Emamectin benzoate (Ref: MK 244)

Emamectin benzoate (Ref: MK 244)	Last updated: 20/03/2024
(Also known as: methylamino abamectin benzoate; abamectin-aminomethyl; Sch 58854)

GENERAL INFORMATION

Description

A semi-synthetic avermectin that is clinically used in veterinary medicine for its anti-helminthic and anti-parasitic activity.

Availability status

Current

Introduction & key dates

1997, registered Israel and Japan; 1999, registered USA

Examples of veterinary uses

Current primary application is the eradication of fish lice in fish farming

Examples of species treated

Fish especially trout and salmon

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Isomeric. Technical material is a mixture of Bla and B1b isomers.

Chemical formula

C₅₆H₈₁NO₁₅ (emamectin B₁a benzoate) + C₅₅H₇₉NO₁₅ (emamectin B₁b benzoate)

Canonical SMILES

CCC(C)C1C(C=CC2(O1)CC3CC(O2)CC=C(C(C(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)OC6CC(C(C(O6)C)OC7CC(C(C(O7)C)NC)OC)OC)C)C.C1=CC=C(C=C1)C(=O)O

Isomeric SMILES

CC[C@H](C)[C@@H]1[C@H](C=C[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([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)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@@H]([C@@H](O7)C)NC)OC)OC)\C)C.C1=CC=C(C=C1)C(=O)O

International Chemical Identifier key (InChIKey)

GCKZANITAMOIAR-PEZUHFCHSA-N

International Chemical Identifier (InChI)

InChI=S/C49H75NO13.C48H73NO13.C7H6O2/c1-12-26(2)44-29(5)18-19-48(63-44)24-35-21-34(62-48)17-16-28(4)43(27(3)14-13-15-33-25-56-46-42(51)30(6)20-36(47(52)59-35)49(33,46)53)60-40-23-38(55-11)45(32(8)58-40)61-39-22-37(54-10)41(50-9)31(7)57-39;1-25(2)42-28(5)17-18-47(62-42)23-34-20-33(61-47)16-15-27(4)43(26(3)13-12-14-32-24-55-45-41(50)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-11)44(31(8)57-39)60-38-21-36(53-10)40(49-9)30(7)56-38;8-7(9)6-4-2-1-3-5-6/h13-16,18-20,26-27,29,31-32,34-46,50-51,53H,12,17,21-25H2,1-11H3;12-15,17-19,25-26,28,30-31,33-45,49-50,52H,16,20-24H2,1-11H3;1-5H,(H,8,9)/b14-13+,28-16+,33-15+;13-12+,27-15+,32-14+;/t26-,27-,29-,31-,32-,34+,35-,36-,37-,38-,39-,40-,41-,42+,43-,44+,45-,46+,48+,49+;26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40-,41+,42+,43-,44-,45+,47+,48+;/m00./s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Insecticide

Substance groups

Micro-organism derived substance

Minimum active substance purity

950 g kg⁻¹ as emamectin benzoate anhydrous

Known relevant impurities

Substance origin

Natural

Mode of action

Non-systemic, acts by causing insect paralysis by suppressing muscle contraction. Glutamate-gated chloride channel (GluCl) allosteric modulator.

Molecular targets

CAS RN

155569-91-8

Alternative/old CAS RN

137512-74-4 / 179607-18-2

EC number

122806

CIPAC number

791.412

US EPA chemical code

122806

PubChem CID

Therapeutic Class

Antiparasitic products, insecticides & repellents: Endectocides

ATCvet Code

QP54AA06

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Fin fish)

Molecular mass

1008.3 + 994.2

PIN (Preferred Identification Name)

IUPAC name

emamectin B1A benzoate

CAS name

(4R)-5-O-demethyl-4-deoxy-4-(methylamino)avermectin A1a + (4R)-5-Odemethyl-25-de(1-methylpropyl)-4-deoxy-4-(methylamino)-25-(1-methylethyl)avermectin A1a (9:1)

Other status information

Relevant Environmental Water Quality Standards

Physical state

White solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Slice 2 Premix

MSD Animal Health UK Ltd

GB National authorisation

Prescription only medicine to be authorised by a veterinarian (POM-V)

Formulation and application details

Available as medicated pre-mix feeds

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

24.0

at 25 °C

Low

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

77.0

n-Hexane at 25 °C

26000

Toluene at 25 °C

2700000

Methanol at 25 °C

48000

Octanol at 25 °C

Melting point (°C)

160.5

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

194

Flashpoint (°C)

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

1.00 X 10⁰⁵

Calculated

Log P

5.0

High

Fat solubility of residues

Solubility

Soluble

Data type

Regulatory data - observed in metabolism and farm animal feeding studies

Density (g ml⁻¹)

1.2

at 23 °C

Dissociation constant pKa) at 25 °C

4.2

pKa(2) = 7.7

Vapour pressure at 20 °C (mPa)

0.004

Low volatility

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

1.7 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

Acidic soln.: 236nm=37100
Neutral soln.: 244nm=32700
Basic soln.: 244nm=28300

Surface tension (mN m⁻¹)

48.8

Refractive Index

Environmental release

Substance may enter the environment via the faeces of treated animals or by leaching from spilt medicated feed.

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

300

Persistent

DT₅₀ (lab at 20 °C)

76.6

Moderately persistent

DT₅₀ (field)

1.1

Non-persistent

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

EU dossier lab studies DT₅₀ range 25.2-207 days, Field studies DT₅₀ range 0.3-2.6 days; DT₅₀ General literature states DT₅₀ estimated at 8-15 months; range 174-427 days (R4)

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Stable

Note

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

Value

Stable

Note

pH 5.2-8.0 - stable, pH 9DT₅₀ 19.5 days at 20-29 °C

Water-sediment DT₅₀ (days)

>120

Slow

Water phase only DT₅₀ (days)

8.7

Moderately fast

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.

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d

Non-mobile

K_oc

377000

Notes and range

Literature values range 25,000 to 729,000 mL g⁻¹

Freundlich

K_f

643.0

Non-mobile

K_foc

72874

¹/_n

0.94

Notes and range

EU dossier K_f range 133.9-2037 mL g⁻¹, K_foc range 6666-278983 mL g⁻¹, ¹/_n range 0.91-0.99, Soils=7

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

-0.04

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

8a-hydroxy-4-deoxy-4-epi-methylamino avermectin B1a (Ref: NOA 438306)

Major fraction

0.111

(4"R)-5-O-demethyl-4"-deoxy-4"-(formylamino)-avermectin A1a

Minor fraction

0.05

aglycone milbemectin B

Minor fraction

0.05

4'-O-de(2,6-dideoxy-3-O-methyl-a-L-arabino-hexapyranosyl)-5-O-demethyl-avermectin A1a

Minor fraction

0.05

(4R)-5-O-demethyl-4-deoxy-4-(methylamino)-28-oxoavermectin A1a (Ref: NOA 438307)

Minor fraction

0.045

N-nitroso MAB1a

Major fraction

0.153

(4R)-5-O-demethyl-4-deoxy-4-(formylmethylamino)-avermectin A1a (Ref: NOA 415692)

Minor fraction

0.061

(4"R)-4"-amino-5-O-demethyl-4"-deoxy-avermectin A1a (Ref: NOA438309)

Minor fraction

0.05

Known groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

Metabolising enzymes

(4"R)-4"-amino-5-O-demethyl-4"-deoxy-avermectin A1a (Ref: NOA438309)

AB1a

Rat (Faeces, Bile, Tissues)

8,9-Z-4"-deoxy-4"-epi-methylamino-avermectin B1a (Ref: NOA438376)

8,9-ZMA

Water

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

81.5

Rat

High

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)

Anas platyrhynchos

High

Birds - Short term dietary (LC₅₀/LD₅₀)

> 570 mg l⁻¹

Anas platyrhynchos

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

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

> 500

Eisenia foetida corr

Moderate

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

2.0

Eisenia foetida corr

Moderate

Soil micro-organisms

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)

0.0036

Apis mellifera

High

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

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)

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

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 LC₅₀ ppm

> 33.8

Coccinella septempunctata Adult

Beneficial insects (Lacewings) as % Mortality at dose 22.5 g ha⁻¹

94.0

Chrysoperla carnea Larva

Beneficial insects (Parasitic wasps) as Mortality LR₅₀ g ha⁻¹

> 0.5

Aphidius rhopalosiphi

Beneficial insects (Predatory mites) as Mortality LR₅₀ g ha⁻¹

0.58

Typhlodromus pyri

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)

0.174

Oncorhynchus mykiss

Moderate

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

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

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

0.001

Daphnia magna

High

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

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

Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)

Americamysis bahia

Moderate

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)

> 0.094

Lemna gibba

Moderate

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

0.0072

Pseudokirchneriella subcapitata

High

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

81.5

Rat

High

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

439

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

0.582

Rat 4 hr (nose only)

Other Mammal toxicity endpoints

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

0.0005

Dog SF=500

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

0.01

Rat SF=500

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

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

0.0003

Dog SF=500

Dermal penetration studies (%)

1-2%

concentration specific

Dangerous Substances Directive 76/464

Exposure Routes

Public

Acceptable for proposed uses

Occupational

Acceptable for proposed uses

Mammalian dose elimination route and rate

Partially metabolised and excreted mainly in the faeces

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

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May cause clinical tremors

Handling issues

Property

Value and interpretation

General

Not explosive or oxidising
Not explected to auto-ignite, Not highly flammable

CLP classification 2013

Health: H301, H311, H318, H319, H331
Environment: H400, H410

WHO Classification

II (Moderately hazardous)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

emamectin benzoate

French

German

Danish

Italian

Spanish

benzoato emamectin

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	20/03/2024
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