Fluoxetine (Ref: LY-110140)

Fluoxetine (Ref: LY-110140)	Last updated: 22/02/2024
(Also known as: Prozac)

GENERAL INFORMATION

Description

Fluoxetine is an SSRI antidepressant used in veterinary medicine

Availability status

Current

Introduction & key dates

circa 1970 discovered; 1977 introduced to market

Examples of veterinary uses

Used to treat behavioural problems, including aggression and obsessive compulsive behaviour

Examples of species treated

Cats; Dogs; Caged birds

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Fluoxetine has a chiral center giving two enantiomers, R-fluoxetine and S-fluoxetine. The two enantiomers of fluoxetine are similarly effective in blocking serotonin reuptake. Technical materrial is an isomeric mixture.

Chemical formula

C₁₇H₁₈F₃NO

Canonical SMILES

CNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

RTHCYVBBDHJXIQ-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C17H18F3NO/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20/h2-10,16,21H,11-12H2,1H3

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
fluoxetine oxalate	Variant

General status

Veterinary substance type

Antidepressant, Medicinal drug

Substance groups

Unclassified substance

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Selective serotinin reuptake inhibitor (SSRI) Class

Molecular targets

[Sodium-dependent serotonin transporter, Antagonist], [ 5-hydroxytryptamine 2A receptor, Antagonist]

CAS RN

54910-89-3

EC number

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Nervous system: Psychoanaleptics

ATCvet Code

QN06AB03

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

309.33

PIN (Preferred Identification Name)

IUPAC name

N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine

CAS name

N-methyl-γ-(4-(trifluoromethyl)phenoxy)benzenepropanamine

Other status information

Marine pollutant

Relevant Environmental Water Quality Standards

Physical state

White crystalline solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Reconcile Chewable tablets for dogs

Forte Healthcare Ltd

GB National authorisation

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

Formulation and application details

Usually supplied in tablet form

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

60.3

Moderate

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

Melting point (°C)

180

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

3.98 X 10⁰⁴

Calculated

Log P

4.6

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

8.7

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)

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)

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

K_oc

Notes and range

Freundlich

K_f

K_foc

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

Metabolising enzymes

para-trifluoromethylphenol

Human (Liver)

Cytochrome P450 3A4
Cytochrome P450 2C19

norfluoxetine

Human (Liver)

Cytochrome P450 2D6
Cytochrome P450 3A4
Cytochrome P450 2C9

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

825

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

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

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)

0.200

Pimephales promelas

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)

0.94

Daphnia magna

Moderate

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

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

> 0.38

Ceriodaphnia dubia LC₅₀

Moderate

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

0.500

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)

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

0.031

Green algae

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)

825

Rat

Moderate

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

500

Rabbit

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 87.5 mg kg⁻¹

Mouse

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 the urine and also identified in breast 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 sexual dysfunction
Possible liver toxicant
May cause drowsiness, tremor, headache, dizziness and blurred vision
May cause nausea, vomiting and abdominal pain

Handling issues

Property

Value and interpretation

General

Oxidising agent
IMDG Transport Hazard Class 9

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

UN3077

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

fluoxetine

French

fluoxetine

German

Fluoxetin

Danish

fluoxetin

Italian

fluoxetina

Spanish

fluoxetina

Greek

Polish

fluoksetyna

Swedish

fluoxetin

Hungarian

fluoxetin

Dutch

fluoxetine

Norwegian

Record last updated:	22/02/2024
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