Milbemectin renewed until 15 November 2040: sum of milbemycin A3 and A4 determined by QuEChERS and LC-MS/MS (LOQ 0.01 mg/kg per analyte), in air HPLC-FLD after derivatisation; ADI lowered from 0.03 to 0.007 mg/kg bw, chironomid studies under OECD TG 218 and 219 by November 2027
Commission Implementing Regulation (EU) 2025/2068, published on 16 October 2025, renews from 16 November 2025 to 15 November 2040 the approval of the acaricide and insecticide milbemectin — a mixture of milbemycin A3 and A4. It is based on the EFSA conclusion of 5 July 2023 (uses among others in strawberries, currants and ornamentals); milbemectin does not meet the criteria for an endocrine disruptor. Aneugenic potential, phototoxicity and interspecies differences in metabolism were not resolved — the applicant must clarify them by 5 November 2027.
- Annex: milbemectin — a mixture of M.A3 (CAS 51596-10-2) and M.A4 (CAS 51596-11-3), CIPAC 660, purity ≥ 950 g/kg; according to EFSA an A3:A4 ratio of about 30:70. Member States must pay attention to the specification of commercial production, personal protective equipment for operators and workers, bees visiting flowering crops at the time of application and aquatic organisms; conditions of use must limit drift to off-field land and water.
- Methods (EFSA): residues in food and feed of plant origin (sum of milbemycin A3 and A4 expressed as milbemectin) — QuEChERS with LC-MS/MS, LOQ 0.01 mg/kg per analyte; the same for food of animal origin. In soil and water the methods determine only milbemycin A4 (0.01 mg/kg and 0.05 µg/L), while the definition covers the sum of A3 and A4 — a data gap. Air: HPLC-FLD after derivatisation to fluorescent anhydrides (0.42 µg/m³, derivatisation efficiency not shown) or LC-MS without derivatisation (not validated for 35 °C and 80 % humidity). Body fluids 0.05 mg/L and tissues 0.01 mg/kg — without a method for 13-hydroxy-MA4.
- Reference values (EFSA): ADI 0.007 mg/kg bw per day from the two-year rat study (in the first assessment the ADI and ARfD were 0.03), ARfD 0.03 mg/kg bw, AOEL and AAOEL 0.014 mg/kg bw (oral absorption 47 %). Bone marrow exposure was not shown in the in vivo micronucleus test, so the negative result was considered unreliable; phototoxicity was not tested for the 290–700 nm range. Proposed MRL for cherries 0.2 mg/kg; no data on residues in pollen and bee products.
- Ecotoxicology (EFSA): high acute risk to bees for field uses and non-permanent protected structures; the aquatic assessment not finalised, and no data on the fate of milbemycin A3 in aquatic systems. By 5 November 2027 the act requires proof of bone marrow exposure or absence of aneugenicity, a comparative in vitro metabolism study including humans, an in vitro phototoxicity study and an updated assessment for sediment organisms with chironomid studies (OECD TG 218 — spiked sediment, TG 219 — spiked water) at the same A3:A4 ratio.