Updated safety evaluation of the food enzyme AMP deaminase from the non‐genetically modified Streptomyces murinus strain AE‐DNTS

TL;DR

This paper evaluates the safety of AMP deaminase, a food enzyme produced by Streptomyces murinus, and concludes it is safe for use in food manufacturing.

Contribution

The study provides a completed safety evaluation of AMP deaminase after addressing previous uncertainties with new data.

Findings

Genotoxicity tests showed no safety concerns.

A 90-day toxicity study in rats identified a no observed adverse effect level of 275 mg TOS/kg bw per day.

The margin of exposure is at least 275,000, indicating safety under intended use conditions.

Abstract

The food enzyme AMP deaminase (AMP aminohydrolase; EC 3.5.4.6) is produced with the non‐genetically modified Streptomyces murinus strain AE‐DNTS by Amano Enzyme Inc. In a previous evaluation, the Panel could not conclude on the safety of this food enzyme due to uncertainties on the characterisation of the food enzyme batches for commercialisation and the batch used in the toxicological studies. In this assessment, the Panel evaluated the new data provided by the applicant and completed the safety evaluation of this food enzyme. The food enzyme is intended to be used in two food manufacturing processes. Dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 0.001 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 275 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, results in a margin of exposure of at least 275,000. Based on the new data provided and the previous evaluation, the Panel concludes that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Tables

TABLE 1. Composition of the food enzyme preparation.

Parameters	Unit	Batches
		1 a	2 a	3 a	4 a , b	5 c
AMP deaminase activity	U/mg d	183,000	153,000	95,000	238,000	100,488
Protein	%	2.9	4.3	3.2	2.7	2.0
Ash	%	13.3	14.8	13.2	6.4	0.7
Water	%	5.0	3.4	2.4	5.9	94.0
Excipient ■■■■■	%	73.1	76.5	77.4	74.0	0
Total organic solids (TOS) e	%	8.6	5.3	7.0	13.7	5.3
AMP deaminase/TOS ratio	U/mg TOS	2,128,000	2,887,000	1,357,000	1,737,000	1,896,000

TABLE 2. Updated intended use and use level of the food enzyme preparation. 30

Food manufacturing process a	Raw material (RM)	Use level (mg TOS/kg RM) b
		Current evaluation b	Previous evaluation b , c
Processing of yeast and yeast products	Yeast biomass	Up to 14.1	2.4–7.1
Processing of plant‐ and fungal derived products
Production of mushroom extracts d	Dried mushrooms 31	Up to 14.1	2.4–7.1

TABLE 3. Summary of the estimated dietary exposure to food enzyme–TOS in six population groups.

Population group	Estimated exposure (mg TOS/kg body weight per day)
	Infants	Toddlers	Children	Adolescents	Adults	The elderly
Age range	3–11 months	12–35 months	3–9 years	10–17 years	18–64 years	≥ 65 years
Min–max mean (number of surveys)	0–0.0001 (12)	0–0.0006 (15)	0–0.0003 (19)	0–0.0002 (21)	0–0.0002 (22)	0–0.0002 (23)
Min–max 95th percentile (number of surveys)	0–0.0006 (11)	0.0001–0.0005 (14)	0.0001–0.0008 (19)	0–0.0004 (20)	0–0.0006 (22)	0–0.0010 (22)

TABLE 4. Qualitative evaluation of the influence of uncertainties on the dietary exposure estimate.

Sources of uncertainties	Direction of impact
Model input data
Consumption data: different methodologies/representativeness/underreporting/misreporting/no portion size standard	+/–
Use of data from food consumption surveys of a few days to estimate long‐term (chronic) exposure for high percentiles (95th percentile)	+
Possible national differences in categorisation and classification of food	+/–
Model assumptions and factors
Exposure to food enzyme–TOS was always calculated based on the recommended maximum use level	+
To estimate the intake of the food enzyme–TOS via its use in yeast processing, FoodEx categories covered not only yeast extracts, but also yeast cell walls.	+
To estimate the intake of the food enzyme–TOS via its use in the production of mushroom extracts, FoodEx categories covered specifically composite foods containing mushroom extracts.	+/–
Use of recipe fractions in disaggregation FoodEx categories	+/–
Use of technical factors in the exposure model	+/–

Full text

INTRODUCTION

1

Article 3 of the Regulation (EC) No 1332/20081 provides definition for ‘food enzyme’ and ‘food enzyme preparation’.

‘Food enzyme’ means a product obtained from plants, animals or microorganisms or products thereof including a product obtained by a fermentation process using microorganisms: (i) containing one or more enzymes capable of catalysing a specific biochemical reaction; and (ii) added to food for a technological purpose at any stage of the manufacturing, processing, preparation, treatment, packaging, transport or storage of foods.

‘Food enzyme preparation’ means a formulation consisting of one or more food enzymes in which substances such as food additives and/or other food ingredients are incorporated to facilitate their storage, sale, standardisation, dilution or dissolution.

Before January 2009, food enzymes other than those used as food additives were not regulated or were regulated as processing aids under the legislation of the Member States. On 20 January 2009, Regulation (EC) No 1332/2008 on food enzymes came into force. This Regulation applies to enzymes that are added to food to perform a technological function in the manufacture, processing, preparation, treatment, packaging, transport or storage of such food, including enzymes used as processing aids. Regulation (EC) No 1331/20082 established the European Union (EU) procedures for the safety assessment and the authorisation procedure of food additives, food enzymes and food flavourings. The use of a food enzyme shall be authorised only if it is demonstrated that:

• it does not pose a safety concern to the health of the consumer at the level of use proposed;
• there is a reasonable technological need;
• its use does not mislead the consumer.

All food enzymes currently on the European Union market and intended to remain on that market, as well as all new food enzymes, shall be subjected to a safety evaluation by the European Food Safety Authority (EFSA) and approval via an EU Community list.

Background and Terms of Reference as provided by the requestor

1.1

Background as provided by the European Commission

1.1.1

Only food enzymes included in the Union list may be placed on the market as such and used in foods, in accordance with the specifications and conditions of use provided for in Article 7(2) of Regulation (EC) No 1332/2008 on food enzymes.

An application has been introduced by the applicant “Amano Enzyme Inc.” for the authorisation of the food enzyme AMP deaminase from a non‐genetically modified strain of Streptomyces murinus (strain AE‐DNTS).

The food enzyme has been assessed by EFSA with an inconclusive opinion on 8 March 2023. The new application contains supplementary information to address the data gaps identified in the scientific opinion (EFSA‐Q‐2015‐00683).

Following the requirements of Article 12.1 of Regulation (EC) No 234/20113 implementing Regulation (EC) No 1331/2008, the Commission has verified that the application falls within the scope of the food enzyme Regulation and contains all the elements required under Chapter II of that Regulation.

Terms of Reference

1.1.2

The Commission requests the European Food Safety Authority (EFSA) to verify the requirements of Article 32b of Regulation (EC) No 178/2002, the suitability of the new data for risk assessment following the requirements of Article 12(2) of Regulation (EU) No 234/2011 and to carry out the safety assessment and the assessment of possible confidentiality requests on the new data only for the following food enzyme: AMP deaminase from a non‐genetically modified strain of Streptomyces murinus (strain AEDNTS) in accordance with Regulation (EC) No 1331/2008 establishing a common authorisation procedure for food additives, food enzymes and food flavourings.4

Interpretation of the Terms of Reference

1.2

The applicant submitted previously an application for AMP deaminase from the non‐genetically modified Streptomyces murinus strain AE‐DNTS, for which EFSA could not conclude on the safety, due to data gap (EFSA CEP Panel, 2023a).

As a follow‐up, the applicant submitted new data. The present opinion assesses the new studies provided and updates the safety evaluation of the food enzyme. Whenever previous evaluation remains unchanged, reference to the previous EFSA opinion is made.

DATA AND METHODOLOGIES

2

Data

2.1

The applicant has submitted a revised dossier in support of the application for authorisation of the food enzyme AMP deaminase from a genetically modified Streptomyces murinus (strain AE‐DNTS). New information, not present in the original application, were submitted and five new annexes were included.

Additional information, requested from the applicant during the assessment phase on 25 March 2024, 9 December 2024, and 10 September 2025 and was received on 31 October 2024, 30 May 2025 and 30 September 2025, respectively (see ‘Documentation provided to EFSA’).

Methodologies

2.2

The assessment was conducted in line with the principles described in the EFSA ‘Guidance on transparency in the scientific aspects of risk assessment’ (EFSA, 2009) and following the relevant guidance documents of the EFSA Scientific Committee.

The ‘Scientific Guidance for the submission of dossiers on food enzymes’ (EFSA CEP Panel, 2021) and the ‘Food manufacturing processes and technical data used in the exposure assessment of food enzymes’ (EFSA CEP Panel, 2023b) have been followed for the evaluation of the application.

Public consultation

2.3

According to Article 32c(2) of Regulation (EC) No 178/20025 and to the Decision of EFSA's Executive Director laying down the practical arrangements on pre‐submission phase and public consultations, EFSA carried out a public consultation on the non‐confidential version of the technical dossier from 07 November to 28 November 2024.6 No comments were received.

ASSESSMENT

3

IUBMB nomenclatureAMP deaminaseSystematic nameAMP aminohydrolaseSynonymsAMP aminase; adenylic acid deaminase; adenylate deaminaseIUBMB No3.5.4.6CAS No9025‐10‐9EINECS No–

AMP deaminases catalyse the deamination of adenosine 5′‐monophosphate (AMP) to produce 5′‐inosine monophosphate. The food enzyme under assessment is intended to be used in two food manufacturing processes: the processing of yeast and yeast products and the processing of plant‐ and fungal derived products for the production of mushroom extracts.

In the previous food enzyme application (EFSA‐Q‐2015‐00683), the food enzyme batches for commercialisation and the batch used for toxicological studies were not fully characterised. Therefore, the TOS values could not be reliably calculated. As a result, EFSA could not establish the representativeness of the batch used for toxicological examination and did not evaluate the toxicological studies (a bacterial reverse mutation assay, an in vitro mammalian chromosomal aberration test and a repeated dose 90‐day oral toxicity study in rodents). Consequently, the Panel could not conclude on the safety of the food enzyme (EFSA CEP Panel, 2023a).

As a follow‐up, the applicant provided additional information on the chemical composition of three food enzyme batches for commercialisation and the batch used for toxicological tests. Furthermore, a new enzyme batch was tested in an additional bacterial reverse mutation assay and in an in vitro micronucleus test. New analyses were also conducted to characterise the production strain and the purity of the food enzyme. In addition, the applicant updated the use levels. The present opinion assessed these new data provided in the application EFSA‐Q‐2023‐00559 and reaches conclusion on the safety of the food enzyme.

Source of the food enzyme

3.1

The AMP deaminase is produced with the non‐genetically modified bacterium Streptomyces murinus strain AE‐DNTS, which is deposited at ■■■■■, with the deposition number NITE SD 00438.7 The production strain was identified as S. murinus by ■■■■■.8 The production strain was derived from the parental strain by classical mutagenesis and selection.9

The WGS of the production strain was interrogated for the presence of antimicrobial resistance and virulence genes using maintained databases with thresholds of > 80% identity and > 70% coverage. ■■■■■.10 This gene is typically located near the oleandomycin biosynthetic gene cluster. However, none of the genes known to be involved in oleandomycin production were found in the genome of the production strain with significant sequence identity.11 ^,^ 12 No other genes involved in the production of known medically important antimicrobials were found in the genome of the production strain.13

Production of the food enzyme

3.2

See the previous evaluation (EFSA CEP Panel, 2023a).

Characteristics of the food enzyme

3.3

Properties of the food enzyme

3.3.1

See the previous evaluation (EFSA CEP Panel, 2023a).

Chemical parameters

3.3.2

Additional data were provided on the chemical parameters of the food enzyme preparation for the four batches that have already been submitted in the previous application (EFSA‐Q‐2015‐00683): three batches for commercialisation (Table 1, batches 1–3)14 and one batch for the repeated dose 90‐day oral toxicity study (Table 1, batch 4).15 In this follow‐up application, the applicant included a new batch of the food enzyme used to conduct a bacterial reverse mutation test and an in vitro micronucleus test (Table 1, batch 5).16 The mean total organic solids (TOS) of the three food enzyme batches intended for commercialisation was 7% and the mean enzyme activity/TOS ratio was 2,124,000 U/mg TOS.

Purity

3.3.3

Batches 1–4 (Table 1) complied with the chemical and microbiological specifications (see previous evaluation, EFSA CEP Panel, 2023a).

The lead content in the newly produced batch 5 (Table 1) was below 5 mg/kg17 ^,^ 18 which complies with the specification for lead as laid down in the general specifications for enzymes used in food processing (FAO/WHO, 2006).

The food enzyme batch 5 (Table 1) complies with the microbiological criteria for total coliforms, Escherichia coli and Salmonella, as laid down in the general specifications for enzymes used in food processing (FAO/WHO, 2006).19 No antimicrobial activity was detected in this batch.20

Three commercial batches were analysed for the presence of oleandomycin. No oleandomycin was detected in any of the tested batches.21 ^,^ 22

Adverse effects caused by the possible presence of other secondary metabolites are addressed by the toxicological examination of the food enzyme.

Viable cells of the production strain

3.3.4

The food enzyme was considered free of viable cells of the production organism (see previous evaluation, EFSA CEP Panel, 2023a).

Toxicological data

3.4

The representativeness of the test item could not be established in the previous evaluation, consequently, the Panel did not evaluate the three toxicological tests provided: a bacterial gene mutation assay (Ames test),23 an in vitro mammalian chromosomal aberration test24 and a repeated dose 90‐day oral toxicity study in rats25 (EFSA CEP Panel, 2023a), which had been conducted using batch 4, (Table 1).

In the context of the current application, EFSA requested an in vitro mammalian cell micronucleus test, and a new bacterial reverse mutation assay (Ames test) was spontaneously provided. The batch used in these toxicological tests was batch 5.

The batches 4 and 5 (Table 1) used in these studies have similar enzyme activity/TOS ratio as the batches used for commercialisation (batches 1–3, Table 1), and thus they are considered suitable as test items.

Following the establishment of the suitability of the test items, the Panel evaluated the newly provided bacterial reverse mutation test, the in vitro mammalian cell micronucleus test, and the previously submitted repeated dose 90‐day oral toxicity study.

Genotoxicity

3.4.1

Bacterial reverse mutation test

3.4.1.1

A bacterial reverse mutation test (Ames test) was performed according to the Organisation for Economic Co‐operation and Development (OECD) Test Guideline 471 (OECD, 2020), Notification No. 0920‐2 (JMHW, 2012) and following Good Laboratory Practice (GLP).26

Four strains of Salmonella Typhimurium (TA98, TA100, TA1535 and TA1537) and Escherichia coli WP2uvrA (pKM101) were used with or without metabolic activation (S9‐mix). A range‐finding test and two main experiments were performed applying the pre‐incubation method.

Based on the results from the range‐finding test, the main experiments were carried out in triplicate, using five concentrations of the food enzyme of 313, 625, 1250, 2500 and 5000 μg TOS/plate.

No cytotoxicity was observed at any concentration of the test substance.

Upon treatment with the food enzyme there was no biologically relevant increase in the number of revertant colonies above the control values, in any strain tested, with or without S9‐mix.

The study was considered reliable without restrictions and the results of high relevance.

The Panel concluded that the food enzyme AMP deaminase did not induce gene mutations under the test conditions applied in this study.

In vitro mammalian cell micronucleus test

3.4.1.2

The in vitro mammalian cell micronucleus test was carried out according to the OECD Test Guideline 487 (OECD, 2016), Notification No. 0920‐2 (JMHW, 2012) and following GLP.27 A range‐finding test and two separate experiments were performed with duplicate cultures of Chinese hamster lung cell line (CHL/IU). The cell cultures were treated with the food enzyme with or without metabolic activation (S9‐mix).

In a range‐finding test the 50% cell growth inhibition concentration (IC_50_) (based on relative increase in cell count (RICC)) was calculated to be at 741 and 784 μg TOS/mL in the short‐term treatment (6‐h exposure and 24‐h recovery period) with and without S9‐mix, respectively, and at 821 μg TOS/mL in a long‐term treatment (24‐h exposure without recovery period) without S9‐mix.

In the first experiment, cells were exposed to the food enzyme and scored for the frequency of binucleated cells with micronuclei (MNBN) at concentrations of 175, 350 and 700 μg TOS/mL in a short‐term treatment either with or without S9‐mix.

In the second experiment, cells were exposed to the food enzyme and scored for MNBN at concentrations of 200, 400 and 800 μg TOS/mL in a long‐term treatment without S9‐mix.

In the short‐term treatment, cytotoxicity of 44% and 19% (based on RICC) was observed at 700 μg TOS/mL, with and without S9‐mix, respectively. In the long‐term treatment cytotoxicity of 40% (based on RICC) was observed at concentration of 700 μg TOS/mL.

The frequency of MNBN was not statistically significantly different to the negative controls at all concentrations tested.

The study was considered reliable without restrictions and the results of high relevance.

The Panel concluded that the food enzyme AMP deaminase did not induce an increase in the frequency of MNBN under the test conditions applied in this study.

Repeated dose 90‐day oral toxicity study in rodents

3.4.2

The repeated dose 90‐day oral toxicity study was performed in accordance with Notifications Nos. 29 and 655 (JMHW, 1996, 1999) and following GLP.28 The study is in accordance with OECD Test Guideline 408 (OECD, 1998) with the following deviations: detailed clinical observations and functional observations were not performed, urea was not determined, epididymides were not weighed, and only two sections of the brain and one level of the spinal cord were examined by microscopy. The Panel considered that these deviations are minor and do not impact on the evaluation of the study.29

Groups of 12 male and 12 female Sprague–Dawley (Crl:CD(SD)) rats received by gavage the food enzyme in doses of 69, 138 or 275 mg TOS/kg body weight (bw) per day. Controls received the vehicle (water for injection).

No mortality was observed.

The body weight was statistically significantly increased on days 63, 73, 80, 84 and 87 of administration in low‐dose males (+9% at all time points). The Panel considered these changes as not toxicologically relevant as they were only observed in one sex, there was no dose–response relationship and the changes were small.

The feed consumption was statistically significantly increased on day 63 of administration in low‐dose males (+7%). The Panel considered the change as not toxicologically relevant as it was only observed in one sex, there was no dose–response relationship, and the change was small.

Haematological investigations revealed a statistically significant increase in the eosinophil count (+67%), in the monocyte percentage (+43%) and in the monocyte count (+62%) in low‐dose males. The Panel considered the changes as not toxicologically relevant as they were only observed in one sex and there was no dose–response relationship.

Clinical chemistry investigations revealed a statistically significant increase in total cholesterol (+40%) and phospholipids (+26%) in mid‐dose males, an increase in alanine aminotransferase in low‐dose females (+84%) and an increase in glucose in mid‐dose females (+15%). The Panel considered these changes as not toxicologically relevant as they were only observed in one sex and there was no dose–response relationship.

The urinalysis revealed a statistically significantly decreased osmolality in high‐dose males (−19%), and a decreased one‐day excretion of potassium in mid‐ and high‐dose males (−23%, −27%). The Panel considered these changes as not toxicologically relevant, as they were only observed in one sex, there were no changes in blood electrolytes and there were no histopathological changes in kidneys.

Statistically significant changes detected in organ weight were a decrease in the absolute testis weight in high‐dose males (−8%) and in the relative testis weight in all male groups (−12%, −9%, −11%), an increase in the absolute adrenal weight (+14%) in mid‐dose females, an increase in the absolute lung weight (+15%) and absolute kidney weight (+8%) in high‐dose females, a decrease in the relative brain weight (−10%) in low‐dose males, a decrease in the relative thyroid weight (−14%) in mid‐dose females and a decrease in the relative ovary weight (−19%) in low‐dose females. The Panel considered the changes as not toxicologically relevant, as they were small (testes, adrenals, lung, kidney, brain and thyroid), there were no histopathological changes in the organs (testes, adrenal, kidney, brain and thyroid), the changes were only observed in one sex (adrenal, lung, kidney, brain and thyroid) and there was no dose–response relationship (brain, adrenals, ovaries, thyroid).

The macroscopic examination revealed dark red areas in the lungs of mid‐ and high‐dose males (1/12, 1/12). The microscopic examination of the lungs revealed minimal to moderate inflammation in the terminal bronchi in mid‐ and high‐dose animals (males: 4/12, 8/12; females: 1/12, 5/12). This change was variably associated with perivascular inflammatory cell infiltration and hyperplasia of bronchiolar mucosa. The Panel considered these changes as procedure related and not adverse based on severity grades. The Panel concluded that these changes represented a local irritating effect following aspiration or regurgitation of the test item.

Moreover, minimal inflammatory cell infiltration of mucosa in the caecum (5/12) and colon (3/12) was observed in high‐dose females. The Panel considered these changes as not toxicologically relevant, as they were of the minimal severity and only observed in one sex.

No other statistically significant or toxicologically relevant differences from controls were reported.

The Panel identified a no observed adverse effect level (NOAEL) of 275 mg TOS/kg bw per day, the highest dose tested.

Allergenicity

3.4.3

See the previous evaluation (EFSA CEP Panel, 2023a).

Dietary exposure

3.5

The current dietary exposure supersedes Section 3.5 of the previous evaluation (EFSA CEP Panel, 2023a).

Revised intended use of the food enzyme

3.5.1

The food enzyme is intended to be used in the same two food manufacturing processes at the revised recommended use levels summarised in Table 2.

TABLE 2: Updated intended use and use level of the food enzyme preparation. 30

The Panel noted an increase in the use levels for both food manufacturing processes, when compared to the previously recommended levels. The applicant ascribes these changes to the availability of actual use levels from food manufacturers.32

Dietary exposure estimation

3.5.2

Chronic exposure to the food enzyme–TOS was calculated using the FEIM webtool33 by combining the maximum recommended use level with individual consumption data (EFSA CEP Panel, 2021). The estimation involved selection of relevant food categories and application of technical conversion factors (EFSA CEP Panel, 2023) together with the input data provided in Appendix C.

Table 3 provides an overview of the derived exposure estimates across all surveys. Detailed mean and 95th percentile exposure to the food enzyme–TOS per age class, country and survey, as well as contribution from each FoodEx category to the total dietary exposure are reported in Appendix A – Tables 1 and 2. For the present assessment, food consumption data were available from 48 dietary surveys (covering infants, toddlers, children, adolescents, adults and the elderly), carried out in 26 European countries (Appendix B). The highest dietary exposure was estimated to be 0.001 mg TOS/kg bw per day in the elderly at the 95th percentile.

Uncertainty analysis

3.5.3

In accordance with the guidance provided in the EFSA opinion related to uncertainties in dietary exposure assessment (EFSA, 2006), the following sources of uncertainties have been considered and are summarised in Table 4.

The conservative approach applied to estimate the dietary exposure to food enzyme–TOS, in particular assumptions made on the occurrence and use levels of this specific food enzyme, is likely to have led to an overestimation of the exposure.

Margin of exposure

3.6

In the previous evaluation, the margin of exposure was not calculated due to the shortcomings identified (EFSA CEP Panel, 2023a). In the current evaluation a comparison of the NOAEL (275 mg TOS/kg bw per day) identified from the 90‐day rat study with the derived exposure estimates of 0–0.0006 mg TOS/kg bw per day at the mean and from 0 to 0.001 mg TOS/kg bw per day at the 95th percentile resulted in a margin of exposure of at least 275,000.

CONCLUSIONS

4

Based on the new data provided and the evaluation of the data previously submitted, the Panel concluded that the food enzyme AMP deaminase produced with the non‐genetically modified Streptomyces murinus strain AE‐DNTS does not give rise to safety concerns under the intended conditions of use.

DOCUMENTATION AS PROVIDED TO EFSA

5

Follow‐up application for authorisation of AMP deaminase from the Streptomyces murinus AE‐DNTS in accordance with Regulation (EC) No 1331/2008. August 2023. Submitted by Amano Enzyme Inc.

Additional information. October 2024. Submitted by Amano Enzyme Inc.

Additional information. May 2025. Submitted by Amano Enzyme Inc.

Additional information. September 2025. Submitted by Amano Enzyme Inc.

ABBREVIATIONSAMPadenosine 5′‐monophosphatebwbody weightCASChemical Abstracts ServiceCEPEFSA Panel on Food Contact Materials, Enzymes and Processing AidsEINECSEuropean Inventory of Existing Commercial Chemical SubstancesFAOFood and Agricultural Organization of the United NationsFEIMFood Enzyme Intake ModelFEZEFSA Panel on Food EnzymesGLPGood Laboratory PracticeICinhibition concentrationIUBMBInternational Union of Biochemistry and Molecular BiologyJECFAJoint FAO/WHO Expert Committee on Food AdditivesJMHWJapanese Ministry of Health and WelfareLOQlimit of quantificationMNBNbinucleated cells with micronucleiMOEmargin of exposureNITENational Institute of Technology and EvaluationNOAELNo Observed Adverse Effect LevelOECDOrganisation for Economic Cooperation and DevelopmentRIICrelative increase in cell countRMraw materialSDS–PAGEsodium dodecyl sulfate–polyacrylamide gel electrophoresisTOStotal organic solidsWGSwhole genome sequencingWHOWorld Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00559

COPYRIGHT FOR NON‐EFSA CONTENT

EFSA may include images or other content for which it does not hold copyright. In such cases, EFSA indicates the copyright holder and users should seek permission to reproduce the content from the original source.

PANEL MEMBERS

José Manuel Barat Baviera, Claudia Bolognesi, Francesco Catania, Gabriele Gadermaier, Ralf Greiner, Baltasar Mayo, Alicja Mortensen, Yrjö Henrik Roos, Marize de Lourdes Marzo Solano, Henk Van Loveren, Laurence Vernis, and Holger Zorn.

LEGAL NOTICE

Relevant information or parts of this scientific output have been blackened in accordance with the confidentiality requests formulated by the applicant pending a decision thereon by EFSA. The full output has been shared with the European Commission, EU Member States (if applicable) and the applicant. The blackening may be subject to review once the decision on the confidentiality requests is adopted by EFSA and in case it rejects some of the confidentiality requests.

Supporting information

APPENDIX A: Dietary exposure estimates to the food enzyme–TOS in details