Diphenhydramine

Diphenhydramine	Last updated: 10/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

Diphenhydramine is a histamine blocker used in veterinary medicine but now considered obsolete

Examples of veterinary uses

Once used in veterinary practice to treat allergies and atopy primarily in dogs but also in some other species.

Examples of species treated

Dogs; Cats; Horses

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Diphenhydramine does not exhibit stereoisomerism, as its molecular structure lacks chiral centres. However, it can adopt different conformational isomers due to rotation around single bonds, particularly in the flexible ethylamine and diphenylmethoxy segments. These conformers may influence its binding affinity to receptors like H₁ histamine and muscarinic acetylcholine receptors, but they do not constitute distinct isomeric forms in the classical sense.

Chemical formula

C₁₇H₂₁NO

Canonical SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

ZZVUWRFHKOJYTH-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
Diphenhydramine hydrochloride	Variant

General status

Veterinary substance type

Medicinal drug: Histamine blocker

Substance groups

Diphenylmethane

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Diphenhydramine competes with free histamine for binding at HA-receptor sites.

Molecular targets

[Histamine H1 receptor, Antagonist], [Muscarinic cholinergic receptors (Ki = 100 to 260 nM for M1 through M5), Antagonist]

CAS RN

58-73-1

Alternative/old CAS RN

1720-32-7; 184163-39-1

EC number

200-396-7

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antihistamines for systemic use: Aminoalkyl ethers

ATCvet Code

QR06AA02

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

255.36

PIN (Preferred Identification Name)

2-(diphenylmethoxy)-N,N-dimethylethanamine

IUPAC name

2-(diphenylmethoxy)-N,N-dimethylethanamine

CAS name

2-((diphenylmethyl)oxy)-N,N-dimethylethanamine

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Powdery solid

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1943, discovered; 1946, first medical use approvals USA

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

AdvaCare Pharma

Example products using this active

Vetadryl

Formulation and application details

Usually supplied as chewable tablets

Commercial production

Diphenhydramine is synthesised through a two-step process. The first step involves the formation of benzhydrol, which serves as the central scaffold. This compound is then reacted with 2-dimethylaminoethanol in the presence of an acid catalyst under reflux conditions in a solvent like toluene. The reaction proceeds via etherification, forming the key diphenylmethoxy linkage that characterises diphenhydramine.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

3060

High

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

Melting point (°C)

161

Boiling point (°C)

150

Degradation point (°C)

Flashpoint (°C)

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

1.86 X 10⁰³

Calculated

Log P

3.27

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

8.89

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)

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 metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

160

Mouse

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 dw soil)

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

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)

> 0.525

Ceriodaphnia dubia

Moderate

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

160

Mouse

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 56.0 mg kg⁻¹

Mouse

Intravenous LD₅₀ = 42.0 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

Excreted mostly unchanged in urine.

Ceriodaphnia dubia

Health issues

Specific human health issues (hazard-based)

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

Possible liver & kidney toxicant
Sedative
CNS depressant
High doses may cause myocardial infarction (heart attack)

Handling issues

Property

Value and interpretation

General

Will produce toxic gases when heated to decomposition

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

diphenhydramine

French

diphenhydramine

German

Danish

Italian

difenhidramina

Spanish

difenhidramina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	10/09/2025
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