other stakeholders, the opportunity to submit additional data (published, unpublished or newly generated) relevant to the evaluation of the genotoxicity of acetaldehyde [FL no: 05.001] when used as a flavouring substance.

EFSA’s preliminary considerations on acetaldehyde genotoxicity assessment

As outlined by EFSA during the stakeholder meeting on acetaldehyde held on 6 February 2026, acetaldehyde raises a potential concern for genotoxicity (i.e. gene mutations and chromosomal aberrations) in vivo, after the oral route, which is relevant to the currently permitted use as a flavouring substance. The main concerns currently identified by EFSA in relation to the genotoxicity of acetaldehyde are summarised below.

As described in ECHA’s RAC Opinion on acetaldehyde (ECHA, 2016)⁷ supporting the harmonised classification of the substance as ‘Muta 2’, acetaldehyde showed positive results in several in vitro genotoxicity tests. It induces gene mutations in different mammalian cell systems, and there is evidence that the substance is clastogenic in vitro. Acetaldehyde also induces DNA strand breaks, DNA adducts and DNA–protein crosslinks in both rodent and human cells.

With regard to the assessment of in vivo genotoxicity via the oral route, limited evidence is currently available, none of which directly investigating gene mutations and chromosomal aberrations at the site of contact following oral exposure.

Albeit limited, however, the available data raise concerns about the potential genotoxicity of acetaldehyde under specific conditions. In particular, Kunugita et al. (2008)¹¹, as cited in ECHA’s RAC Opinion on acetaldehyde, reported genotoxic effects in vivo in Aldh2–/– knockout mice following oral exposure, whereas no such effects were observed in wild-type mice. Aldh2–/– knockout mice lack a functional aldehyde dehydrogenase 2 (ALDH2) enzyme, which plays a key role in the detoxification of acetaldehyde to acetic acid. The positive findings in these knockout mice highlight the genotoxic potential of acetaldehyde when detoxification capacity is impaired.

The findings from this study indicate that ALDH2-deficient individuals, i.e. individuals with reduced or absent ALDH2 enzymatic activity, may be more susceptible to the genotoxic effects of acetaldehyde exposure because of their reduced capacity to metabolise acetaldehyde effectively, both at site-of-contact tissues (e.g. the buccal cavity, oesophagus) and systemically.

EFSA is also concerned about the potential genotoxicity of acetaldehyde in the general population, including in individuals without ALDH2 deficiency, when acetaldehyde comes into contact with tissues that naturally express low levels of detoxifying enzymes, such as site-of-contact tissues. Accumulation of acetaldehyde in such tissues may increase genotoxic risk because of insufficient local detoxification, even in individuals with normal ALDH2 activity.

In addition to the genotoxicity concern, the substance is also classified as ‘Carc 1B’, i.e. presumed to have carcinogenic potential for humans, based on evidence of carcinogenicity available from animal studies, particularly the induction of malignant tumours at site-of-contact tissues (i.e. in the respiratory tract), following inhalation exposure (ECHA, 2016)⁷.

Type of information and data sought

Acetaldehyde represents one of those cases, described in the EFSA’s Scientific Committee Scientific Opinion on the clarification of some aspects related to genotoxicity assessment (EFSA SC, 2017)¹² referring to regulated ‘old’ substances that have undergone assessment and approval in the past under provisions not reflecting the current state of scientific development or current data requirements. 

For the present genotoxicity assessment, the FAF Panel acknowledges uncertainties in the evaluation of the genotoxic potential of acetaldehyde at site-of-contact tissues following oral exposure. These are primarily related to methodological constraints associated with the validated testing methods included in the testing strategy recommended by the EFSA Scientific Committee (EFSA SC, 2011)¹³. In particular, these include the absence of validated assays for detecting chromosomal aberrations in the gastrointestinal tract and the cross-linking properties of the substance, which limit the applicability and interpretability of any comet assay.

In line with the recommendations of the EFSA Scientific Committee in its 2017 opinion12, a documented weight-of-evidence approach should therefore be applied to the evaluation and interpretation of genotoxicity data, taking into account not only the quality and availability of the genotoxicity data themselves, but also all other relevant information that may be available. Where the available genotoxicity studies do not allow a conclusion to be drawn with sufficient confidence, i.e. where a high level of uncertainty remains, all available information that may reduce that uncertainty should be considered.

Considering the above, EFSA is launching this open call for data to gather all relevant available information and any newly generated data addressing the concerns outlined above under “EFSA’s concerns on acetaldehyde genotoxicity”, with a view to supporting a comprehensive weight-of-evidence assessment of the genotoxic potential of acetaldehyde when used as a flavouring substance.

This call reflects EFSA’s scientific and regulatory commitment to ensuring consumer protection and to promoting transparency and stakeholder involvement in the risk assessment process. 

Deadlines for submission of data and disclosure of contact details

Interested parties and stakeholders should submit the relevant data to support the safety assessment of the flavouring substance acetaldehyde [FL-no: 05.001] in relation to genotoxicity, by 31 December 2027.

Within 4 weeks from the publication of this call, please communicate in writing by e-mail to: RAL [at] efsa.europa.eu, your availability to submit the relevant information by the timeline specified above.

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 parties to provide the data needed, we are seeking your consent to disclose the name and address of your organisation/business to the other parties that has 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.

Confidentiality

In order to comply with its requirements for proactive transparency, EFSA must, inter alia, make public the information on which its scientific outputs are based, as outlined in Article 38(1)(d) of Regulation (EC) No 178/2002¹⁴, the “General Food Law” (GFL) and Article 6(1)(i) of EFSA’s Practical Arrangements concerning transparency and confidentiality (“EFSA’s Practical Arrangements”). Information/data received in the context of the present call are subject to the afore-mentioned proactive transparency requirements insofar as they will constitute information on which scientific outputs, including scientific opinions, are based. 

However, in accordance with Articles 39-39(e) of the GFL confidential status may be awarded to information the disclosure of which might potentially harm the information owner to a significant degree. Provided that the conditions set out in Articles 39-39(e) and further detailed in EFSA’s Practical Arrangements are satisfied, EFSA must not make public any information/data for which confidential treatment has been requested and duly justified pending its confidentiality assessment where urgent action is essential to protect human health, animal health or the environment.
As mentioned above, EFSA’s proactive transparency obligations require publication of any data used in EFSA’s Scientific Outputs.  To ensure compliance with EFSA’s transparency requirements and avoid possible disclosure of confidential information interested parties may claim:

1. Confidentiality Requests for Personal Data and CBI
If your submission includes Personal Data (e.g.  name and surname, email address) or Confidential Business Information (CBI) (e.g. commercial links to producers, information revealing sourcing, market shares or business strategy, the manufacturing/production process), please: 
•    Submit via Portalino both a confidential version (in which confidential information has been earmarked but remains visible) and a non-confidential version (in which confidential information has been irreversibly redacted) of the completed form.  
•    Submit via Portalino a separate confidentiality request for each part of your data that you want to claim confidential, using applicable legal grounds listed below.
You may claim confidentiality provided that:
i.    the information falls within the scope of the closed list of information items listed in the Annex to EFSA’s Practical Arrangements and
ii.    the confidentiality request is accompanied by a verifiable justification that demonstrates how the public disclosure of the information/data for which confidential status is requested would harm your interests to a significant degree. 
iii.    When claiming confidentiality for some of the information/data, both a non-confidential (public dissemination) and a confidential version of the information/data must be submitted as indicated here. A separate confidentiality request must be submitted for each document and for each legal ground under which information is claimed confidential. A precise description of the information/data claimed confidential must be provided to enable a clear identification and the information/data claimed confidential must be earmarked in the confidential version and redacted in the non-confidential version.

For submissions which do not contain any confidential information, only a non-confidential (public dissemination) version needs be uploaded to Portalino. Additional information can be found in the User Guide on Confidentiality.

2. Portalino Registration Process
To submit data via Portalino, follow these steps:
1.    Register in Connect.EFSA using this form
2.    Create a profile in Portalino by sending an email to servicedesk [at] efsa.europa.eu with the following info:
a.    scope: Call for data on acetaldehyde EFSA-Q-2025-00509
b.    full name, business/personal email
c.    in the heading of the email please insert: Call for data on acetaldehyde EFSA-Q-2025-00509
Note: Registration may take a few days, so we encourage you to start the process immediately to meet the deadline. When accessing Portalino, you will use the email and log-in info created by EFSA during the steps above (e.g. ending with “@net.efsa.europa.eu”).

Submission of information/data

Interested business operators and/or parties should submit the information/data in electronic format exclusively via the tool Submission Builder “Portalino”.
Submission of data in any other form (email, third party e-submission platforms, etc) will not be accepted. 
Interested business operators and/or interested parties should submit the following information to EFSA via Portalino, clearly stating: 
•    in the Subject of the submission: Call for data on acetaldehyde EFSA-Q-2025-00509 
•    The contact details (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.

Information on how to use Portalino is available here.

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

Correspondence

Please address any enquiries to RAL [at] efsa.europa.eu (RAL[at]efsa[dot]europa[dot]eu). 

Please remember to indicate in the title of your email: Call for data on acetaldehyde EFSA-Q-2025-00509.

Footnotes

[1] Regulation (EC) No 1334/2008 of the European Parliament and of the Council of 16 December 2008 on flavourings and certain food ingredients with flavouring properties for use in and on foods and amending Council Regulation (EEC) No 1601/91, Regulations (EC) No 2232/96 and (EC) No 110/2008 and Directive 2000/13/EC. OJ L 354, 31.12.2008, pp. 34–50.

[2] https://iris.who.int/server/api/core/bitstreams/17dbd08f-55c7-4978-a974-5565113d9eee/content

[3] Commission Regulation (EC) No 1565/2000 of 18 July 2000 laying down the measures necessary for the adoption of an evaluation programme in application of Regulation (EC) No 2232/96 of the European Parliament and of the Council. OJ L 180, 19.7.2000, pp. 8–16

[4] https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8364

[5] https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8367

[6] https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8368

[7] ECHA (European Chemicals Agency), 2016. Opinion of the committee for risk assessment on the proposal for the harmonised classification and labelling at EU level; acetaldehyde; ethanal. Available online: https://echa.europa.eu/documents/10162/0dae8db6-8f8c-428d-b591-7e5f04fc6b08

[8] https://open.efsa.europa.eu/questions/EFSA-Q-2025-00509

[9] Stakeholders Meeting on Acetaldehyde | EFSA

[10] https://www.efsa.europa.eu/sites/default/files/2026-02/IOFI%20presentation.pdf

[11] Kunugita N, Isse T, Oyama T, Kitagawa K, Ogawa M, Yamaguchi T, et al. Increased frequencies of micronucleated reticulocytes and T-cell receptor mutation in Aldh2 knockout mice exposed to acetaldehyde. J Toxicol Sci. 2008;33(1):31-6.

[12] EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst KI, Mosesso P, Nielsen E, van Benthem J, Carfì M, Georgiadis N, Maurici D, Parra Morte J and Schlatter J, 2017. Scientific Opinion on the clarification of some aspects related to genotoxicity assessment. EFSA Journal 2017;15(12):5113, 25 pp. https://doi.org/10.2903/j.efsa.2017.5113

[13] EFSA Scientific Committee; Scientific Opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA Journal2011;9(9):2379. [69 pp.] doi:10.2903/j.efsa.2011.2379  

[14] Regulation (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 Official Journal L 031, 01/02/2002 P. 0001 – 0024