NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	33419-42-0
Chemical Name	Etoposide
Substance ID	m-nite-33419-42-0_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance contains oxygen which is chemically bonded only to carbon or hydrogen.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	LD50 values of 1949 (male) and 1784 (female) mg/kg bw for rats (RTECS (2009), KSRNAM Kiso to Rinsho. Clinical Report. vol. 19, 3473 (1985)) correspond to Category 4.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Skin corrosion/irritation	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Skin sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	Based on positive results in rat and mouse spermatid micronucleus tests as well as a mouse metaphase oocyte chromosomal aberration test and an aneuploidy test (intraperitoneal injection) (IARC vol. 76 (2000)), the substance was classified into Category 1B. As relevant information, from in vitro mutagenicity tests, the results in most Ames tests were negative and results in cell chromosomal aberration tests and micronucleus tests were positive (IARC vol. 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	Based on the classification of "Group 1" in IARC (IARC vol. 100A (2008)), the substance was classified into Category 1A. Many reports of myeloid leukaemia after treatment of cancer patients with the substance as a cytostatic drug were published. However, in a knockout mouse model test, increased incidence of leukaemia was not observed (IARC vol. 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Reproductive toxicity	Category 1A,	Danger	H360 H362	P308+P313 P201 P202 P260 P263 P264 P270 P280 P405 P501	The substance is used as an anticancer agent. In a test of 20 young and two older (=<50 years) women with gestational trophoblastic disease treated orally with etoposide, transient ovarian failure lasting two to four months was observed in five of the young women, and the two older women both had permanent ovarian failure (IARC vol. 76 (2000)). It was reported that the substance was used to induce abortion in two cases of ectopic pregnancy (IARC vol. 76 (2000)). Since these data show clear evidences of reproductive and developmental toxicity without dosage data, the substance was classified into Category 1A. Based on a report in an etoposide package insert that "If mothers take this drug, they must be instructed not to breast feed. The excretion into breast milk was reported in animals (rats)", the substance was classified as "Effects on or via lactation".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 2 (systemic)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	From information under the Adverse Reactions section of the package insert of Etoposide, there are the following reports; myelosuppression (pancytopenia, leukopenia, neutropenia, thrombocytopenia and hemorrhage, anemia, etc.), anaphylactic reaction (cyanosis, dyspnea, chest discomfort, reduction in blood pressure), interstitial pneumonia with fever, cough, dyspnea, chest x-ray abnormality, eosinophilia and etc., kidney or liver dysfunction, nausea, vomiting, anorexia, stomatitis, diarrhea, abdominal pain, constipation, rash, alopecia, erythema, itching, pigmentation, headache, numbness, transient cortical blindness, tachycardia, abnormal ECG, cardiac arrhythmia, reduction in blood pressure, electrolyte abnormality, malaise, fever, facial flushing, edema, decreased serum total protein, and dysgeusia. Since it is unclear whether these are acute effects, the substance was classified into Category 2 (systemic toxicity). As relevant information, it was reported that after intravenous infusion of a single dose of etoposide phosphate to dogs, leukopenia and thrombocytopenia was observed (IARC vol. 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (bone marrow, lung, systemic)	Danger	H372	P260 P264 P270 P314 P501	From information under the Adverse Reactions section of the package insert of Etoposide, there are the following reports; significant adverse reactions: myelosuppression (pancytopenia, leukopenia, neutropenia, thrombocytopenia and hemorrhage, anemia, etc.), anaphylactic reaction (cyanosis, dyspnea, chest discomfort, reduction in blood pressure), interstitial pneumonia (interstitial pneumonia with fever, cough, dyspnea, chest x-ray abnormality, eosinophilia, etc.). Based on the data, the substance was classified into Category 1 (bone marrow, lung, systemic toxicity). As relevant information, there are the following reports; other adverse reactions: kidney or liver dysfunction, nausea, vomiting, anorexia, stomatitis, diarrhea, abdominal pain, constipation, rash, alopecia, erythema, itching, pigmentation, headache, numbness, transient cortical blindness, tachycardia, abnormal ECG, cardiac arrhythmia, reduction in blood pressure, electrolyte abnormality, malaise, fever, facial flushing, edema, decreased serum total protein, and dysgeusia. As relevant information, myelosuppression, leukopenia and neutropenia were reported as toxic effects in humans following oral and intravenous administration of the substance (IARC vol. 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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