Milbemycin A4

Milbemycin A4	Last updated: 30/06/2022
(Not known by any other names)

Data alerts

The following alerts are based on the data in the tables below. An absence of an alert does not imply the substance has no implications for human health, biodiversity or the environment but just that we do not have the data to form a judgement.

Environmental fate	Ecotoxicity	Human health
Environmental fate Moderate alert: Potential for particle bound transport: Medium	Ecotoxicity High alert: Fish acute ecotoxicity: High; Fish chronic ecotoxicity: High; Daphnia acute ecotoxicity: High; Daphnia chronic ecotoxicity: High; Bees acute contact ecotoxicity: High; Bees acute oral ecotoxicity: High	Human health Moderate alert: Mammals acute toxicity: Moderate; Possible Carcinogen; Possible Reproduction/development effects; Neurotoxicant

GENERAL INFORMATION

Description

An active isomer of milbemectin with acaricidal activity and is used as an antibiotic drug.

Example pests controlled

Spider mites; Tarsonemid mites; Leaf miners

Example applications

Soft fruit including Straweberry, blackberry, currants, raspberry, gooseberry; Apple, Pear, Cherry, Plum; Orange; Eggplants; Ornamentals

Efficacy & activity

Efficacy proven via field trials

Appearance and life cycle

Availability status

Current

Introduction & key dates

Taxonomic classification

UK regulatory status

UK COPR regulatory status

Approved

Date COPR inclusion expires

31/07/2024

UK LERAP status

No UK approval for use

EC Regulation 1107/2009 (repealing 91/414)

EC Regulation 1107/2009 status

Approved

Dossier rapporteur/co-rapporteur

Germany/Netherlands

Date EC 1107/2009 inclusion expires

31/07/2023

EU Candidate for substitution (CfS)

Listed in EU database

Yes

Approved for use (✓) under EC 1107/2009 in the following EU Member States

ATAustria	BEBelgium	BGBulgaria	CYCyprus	CZCzech Republic	DEGermany	DKDenmark	EEEstonia	ELGreece
✓	✓	✓	✓	✓	✓	✓		✓
ESSpain	FIFinland	FRFrance	HRCroatia	HUHungary	IEIreland	ITItaly	LTLithuania	LULuxembourg
✓		✓		✓		✓		✓
LVLatvia	MTMalta	NLNetherlands	PLPoland	PTPortugal	RORomania	SESweden	SISlovenia	SKSlovakia
		✓	✓		✓	✓	✓

Additional information

Known to be used in the following countries

Chemical structure

Isomerism

Milbemectin is a complex molecule with 10 chiral features. Milbemycin A4 is one of the most biologically active isomers.

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

Biopesticide type

Insecticide, Acaricide

Substance groups

Micro-organism derived substance

Minimum active substance purity

950 g kg⁻¹

Known relevant impurities

EU 2017 dossier: None declared

Substance origin

Natural

Mode of action

Not applicable

Substance source

Substance production

Uses

Target pests

Target host

Farming system suitability

CAS RN

51596-11-3

EC number

CIPAC number

660

US EPA chemical code

Not applicable

PubChem CID

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

Other status information

Relevant Environmental Water Quality Standards

Herbicide Resistance Classification (HRAC)

Not applicable

Herbicide Resistance Classification (WSSA)

Not applicable

Insecticide Resistance Classification (IRAC)

Fungicide Resistance Classification (FRAC)

Not applicable

Examples of recorded resistance

Physical state

White crystalline solid

Formulations

Property

Product

Manufacturer

Example products

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

4.55

Low

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

203000

Acetone for milbemectin

3450

n-Octanol for milbemectin

25900

o-Xylene for milbemectin

251000

Methanol

Melting point (°C)

191

Boiling point (°C)

Boiling not observed

Degradation point (°C)

Flashpoint (°C)

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

1.00 X 10⁰⁷

Calculated

Log P

7.0

at 25 °C

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.2

Dissociation constant pKa) at 25 °C

Not applicable

No dissociation

Vapour pressure at 20 °C (mPa)

4.3 X 10^-07

Low volatility

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

1.55

Moderately volatile

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

Neutral pH: 238nm=31300, 244nm=34300, 252nm=22100
Acid pH: 238nm=26200, 244nm=28400, 252nm=18300
Basic pH: 238nm=28500, 244nm=31200, 252nm=20200

as milbemectin

Surface tension (mN m⁻¹)

49.4

Degradation

Property

Value

Source; quality score; and other information

Interpretation

General biodegradability

Not readily biodegradable

Soil degradation (days) (aerobic)

DT₅₀ (typical)

36.1

Moderately persistent

DT₅₀ (lab at 20 °C)

36.1

Moderately persistent

DT₅₀ (field)

11.5

Non-persistent

DT₉₀ (lab at 20 °C)

143

Persistent

DT₉₀ (field)

DT₅₀ modelling endpoint

Note

EU 2017 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

Dissipation rate RL₅₀ on plant matrix

Value

Note

Dissipation rate RL₅₀ on and in plant matrix

Value

Note

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)

2.9

Moderately fast

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d

Non-mobile

K_oc

70636

Notes and range

Estimated

Freundlich

K_f

60.6

Slightly mobile

K_foc

2817

¹/_n

0.97

Notes and range

EU 2017 dossier K_f range 12.2-138 g/Kg, K_foc range 1370-4059 g/Kg, ¹/_n range 0.875-1.04, Soils =4

pH sensitivity

None

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

0.140

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 for milbemectin

Moderate

Mammals - Short term dietary NOEL

(mg kg⁻¹)

(ppm diet)

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

Birds - Acute LD₅₀ (mg kg⁻¹)

347

Anas platyrhynchos for milbemectin

Moderate

Birds - Short term dietary (LC₅₀/LD₅₀)

1922 mg kg feed⁻¹

Anas platyrhynchos for milbemectin

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

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

28.5

Moderate

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

0.109

Moderate

Soil micro-organisms

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

Dose: 0.1mg kg⁻¹ soil Milbemectin

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

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 pollinators (1)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Other pollinators (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

Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

0.044

Oncorhynchus mykiss for milbemectin

High

Fish - Chronic 21 day NOEC (mg l⁻¹)

0.00065

Oncorhynchus mykiss for milbemectin 88days

High

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

0.011

Daphnia magna for milbemectin

High

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

0.000012

Daphnia magna for milbemectin

High

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 - Acute 7 day EC₅₀, biomass (mg l⁻¹)

> 0.62

Lemna gibba IC50

Moderate

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

> 2.0

Selenastrum capricornutum or milbemectin

Moderate

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

Mesocosm study data

NOEAEC mg l⁻¹

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 for milbemectin

Moderate

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

5000

Rat for milbemectin

Mammals - Inhalation LC₅₀ (mg l⁻¹)

1.9

Rat 4 hr (whole body) for milbemectin

Other Mammal toxicity endpoints

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

0.007

Rat 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

No acceptable risks identified

Occupational

No unacceptable risks identified when using PPE/PPC

Mammalian dose elimination route and rate

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 especially in vulnerable groups
Possible CNS toxicant

Handling issues

Property

Value and interpretation

General

Not oxidising or explosive
Not expected to autoignite; Not highly flammable

CLP classification 2013

Health: H302, H332, H373, H351, H361d
Environment: H400, H410

WHO Classification

NL (Not listed)

UN Number

Waste disposal & packaging

TRANSLATIONS

Language

Name

English

milbemycin A4

French

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Danish

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Polish

Swedish

Hungarian

Dutch

Record last updated:	30/06/2022
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