NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	79217-60-0
Chemical Name	Cyclosporine
Substance ID	m-nite-79217-60-0_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	Based on a LD50 value of 1500 mg/kg for rats (IARC 50 (1990)), the substance was classified into Category 4. [Cyclosporine mixture contains cyclosporine A as a major component, and most of the available data are related to cyclosporine A. Therefore, data for cyclosporine A were mainly used as the basis of classifications for health hazards]	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	Not classified	- -	-	-	Based on negative results in a mouse dominant lethal test as well as mouse and hamster bone marrow chromosomal aberration tests and micronucleus test (IARC 50 (1990)), the substance was classified as "Not classified". As relevant information, there is a report of a negative mouse unscheduled DNA synthesis test (IARC 50 (1990)), and, from in vitro mutagenicity tests, there are reports of a negative Ames test and a negative hamster V79 cell HPRT mutation test (IARC 50 (1990)).	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), 50 (1990)) and classification of "K" in NTP (NTP ROC 11th, 2004)), the substance was classified into Category 1A. Numerous case reports were published of neoplasms occurring in organ transplant recipients who received only the substance (ciclosporin) and the majority of these neoplasms were lymphomas, commonly of the gastrointestinal tract, but malignancies at other sites have also been seen (IARC 50 (1990)). In animal tests where mice were fed for 78 week and rats were fed for 95 - 105 weeks, mortality was higher in the high-dose group but no increase in the incidence of tumours was observed (IARC 50 (1990)).	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	There is a report that exposure to the substance during pregnancy induced preterm delivery and low birthweight but no significant risk for infant. The substance is not considered to be a teratogen (HSDB (2009), Birth Defects (3rd, 2000)). Foot skeletal malformation, hypospadias and finger flexure in infant were reported (Birth Defects (3rd, 2000)). While there was no teratogenic effect in rat and rabbit tests (IARC vol. 50 (1990), increased resorptions, embryolethaity, fatal and offspring growth retardations were seen in rats and rabbits at maternally toxic doses. Teratogenic effects were observed in a mouse test (Birth Defects (3rd, 2000)). There is evidence of human reproductive toxicity, therefore, the substance corresponds to known human reproductive toxicant and was classified into Category 1A. In addition, based on reports of "the substance has also been detected in breast milk" (IARC vol. 50 (1990)), and "the substance has been reported to pass into breast milk, so mothers should avoid breast-feeding during treatment period" (JAPIC prescription drug book (2010)), 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 1 (immune system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	Based on a report that the substance is a powerful immunosuppressive agent usually used in organ transplantation to prevent rejection (JAPIC prescription drug book (2010)), the substance was classified into Category 1 (immune system).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (kidney, liver, central nervous system, immune system, systemic)	Danger	H372	P260 P264 P270 P314 P501	Based on the following reports: the substance is an immunosuppressive agent; significant side effects such as renal dysfunction can occur at high incidence, of which the primary mechanism likely involves the dose-dependent renal vasoconstriction; hepatic disorder (elevated hepatic enzyme and bilirubin level, jaundice) may occur; central nervous system disorder such as reversible posterior leukoencephalopathy syndrome and hypertensive encephalopathy may occur (JAPIC prescription drug book (2010)), the substance was classified into Category 1 (kidney, liver, central nervous system). In addition, there are the following reports related to other significant side effects: serious infectious disease by bacteria or virus including pneumonia, sepsis, urinary tract infection, herpes simplex, herpes zoster can concur; and may rapidly deteriorate under strongly immunosuppressed conditions; acute pancreatitis, thrombotic microangiopathy, rhabdomyolysis may occur; and the probability of developing malignant tumor may increase due to excess immunosuppression (JAPIC prescription drug book (2010)). Since many of these side effects are considered to involve the immune system and some serious systemic disorders are included, the substance was classified into Category 1 (immune system, systemic toxicity). Based on all information, classification is Category 1 (kidney, liver, central nervous system, 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.

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