NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	15663-27-1
Chemical Name	(SP-4-2)-Diamminedichloroplatinum (Cisplatin)
Substance ID	m-nite-15663-27-1_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	- -	-	-	Information is available that water solubility is 0.253 g/100 g (25 degC) (Merck (14th, 2006)) though it contains metals.	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 inorganic compound containing halogen atoms (Cl).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Inorganic compound	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 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	Based on a LD50 value of approximately 20 mg/kg for rats (EHC No. 125 (1991)), the substance was classified into Category 2.	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	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).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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.	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 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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the IARC's classification result (1)-(3) and test results of (4)-(6), it was classified in Category 1B. After reviewing the previous classification due to the revision of the classification by IARC, the category remained to be 1B for this substance because the IARC's revised classification is for the combined use with other substances. Combination therapy of etoposide, this substance, and bleomycin is carcinogenic to humans as shown in (7), (8). [Evidence Data] (1) As for the carcinogenicity of this substance alone, it was classified in Group 2A by IARC (IARC Suppl. 7 (1987)) and in R by NTP (NTP RoC (14th, 2016)). (2) IARC classified combination of etoposide, this substance, and bleomycin in Group 1 based on increased acute myeloid leukemia, that was the result of reevaluation of cohort studies in the 1990s (IARC 100A (2012)). (3) Induced acute myeloid leukemia exhibits distinctive characteristics of that caused by topoisomerase II inhibitors such as etoposide, but this substance is not involved in topoisomerase II inhibition. Etoposide alone was also classified in Group 1 (IARC 100A (2012)). (4) In a test in which mice were given multiple intraperitoneal doses, an increased incidence of lung adenoma was observed (IARC Suppl. No.7 (1987)). (5) In a test in which mice were given an application of croton oil on the skin as a promoter and intraperitoneal doses, an increased incidence of skin papilloma was observed (IARC Suppl. No.7 (1987)). (6) In two tests in which rats were given multiple intraperitoneal doses, leukemia was induced (IARC Suppl. No.7 (1987)). [Reference Data, etc.] (7) As the result of reevaluation of many cohort studies on combination therapy of etoposide, this substance, and bleomycin in the 1990s, increases in acute myeloid leukemia were observed (IARC 100A (2012)). (8) This substance is used in the treatment of tumors of the testis, usually as a major component of combination chemotherapy regimens, and particularly with bleomycin and etoposide (IARC 100A (2012)).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 1B,	Danger	H360 H362	P308+P313 P201 P202 P260 P263 P264 P270 P280 P405 P501	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".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 1 (digestive organ, bone marrow, kidney, nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (bone marrow, kidney, nervous system, gastrointestinal system, systemic)	Danger	H372	P260 P264 P270 P314 P501	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).	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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