GHS Classification Result

Chemical Name：(SP-4-2)-Diamminedichloroplatinum, (alias Cisplatin)
CAS：15663-27-1

Result：
ID: 21A3741
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 - - - - No data available.
12 Substances and mixtures which, in contact with water, emit flammable gases Not classified - - - - Information is available that water solubility is 0.253 g/100 g (25 degC) (Merck (14th, 2006)) though it contains metals.
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 inorganic compound containing halogen atoms (Cl).
15 Organic peroxides Not applicable - - - - Inorganic compound
16 Corrosive to metals Classification not possible - - - - Test methods applicable to solid substances are not available.

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity （Oral） Category 2 Danger H300: Fatal 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 approximately 20 mg/kg for rats (EHC No. 125 (1991)), the substance was classified into Category 2.
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 Not classified - - - - Based on a result of "mild irritant" with a skin primary irritation index of 0.13 in a rabbit patch test (24-hour application) (EHC No. 125 (1991)), the substance was classified as "Not classified" in JIS Classification (correspond to Category 3 in GHS classification).
3 Serious eye damage/eye irritation Category 2A Warning H319: Causes serious eye irritation P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P337+P313: If eye irritation persists: Get medical advice/attention.
P264: Wash ... thoroughly after handling.
P280: Wear protective gloves/protective clothing/eye protection/face protection. 		Based on a result of "severely irritating" in a rabbit test (EHC No. 125 (1991)), the substance was classified into Category 2A. As relevant information, there is a report that the dusts of soluble platinum salts cause a burning sensation in the eyes, lacrimation, and conjunctival hyperemia, sometimes associated with photophobia, which suggests that the corneal epithelium may be involved (HSDB (2009)).
4 Respiratory sensitization Classification not possible - - - - Classification not possible due to lack of data for respiratory sensitization. There is a report of "neutral complexes of platinum such as this substance are not allergenic, since they probably do not react with proteins to form a complete antigen" (EHC 125 (1991)).
4 Skin sensitization Not classified - - - - Based on a report of "neutral complexes of platinum such as this substance are not allergenic, since they probably do not react with proteins to form a complete antigen" (EHC No. 125 (1991)), the substance was classified into Category 1.
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 a positive result in a mouse spermatocyte chromosomal aberration test (in vivo test) (PATTY (5th, 2001)), the substance was classified into Category 1B. As relevant information, there are other in vivo test reports of a negative mouse dominant lethal test (IARC suppl. 7 (1987)), positive mouse and rat bone marrow chromosomal aberration tests (EHC No. 125 (1991), PATTY (5th, 2001)), a positive mouse bone marrow sister chromatid exchange test (EHC No. 125 (1991)), and a positive mouse somatic cell DNA adduct formation test (PATTY (5th, 2001)). From in vitro mutagenicity tests, there are reports of a positive Ames tests, a positive chromosomal aberration tests and a positive micronucleus tests (EHC No. 125 (1991), IARC vol. 26 (1981), NTP DB (access on Oct. 2009)).
6 Carcinogenicity Category 1B 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 2A" in IARC (IARC suppl. 7 (1987)), the substance was classified into Category 1B. No epidemiological test of the substance as a single agent are available. Among animal examinations, intraperitoneal administrations to mice increased the incidence of lung adenomas and similar treatments increased the incidence of skin papillomas in mice given promoting treatment of croton oil applied to the skin. In two tests, multiple intraperitoneal injections to rats induced leukaemia (IARC suppl. 7 (1987)).
7 Reproductive toxicity Category 1B, 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. 		There are human case reports that among 13 women treated with cytostatic drugs containing the substance during the first trimester of pregnancy, lower birth weight was noted in two of five mothers who continued the pregnancy until child birth and spontaneous abortions occurred in 4 women (PATTY (5th, 2001)). The substance was shown to cause azoospermia within 2 months after initiation of treatment (HSDB (2009)). In the substance's package insert, it is reported that "This drug should not be given to pregnant women and women suspected of being pregnant", "(in animal tests) teratogenic effects and increased fetal lethality in rats and increased fetal lethality in rabbits were observed and teratogenic and fetal lethal effects were reported in mice." "If mothers take this drug, they must be instructed not to breast feed (the substance was reported to pass into breast milk" (cisplatin drug RANDA Injection package insert (2009)). Based on this information, the substance was classified into Category 1A, "Effects on or via lactation".
8 Specific target organ toxicity - Single exposure Category 1 (digestive system, bone marrow, kidney, nervous system) Danger H370: Causes damage to organs (digestive system, bone marrow, kidney, nervous system) 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 ... 		The substance was used as an antineoplastic drug, so human toxicity data are available from adverse drug reaction reports for treated patients. There are no data for the oral, dermal and inhalation routes and it is difficult to determine whether a single dose or repeated doses were involved. The following symptoms are reported as the substance's acute toxicity: intractable nausea and vomiting as toxicity to the gut; leucopenia, thrombocytopenia as toxicity to the bone marrow (IARC vol. 26 (1981)), renal tubular function impairment as toxicity to the kidney, decreased hearing, "thick" speech, impairment of taste, numbness of hands, gait disturbances, loss of reduction of deep tendon reflexes, disorientation, paranoia, sensory function loss and motor function loss as toxicity to the nervous system (PIM 132 (1992)). The substance was classified into Category 1 (alimentary system, bone marrow, kidney, nervous system). As relevant information, mild and transient liver toxicity has occurred (PIM 132 (1992)). However, this information was not used as the basis of classification since there is a report that rarer risks include hepatic effects (PIM 132 (1992)).
9 Specific target organ toxicity - Repeated exposure Category 1 (bone marrow, kidney, nervous system, digestive system, systemic toxicity) Danger H372: Cause damage to organs through prolonged or repeated exposure (bone marrow, kidney, nervous system, digestive 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 ... 		The substance was used as antineoplastic drug, so human toxicity data are available from adverse drug reaction reports for treated patients. There are no data for oral, dermal or inhalation routes of exposure. The following symptoms are reported as long term therapy effects; anemia, thrombocytopenia, leucopenia as toxicity to the bone marrow, remarkable decrease in glomerular filtration rate as toxicity to the kidney, peripheral neuropathy, optic neuritis, papilledema, vibration sensory and hyporeflexia of the ankle, epileptic seizure, marked nausea and vomiting, and gastrointestinal disorder as toxicity to the gut (PATTY (5th, 2001), PIM 132 (1992)). Based on all the data, the substance was classified into Category 1 (bone marrow, kidney, nervous system, alimentary system). In the substance's package insert, there are the following reports as significant adverse reactions; acute renal failure, myelosuppression such as pancytopenia, shock, anaphylactoid reaction, decreased hearing, hearing loss, tinnitus, papilledema, retrobulbar neuritis, cortical blindness, cerebral infarction, transient ischemic attack, hemolytic-uremic syndrome, myocardial infarction, angina pectoris, congestive heart failure, cardiac arrhythmia, hemolytic anemia, interstitial pneumonitis, syndrome of inappropriate secretion of antidiuretic hormone, fulminant hepatitis, hepatic dysfunction, jaundice, gastrointestinal hemorrhage, peptic ulcer, gastrointestinal perforation, acute pancreatitis, hyperglycemia, exacerbation of diabetes, and rhabdomyolysis (cisplatin drug RANDA Injection package insert (2009)). Based on the information, the substance was classified into Category 1 (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）

To GHS Information