Spinosad (Ref: XDE 105)

Spinosad (Ref: XDE 105)	Last updated: 25/07/2024
(Also known as: DE 105; BBF 05897; GF-976)

GENERAL INFORMATION

Description

A systemic parasiticide used in veterinary medicine

Availability status

Current

Introduction & key dates

1982, first identified; 1997, commercially introduced

Examples of veterinary uses

Mainly used to control flea infestations

Examples of species treated

Sheep; Goats; Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

A chiral molecule. The technical material is a mixture of spinosyn A (50-95%) and spinosyn D. ( 5-50%)

Chemical formula

C₄₁H₆₅NO₁₀ (spinosyn A) + C₄₂H₆₇NO₁₀ (spinosyn D)

Canonical SMILES

CCC1CCCC(C(C(=O)C2=CC3C4CC(CC4C=CC3C2CC(=O)O1)OC5C(C(C(C(O5)C)OC)OC)OC)C)OC6CCC(C(O6)C)N(C)C.CCC1CCCC(C(C(=O)C2=CC3C4CC(CC4C(=CC3C2CC(=O)O1)C)OC5C(C(C(C(O5)C)OC)OC)OC)C)OC6CCC(C(O6)C)N(C)C

Isomeric SMILES

CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C=C[C@H]3[C@@H]2CC(=O)O1)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C.CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C(=C[C@H]3[C@@H]2CC(=O)O1)C)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C

International Chemical Identifier key (InChIKey)

JFLRKDZMHNBDQS-SGSTVUCESA-N

International Chemical Identifier (InChI)

InChI=1S/C42H71NO9/c1-10-27-12-11-13-35(52-38-17-16-34(43(5)6)25(4)49-38)24(3)39(45)33-21-31-29(32(33)22-37(44)51-27)15-14-26-19-28(20-30(26)31)50-36-18-23(2)40(46-7)42(48-9)41(36)47-8/h23-36,38,40-42H,10-22H2,1-9H3

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Lousicide

Substance groups

Micro-organism derived substance

Minimum active substance purity

850 g kg⁻¹ - 50-95% spinosyn A & 5-50% spinosyn D

Known relevant impurities

EU dossier - None declared

Substance origin

Natural

Mode of action

Contact and stomach action. Acts by exciting the insect nervous system, leading to involuntary muscle contractions and paralysis. Nicotinic acetylcholine receptor (nAChR) channel blocker – Site I.

Molecular targets

CAS RN

168316-95-8

EC number

434-300-1

CIPAC number

636

US EPA chemical code

110003

PubChem CID

Therapeutic Class

Antiparasitic products, Insecticides and Repellents: Other ectoparasiticides for systemic use

ATCvet Code

QP53BX03

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

731.98+745.98

PIN (Preferred Identification Name)

IUPAC name

mix of 50-95% (2R,3aS,5aR,5bS,9S,13S,14R,16aS,16bR)-2-(6-deoxy-2,3,4-tri-O-methyl-αL-mannopyranosyloxy)-13-(4-dimethylamino-2,3,4,6-tetradeoxy-β-D-erythropyranosyloxy)-9-ethyl-2,3,3a,5a,5b,6,7,9,10,11,12,13,14,15,16a,16b-hexadecahydro-14-methyl-1H-as-indaceno[3,2-d]oxacyclododecine-7,15-dione and 50-5% (2S,3aR,5aS,5bS,9S,13S,14R,16aS,16bS)-2-(6-deoxy-2,3,4-tri-O-methyl-α-L-mannopyranosyloxy)-13-(4-dimethylamino-2,3,4,6-tetradeoxy-β-D-erythropyranosyloxy)-9-ethyl-2,3,3a,5a,5b,6,7,9,10,11,12,13,14,15,16a,16b-hexadecahydro-4,14-dimethyl-1H-as-indaceno[3,2-d]oxacyclododecine-7,15-dione

CAS name

2R,3aS,5aR,5bS,9S,13S,14R,16aS,16bR)-2-((6-deoxy-2,3,4-tri-O-methyl-α-L-mannopyranosyl)oxy)-13-(((2R,5S,6R)-5-(dimethylamino)tetrahydro-6-methyl-2H-pyran-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-14-methyl-1H-as-indaceno[3,2-d]oxacyclododecin-7,15-dione mixture with (2S,3aR,5aS,5bS,9S,13S,14R,16aS,16bS)-2-[(6-deoxy-2,3,4-tri-O-methyl-α-L-mannopyranosyl)oxy]-13-[[(2R,5S,6R)-5-(dimethylamino)tetrahydro-6-methyl-2H-pyran-2-yl)oxy)-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-4,14-dimethyl-1H-as-indaceno(3,2-d)oxacyclododecin-7,15-dione

Other status information

Relevant Environmental Water Quality Standards

Physical state

Technical substance is a white-grey crystalline solid

Related substances & organisms

spinosyn A

spinosyn D

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Elanco AH0498 Extinosad Aerosol for Wounds

Elanco Australasia Pty Ltd

Not licensed

Zotel Lice Lousicide for Sheep Pour-On

Troy Laboratories Pty Ltd

Not licensed

Comfortis 1040mg Chewable Tablets for Dogs

Elanco GmbH

Not licensed

Formulation and application details

Available in a range of formulations including pour-ons and chewable tablets

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

7.6

Low

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

168000

Acetone

36900

Ethyl acetate

4480

Hexane

190000

Methanol

Melting point (°C)

136

Boiling point (°C)

225

Degradation point (°C)

Flashpoint (°C)

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

1.26 X 10⁰⁴

Calculated

Log P

4.1

High

Fat solubility of residues

Solubility

Soluble

Data type

Regulatory data - observed in metabolism and farm animal feeding studies

Density (g ml⁻¹)

0.51

Dissociation constant pKa) at 25 °C

8.0

Mean of protonated spinosyn A & D

Vapour pressure at 20 °C (mPa)

1.00 X 10^-02

Low volatility

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

1.89 X 10^-07

Non-volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

Surface tension (mN m⁻¹)

41.5

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

Non-persistent

DT₅₀ (lab at 20 °C)

Non-persistent

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

3.3

Note

More accurate data can be found under the separate synosad components - spinosyn A and spinosyn D

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

0.9

Fast

Note

Spinosyn A: DT₅₀ 0.96 days at pH 7 and 25 °C distilled water, 0.18 days at pH 9.2 and 25 °C pond water; Spinosyn D: DT₅₀ 0.84 days at pH 7 and 25 °C distilled water, 0.18 days at pH 9.2 and 25 °C pond wate

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

Value

Stable

Note

Stable pH 5 and pH 7, DT₅₀ 200 days for spinosyn A and 259 days for spinosyn D at pH 9, all at 25 °C

Water-sediment DT₅₀ (days)

Water 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

[Clemetine: No residue decay after 32 days in cold storage; Field study]

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

Non-mobile

K_oc (mL g⁻¹)

34600

Notes and range

Other sources: Spinosad A 16400 mL g⁻¹, Spinosad D 20000 mL g⁻¹ (DW4). More accurate data can be found under the separate synosad components - spinosyn A and spinosyn D

Freundlich

K_f (mL g⁻¹)

K_foc (mL g⁻¹)

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

-0.63

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

0.1

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

spinosyn B

Major fraction

0.216

N-demethylated spinosyn D

Major fraction

0.108

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)

> 2000

Rat

Low

Mammals - Short term dietary NOEL

(mg kg⁻¹)

Rat

High

(ppm diet)

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

Rat Reproductive NOAEL

Moderate

Birds - Acute LD₅₀ (mg kg⁻¹)

> 2000

Anas platyrhynchos

Low

Birds - Short term dietary (LC₅₀/LD₅₀)

> 5156 mg kg feed⁻¹

Anas platyrhynchos

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

68.35

Anas platyrhynchos NOAEL

Moderate

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

> 458

Eisenia foetida corr

Moderate

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

1.79

Eisenia foetida corr

Moderate

Soil micro-organisms

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

Dose: 7.2 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)

0.0036

Apis mellifera

High

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

0.057

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)

> 0.37

Bombus terrestris

High

Literature LD₅₀ values range 0.37-17.2 µg bee⁻¹

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

0.385

Bombus terrestris

High

Mason bees (Osmia spp.)

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

2.59

Osmia bicornis

Moderate

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)

1.25

Megachile rotundata

Moderate

Mode of exposure

Contact

Other bee species (2)

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

0.012

Melipona quadrifasciata

High

Mode of exposure

Oral

Beneficial insects (Ladybirds) as Mortality, LC₅₀ ppm

> 28.4

Coccinella septempunctata Larva

Beneficial insects (Lacewings) as Mortality Contact LC₅₀ ppm

> 106.2

Chrysoperla carnea Larva

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

0.37

Aphidius rhopalosiphi

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

8.54

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)

Oncorhynchus mykiss

Moderate

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

1.22

Oncorhynchus mykiss

Moderate

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

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

> 1.0

Daphnia magna

Moderate

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

0.0012

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)

0.0016

Chironomus riparius 25 day

High

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

0.0585

Chironomus riparius

High

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

10.6

Lemna minor

Low

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

6.1

Anabaena flos-aquae

Moderate

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

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 2000

Rat

Low

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

5000

Rabbit

Mammals - Inhalation LC₅₀ (mg l⁻¹)

> 5.18

Rat 4 hr (nose only)

Other Mammal toxicity endpoints

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

0.024

Rat SF=100

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

0.1

Rat SF=100

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

0.04

Rabbit SF=100

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

0.02

Dog SF=100

Dermal penetration studies (%)

0.1-10.0

concentration dependent

Dangerous Substances Directive 76/464

Exposure Routes

Public

No unacceptable risks to bystanders identified

Occupational

No unacceptable risks to operators or other workers identified
May be absorbed into the body by ingestion

Mammalian dose elimination route and rate

Rapid excretion around 90% in 168 hrs, primarily via faeces with extensive metabolism

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

General human health issues

Possible thyroid, spleen, liver & lymph nodes toxicant
May cause inflammation of various organs

Handling issues

Property

Value and interpretation

General

Prevent generation of dust
Not explosive or oxidising
IMDG Transport Hazard Class 9
Not expected to auto-ignite; Not highly flammable

CLP classification 2013

Health: H361f
Environment: H400, H410

WHO Classification

III (Slightly hazardous)

UN Number

UN3077

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

spinosad

French

spinosad

German

Spinosad

Danish

spinosad

Italian

spinosad

Spanish

spinosad

Greek

Polish

spinosad

Swedish

spinosad

Hungarian

Dutch

spinosad

Norwegian

spinosad

Record last updated:	25/07/2024
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