Tylosin

Tylosin	Last updated: 24/02/2024
(Also known as: tylosin A)

GENERAL INFORMATION

Description

A macrolide broad spectrum natural antibiotic licensed for use in livestock

Availability status

Current

Introduction & key dates

1961, early use record

Examples of veterinary uses

Used for the treatment of various infections e.g. pneumonia, foot rot and shipping fever in cattle. Banned in EU as growth promotor; Not approved as a feed additive in EU

Examples of species treated

Cattle; Pigs; Poultry

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Isomeric

Chemical formula

C₄₆H₇₇NO₁₇

Canonical SMILES

CCC1C(C=C(C=CC(=O)C(CC(C(C(C(CC(=O)O1)O)C)OC2C(C(C(C(O2)C)OC3CC(C(C(O3)C)O)(C)O)N(C)C)O)CC=O)C)C)COC4C(C(C(C(O4)C)O)OC)OC

Isomeric SMILES

CC[C@@H]1C(/C=C(/C=C/C(=O)[C@@H](C[C@@H]([C@@H](C([C@@H](CC(=O)O1)O)C)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)O)(C)O)N(C)C)O)CC=O)C)\C)COC4[C@@H]([C@@H]([C@@H]([C@H](O4)C)O)OC)OC

International Chemical Identifier key (InChIKey)

WBPYTXDJUQJLPQ-TZNGNTBMSA-N

International Chemical Identifier (InChI)

InChI=1S/C46H77NO17/c1-13-33-30(22-58-45-42(57-12)41(56-11)37(52)26(5)60-45)18-23(2)14-15-31(49)24(3)19-29(16-17-48)39(25(4)32(50)20-34(51)62-33)64-44-38(53)36(47(9)10)40(27(6)61-44)63-35-21-46(8,55)43(54)28(7)59-35/h14-15,17-18,24-30,32-33,35-45,50,52-55H,13,16,19-22H2,1-12H3/b15-14+,23-18+/t24-,25+,26-,27-,28+,29+,30-,32-,33-,35+,36-,37-,38-,39-,40-,41-,42-,43+,44+,45-,46-/m1/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antibiotic, Antibacterial, Feed additive, Growth promotor

Substance groups

Macrolide

Minimum active substance purity

Known relevant impurities

Substance origin

Natural

Mode of action

Inhibits bacterial protein synthesis

Molecular targets

[50S ribosomal protein L10, Antagonist]

CAS RN

1401-69-0

EC number

215-754-8

CIPAC number

US EPA chemical code

PubChem CID

5280440

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for systemic use, Antibacterials for intramammary use

ATCvet Code

QJ01FA90; QJ51FA90

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: All food producing species)

Molecular mass

916.10

PIN (Preferred Identification Name)

IUPAC name

2-[(4R,6S,7R,9R,11E,13E,16R)-6-[(2R,3R,4R,5S,6R)-5-[(2S,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-16-ethyl-4-hydroxy-15-[[(3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-2,10-dioxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde

CAS name

Other status information

Possible groundwater contaminant

Relevant Environmental Water Quality Standards

Physical state

White or off-white coloured powder

Related substances & organisms

tylosin tartrate

tylosin phosphate

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Bilosin 200 mg/ml injection

Bimeda Chemicals Ltd

UK National authorisation

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

Pharmasin Granules for drinking water

Huvepharma N.V.

GB National authorisation

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

Tylan Solution for Injection

Elanco Europe Ltd

UK National authorisation

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

Tylucyl Solution for Injection

Vetoquinol UK Ltd

GB National authorisation

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

Formulation and application details

Usually formulated as a solution for injection or as granules for use as a drinking water additive

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

5000

High

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

Melting point (°C)

130

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

2.57 X 10⁰³

Calculated

Log P

3.41

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

13.0

Vapour pressure at 20 °C (mPa)

2.63 X 10^-29

Low volatility

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

2.0 X 10^-26

Non-volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

UV max: approx 282nm

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Monitoring studies have identified this substance in livestock slurries

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

Moderately persistent

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

General literature varies: DT₅₀ >5 days to 95-97 days

Manure DT₅₀ (days)

5.0

DT₅₀ 4.2 days in slurry/sand & 5.7 days slurry/sandy loam;

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

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

Value

Note

Water-sediment DT₅₀ (days)

Water phase only DT₅₀ (days)

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)

52.4

Slightly mobile

K_oc (mL g⁻¹)

3744

Notes and range

Literatue data: K_d range 8.3-128 mL g⁻¹, K_oc values range 553-7988 mL g⁻¹, soils=4

Freundlich

K_f (mL g⁻¹)

4.4

Moderately mobile

K_foc (mL g⁻¹)

323.7

¹/_n

1.15

Notes and range

Literatue data: K_f range 2.3-7.0 mL g⁻¹, K_foc range 153.3-518.2 mL g⁻¹, ¹/_n range 1.06-1.20, soils=4

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

2.95

Calculated

High leachability

Bio-concentration factor

BCF (l kg⁻¹)

Low potential

CT₅₀ (days)

Not available

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

dihydrodesmycosin

Animal

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5000

Rat

Low

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)

> 2122

Gallus domesticus

Low

Birds - Short term dietary (LC₅₀/LD₅₀)

4710 mg kg feed⁻¹

Colinus virginianus

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

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

4530

Aporrectodea caliginosa

Low

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

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)

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

Notes

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)

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)

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)

483

Daphnia magna

Low

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

Daphnia magna

Low

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

45.0

Lemna gibba NOEC 7 day

Low

Aquatic plants (rooted, growth) - Acute 14 day EC₅₀, biomass (mg l⁻¹)

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

1.38

Pseudokirchneriella subcapitata

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)

High (class III)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5000

Rat

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 600 mg kg⁻¹

Rat

Intravenous LD₅₀ = 600 mg kg⁻¹

Rat

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

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

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

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

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Occupational exposure may occur through inhalation and dermal contact

Mammalian dose elimination route and rate

Excreted rapidly in urine. Also found in milk

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

No data found

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May cause diarrhoea and gastrointestinal disturbance

Handling issues

Property

Value and interpretation

General

When heated to decomposition it emits toxic fumes of nitrogen oxide

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

tylosin

French

tylosine

German

Danish

Italian

Spanish

tilosina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	24/02/2024
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