Diltiazem	Last updated: 18/05/2024
(Also known as: d-cis-diltiazem )

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GENERAL INFORMATION

Description	A non-dihydropyridine (non-DHP) veterinary drug usually formulated as the hydrochloride
Availability status	Current
Introduction & key dates	-
Examples of veterinary uses	Used in the treatment of atrial fibrillation, supraventricular tachycardias, hypertrophic cardiomyopathy and hypertension
Examples of species treated	Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)	Approved
EU Regulatory approval status	Approved

Chemical structure

Isomerism	Isomeric
Chemical formula	C₂₂H₂₆N₂O₄S
Canonical SMILES	CC(=O)OC1C(SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC
Isomeric SMILES	CC(=O)O[C@@H]1[C@@H](SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC
International Chemical Identifier key (InChIKey)	HSUGRBWQSSZJOP-RTWAWAEBSA-N
International Chemical Identifier (InChI)	InChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1
2D structure diagram/image available?	Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
diltiazem	-

General status

Veterinary substance type	Vasodilator, Medicinal drug
Substance groups	Unclassified substance
Minimum active substance purity	-
Known relevant impurities	-
Substance origin	Synthetic
Mode of action	A calcium channel blocker
Molecular targets	[Voltage-dependent calcium channel gamma-1 subunit, Antagonist]
CAS RN	42399-41-7
EC number	255-796-4
CIPAC number	-
US EPA chemical code	-
PubChem CID	-
Therapeutic Class	Cardiobascular system: Calcium channel blockers
ATCvet Code	QC08DB01
Controlled Drug?	No
Regulation 37/2010 MRL Classification	-
Molecular mass	414.52
PIN (Preferred Identification Name)	-
IUPAC name	cis-(+)-[2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl)-3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9,11-trien-4-yl]ethanoate
CAS name	-
Other status information	-
Relevant Environmental Water Quality Standards	-
Physical state	White crystalline powder
Related substances & organisms	diltiazem hydrochloride

Formulations

Property	Product	Manufacturer	Authorisation Route	Legal Class (GB/UK)
Example products (past and present) using this active	-	-	-	-
Formulation and application details	Generally formulated as oral tablets using the hydrochloride salt

ENVIRONMENTAL FATE

Property		Value	Source; quality score; and other information	Interpretation
Solubility - In water at 20 °C (mg l⁻¹)		465	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	Moderate
Solubility - In organic solvents at 20 °C (mg l⁻¹)		-	-	-
Melting point (°C)		231	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data	-
Boiling point (°C)		Decomposes before boiling	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	-
Degradation point (°C)		212	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	-
Flashpoint (°C)		-	-	-
Octanol-water partition coefficient at pH 7, 20 °C	P	6.17 X 1002	Calculated	-
	Log P	2.79	R4 R = Peer reviewed scientific publications 4 = Verified data	Moderate
Fat solubility of residues	Solubility	-	-	-
	Data type	-	-	-
Density (g ml⁻¹)		-	-	-
Dissociation constant pKa) at 25 °C		8.90	R4 R = Peer reviewed scientific publications 4 = Verified data	-
		-
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	Kd (mL g⁻¹)	-	-	-
	Koc (mL g⁻¹)	-
	Notes and range	-
Freundlich	Kf (mL g⁻¹)	-	-	-
	Kfoc (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
N-demethyldiltiazem	-	Human (Liver)	-
deacetyldiltiazem	-	Human	-
desacetyldiltiazem	-	Human	-

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property		Value	Source; quality score; and other information	Interpretation
Mammals - Acute oral LD₅₀ (mg kg⁻¹)		740	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data 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)		-	-	-
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	-	-	-
	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)		15.0	R4 R = Peer reviewed scientific publications 4 = Verified data Oryzias latipes	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)		28.0	R4 R = Peer reviewed scientific publications 4 = Verified data 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)		-	-	-
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, growth) - Acute 7 day EC₅₀, biomass (mg l⁻¹)		-	-	-
Aquatic plants (rooted, growth) - Acute 14 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	-	-	-
	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)		740	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data Mouse	Moderate
Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)		-	-	-
Mammals - Inhalation LC₅₀ (mg l⁻¹)		-	-	-
Other Mammal toxicity endpoints		Intraperitoneal LDLo = 220 mg kg⁻¹	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source Mouse	-
		Intravenous LD₅₀ = 61 mg kg⁻¹	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source 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		Metabolised in the liver and excreted in the urine	A5 A = EU regulatory and evaluation data as published by EC, EFSA (RAR, DAR & Conclusion dossiers), EMA (e.g. EU Annex III PIC DGD) (EU - Pesticides database; EFSA Scientific Publications ) 5 = Verified data used for regulatory purposes	-

Health issues

Specific human health issues		Carcinogen Genotoxic Endocrine disruptor XNo, known not to cause a problem A0 A = Chromosome aberration (EFSA database) 0 = No data ; B0 B = DNA damage/repair (EFSA database) 0 = No data ; C0 C = Gene mutation (EFSA database) 0 = No data ; D0 D = Genome mutation (EFSA database) 0 = No data ; E0 E = Unspecified genotoxicity type (miscellaneous data source) 0 = No data No data found Reproduction / development effects Acetyl cholinesterase inhibitor Neurotoxicant ✓Yes, known to cause a problem No data found ✓Yes, known to cause a problem Respiratory tract irritant Skin irritant Skin sensitiser XNo, known not to cause a problem XNo, known not to cause a problem No data found Eye irritant Phototoxicant   XNo, known not to cause a problem No data found
General human health issues		May cause anorexia, vomiting, diarrhoea, abdominal pain, paralytic ileus and dyspepsia Teratogenic

Handling issues

Property	Value and interpretation
General	No information available
CLP classification 2013	-
WHO Classification	Not listed (Not listed)
UN Number	-
Waste disposal & packaging	-
Shelf-life, storage, stability and reactivity	-

TRANSLATIONS

Language	Name
English	diltiazem
French	-
German	-
Danish	-
Italian	-
Spanish	-
Greek	-
Polish	-
Swedish	-
Hungarian	-
Dutch	-
Norwegian	-

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Record last updated:	18/05/2024
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