NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	50-18-0
Chemical Name	Cyclophosphamide anhydride
Substance ID	m-nite-50-18-0_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	- -	-	-	Test methods applicable to solid (melting point <= 140 degC) substances are not 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	- -	-	-	The substance is considered to be stable against water since data are available that water solubility is 40 g/L (Merck (14th, 2006) though it contains phosphorus.	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	Classification not possible	- -	-	-	Classification is not possible since no data are available though the substance is an organic compound containing oxygen which is chemically bonded to phosphorus.	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	- -	-	-	Classification is not possible since no data are available though the substance is solid (melting point <= 55 degC).	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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Based on a LD50 value of 180 mg/kg for rats (IARC 26 (1981)), the substance was classified into Category 3.	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	- -	-	-	Classification not possible due to lack of data. Although there is a report that the substance can irritate the skin (SITTIG (5th, 2008)), the details are not clear.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Although there is a report that the substance can irritates the eyes and may cause severe damage (SITTIG (5th, 2008)), the details are not clear.	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 dominant lethal tests (in vivo heritable germ cell mutagenicity test) (IARC vol. 26 (1981)), the substance was classified into Category 1B. As relevant information, there are reports of positive chromosomal aberration tests using Chinese hamster and mouse spermatogonial (in vivo mutagenicity tests in germ cell) (IARC vol. 26 (1981)) and positive mouse and rat micronucleus tests using bone marrow and peripheral blood (in vivo somatic cell mutagenicity tests) (NTP DB (access on Oct. 2009)). For humans, it was reported that there was an increase in the number of chromosomal aberrations in the peripheral blood lymphocytes of children treated with cyclophosphamide for nonmalignant conditions. A similar effect in the peripheral blood lymphocytes was found in patients with rheumatoid arthritis following cyclophosphamide treatment. At 3 or 24-hour after an i.v. administration of cyclophosphamide, patients with recurrent ovarian or uteral carcinoma exhibited similar lymphocytes effects. Changes in bone marrow and lymph-node cells of patients with lymphogranulomatosis were observed at 24 - 72-hour after a single dose of cyclophosphamide (IARC 26 (1981)).	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 100A (2008)), the substance was classified into Category 1A. There were at least 30 case reports of malignancy (nonlymphocytic leukaemias, bladder cancers) in patients treated with the substance, and additionally the 83 cases of second malignancy (nonlymphocytic leukaemias, bladder cancers) were reported (IARC 26 (1981)). Additionally, in a rat lifetime oral administration test, it was reported that organ-specific effects on the urinary bladder were observed and bladder cancers appeared as with human (IARC 26 (1981)).	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	It was reported that cyclophosphamide can damage the germinal cells in males and females and cause sterility in people of either sex (IARC 26 (1981)). It was also reported that no big toes or their respective metatarsals and phalanges, cleft palate, no coronary artery, eye and ear malformation and multiple abnormality were observed in infants from woman treated by the substance during pregnancy (IARC 26 (1981), Birth Defects (3rd, 2000)). Therefore, the substance was classified into Category 1A. In addition, the substance was classified as "Effects on or via lactation" based on a report that the excretion into breast milk was reported (JAPIC prescription drug book (2010)). Tests in animals have shown that cyclophosphamide is teratogenic in animal species such as mice, rats and rabbits (IARC 26 (1981)). There are reports of various malformations such as ophthalmic abnormality and skeletal defects (limb, finger) in rat and mouse tests (IARC vol. 26 (1981), Birth Defects (3rd, 2000)) and cleft palate and agnathia in a rabbit test (Birth Defects (3rd, 2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 1 (bone marrow)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	Based on a report that the substance is an antitumor drug, has significant side effects, myelosuppression (cause leukopenia and thrombocytopenia) (JAPIC prescription drug book (2010)), the substance was classified into Category 1 (bone marrow). As relevant information, in mouse, rat and dog tests, leucopenia and depression of thrombocytes were reported (IARC 26 (1981)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (bone marrow, heart, liver, immune system, systemic)	Danger	H372	P260 P264 P270 P314 P501	Based on a report that the substance is an antineoplastic drug, has significant side effects, myelosuppression (cause pancytopenia, anemia, thrombocytopenia and hemorrhage) (JAPIC prescription drug book (2010)), and a report that myocardial disorder and cardiac failure occur at a frequency of 0.1 - 0.5% or less (JAPIC prescription drug book (2010)), the substance was classified into Category 1 (bone marrow, heart). Since impaired liver function and jaundice are reported as significant side effects while the incidence is not specified (JAPIC prescription drug book (2010)), the substance was classified into Category 1 (liver). Additionally, it was reported that administration of the substance can cause anaphylactoid reaction, hemorrhagic cystitis, and oculomucocutaneous syndrome (Stevens-Johnson syndrome), however, frequencies are not specified. The substance can also cause ileus, gastrointestinal hemorrhage and interstitial pneumonia at a frequency of 0.1 - 0.5% or less (JAPIC prescription drug book (2010)). Since these symptoms are considered to involve the immune system, but the affected organ cannot be identified, the substance was classified into Category 1 (immune system, systemic toxicity). Based on all information, classification is Category 1 (bone marrow, heart, liver, immune system, systemic toxicity).	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.

To GHS Information