# L_2021147EN.01000801.xml

| 30.4.2021 | EN | Official Journal of the European Union | L 147/8 |
| --- | --- | --- | --- |

30.4.2021

EN

Official Journal of the European Union

L 147/8

---

COMMISSION IMPLEMENTING REGULATION (EU) 2021/709

of 29 April 2021

concerning the authorisation of L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 as a feed additive for all animal species

(Text with EEA relevance)

THE EUROPEAN COMMISSION,

Having regard to the Treaty on the Functioning of the European Union,

Having regard to Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition (1), and in particular Article 9(2) thereof,

Whereas:

| (1) | Regulation (EC) No 1831/2003 provides for the authorisation of additives for use in animal nutrition and for the grounds and procedures for granting such authorisation. |
| --- | --- |

(1)

Regulation (EC) No 1831/2003 provides for the authorisation of additives for use in animal nutrition and for the grounds and procedures for granting such authorisation.

| (2) | In accordance with Article 7 of Regulation (EC) No 1831/2003 an application was submitted for the authorisation of L-histidine monohydrochloride monohydrate. The application was accompanied by the particulars and documents required under Article 7(3) of that Regulation. |
| --- | --- |

(2)

In accordance with Article 7 of Regulation (EC) No 1831/2003 an application was submitted for the authorisation of L-histidine monohydrochloride monohydrate. The application was accompanied by the particulars and documents required under Article 7(3) of that Regulation.

| (3) | The application concerns the authorisation of L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 as a feed additive for all animal species, to be classified in the category ‘nutritional additives’. |
| --- | --- |

(3)

The application concerns the authorisation of L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 as a feed additive for all animal species, to be classified in the category ‘nutritional additives’.

| (4) | The European Food Safety Authority (‘the Authority’) concluded in its opinion of 30 September 2020 (2) that, under the proposed conditions of use, L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212, when supplemented at levels appropriate to the requirements of the target species, does not have an adverse effect on animal health, consumer health or the environment. With respect to the safety of the user of the additive, the Authority stated that L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 is a skin sensitiser and that there is a risk from exposure to endotoxins by inhalation. Therefore, appropriate protective measures should be taken for this additive to prevent adverse effects on human health, in particular as regards the users of the additive. Furthermore, the Authority concluded that L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 is an efficacious source of the essential amino acid L-histidine for animal nutrition and that in order to be efficacious in ruminants, the additive should be protected against degradation in the rumen. The Authority considered that there is no need for specific requirements of post-market monitoring. It also verified the report on the method of analysis of the feed additive in feed submitted by the Reference Laboratory set up by Regulation (EC) No 1831/2003. |
| --- | --- |

(4)

The European Food Safety Authority (‘the Authority’) concluded in its opinion of 30 September 2020 (2) that, under the proposed conditions of use, L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212, when supplemented at levels appropriate to the requirements of the target species, does not have an adverse effect on animal health, consumer health or the environment. With respect to the safety of the user of the additive, the Authority stated that L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 is a skin sensitiser and that there is a risk from exposure to endotoxins by inhalation. Therefore, appropriate protective measures should be taken for this additive to prevent adverse effects on human health, in particular as regards the users of the additive. Furthermore, the Authority concluded that L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 is an efficacious source of the essential amino acid L-histidine for animal nutrition and that in order to be efficacious in ruminants, the additive should be protected against degradation in the rumen. The Authority considered that there is no need for specific requirements of post-market monitoring. It also verified the report on the method of analysis of the feed additive in feed submitted by the Reference Laboratory set up by Regulation (EC) No 1831/2003.

| (5) | The assessment of that substance shows that the conditions for authorisation, as provided for in Article 5 of Regulation (EC) No 1831/2003, are satisfied. Accordingly, the use of that substance should be authorised as specified in the Annex to this Regulation. |
| --- | --- |

(5)

The assessment of that substance shows that the conditions for authorisation, as provided for in Article 5 of Regulation (EC) No 1831/2003, are satisfied. Accordingly, the use of that substance should be authorised as specified in the Annex to this Regulation.

| (6) | The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Plants, Animals, Food and Feed, |
| --- | --- |

(6)

The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Plants, Animals, Food and Feed,

HAS ADOPTED THIS REGULATION:

Article 1

L-histidine monohydrochloride monohydrate produced by Escherichia coli KCCM 80212 specified in the Annex, belonging to the additive category ‘nutritional additives’ and to the functional group ‘amino acids, their salts and analogues’, is authorised as a feed additive subject to the conditions laid down in that Annex.

Article 2

This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, 29 April 2021.

For the Commission

The President

Ursula VON DER LEYEN

---

(1)  
  OJ L 268, 18.10.2003, p. 29.

1

(2)  
  EFSA Journal 2020;18(11):6287.

2

EFSA Journal

---

ANNEX

| Identification number of the additive | Name of the holder of authorisation | Additive | Composition, chemical formula, description, analytical method | Species or category of animal | Maxi-mum age | Minimum content | Maximum content | Other provisions | End of period of authorisation |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| mg/kg of complete feed with a moisture content of 12 % |
| Category of nutritional additives. Functional group: amino acids, their salts and analogues. |
| 3c352i | - | L-histidine monohydrochloride monohydrate | Additive composition:

  Powder with a minimum content of
  98 % L-histidine monohydrochloride monohydrate and
  72 % histidine and
  a maximum content of 100 ppm histamine | All animal species | - | - | - | 1. | L-histidine monohydrochloride monohydrate may be placed on the market and used as an additive consisting of a preparation. |

Identification number of the additive

Name of the holder of authorisation

Additive

Composition, chemical formula, description, analytical method

Species or category of animal

Maxi-mum age

Minimum content

Maximum content

Other provisions

End of period of authorisation

mg/kg of complete feed with a moisture content of 12 %

Category of nutritional additives. Functional group: amino acids, their salts and analogues.

3c352i

-

L-histidine monohydrochloride monohydrate

Additive composition:

Powder with a minimum content of

98 % L-histidine monohydrochloride monohydrate and

72 % histidine and

a maximum content of 100 ppm histamine

All animal species

-

-

-

1.

L-histidine monohydrochloride monohydrate may be placed on the market and used as an additive consisting of a preparation.

| 2. | In the directions for use of the additive and premixture, the storage conditions and the stability to heat treatment shall be indicated. |
| --- | --- |

2.

In the directions for use of the additive and premixture, the storage conditions and the stability to heat treatment shall be indicated.

| 3. | Declaration to be made on the label of the additive and premixture:






  — | ‘The supplementation with L-histidine monohydrochloride monohydrate shall be limited to the nutritional requirements of the target animal, which depend on the species, the physiological state of the animal, the performance level, the environmental conditions, the level of other amino acids in the diet and the level essential trace elements such as copper and zinc.’ |
| --- | --- | --- |

3.

Declaration to be made on the label of the additive and premixture:

—

‘The supplementation with L-histidine monohydrochloride monohydrate shall be limited to the nutritional requirements of the target animal, which depend on the species, the physiological state of the animal, the performance level, the environmental conditions, the level of other amino acids in the diet and the level essential trace elements such as copper and zinc.’

| — | Histidine content. |
| --- | --- |

—

Histidine content.

| 4. | The endotoxin content of the additive and its dusting potential shall ensure a maximal endotoxin exposure of 1 600 IU endotoxins/m3 air (2). |
| --- | --- |

4.

The endotoxin content of the additive and its dusting potential shall ensure a maximal endotoxin exposure of 1 600 IU endotoxins/m3 air (2).

| 5. | For users of the additive and premixtures, feed business operators shall establish operational procedures and organisational measures to address the potential risks by inhalation or dermal contact. Where those risks cannot be eliminated or reduced to a minimum by such procedures and measures, the additive and premixtures shall be used with appropriate personal protective equipment, including breathing protection, safety glasses and gloves. |
| --- | --- |

5.

For users of the additive and premixtures, feed business operators shall establish operational procedures and organisational measures to address the potential risks by inhalation or dermal contact. Where those risks cannot be eliminated or reduced to a minimum by such procedures and measures, the additive and premixtures shall be used with appropriate personal protective equipment, including breathing protection, safety glasses and gloves.

20.5.2031

Characterisation of the active substance:

L-histidine monohydrochloride monohydrate produced by fermentation with Escherichia coli KCCM 80212

Chemical formula: C3H3N2-CH2-CH(NH2)-COΟΗ·ΗCl·Η2O

CAS number: 5934-29-2

Einecs number 211-438-9

Analytical method
   (1):

For the quantification of histidine in the feed additive:

| — | high performance liquid chromatography coupled with photometric detection (HPLC-UV) |
| --- | --- |

—

high performance liquid chromatography coupled with photometric detection (HPLC-UV)

| — | ion exchange chromatography coupled with post-column derivatisation and optical detection (IEC-VIS/FLD) |
| --- | --- |

—

ion exchange chromatography coupled with post-column derivatisation and optical detection (IEC-VIS/FLD)

For the quantification of histidine in premixtures, feed materials and compound feed:

| — | ion exchange chromatography coupled with post-column derivatisation and photometric detection (IEC-VIS), Commission Regulation (EC) No 152/2009 (Annex III, F) |
| --- | --- |

—

ion exchange chromatography coupled with post-column derivatisation and photometric detection (IEC-VIS), Commission Regulation (EC) No 152/2009 (Annex III, F)

For the quantification of histamine in the feed additive:

| — | high performance liquid chromatography coupled to a spectrophotometric detection (HPLC-UV) |
| --- | --- |

—

high performance liquid chromatography coupled to a spectrophotometric detection (HPLC-UV)

---

(1)  Details of the analytical methods are available at the following address of the Reference Laboratory: https://ec.europa.eu/jrc/en/eurl/feed-additives/evaluation-reports

(2)  Exposure calculated based on the endotoxin level and the dusting potential of the additive according to the method used by EFSA (EFSA Journal 2015;13(2):4015); analytical method: European Pharmacopoeia 2.6.14. (bacterial endotoxins).

---