Piperazine

Piperazine	Last updated: 22/01/2024
(Also known as: hexahydropyrazine; piperazidine; diethylenediamine; dispermine; 1,4-piperazine)

GENERAL INFORMATION

Description

Medicinal drug used in the treatment of intestinal roundworm infections. It is often formulated using the citrate.

Availability status

Current

Introduction & key dates

1953, first use as an anthelmintic

Examples of veterinary uses

Used in the treatment of intestinal infections/ infestations

Examples of species treated

Cats; Dogs; Poultry; Horses; Pigs

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Chemical formula

C₄H₁₀N₂

Canonical SMILES

C1CNCCN1

Isomeric SMILES

International Chemical Identifier key (InChIKey)

GLUUGHFHXGJENI-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
piperazine	-

General status

Veterinary substance type

Anthelmintic, Medicinal drug, Antiparastic

Substance groups

Hetrocyclic

Minimum active substance purity

99.9

Known relevant impurities

None declared

Substance origin

Synthetic

Mode of action

Acts by paralysing the parasite. Acts as a weak GABA-mimetic and causes a flaccid, reversible paralysis of body wall muscle

Molecular targets

[Gamma-aminobutyric-acid (GABA) receptor subunit beta-3, Agonist]

CAS RN

110-85-0

EC number

203-808-3

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antiparasitic products, insecticides & repellents: Anthelmintics

ATCvet Code

QP52AH01

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Porcine, Chicken)

Molecular mass

86.14

PIN (Preferred Identification Name)

IUPAC name

1,4-diethylenediamine

CAS name

hexahydro-1,4-diazine

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white or colourless deliquescent crystals

Related substances & organisms

piperazine citrate

piperazine phosphate

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Formulation and application details

Usually supplied as tablets or solutions for oral use utilisng the citrate salt

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

150000

at pH 12

High

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

Melting point (°C)

107

Boiling point (°C)

148

Degradation point (°C)

Flashpoint (°C)

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

7.59 X 10^-02

Calculated

Log P

-1.12

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.1

Dissociation constant pKa) at 25 °C

4.19

Strong base

Vapour pressure at 20 °C (mPa)

21280

Highly volatile. If applied directly to plants or soil, drift is a concern & mitigation is advisable

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

Does not absorb at wavelengths >290 nm

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

Very mobile

K_oc

3.1

Notes and range

Estimated

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)

3.9

Cyprinus carpio

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

Metabolising enzymes

N -mononitrosopiperazine

MNPz

Human (Liver)

N-nitroso-3-hydroxypyrrolidine
Note: Secondary metabolite

NHPYR

Human (Liver)

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)

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)

> 100

Unknown species

Low

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)

> 21.0

Daphnia magna

Moderate

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

> 12.5

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 - Acute 7 day EC₅₀, biomass (mg l⁻¹)

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

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)

> 5000

Rat

Low

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

4000

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

> 5.4

Rat 2 hr

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 3700 mg kg⁻¹

Rat

Intravenous LD₅₀ = 1340 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

Urinary excretion is the primary route of elimination in humans

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

No data found

; ; ; ;

No data found

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

No data found

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

No data found

General human health issues

May induce chronic bronchitis and cause breathing difficulties

Handling issues

Property

Value and interpretation

General

Corrosive
Hygroscopic
Flammable
IMDG Transport Hazard Class 8
Explosion limits in air: 4-14 % vol

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

UN2579

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

piperazine

French

German

Piperazin

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	22/01/2024
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