Commission Implementing Regulation (EU) 2025/2068 of 15 October 2025 renewing the approval of the active substance milbemectin in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council, and amending Commission Implementing Regulation (EU) No 540/2011

Renewal of the approval of the active substance

Article 1

The approval of the active substance milbemectin, as specified in Annex I to this Regulation, is renewed, subject to the conditions laid down in that Annex.

Amendments to Implementing Regulation (EU) No 540/2011

Article 2

The Annex to Implementing Regulation (EU) No 540/2011 is amended in accordance with Annex II to this Regulation.

Entry into force and date of application

Article 3

This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union . It shall apply from 16 November 2025.

ANNEX ISupplementary provisions

ANNEX I Common Name, Identification Numbers IUPAC Name Purity  ( 1 ) Date of approval Expiration of approval Specific provisions Milbemectin Milbemectin is a mixture of M.A 3 and M.A 4 CAS No: M.A 3 : 51596-10-2 M.A 4 : 51596-11-3 CIPAC No: 660 M.A 3 : (10E,14E,16E)- (1R,4S,5′S,6R,6′R,8R,13R, 20R,21R,24S)- 21,24-dihydroxy-5′,6′,11,13,22-pentamethyl-(3,7,19-trioxatetracyclo[15.6.1.1 4,8 .0 20,24 ] pentacosa-10,14,16, 22-tetraene)-6-spiro-2′- (tetrahydropyran)-2-one; M.A 4 : (10E,14E,16E)- (1R,4S,5′S,6R,6′R,8R,13R, 20R,21R,24S)-6′-ethyl-21,24- dihydroxy-5′,11,13,22-tetramethyl-(3,7,19-trioxatetracyclo[15.6.1.1 4,8 .0 20,24 ] pentacosa-10,14,16,22-tetraene)-6- spiro-2′-(tetrahydropyran)-2-one ≥ 950 g/kg 16 November 2025 15 November 2040 For the implementation of the uniform principles as referred to in Article 29(6) of Regulation (EC) No 1107/2009, the conclusions of the renewal report on milbemectin, and in particular Appendices I and II thereto, shall be taken into account. In this overall assessment Member States shall pay particular attention to: — the specification of the technical material as commercially manufactured; — the protection of operators and workers ensuring that conditions of use include the application of adequate personal protective equipment; — the protection of bees and pollinators that may be exposed to the active substance by visiting the flowers present in the crop at the time of application; — the protection of aquatic organisms. Conditions of use shall include risk mitigation measures, in particular to reduce drift to terrestrial and aquatic areas outside the treated field, where appropriate. The applicant shall submit confirmatory information as follows: 1. to confirm that the bone marrow was exposed in the available in vivo micronucleus test or to confirm the absence of the aneugenic potential of milbemectin; 2. an in vitro comparative metabolism study with milbemectin (at least in the pivotal species used to characterise milbemectin’s toxicity and in comparison with human metabolism); 3. an in vitro phototoxicity study with milbemectin, testing the range of wavelengths (between 290 and 700 nm) where the absorption coefficient is > 10 L x mol -1 x cm -1 ; 4. an updated risk assessment for the aquatic sediment organisms in accordance with the EFSA Guidance document on tiered risk assessment for plant protection products for aquatic organisms in edge of field surface waters. To allow for proper comparison of the sensitivity with other species, this confirmatory information should include a spiked-sediment test (OECD TG 218) and spiked-water test (OECD TG 219) with Chironomidae exposed to milbemectin, where milbemycin A 3 /milbemycin A 4 is present in the same ratio than in other ecotoxicology studies. The applicant shall submit to the Commission, the Member States and the Authority the information referred to the points above by 5 November 2027. ( 1 )   Further details on the identity and specification of the active substance are provided in the renewal report.

ANNEX IISupplementary provisions

ANNEX II The Annex to Implementing Regulation (EU) No 540/2011 is amended as follows: (1) in Part A, entry 110 on milbemectin is deleted; (2) in Part B, the following entry is added: No Common Name, Identification Numbers IUPAC Name Purity  ( 1 ) Date of approval Expiration of approval Specific provisions ‘176 Milbemectin Milbemectin is a mixture of M.A 3 and M.A 4 CAS No: M.A 3 : 51596-10-2 M.A 4 : 51596-11-3 CIPAC No: 660 M.A 3 : (10E,14E,16E)- (1R,4S,5′S,6R,6′R,8R,13R, 20R,21R,24S)- 21,24-dihydroxy-5′,6′,11,13,22-pentamethyl-(3,7,19-trioxatetracyclo[15.6.1.1 4,8 .0 20,24 ] pentacosa-10,14,16, 22-tetraene)-6-spiro-2′- (tetrahydropyran)-2-one; M.A 4 : (10E,14E,16E)- (1R,4S,5′S,6R,6′R,8R,13R, 20R,21R,24S)-6′-ethyl-21,24- dihydroxy-5′,11,13,22-tetramethyl-(3,7,19-trioxatetracyclo[15.6.1.1 4,8 .0 20,24 ] pentacosa-10,14,16,22-tetraene)-6- spiro-2′-(tetrahydropyran)-2-one ≥ 950 g/kg 16 November 2025 15 November 2040 For the implementation of the uniform principles as referred to in Article 29(6) of Regulation (EC) No 1107/2009, the conclusions of the renewal report on milbemectin, and in particular Appendices I and II thereto, shall be taken into account. In this overall assessment Member States shall pay particular attention to: — the specification of the technical material as commercially manufactured; — the protection of operators and workers ensuring that conditions of use include the application of adequate personal protective equipment; — the protection of bees and pollinators that may be exposed to the active substance by visiting the flowers present in the crop at the time of application; — the protection of aquatic organisms. Conditions of use shall include risk mitigation measures, in particular to reduce drift to terrestrial and aquatic areas outside the treated field, where appropriate. The applicant shall submit confirmatory information as follows: 1. to confirm that the bone marrow was exposed in the available in vivo micronucleus test or to confirm the absence of the aneugenic potential of milbemectin; 2. an in vitro comparative metabolism study with milbemectin (at least in the pivotal species used to characterise milbemectin’s toxicity and in comparison with human metabolism); 3. an in vitro phototoxicity study with milbemectin, testing the range of wavelengths (between 290 and 700 nm) where the absorption coefficient is > 10 L x mol -1 x cm -1 ; 4. an updated risk assessment for the aquatic sediment organisms in accordance with the EFSA Guidance document on tiered risk assessment for plant protection products for aquatic organisms in edge of field surface waters. To allow for proper comparison of the sensitivity with other species, this confirmatory information should include a spiked-sediment test (OECD TG 218) and spiked-water test (OECD TG 219) with Chironomidae exposed to milbemectin, where milbemycin A 3 /milbemycin A 4 is present in the same ratio than in other ecotoxicology studies. The applicant shall submit to the Commission, the Member States and the Authority the information referred to the points above by 5 November 2027. ( 1 )   Further details on the identity and specification of the active substance are provided in the renewal report.’