Diazepam

Diazepam	Last updated: 21/05/2024
(Also known as: methyl diazepinone; diacepin)

GENERAL INFORMATION

Description

A veterinary drugs used for its antianxiety, muscle relaxant and hypnotic properties

Availability status

Current

Introduction & key dates

1960, first approval for use in humans

Examples of veterinary uses

Has a variety of applications including use as an appetite stimulant and to control seizures

Examples of species treated

Cats; Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Chemical formula

C₁₆H₁₃ClN₂O

Canonical SMILES

CN1C(=O)CN=C(C2=C1C=CC(=C2)Cl)C3=CC=CC=C3

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

AAOVKJBEBIDNHE-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
diazepam	-

General status

Veterinary substance type

Medicinal drug: sedative

Substance groups

Benzodiazepine

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

A positive allosteric modulators of the GABA type A receptors (GABAA).

Molecular targets

[Gamma-aminobutyric acid receptor subunit alpha-1, Potentiator], [Gamma-aminobutyric acid receptor subunit alpha-2, Potentiator], [Gamma-aminobutyric acid receptor subunit alpha-3, Potentiator], [Gamma-aminobutyric acid receptor subunit alpha-5, Potentiator]

CAS RN

439-14-5

EC number

207-122-5

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Anxiolytics: Benzodiazepine derivatives

ATCvet Code

QN05BA01

Controlled Drug?

UK: Class C, Schedule 4 Pt1; EU: UN71, Class IV

Regulation 37/2010 MRL Classification

Molecular mass

284.76

PIN (Preferred Identification Name)

7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

IUPAC name

7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

CAS name

7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to yellow coloured crystalline powder

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Ziapam 5 mg/ml solution

Laboratoire TVM

Not licensed

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

at 25 °C

Moderate

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

500000

Chloroform

25.6

Ether

62500

Methanol

Melting point (°C)

131.5

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

Log P

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

3.4

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.

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

oxazepam

Humans; Animals

desmethyldiazepam
Note: Main active metabolite

Humans; Animals

temazepam

Humans; Animals

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

249

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)

> 12.6

Gambusia holbrooki

Moderate

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

72.0

Danio rerio 14 day

Low

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

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

0.05

Daphnia magna as mol/L

High

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)

> 12.0

Artemia parthenogenetica

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)

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

249

Rat

Moderate

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

800

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 37.0 mg kg⁻¹

Mouse

Intravenous LD₅₀ = 25.0 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

Hepatic metabolism via Cytochrome P450 enzyme system, excreted mainly in the urine

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

CNS toxicant
May cause dermatitis
Lung sensitiser
Possible teratogenic effects

Handling issues

Property

Value and interpretation

General

Will release toxic gases if heated to decomposition
Not compatible with oxidising agents or strong alkalis
IMDG Transport Hazard Class 6.1

CLP classification 2013

Health: H301, H311

WHO Classification

Not listed (Not listed)

UN Number

UN2811

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

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Name

English

diazepam

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Swedish

Hungarian

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Record last updated:	21/05/2024
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