Cyclosporin A

Cyclosporin A	Last updated: 12/09/2025
(Also known as: cyclosporin; CsA; cyclosporine; antibiotic S 7481F1 ; ciclosporin; ciclosporin A)

GENERAL INFORMATION

Description

A steroid-sparing immunosuppressant veterinary medication

Examples of veterinary uses

Used mainly to treat autoimmune and inflammatory conditions including skin issues such as psoriasis, dermatitis, ulcerative colitis and rheumatoid arthritis. It is also used to used to treat dry eye conditions and pannus in dogs.

Examples of species treated

Dogs; Cats; Horses

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved - usually available as a prescription only medicine to be authorised by a veterinarian (POM-V)

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Cyclosporin, particularly cyclosporin A, exhibits stereoisomerism and conformational isomerism due to its structure as a cyclic undecapeptide composed of several chiral amino acids. Each amino acid contributes to the molecule’s overall chirality, and the cyclic nature allows for multiple conformers, distinct spatial arrangements that arise from rotation around single bonds without breaking the peptide ring. Additionally, enantiomers and structural isomers of cyclosporin analogues exist, such as cyclosporin H and isocyclosporin A, which differ in stereochemistry or connectivity but retain similar molecular formulas.

Chemical formula

C₆₂H₁₁₁N₁₁O₁₂

Canonical SMILES

CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)CC=CC)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C

Isomeric SMILES

CC[C@H]1C(=O)N(CC(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1)[C@@H]([C@H](C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C

International Chemical Identifier key (InChIKey)

PMATZTZNYRCHOR-CGLBZJNRSA-N

International Chemical Identifier (InChI)

InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
cyclosporin A	-

General status

Veterinary substance type

Medicinal drug; Fungicide

Substance groups

Diderophore

Minimum active substance purity

98%

Known relevant impurities

Substance origin

Synthetic

Mode of action

Prevents the dephosphorlyation of NF-AT by binding to cyclophilin. Calcineurin inhibitor

Molecular targets

[Calcium signal-modulating cyclophilin ligand, Binder], [Calcineurin subunit B type 2, Inhibitor], [Peptidyl-prolyl cis-trans isomerase A, inhibitor], [Peptidyl-prolyl cis-trans isomerase F, mitochondrial, Binder]

CAS RN

59865-13-3

EC number

611-907-1

CIPAC number

US EPA chemical code

PubChem CID

5284373

Therapeutic Class

Antineoplastic & immunomodulating agents: Immunosuppressants; Sensory Organs: Ophthalmologicals

ATCvet Code

QL04AD01; QS01XA18

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

1202.61

PIN (Preferred Identification Name)

30-ethyl-33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone

IUPAC name

CAS name

(E)-14,17,26,32-tetrabutyl-5-ethyl-8-(1-hydroxy-2-methylhex-4-enyl) -1,3,9,12,15,18,20,23,27-nonamethyl-11,29-dipropyl-1,3,6,9,12,15,18,21,24,27,30- undecaazacyclodotriacontan-2,4,7,10,13,16,19,22,25,28,31-undecaone

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

White powdery solid

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1971, discovered

Example manufacturers & suppliers of products using this active now or historically

Elanco GmbH
Novartis Animal Health
Virbac Ltd

Example products using this active

Atopica Soft Capsules
Optimmune Ophthalmic Ointment
Cyclavance Oral Solution

Formulation and application details

Available in a variety of formulations including liquids, ointments and tablets for oral administration

Commercial production

Cyclosporin A is produced through microbial fermentation, primarily using the fungus Tolypocladium inflatum under submerged culture conditions. The process begins with cultivating the fungus in a nutrient-rich medium containing carbon sources like sorbose or myo-inositol, which significantly influence yield. Fermentation typically lasts around 10 days, during which the fungus synthesises cyclosporin as a secondary metabolite. To enhance production, strategies such as mutant strain development, optimised feeding schedules, and controlled environmental conditions are employed. After fermentation, the broth undergoes downstream processing, including filtration, solvent extraction, and purification via chromatography to isolate cyclosporin A in its active form.

Impact on climate of production and use

As microbial-based products tend to use fermentation-based production processes rather than chemical synthesis, they typically have a lower fossil fuel input in formulation and active ingredient creation, and also have reduced downstream emissions due to biodegradability and minimal soil disruption, their life-cycle GHG emissions are expected to be low. Whilst hard and precise data is not available, broad estimates suggest that typically emissions are likely to be below 5 kg CO₂e/kg.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

28.6

Moderate

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

200000

Ethanol

100000

DMSO

Melting point (°C)

150

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

8.32 X 10⁰²

Calculated

Log P

2.92

Moderate

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

Vapour pressure at 20 °C (mPa)

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

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)

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

Composed soil

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)

K_oc (mL g⁻¹)

Notes and range

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

Bio-concentration factor

BCF (l kg⁻¹)

CT₅₀ (days)

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

Metabolite AM1; cyclosprorin M17

Human (Liver)

Metabolite AM4N

Human (Liver)

Metabolite AM9

Human (Liver)

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 1480

Rat

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)

Birds - Short term dietary (LC₅₀/LD₅₀)

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

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

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

Soil micro-organisms

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

Non-target plants

Vegetative vigour ER₅₀ (g ha⁻¹)

Seedling emergence ER₅₀ (g ha⁻¹)

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)

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)

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, fonds growth, fresh) - 7 day (mg l⁻¹)

Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)

Algae - Acute (growth rate, fresh; mg l⁻¹)

Algae - Chronic (growth rate, fresh; 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)

> 1480

Rat

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 147 mg kg⁻¹

Rat

Subcutaneous LD₅₀ = 286 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

Mammalian dose elimination route and rate

Extensively metabolised in the liver and excreted in human bile, faeces, blood, & urine. Excreted into human breast milk

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

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

Possible liver and kidney toxicant
May cause gingival hyperplasia, convulsions, peptic ulcers, pancreatitis, fever
Ingestion can cause vomiting, diarrhoea, confusion & hypercholesterolemia
CLP data - known carcinogen
May elevate blood pressure

Handling issues

Property

Value and interpretation

General

Incompatible with strong oxidising agents

CLP classification 2013

Health: H302, H350, H360fd

WHO Classification

Not listed (Not listed)

UN Number

Not registered

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

Store \at around 25 DegC. Do not refridgerate. Generally chemically stable

TRANSLATIONS

Language

Name

English

cyclosporin A

French

ciclosporine

German

Danish

Italian

Spanish

ciclosporina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	12/09/2025
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