NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	7481-89-2
Chemical Name	4-Amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl］pyrimidine-2-one, (alias Zalcitabine)
Substance ID	m-nite-7481-89-2_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)	Classification not possible	- -	-	-	Classification not possible due to lack of data. As relevant information, a lethal dose is 2 g/kg and more for rats (RTECS (2004)).	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	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	Based on a positive result from an in vivo mouse somatic cell (bone marrow and peripheral blood) micronucleus test (NTP DB (access on Oct. 2009), IARC 76 (2000)), the substance was classified into Category 2. As relevant information, from in vitro mutagenicity tests, there are reports of weakly positive (NTP DB (access on Oct. 2009)) and negative (IARC 76 (2000)) Salmonella typhimurium mutation tests, negative gene mutation tests using Chinese hamster lung cells and mouse lymphoma cells (IARC 76 (2000)), positive chromosomal aberration tests using Chinese hamster ovary cells and human lymphocytes (NTP DB (access on Oct. 2009), IARC 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	Based on the classification of "Group 2B" in IARC (IARC vol. 76 (2000)), the substance was classified into Category 2. In 6-month oral administration tests in B6C3F1 mice and NIH Swiss mice, a treatment-associated mortality was seen in NIH Swiss male and female mice and B6C3F1 female mice, but not in B6C3F1 male mice. The incidences of thymic lymphoma were higher in both strains of male and female mice of the treated groups but 0% in each control group. The deaths were due to thymic lymphomas in the females, whereas the male mice died from toxic effects such as anaemia (IARC 76 (2000)). Additionally, some cases of non-Hodgkin lymphoma were seen in HIV-infected patients treated with the substance (IARC 76 (2000)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Reproductive toxicity	Category 2,	Warning	H361 H362	P308+P313 P201 P202 P260 P263 P264 P270 P280 P405 P501	In a developmental toxicity test in C57BL/6N mice administered by gavage during organogenesis period, the mean litter size was decreased and the percentage of resorptions per litter was increased at a high dose level (2000 mg/kg/day) at which maternal weight gain were decreased (IARC 76 (2000)). Additionally, the number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percentage of malformed fetuses per litter were increased at 1000 mg/kg and higher (IARC 76 (2000)). Based on this result, the substance was classified into Category 2. The malformations included open eyelids, micrognathia, kinked tail, clubbed paws, and cleft palate. Based on a report that mothers must be instructed not to breast feed when taking this drug (the excretion into breast milk was reported in animals (rats)) (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	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, pancreas, liver, heart, blood, systemic)	Danger	H372	P260 P264 P270 P314 P501	The substance is an antiviral drug. In it's package insert, there are the following reports as significant adverse reactions; peripheral neuropathy, suicide attempt, epileptic seizure, convulsion, paralysis, acute psychiatric disorder can occur, pancreatitis (hemorrhagic) can occur, severe hepatic steatosis, serious hepatic dysfunction can occur, cardiomyopathy, and cardiac failure can occur (JAPIC prescription drug book (2010)). Based on these reports, the substance was classified into Category 1 (nervous system, pancreas, liver, heart). In addition, of 285 AIDS patients with CD4 counts of <=300 cells/microL, who received the substance for 17 months, 14% had anaemia or neutropenia, (IARC 76 (2000). Anemia was reported in 3.1-8.4% of patients who received the substance alone or in conjunction with zidovudine and leukopenia, neutropenia and thrombocytopenia occurred (HSDB (2004)). Based on the data, the substance was classified into Category 1 (blood system). In addition, there are the following reports as significant adverse reactions; lactic acidosis, esophageal and intraoral ulcer, anaphylactic reaction, and subarachnoid hemorrhage (JAPIC prescription drug book (2010)). Since these symptoms cannot identify the affected organ, the substance was classified into Category 1 (systemic toxicity). Based on all information, the substance was classified into Category 1 (nervous system, pancreas, liver, heart, blood 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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