MITOTOX

Drug

D1392 | Chlorambucil

Properties

Molecular Formula	C14H19Cl2NO2
Molecular Weight	304.2
Structure
State	solid
Route of elimination	Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.
Protein binding	0.99
Half life	1.5 hours

Therapeutic Classification Source: DrugBank

L01AA02 Chlorambucil

[L01AA] Nitrogen mustard analogues

[L01A] ALKYLATING AGENTS

[L01] ANTINEOPLASTIC AGENTS

[L] Antineoplastic and immunomodulating agents

Mitochondrial Toxicity Evaulation

Toxicity	Dose	Time	Species	Model	Method	Action	Positive criterion	Reference
MEMBRANE POTENTIAL	> 200 µM	30 mins	mouse	liver mitochondria	Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss)	decrease	EC20	36
RESPIRATION	138.7 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition.	decrease	EC20	36
RESPIRATION	140.9 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition.	decrease	EC20	36
SWELLING	> 200 µM	30 mins	mouse	liver mitochondria	swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling )	increase	EC20	36

Targets

Target	Dose	Time	Species	Model	Method	Action	Positive criterion	Reference
NADH:ubiquinone reductase	138.7 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition.	inhibit	EC20	36
Succinate dehydrogenase	140.9 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition.	inhibit	EC20	36
Cytochrome c	> 200 µM	30 mins	mouse	liver mitochondria	Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline)	release	EC20	36

GHS Hazard Tables Source: PubChem

Pictogram	Signal	Statements	Precautionary Statement Codes
	Danger	Aggregated GHS information provided by 45 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral] H315 (95.56%): Causes skin irritation [Warning Skin corrosion/irritation] H319 (95.56%): Causes serious eye irritation [Warning Serious eye damage/eye irritation] H335 (88.89%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure Respiratory tract irritation] H350 (95.56%): May cause cancer [Danger Carcinogenicity] H360 (13.33%): May damage fertility or the unborn child [Danger Reproductive toxicity] Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.	P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
	Danger	H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity] H350: May cause cancer [Danger Carcinogenicity] H360: May damage fertility or the unborn child [Danger Reproductive toxicity] H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure] H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]	P201, P202, P260, P264, P270, P281, P307+P311, P308+P313, P314, P321, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Pictogram

Signal

Statements

Precautionary Statement Codes

Danger

Aggregated GHS information provided by 45 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

H315 (95.56%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (95.56%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (88.89%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure

Respiratory tract irritation]

H350 (95.56%): May cause cancer [Danger Carcinogenicity]

H360 (13.33%): May damage fertility or the unborn child [Danger Reproductive toxicity]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Danger

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H350: May cause cancer [Danger Carcinogenicity]

H360: May damage fertility or the unborn child [Danger Reproductive toxicity]

H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P201, P202, P260, P264, P270, P281, P307+P311, P308+P313, P314, P321, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Indications Source: SIDER

External IDs

DrugBank	DB00291
CAS Number	305-03-3, 38186-88-8
PubChem Compound	2708