GHS Classification Result

Chemical Name:Cyclophosphamide anhydride
CAS:50-18-0

Result:
ID: 21A3731
Classifier: Ministry of Health, Labour and Welfare (MHLW), Ministry of the Environment (MOE)
Year Classified: FY2009
Reference Manual: GHS Classification Guidance by the Japanese Government (March, 2009)

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Explosives Not applicable - - - - There are no chemical groups associated with explosive properties present in the molecules.
2 Flammable gases (including chemically unstable gases) Not applicable - - - - Solid (GHS definition)
3 Aerosols Not applicable - - - - Not aerosol products.
4 Oxidizing gases Not applicable - - - - Solid (GHS definition)
5 Gases under pressure Not applicable - - - - Solid (GHS definition)
6 Flammable liquids Not applicable - - - - Solid (GHS definition)
7 Flammable solids Classification not possible - - - - No data available.
8 Self-reactive substances and mixtures Not applicable - - - - There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9 Pyrophoric liquids Not applicable - - - - Solid (GHS definition)
10 Pyrophoric solids Classification not possible - - - - No data available.
11 Self-heating substances and mixtures Classification not possible - - - - Test methods applicable to solid (melting point <= 140 degC) substances are not available.
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.
13 Oxidizing liquids Not applicable - - - - Solid (GHS definition)
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.
15 Organic peroxides Not applicable - - - - Organic compounds containing no bivalent -O-O- structure
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).

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity (Oral) Category 3 Danger H301: Toxic if swallowed P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment (see ... on this label).
P330: Rinse mouth.
P405: Store locked up.
P501: Dispose of contents/container to ...
Based on a LD50 value of 180 mg/kg for rats (IARC 26 (1981)), the substance was classified into Category 3.
1 Acute toxicity (Dermal) Classification not possible - - - - No data available.
1 Acute toxicity (Inhalation: Gases) Not applicable - - - - Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible - - - - No data available.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible - - - - No data available.
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.
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.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - No data available.
5 Germ cell mutagenicity Category 1B Danger H340: May cause genetic defects P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
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)).
6 Carcinogenicity Category 1A Danger H350: May cause cancer P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
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)).
7 Reproductive toxicity Category 1A, Additional category: Effects on or via lactation Danger H360: May damage fertility or the unborn child
H362: May cause harm to breast-fed children
P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P263: Avoid contact during pregnancy/while nursing.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
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)).
8 Specific target organ toxicity - Single exposure Category 1 (bone marrow) Danger H370: Causes damage to organs (bone marrow) P307+P311: IF exposed: Call a POISON CENTER or doctor/physician.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment (see ... on this label).
P405: Store locked up.
P501: Dispose of contents/container to ...
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)).
9 Specific target organ toxicity - Repeated exposure Category 1 (bone marrow, heart, liver, immune system, systemic toxicity) Danger H372: Cause damage to organs through prolonged or repeated exposure (bone marrow, heart, liver, immune system, systemic toxicity) P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ...
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).
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment (Acute) Classification not possible - - - - No data available.
11 Hazardous to the aquatic environment (Long-term) Classification not possible - - - - No data available.


NOTE:
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.

Reference:
Reference Manual

Definitions / Abbreviations

Model Label by MHLW

MHLW Website (in Japanese Only)

Model SDS by MHLW

MHLW Website (in Japanese Only)


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