CAS 33419-42-0|Etoposide

Introduction：Basic information about CAS 33419-42-0|Etoposide, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Etoposide BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles411
8. Synonyms

Common Name	Etoposide
CAS Number	33419-42-0	Molecular Weight	588.557
Density	1.6±0.1 g/cm3	Boiling Point	798.1±60.0 °C at 760 mmHg
Molecular Formula	C₂₉H₃₂O₁₃	Melting Point	236-251ºC
MSDS	USA	Flash Point	263.6±26.4 °C
Symbol	GHS07, GHS08	Signal Word	Danger

Names

Name	etoposide
Synonym	More Synonyms

Etoposide BiologicalActivity

Description	Etoposide is a chemotherapy medication used for the treatments of a number of types of cancer. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA.
Related Catalog	Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Autophagy >>MitophagySignaling Pathways >>Cell Cycle/DNA Damage >>TopoisomeraseResearch Areas >>Cancer
Target	Topoisomerase II
In Vitro	Etoposide is capable of causing cytotoxicity on pancreatic β-cells by inducing apoptosis through the JNK/ERK-mediated GSK-3 downstream-triggered mitochondria-dependent signaling pathway in RIN-m5F cells[1]. Etoposide and Bevacizumab significantly abolish P1 sphere-forming ability, an effect associated with apoptosis of this subset of cells[2].
In Vivo	Etoposide (50 μM) and Bevacizumab-treated hypoxic cells injected intravenously into immunodeficient mice reveals a reduced capacity to induce lung colonies, which also appear with a longer latency period[2]. Etoposide (10 mg/kg/day, i.v.) with ifosfamide and carboplatin, reduces the tumor volume in the hepatoblastoma cell injected NMRI nude mice[3].
Kinase Assay	RIN-m5F cells are seeded and treated with Etoposide (10-50 μM) in the absence or presence of Z-DEVD-FMK (20 μM). At the end of treatments (for 24 h), the cell lysates are incubated at 37°C with 10 μM Ac-DEVD-AMC, a caspase-3/CPP32 substrate, for 1 h. The fluorescence of the cleaved substrate is measured by a spectrofluorometer with an excitation wavelength at 380 nm and an emission wavelength at 460 nm. Protein levels of cell lysate samples are determined using the bicinchoninic acid protein assay kit with an absorption band of 570 nm to normalize the cell numbers between control and etoposide-treated groups.
Cell Assay	RIN-m5F cell is a rat pancreatic β-cell line, and cultured in a humidified chamber with a 5% CO2-95% air mixture at 37°C and maintained in RPIM 1640 medium supplemented with 10% fetal bovine serum (FBS) and antibiotics (100 U/mL of penicillin and 100 μg/mL of streptomycin). RIN-m5F cells are seeded (2 × 104 cells/well) in 96-well plates and allowed to adhere and recover overnight. The cells are changed to fresh media and then incubated with Etoposide (1-100 μM) in the absence or presence of the pharmacological inhibitors (lithium chloride (LiCl)-50 μM; SP600125-20 μM; PD98059-20 μM) for 24 h.
Animal Admin	The in vivo model for nude mice HB (NMHB) has been established. Only HB cells with embryonal components are grafted and reproduced successfully in this model. Each NMHB subsequently is transplanted into 50 mice for treatment groups. Treatment is initiated when the majority of the tumors reach a volume of 50-100 mm3. The mice are stratified according to their tumor volume and randomLy assigned to groups of ten animals each. The animals injected with tumor are given ifosfamide, cisplatin, doxorubicin, etoposide (10 mg/kg/day, i.v.), and carboplatin as single agents in two blocks. One group of ten animals for each original xenograft served as a control group. After initiation of treatment, the tumor growth is recorded at 5-day intervals for 25-30 days and the relative tumor volumes are calculated. Twenty-four hours before the animals are sacrificed, bromodeoxyuridine (BrdU) is injected intraperitoneally for the semiquantitative determination of proliferation activity of the tumor cells (50 μg of BrdU/g body weight).
References	[1]. Lee KI, et al. Etoposide induces pancreatic β-cells cytotoxicity via the JNK/ERK/GSK-3 signaling-mediated mitochondria-dependent apoptosis pathway. Toxicol In Vitro. 2016 Jul 26. pii: S0887-2333(16)30147-3. [2]. Calvani M, det al. Etoposide-Bevacizumab a new strategy against human melanoma cells expressing stem-like traits. Oncotarget. 2016 Jun 9. doi: 10.18632/oncotarget.9939. [3]. Fuchs, J., et al. Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma. Cancer, 1998. 83(11): p. 2400-7.

Chemical & Physical Properties

Density	1.6±0.1 g/cm3
Boiling Point	798.1±60.0 °C at 760 mmHg
Melting Point	236-251ºC
Molecular Formula	C₂₉H₃₂O₁₃
Molecular Weight	588.557
Flash Point	263.6±26.4 °C
Exact Mass	588.184265
PSA	160.83000
LogP	0.30
Vapour Pressure	0.0±3.0 mmHg at 25°C
Index of Refraction	1.662
InChIKey	VJJPUSNTGOMMGY-NBJJDLTASA-N
SMILES	COc1cc(C2c3cc4c(cc3C(OC3OC5COC(C)OC5C(O)C3O)C3COC(=O)C23)OCO4)cc(OC)c1O

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KC0190000

CHEMICAL NAME :: Epipodophyllotoxin-beta-D-ethyliden-glucoside, 4'-demethyl-

CAS REGISTRY NUMBER :: 33419-42-0

LAST UPDATED :: 199806

DATA ITEMS CITED :: 90

MOLECULAR FORMULA :: C29-H32-O13

MOLECULAR WEIGHT :: 588.61

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 16 mg/kg/5D-I

TOXIC EFFECTS :: Blood - agranulocytosis Blood - aplastic anemia Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 160 ug/kg/3M-C

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 2630 ug/kg/10D-I

TOXIC EFFECTS :: Blood - agranulocytosis Blood - aplastic anemia Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 183 mg/kg/2H-C

TOXIC EFFECTS :: Behavioral - ataxia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 57 ug/kg/2M-C

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1784 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 39 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >200 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 58 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 215 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 64 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 143 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15070 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 147 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 37 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1400 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1820 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in spleen

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 56 mg/kg/5W-C

TOXIC EFFECTS :: Liver - other changes Endocrine - other changes Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 182 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 700 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1165 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 70 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 116 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 312 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 14630 ug/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 132 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 44 mg/kg

SEX/DURATION :: multigenerations

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 14 mg/kg

SEX/DURATION :: male 5 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 45 mg/kg

SEX/DURATION :: male 90 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 1400 mg/kg

SEX/DURATION :: male 28 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2 mg/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1500 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - oogenesis Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 70 mg/kg

SEX/DURATION :: male 5 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 29120 ug/kg

SEX/DURATION :: male 26 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Unscheduled DNA synthesis

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Mammal - species unspecified Ascites tumor

DOSE/DURATION :: 50 umol/L

REFERENCE :: PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 24,309,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3180 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 9321 (estimated) No. of Female Employees: 8677 (estimated)

Safety Information

Symbol	GHS07, GHS08
Signal Word	Danger
Hazard Statements	H302-H350
Precautionary Statements	P201-P280-P301 + P312 + P330-P308 + P313
Personal Protective Equipment	Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes	T:Toxic
Risk Phrases	R45;R22
Safety Phrases	S53-S45
RIDADR	UN 3249
WGK Germany	3
RTECS	KC0190000
Packaging Group	II
Hazard Class	6.1(a)
HS Code	2932999099

Customs

HS Code	2932999099
Summary	2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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Synonyms

(5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one

VP-16-213

4'-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside)

Vepeside

Etoposide

4'-Demethylepipodophyllotoxin ethylidene-β-D-glucoside

EPEG

MFCD00869325

Etoposide [USAN:BAN:INN:JAN]

Etoposide USP26

Etoposide (VP16)

(5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1R)-ethylidene]-β-D-glucopyranoside

(5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-méthylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(4-hydroxy-3,5-diméthoxyphényl)-5,8,8a,9-tétrahydrofuro[3',4':6,7]naphto[2,3-d][1,3]dioxol-6(5aH)-one

4′-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside)

Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 9-[[4,6-O-[(1R)-ethylidene]-β-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)-

4‘-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside)

EINECS 251-509-1

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