Assessment of the feed additives thiamine hydrochloride (3a820) and thiamine mononitrate (3a821) (vitamin B1 ) for all animal species for the renewal of their authorisation (Kaesler Nutrition GmbH)

TL;DR

This paper assesses the safety of two forms of vitamin B1 for use in animal feed and concludes they are safe for animals, consumers, and the environment.

Contribution

The paper provides a renewed safety evaluation of thiamine hydrochloride and thiamine mononitrate for use in animal feed.

Findings

Thiamine mononitrate and thiamine hydrochloride are safe for all animal species.

Both additives are irritants to skin and eyes and can cause sensitization.

No efficacy assessment was needed for the renewal of authorization.

Abstract

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of thiamine hydrochloride and thiamine mononitrate (vitamin B1) for the renewal of its authorisation as nutritional feed additives for all animal species. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that thiamine mononitrate and thiamine hydrochloride remain safe for all animal species, consumers and the environment. Regarding the user safety, both thiamine salts are regarded as skin and eye irritants, and skin and respiratory sensitisers. The Panel concluded there is no need for assessing the efficacy of the additives in the context of the renewal of the authorisation.

Tables

TABLE 1. Data on the batch‐to‐batch variation and impurities of thiamine hydrochloride.

Parameter	Specification	Analysis
		Average	Range	# batches
Batch‐to‐batch variation
Thiamine hydrochloride (% on dry matter basis) 1	98.5	99.86	99.70–100	8
Moisture (%)		3.03	2.57–3.43	8
Impurities
Sulphated ash (%)			0.01–0.03	8
Sulphates (mg/kg)			< 300	8
Impurity A (%) 2			< 0.05	5
Impurity B (%) 3			< 0.05	5
Impurity C (%) 4			< 0.05	5
Unspecified Impurities (%) 5			< 0.05	5
Total Impurities (%) 6			< 0.05	5
Residual solvents (mg/kg)
Ethanol			< 2.5	5
Methanol			35–139	5

TABLE 2. Physico‐chemical properties of thiamine hydrochloride.

Physical properties	Range	No. of batches
Physical form	Solid
Density (kg/m3)	270–300	5
Dusting potential (Stauber Heubach) (mg/m3)	4800–5500	3
Stability (% recovery)
Shelf‐life
Room temperature, 6 months	99.7–102.0	3
Stability in premixtures
Room temperature, 6 months	66–73	3
Stability in feed
Mash, room temperature 3 months	71–80	3
Pelleting 75°C	97–100	3
Pelleted, room temperature, 3 months	92–94	3
Stability in water
0.2% thiamine hydrochloride, 20°C, 48 h	148–192	3
Homogeneity (coefficient of variation, %)
Feed, 0.2% thiamine hydrochloride	3.2	1

TABLE 3. Data on the batch‐to‐batch variation and impurities of thiamine mononitrate.

Parameter	Specification	Analysis
		Average	Range	No. of batches
Batch‐to‐batch variation
Thiamine mononitrate 1 (% on dry matter basis)	98	99.85	99.70–100	8
Loss on drying (%)		0.11	0.07–0.15	8
Impurities
Sulphated ash (%)			0.01–0.04	8
Chloride (mg/kg)			< 0.06	8
Impurity A (%) 2			0.11–0.12	5
Impurity B (%) 3			< 0.05	5
Impurity C (%) 4			< 0.05	5
Unspecified impurities (%) 5			< 0.05	5
Total Impurities (%) 6			0.11–0.12	5
Residual solvents (mg/kg)
Methanol			< 4.5–6	5

TABLE 4. Physico‐chemical properties of thiamine mononitrate.

Physical properties	Range	#batches
Physical form	Solid
Density (kg/m3)	300–330	5
Dusting potential (Stauber Heubach) (mg/m3)	14,600‐16,900	3
Stability (% recovery)
Shelf‐life
Room temperature, 6 months	101–108	3
Stability in premixtures
Room temperature, 6 months	93–106	3
Stability in feed
Mash, room temperature, 3 months	78–95	3
Pelleting 75°C	93–100	3
Pelleted, room temperature, 3 months	97–107	3
Stability in water
0.2% thiamine mononitrate, 20°C, 48 h	155–170	3
Homogeneity (coefficient of variation, %)
Feed, 0.2% thiamine mononitrate	5.9	1

Full text

INTRODUCTION

1

Background and Terms of Reference

1.1

Regulation (EC) No 1831/20031 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 14(1) of that Regulation lays down that an application for renewal shall be sent to the Commission at the latest one year before the expiry date of the authorisation.

The European Commission received a request from Kaesler Nutrition GmbH2 for the renewal of the authorisation of thiamine hydrochloride (3a820) and thiamine mononitrate (3a821), when used as feed additives for all animal species (category: nutritional additives; functional group: vitamins, pro‐vitamins and chemically well‐defined substances having similar effect).

According to Article 7(1) of Regulation (EC) No 1831/2003, the Commission forwarded the application to the European Food Safety Authority (EFSA) as an application under Article 14(1) (renewal of the authorisation). The dossier was received on 08 July 2024 and the general information and supporting documentation are available at https://open.efsa.europa.eu/questions/EFSA‐Q‐2024‐00449. The particulars and documents in support of the application were considered valid by EFSA as of 7 Nov 2024.

According to Article 8 of Regulation (EC) No 1831/2003, EFSA, after verifying the particulars and documents submitted by the applicant, shall undertake an assessment in order to determine whether the feed additive complies with the conditions laid down in Article 5. EFSA shall deliver an opinion on the safety for the target animals, consumer, user and the environment and on the efficacy of the feed additives consisting of thiamine hydrochloride (3a820) and thiamine mononitrate (3a821), when used under the proposed conditions of use (see Section 3.1.3).

Additional information

1.2

The additives thiamine hydrochloride (3a820) and thiamine mononitrate (3a821) are currently authorised3 for use in feed for all animal species as nutritional additives. Thiamine hydrochloride is also authorised as a flavouring compound in feed for all animal species (2b16027).4

EFSA issued three opinions on the safety and efficacy of vitamin B_1_ as thiamine mononitrate and as thiamine hydrochloride when used as nutritional additives in feed for all animal species (EFSA FEEDAP Panel, 2011a, 2011b, 2011c).

DATA AND METHODOLOGIES

2

Data

2.1

The present assessment is based on data submitted by the applicant in the form of a technical dossier5 in support of the authorisation request for the use of thiamine hydrochloride (3a820) and thiamine mononitrate (3a821) as feed additives.

In accordance with Article 38 of the Regulation (EC) No 178/20026 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 of the Decision of EFSA's Executive Director laying down practical arrangements concerning transparency and confidentiality,7 a non‐confidential version of the dossier has been published on Open.EFSA.

According to Article 32c(2) of Regulation (EC) No 178/2002 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 06 March to 27 March 2025 for which no comments were received.

The confidential version of the technical dossier was subject to a target consultation of the interested Member States from 12 November 2024 to 12 February 2025; the comments received were considered for the assessment.

The FEEDAP Panel used the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA or other expert bodies, peer‐reviewed scientific papers, other scientific reports and experts' (elicitation) knowledge, to deliver the present output.

The European Union Reference Laboratory (EURL) considered that the conclusions and recommendations reached in the previous assessment regarding the methods used for the control of the thiamine hydrochloride (3a820) and thiamine mononitrate (3a821) in animal feed are valid and applicable for the current application.8

Methodologies

2.2

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of thiamine hydrochloride and thiamine mononitrate is in line with the principles laid down in Regulation (EC) No 429/20089 and the relevant guidance document: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2021).

ASSESSMENT

3

Vitamin B_1_ is currently authorised in the form of thiamine hydrochloride and thiamine mononitrate as nutritional additives for use in feed and water for drinking for all animal species. The present application is for the renewal of the above authorisations.

Characterisation

3.1

Thiamine hydrochloride and thiamine mononitrate are produced by chemical synthesis, and they appear as white or almost white to pale yellow crystalline powders or small crystals. Thiamine hydrochloride is used as such while thiamine mononitrate may be used in the form of a preparation.10

Thiamine hydrochloride

3.1.1

Thiamine hydrochloride (IUPAC name 3‐[(4‐amino‐2‐methylpyrimidin‐5‐yl)methyl]‐5‐(2‐hydroxyethyl)‐4‐methylthiazolium chloride hydrochloride) has the EINECS number 200‐641‐8, the CAS number 67‐03‐8, a molecular formula C_12_H_17_N_4_OS^+^Cl^−^•HCl and a molecular weight of 337.3 g/mol.

Thiamine hydrochloride is authorised as a solid product, produced by chemical synthesis with a minimum purity of 98.5% on anhydrous basis.

The applicant stated that the manufacturing processes remained unchanged since the previous authorisation.11

The data provided by the applicant on the batch‐to‐batch variation and impurities12 of the additive are reported in Table 1 and the physico‐chemical properties13 in Table 2.

The data provided by the applicant showed that residual solvents are below the limits set by the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) Guideline (EMA, 2023), and therefore are considered to be in compliance with the specifications set in the Regulation (EU) No 2015/897. The Panel notes that the levels of the substance‐related impurities comply with the limits of the PhEur (European Pharmacopoeia (PhEur), 2025a). The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.

Considering that the composition and the manufacturing of the additive has not been modified, the data on the physico‐chemical properties already evaluated in the previous opinions are considered to still apply (EFSA FEEDAP Panel, 2011a, 2011c). The applicant provided new data on the density, dusting potential and stability which are reported in Table 2.

The FEEDAP Panel notes the unrealistically high recoveries in the stability studies in water.

Thiamine mononitrate

3.1.2

Thiamine mononitrate (IUPAC name 3‐[(4‐amino‐2‐methylpyrimidin‐5‐yl)methyl]‐5‐(2‐hydroxyethyl)‐4‐methylthiazolium nitrate, synonyms: vitamin B 1, aneurine) is identified by the CAS number 532‐43‐4 and the EINECS number 208‐537‐4. The molecular formula of thiamine mononitrate is C_12_H_17_N_4_OS•NO_3_, and its molecular weight is 327.36 g/mol.

Thiamine mononitrate is authorised as a solid product, produced by chemical synthesis with a minimum purity of 98%, on anhydrous basis.

The applicant stated that the manufacturing processes remained unchanged since the previous authorisation.

The data provided by the applicant on the batch‐to‐batch variation and impurities14 of thiamine mononitrate are reported in Table 3, while the physico‐chemical properties15 are reported in Table 4.

The data provided by the applicant showed compliance with the specifications set in the Regulation (EU) 2015/897. The Panel notes that the levels of the substance‐related impurities comply with the limits of the PhEur (European Pharmacopoeia (PhEur), 2025b) and those of residual solvents are below the limits set by VICH Guideline (EMA, 2023). The FEEDAP Panel considers that the amounts of the detected impurities do not raise safety concerns.

Considering that the composition and the manufacturing of the additive has not been modified, the data on the physico‐chemical properties already evaluated in the previous opinions are considered to still apply (EFSA FEEDAP Panel, 2011a, 2011c). The applicant provided new data on the density, dusting potential and stability which are reported in Table 4.

The FEEDAP Panel notes the unrealistically high recoveries in the stability studies in water.

The current authorisation states that thiamine mononitrate may be placed on the market and used as an additive consisting of a preparation. The applicant provided an example of a preparation in which amorphous silicon dioxide is added up to 0.8%. However, no data on the characterisation of this preparation was submitted although requested.

Conditions of use

3.1.3

Thiamine hydrochloride and thiamine mononitrate are authorised for use in feed for all animal species and categories without a minimum or maximum content.

Under other provisions of the two authorisations, it is stated the following.

1. In the directions for use of the additive and premixture, indicate the storage and the stability conditions.
2. Thiamine hydrochloride/thiamine mononitrate may be used via water for drinking.
3. For safety: breathing protection, safety glasses and gloves shall be worn during handling.

In addition, for thiamine mononitrate:

• 4Thiamine mononitrate may be placed on the market and used as an additive consisting of a preparation.

The applicant did not request any change in the current conditions of the authorisation.

Safety

3.2

The safety of vitamin B_1_ in the form of thiamine mononitrate and thiamine hydrochloride was evaluated in previous opinions (EFSA FEEDAP Panel, 2011a, 2011b, 2011c). The FEEDAP Panel concluded that the additives are safe for the target animals, for the consumers and for the environment. Regarding user safety, the Panel concluded that both thiamine salts should be regarded as skin and eye irritants, and skin and respiratory sensitisers.

The applicant stated that no incidents or accidents were reported16 with regard to the safety for the target animals, consumers, users and the environment since the additives were first authorised.

Extensive literature search

3.2.1

The applicant performed two extensive literature searches to provide evidence that the additive remains safe under the approved conditions for the target species, consumers, users and the environment.17 The first search covered the period 2010–2024 using the following databases: Scopus, Web of Science and the meta database of Wageningen University,18 and was intended to support all safety aspects. The second one was performed on the same databases with no time limits and was intended to support the safety for the target animals.19 The search protocol described the inclusion and exclusion criteria applied for the screening process. A total of 90 hits were considered for the screening and after applying the exclusion criteria, a total of 4 hits were considered eligible and relevant by the applicant for the safety of additive. The FEEDAP Panel assessed all the papers and concluded that none of them identified new information that would lead to reconsider its previous conclusions with regard to the safety for the target species, consumers, users and the environment.

Conclusion on the safety

3.2.2

Considering all the above, the FEEDAP Panel concludes that thiamine hydrochloride and thiamine mononitrate remain safe for the target species, consumers and the environment under the conditions of the authorisation. Regarding user safety, both thiamine salts are regarded as skin and eye irritants, and skin and respiratory sensitisers. Any exposure is considered a risk. These conclusions would apply, in principle, to any preparations produced with the thiamine mononitrate.

Efficacy

3.3

The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additives. Therefore, there is no need for assessing the efficacy of the additives in the context of the renewal of the authorisation.

Post‐market monitoring

3.4

The FEEDAP Panel considers that there is no need for specific requirements for a post‐market monitoring plan other than those established in the Feed Hygiene Regulation20 and Good Manufacturing Practice.

CONCLUSIONS

4

The applicant demonstrated that the additives currently in the market comply with the conditions of authorisation.

The use of thiamine hydrochloride and thiamine mononitrate in animal nutrition remains safe for the target species, the consumers and the environment under the approved conditions of use.

Regarding user safety, both thiamine salts are regarded as skin and eye irritants, and skin and respiratory sensitisers. Any exposure is considered a risk. These conclusions would apply, in principle, to any preparations produced with thiamine mononitrate.

There is no need for assessing the efficacy of the additives in the context of the renewal of the authorisation.

ABBREVIATIONSCASChemical Abstracts ServiceEINECSEuropean Inventory of Existing Chemical SubstancesELSExtensive Literature SearchEMAEuropean Medicines AgencyEURLEuropean Union Reference LaboratoryFEEDAPEFSA Scientific Panel on Additives and Products or Substances used in Animal FeedIUPACInternational Union of Pure and Applied ChemistryPhEurEuropean PharmacopoeiaVICHVeterinary International Conference on Harmonization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2024‐00449

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PANEL MEMBERS

Roberto Edoardo Villa, Giovanna Azimonti, Eleftherios Bonos, Henrik Christensen, Mojca Durjava, Birgit Dusemund, Ronette Gehring, Boet Glandorf, Maryline Kouba, Marta López‐Alonso, Francesca Marcon, Carlo Nebbia, Alena Pechová, Miguel Prieto‐Maradona, Ilen Röhe, and Katerina Theodoridou.