Milbemectin (Ref: SL 8601)

Milbemectin (Ref: SL 8601)	Last updated: 31/10/2024
(Also known as: B 41; E 187)

GENERAL INFORMATION

Description

An insecticide and acaricide effective against all development stages of mites and some other insects.

Availability status

Current

Introduction & key dates

1972, first isolated; 1990, registered Japan

Examples of veterinary uses

Examples of species treated

Approval status

VMR 2013/2033 approval status (GB/UK)

EU Regulatory approval status

Chemical structure

Isomerism

Milbemectin is a complex molecule with 10 chiral features. The technical material is a mixture of two related compounds: milbemycin A3 (25-35%) and milbemycin A4 (65-75%). Both are chiral.

Chemical formula

C₃₁H₄₄O₇ (milbemycin A₃) + C₃₂H₄₆O₇ (milbemycin A₄)

Canonical SMILES

CC1CCC2(CC3CC(O2)CC=C(CC(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)C)OC1C

Isomeric SMILES

C[C@H]1CC[C@]2(C[C@@H]3C[C@H](O2)C/C=C(/C[C@H](/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)O[C@@H]1C

International Chemical Identifier key (InChIKey)

VOZIAWLUULBIPN-LRBNAKOISA-N

International Chemical Identifier (InChI)

InChI=1S/C31H44O7/c1-18-7-6-8-23-17-35-28-27(32)21(4)14-26(31(23,28)34)29(33)36-25-15-24(10-9-19(2)13-18)38-30(16-25)12-11-20(3)22(5)37-30/h6-9,14,18,20,22,24-28,32,34H,10-13,15-17H2,1-5H3/b7-6+,19-9+,23-8+/t18-,20-,22?,24?,25-,26-,27+,28+,30-,31+/m0/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Substance groups

Micro-organism derived substance

Minimum active substance purity

950 g kg⁻¹

Known relevant impurities

EU dossier - None declared

Substance origin

Natural

Mode of action

Contact and stomach action, acting on the targets nervous system. Glutamate-gated chloride channel (GluCl) allosteric modulator.

Molecular targets

[Glycine receptor subunit alpha-3, Agonist], [Gamma-aminobutyric-acid (GABA) receptor subunit beta-3, Agonist]

CAS RN

51596-11-3 (MA4)

EC number

CIPAC number

660

US EPA chemical code

PubChem CID

Therapeutic Class

ATCvet Code

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

535.7

PIN (Preferred Identification Name)

IUPAC name

CAS name

(6R,25R)-5-O-demethyl-28-deoxy-6,28-epoxy-25-ethylmilbemycin B mixture with (6R,25R)-5-O-demethyl-28-deoxy-6,28-epoxy-25-methylmilbemycin B

Other status information

PAN listed Highly Hazardous Chemical

Relevant Environmental Water Quality Standards

Physical state

White crystalline powder

Related substances & organisms

milbemycin A3

milbemycin A4

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

Solubility - In water at 20 °C (mg l⁻¹)

0.007

Low

Solubility - In organic solvents at 20 °C (mg l⁻¹)

243000

Ethyl acetate

5060

n-Heptane

251000

Methanol

284000

Xylene

Melting point (°C)

205.2

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

275

Flashpoint (°C)

Octanol-water partition coefficient at pH 7, 20 °C

6.31 X 10⁰⁶

Calculated

Log P

6.8

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.13

Dissociation constant pKa) at 25 °C

Not applicable

No dissociation

Vapour pressure at 20 °C (mPa)

1.30 X 10^-02

at 20 °C

Low volatility

Henry's law constant at 25 °C (Pa m³ mol⁻¹)

9.93 X 10^-04

Non-volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

Maximum UV-vis absorption L mol⁻¹ cm⁻¹

At all pHs - Max @ 244nm & shoulders @ 238nm & 252nm

Surface tension (mN m⁻¹)

49.4

99.67%

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

Moderately persistent

DT₅₀ (lab at 20 °C)

Moderately persistent

DT₅₀ (field)

8.5

Non-persistent

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Lab studies DT₅₀ range for milbemycin A4 21-82 days, field study DT₅₀ range for milbemcyin A3 8.1-8.8 days (USA)

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

3.1days at pH5

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

2.6

Non-persistent

Note

pH variable: 0.93days at pH5, 4.1days at pH9

Water-sediment DT₅₀ (days)

Moderately fast

Water phase only DT₅₀ (days)

2.0

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

K_d (mL g⁻¹)

Slightly mobile

K_oc (mL g⁻¹)

2975

Notes and range

Industry data K_oc range 1550-4400 mL g⁻¹

Freundlich

K_f (mL g⁻¹)

63.3

Slightly mobile

K_foc (mL g⁻¹)

2843

¹/_n

0.98

Notes and range

EU dossier K_f range 12-153 g/Kg, K_foc range 1550-4400 g/Kg, Soils =4

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

0.51

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

Whole fish

Low potential

CT₅₀ (days)

Not available

Known soil metabolites

Metabolite

Major/Minor fraction

$Click here for further information on Major/Minor fraction$

Estimated maximum occurrence fraction

Notes

27-hydroxy-milbemycin A4

Major fraction

0.142

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)

456

Rat

Moderate

Mammals - Short term dietary NOEL

(mg kg⁻¹)

3.0

Rat

High

(ppm diet)

Mammals - Chronic 21d NOAEL (mg kg⁻¹ bw d⁻¹)

Birds - Acute LD₅₀ (mg kg⁻¹)

347

Anas platyrhynchos

Moderate

Birds - Short term dietary (LC₅₀/LD₅₀)

199 mg kg feed⁻¹

Anas platyrhynchos

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹)

28.5

Eisenia foetida

Moderate

Earthworms - Chronic NOEC, reproduction (mg kg⁻¹)

0.109

Eisenia foetida

Moderate

Soil micro-organisms

Nitrogen mineralisation: No significant adverse effect
Carbon mineralisation: No significant adverse effect

Dose: 0.1 mg kg⁻¹ soil

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

Non-target plants

Honeybees (Apis spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

0.025

Apis mellifera

High

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

0.026

Apis mellifera

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

Bombus terrestris

Moderate

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

> 10

Bombus terrestris

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)

Beneficial insects (Lacewings)

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

Beneficial insects (Ground beetles)

Aquatic ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

0.0044

Oncorhynchus mykiss

High

Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)

0.00065

Anas platyrhynchos

High

Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

0.07

Danio rerio EC₅₀ Embryo

High

Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

0.011

Daphnia magna

High

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

0.00012

Daphnia magna

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)

0.0063

Chironomus riparius

High

Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)

Aquatic plants - Acute 7 day EC₅₀, biomass (mg l⁻¹)

> 0.62

Lemna gibba

Moderate

Algae - Acute 72 hour EC₅₀, growth (mg l⁻¹)

Algae - Chronic 96 hour NOEC, growth (mg l⁻¹)

> 2.0

Selenastrum capricornutum 120 hr

Low

Mesocosm study data

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)

456

Rat

Moderate

Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)

5000

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

> 3.0

Rat 4 hr (whole body)

Other Mammal toxicity endpoints

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

0.03

Dog SF=100

ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)

0.03

Dog SF=100

AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)

AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)

0.014

Dog SF=100

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Mammalian dose elimination route and rate

Extensively metabolised and elimination is mainly faecal (85-100%) with some urinary: (5-9) % in 24 hrs

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

No data found

General human health issues

Possible liver, kidney, adrenals and uterus toxicant
CLP data - suspected carcinogen
Possible CNS toxicant

Handling issues

Property

Value and interpretation

General

Prevent generation of mists
Not explosive or oxidising
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

milbemectin

French

milbectine

German

Milbemectin

Danish

milbemectin

Italian

milbemectina

Spanish

milbemectin

Greek

Polish

milbemektyna

Swedish

Hungarian

Dutch

Norwegian

milbemektin

Record last updated:	31/10/2024
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