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Milbemycin A4
Last updated: 18/02/2026
(Not known by any other names)
GENERAL INFORMATION
Description
An active and the most dominant component of milbemectin with acaricidal activity and is used as an antibiotic drug.
Examples of veterinary uses
-
Examples of species treated
-
Approval status
VMR 2013/2033 approval status (GB/UK)
-
EU Regulatory approval status
-
Chemical structure
Isomerism
Milbemycin A4 exhibits intricate stereoisomerism due to its highly complex macrocyclic structure, which includes ten defined chiral centres and multiple double bonds that display geometric (E/Z) isomerism. These stereochemical features result in a rigid three-dimensional conformation essential for its biological activity.
Chemical formula
C₃₂H₄₆O₇
Canonical SMILES
CCC1C(CCC2(O1)CC3CC(O2)CC=C(CC(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)C)C
Isomeric SMILES
CCC1C(CC[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/CC(/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)\C)C
International Chemical Identifier key (InChIKey)
VOZIAWLUULBIPN-DFYAAVTESA-N
International Chemical Identifier (InChI)
InChI=1S/C32H46O7/c1-6-27-21(4)12-13-31(39-27)17-25-16-24(38-31)11-10-20(3)14-19(2)8-7-9-23-18-36-29-28(33)22(5)15-26(30(34)37-25)32(23,29)35/h7-10,15,19,21,24-29,33,35H,6,11-14,16-18H2,1-5H3/b8-7+,20-10+,23-9+/t19?,21?,24-,25+,26+,27?,28-,29-,31-,32-/m1/s1
2D structure diagram/image available?
Yes
General status
Veterinary substance type
-
Substance groups
Micro-organism derived substance
Minimum active substance purity
617.5 g A4/kg milbemectin
Known relevant impurities
EU 2017 dossier: None declared
Substance origin
Natural
Mode of action
Not applicable
Molecular targets
[Glycine receptor subunit alpha-3, Agonist], [Gamma-aminobutyric-acid (GABA) receptor subunit beta-3, Agonist]
CAS RN
51596-11-3
EC number
-
CIPAC number
660
US EPA chemical code
Not applicable
PubChem CID
-
Therapeutic Class
-
ATCvet Code
-
Controlled Drug?
-
Regulation 37/2010 MRL Classification
-
Molecular mass
542.7
PIN (Preferred Identification Name)
-
IUPAC name
(10E,14E,16E,22Z)-(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. 14.8020,24]pentacosa-10,14,16,22-tetraene-6-spiro-2’-tetrahydropyran-2-one
CAS name
(6R,25R)-5-O-demethyl-28-deoxy-6,28-epoxy-25-ethylmilbemycin B
Global Governance status: Listed (✓) under
UK Poisons List Order 1972 Rotterdam Convention Montreal Protocol
XNo
The Poisons List Order 1972
XNo
Rotterdam Convention
XNo
Montreal Protocol
Stockholm Convention OSPAR EU Water Framework Directive
XNo
Stockholm Convention
XNo
OSPAR
XNo
EU Water Framework Directive
Relevant Environmental Water Quality Standards
-
Forever chemical
-
Other status information
-
Physical state
White crystalline solid
Commercial
Property
Value
Availability status
Current
Introduction & key dates
1960, introduced Japan
Example manufacturers & suppliers of products using this active now or historically
  • Belchim Crop protection
Example products using this active
  • MilbeKNOCK miticide
Formulation and application details
Used as a foliar spray
Commercial production
Milbemycin A4 is produced commercially through a fermentation process involving the bacterium Streptomyces spp. The bacterium is cultured in a fermentation broth, where it produces milbemycins, including A4. The fermentation broth is processed to extract the milbemycins, purified to isolate milbemycin A4 from other components and formulated.
Impact on climate of production and use
As microbial-based products tend to use fermentation-based production processes rather than chemical synthesis, they typically have a lower fossil fuel input in formulation and active ingredient creation, and also have reduced downstream emissions due to biodegradability and minimal soil disruption, their life-cycle GHG emissions are expected to be low. Whilst hard and precise data is not available, broad estimates suggest that typically emissions are likely to be below 5 kg CO₂e/kg.
ENVIRONMENTAL FATE
Property
Value
Source; quality score; and other information
Interpretation
Solubility - In water at 20 °C at pH 7 (mg l⁻¹)
4.55
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Low
Solubility - In organic solvents at 20 °C (mg l⁻¹)
203000
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Acetone for milbemectin		 -
3450
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
n-Octanol for milbemectin		 -
25900
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
o-Xylene for milbemectin		 -
251000
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Methanol		 -
Melting point (°C)
191
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Boiling point (°C)
Decomoposes before boiling
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Degradation point (°C)
275
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Flashpoint (°C)
- - -
Octanol-water partition coefficient at pH 7, 20 °C
P
1.00 X 1007 Calculated -
Log P
7.0
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
at 25 °C		 High
Fat solubility of residues
Solubility
- - -
Data type
- - -
Density (g ml⁻¹)
1.2
Q2 Q = Miscellaneous data from online sources
2 = Unverified data of unknown source
 -
Dissociation constant pKa) at 25 °C
Not applicable
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
No dissociation
Vapour pressure at 20 °C (mPa)
1.3 X 10-02
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
at 25 °C		 Low volatility
Henry's law constant at 25 °C (Pa m³ mol⁻¹)
1.59 X 10-03
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Non-volatile
Volatilisation as max % of applied dose lost
From plant surface
- - -
From soil surface
- - -
Maximum UV-vis absorption L mol⁻¹ cm⁻¹
Neutral pH: 238nm=27400, 244nm=30100, 252nm=19500
Acid pH: 238nm=28500, 244nm=31300, 252nm=20300
Basic pH: 238nm=28500, 244nm=31200, 252nm=20200
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Surface tension (mN m⁻¹)
49.4
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Refractive Index
- - -
Environmental release
-
Degradation
Property
Value
Source; quality score; and other information
Interpretation
Soil degradation (days) (aerobic)
DT₅₀ (typical)
36.1
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderately persistent
DT₅₀ (lab at 20 °C)
36.1
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderately persistent
DT₅₀ (field)
11.5
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Non-persistent
DT₉₀ (lab at 20 °C)
143
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Persistent
DT₉₀ (field)
- - -
Note
EU 2023 dossier lab studies DT₅₀ range 20.3-81.8 days, DT₉₀ range 70.1-275 days, Soils =4; EU 2002 dossier field studies DT₅₀ range 10.0-12.9 days, soils =2
Manure DT₅₀ (days)
- - -
Aqueous photolysis DT₅₀ (days) at pH 7
Value
2.6
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderately fast
Note
pH variable: 0.93 days at pH5, 4.1days at pH9
Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7
Value
260
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
as milbemectin		 Persistent
Note
pH variable: 12 days at pH5, 226 days at pH9 as milbemectin
Water-sediment DT₅₀ (days)
86
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderately fast
Water phase only DT₅₀ (days)
2.9
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderately fast
Sediment phase only DT₅₀ (days)
- - -
Air degradation
As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below.
Decay in stored produce DT₅₀
-
Soil adsorption and mobility
Property
Value
Source; quality score; and other information
Interpretation
Linear
Kd (mL g⁻¹)
-
Q2 Q = Miscellaneous data from online sources
2 = Unverified data of unknown source
 Non-mobile
Koc (mL g⁻¹)
70636
Notes and range
Estimated
Freundlich
Kf (mL g⁻¹)
60.6
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Slightly mobile
Kfoc (mL g⁻¹)
2817
1/n
0.97
Notes and range
EU 2023 dossier Kf range 12.2-138 g/Kg, Kfoc range 1370-4059 g/Kg, 1/n range 0.875-1.04, Soils =4
pH sensitivity
No
Fate indices
Property
Value
Source; quality score; and other information
Interpretation
GUS leaching potential index
0.58 Calculated Low leachability
Bio-concentration factor
BCF (l kg⁻¹)
114
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Whole fish		 Threshold for concern
CT₅₀ (days)
Not available -
Known soil metabolites
Metabolite
Major/Minor fraction
Estimated maximum occurrence fraction
Notes
27-hydroxy-milbemycin A4
Major fraction 0.341 -
27-keto-milbemycin A4
Major fraction 0.118 -
Known groundwater metabolites

None

Other known metabolites

None

ECOTOXICOLOGY
Terrestrial ecotoxicology
Property
Value
Source; quality score; and other information
Interpretation
Mammals - Acute oral LD₅₀ (mg kg⁻¹)
340
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Rat		 Moderate
Mammals - Short Term Oral NOAEL (mg kg⁻¹ bw d⁻¹)
- - -
Mammals - Long Term (Chronic) Oral NOAEL (mg kg⁻¹ bw d⁻¹)
- - -
Birds - Acute LD₅₀ (mg kg⁻¹)
347
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Anas platyrhynchos as milbemectin		 Moderate
Birds - Short term dietary LC₅₀ (mg kg⁻¹ bw d⁻¹)
199
Q3 Q = Miscellaneous data from online sources
3 = Unverified data of known source
Anas platyrhynchos as milbemectin		 -
Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)
5.0
Q3 Q = Miscellaneous data from online sources
3 = Unverified data of known source
Anas platyrhynchos as milbemectin		 High
Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹ dw soil)
28.5
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 Moderate
Earthworms - Chronic NOEC, reproduction (mg kg⁻¹ dw soil)
0.217
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Eisenia foetida		 Moderate
Soil micro-organisms
Nitrogen mineralisation: No significant adverse effect
Carbon mineralisation: No significant adverse effect
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes

Dose: 0.1 mg kg⁻¹ soil Milbemectin		 -
Collembola
Acute LC₅₀ (mg kg⁻¹)
- - -
Chronic NOEC (mg kg⁻¹)
- - -
Non-target plants
Vegetative vigour ER₅₀ (g ha⁻¹)
- - -
Seedling emergence ER₅₀ (g ha⁻¹)
> 270
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
2 plant species tested		 -
Honeybees (Apis spp.)
Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
0.026
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Apis mellifera as milbemectin		 High
Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
0.40
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Apis mellifera as milbemectin		 High
Unknown mode acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
- - -
Chronic
- - -
Notes
-
Bumblebees (Bombus spp.)
Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
> 9.7
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Bombus terrestris as milbemectin		 Moderate
-
Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
> 10
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Bombus terrestris as milbemectin		 Moderate
-
Mason bees (Osmia spp.)
Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
- - -
Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)
- - -
Other bee species (1)
Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)
- - -
Mode of exposure
-
Other bee species (2)
Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)
- - -
Mode of exposure
-
Beneficial insects (Ladybirds) as Mortality LR₅₀ g ha⁻¹, Extended lab study
> 1.0
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Coccinella septempunctata as milbemectin		 Moderate
Beneficial insects (Lacewings) as Mortality LR₅₀ g ha⁻¹, Extended lab study
> 27.9
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Chrysoperla carnea as milbemectin Larva		 Moderate
Beneficial insects (Parasitic wasps) as Mortality LR₅₀m g ha⁻¹ 48 hr, Std lab test
< 25
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Aphidius rhopalosiphi as milbemectin		 Moderate
Beneficial insects (Predatory mites) as Mortality LR₅₀ g ha⁻¹ 48 hr, Std lab test
< 25
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Typhlodromus pyri as milbemectin		 Moderate
Beneficial insects (Ground beetles)
- - -
Beneficial insects (Butterflies)
Contact
- - -
Notes
-
Oral
- - -
Notes
-
Aquatic ecotoxicology
Property
Value
Source; quality score; and other information
Interpretation
Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)
0.044
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Oncorhynchus mykiss as milbemectin		 High
Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)
0.00065
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Oncorhynchus mykiss as milbemectin 88days		 High
Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)
- - -
Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)
0.011
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Daphnia magna as milbemectin		 High
Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)
0.000012
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Daphnia magna as milbemectin		 High
Tropical Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)
- - -
Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)
- - -
Sediment dwelling organisms - Acute 96 hour LC₅₀ (mg l⁻¹)
- - -
Sediment dwelling organisms - Chronic 28 day NOEC, static, water (mg l⁻¹)
- - -
Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)
- - -
Aquatic Plants (free-floating, fonds growth, fresh) - 7 day (mg l⁻¹) (IC50)
> 0.62
P3 P = Other non-EU, UK or US Governments and Regulators
3 = Unverified data of known source
Lemna gibba		 Moderate
Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)
- - -
Algae - Acute (growth rate, fresh; mg l⁻¹) (120 hr ErC₅₀, Static)
> 2,0
A4 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
4 = Verified data
Raphidocelis subcapitata as milbemectin		 Low
Algae - Chronic (growth rate, fresh; mg l⁻¹)
- - -
Mesocosm study data
NOEAEC mg l⁻¹
- - -
NOEAEC mg l⁻¹
- - -
Marine bivalves
- - -
HUMAN HEALTH AND PROTECTION
General
Property
Value
Source; quality score; and other information
Interpretation
Threshold of Toxicological Concern (Cramer Class)
High (class III) - -
Mammals - Acute oral LD₅₀ (mg kg⁻¹)
340
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Rat		 Moderate
Mammals - Short Term Oral NOAEL (mg kg⁻¹ bw d⁻¹)
- - -
Mammals - Long Term (Chronic) Oral NOAEL (mg kg⁻¹ bw d⁻¹)
- - -
Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)
> 2000
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Rat		 -
Mammals - Inhalation LC₅₀ (mg l⁻¹)
1.9
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Rat 4 hr (whole body) as Milbemycin		 -
Other Mammal toxicity endpoints
- - -
ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)
0.007
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Rat SF=100 as milbemectin		 -
ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)
0.03
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Dog SF=100 as milbemectin		 -
AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)
0.014
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Dog SF=100 as milbemectin		 -
AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)
0.014
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
Dog SF=100 as milbemectin		 -
Dermal penetration studies (%)
2-19
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
concentration dependent as milbemectin		 -
Dangerous Substances Directive 76/464
- - -
Exposure Routes
Public
No acceptable risks identified
Occupational
No unacceptable risks identified when using PPE/PPC
Mammalian dose elimination route and rate
Extensively metabolised and elimination is mainly faecal (85-100%) with some urinary: (5-9) % in 24 hrs
A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications )
5 = Verified data used for regulatory purposes
 -
Health issues
Specific human health issues (hazard-based)
Carcinogen
Genotoxic
Endocrine disruptor
?Possibly, status not identified
A3 A = Chromosome aberration (EFSA database)
3 = Negative
;
B0 B = DNA damage/repair (EFSA database)
0 = No data
;
C0 C = Gene mutation (EFSA database)
0 = No data
;
D0 D = Genome mutation (EFSA database)
0 = No data
;
E3 E = Unspecified genotoxicity type (miscellaneous data source)
3 = Negative
 No data found
Reproduction / development effects Acetyl cholinesterase inhibitor Neurotoxicant
?Possibly, status not identified
XNo, known not to cause a problem
?Possibly, status not identified
Respiratory tract irritant Skin irritant Skin sensitiser
XNo, known not to cause a problem
XNo, known not to cause a problem
XNo, known not to cause a problem
Eye irritant Phototoxicant  
XNo, known not to cause a problem
 No data found  
General human health issues
Possible liver, kidney, adrenals and uterus toxicant especially in vulnerable groups
Possible CNS toxicant
CLP data - suspected carcinogen
Handling issues
Property
Value and interpretation
General
Not oxidising or explosive
Not expected to auto-ignite; Not highly flammable
CLP classification 2013
Health: H302, H332, H351, H361d, H373
Environment: H400, H410
WHO Classification
Not listed (Not listed)
UN Number
-
Waste disposal & packaging
-
Shelf-life, storage, stability and reactivity
-
TRANSLATIONS
Language
Name
English
milbemycin A4
French
-
German
-
Danish
-
Italian
-
Spanish
-
Greek
-
Polish
-
Swedish
-
Hungarian
-
Dutch
-
Norwegian
-
Record last updated: 18/02/2026
Contact: aeru@herts.ac.uk
Please cite as: Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242

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