NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	1069-66-5
Chemical Name	Sodium valproate
Substance ID	m-nite-1069-66-5_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 molecule.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not an aerosol product.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
7	Flammable solids	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
10	Pyrophoric solids	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	Not containing metals or semimetals (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	An organic compound that contains oxygen which is ionically bonded to sodium. Therefore, it is conceivable that the oxygen does not contribute to oxidation of other substances.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	An organic compound that does not contain -O-O- structure.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
16	Corrosive to metals	Classification not possible	- -	-	-	No established test method suitable for solid substances.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
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	From an LD50 value of 1700 mg/kg for mice (PIM 551 (1997), corresponding to List 1), it was classified in Category 4.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	"Solids" according to GHS definition.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
2	Skin corrosion/irritation	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Skin sensitization	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
5	Germ cell mutagenicity	Not classified	- -	-	-	There is no information on this substance. But it was classified as "Not classified," because valproic acid showed negatives in both a dominant lethal test using mice (in vivo heritable germ cell mutagenicity test) and a chromosomal aberration test using rat bone marrow (in vivo somatic cell mutagenicity test) (Physicians' Desk Reference 64th (2010)). Besides, the valproic acid showed a negative result in an Ames test as an in vitro test. (NTP DB 956843 (1990))	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
6	Carcinogenicity	Classification not possible	- -	-	-	Lack of data. In administration to rats or mice for respective two years or a longer period, an increased incidence of fibrosarcoma in male rats and an increased incidence of benign pulmonary adenomatosis in male mice were reported, and unknown importance to humans of these findings was remarked. (PIM 551 (1997))	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
7	Reproductive toxicity	Category 1A,	Danger	H360 H362	P308+P313 P201 P202 P260 P263 P264 P270 P280 P405 P501	It is reported that an increased incidence of exencephaly, and craniofacial and urogenital anomalies and severe axial skeletal malformations accompanied by exencephaly-related abnormalities such as the absence of the skull, hemorrhage, and degeneration of the exposed brain, polyhydramnios were consistently observed by the administration to mice on day 7 and 8 of gestation reported. (HSDB (2009)) Besides, this substance is used as an antiepileptic medicine in humans. Including the information that women dosed ingredients of this substance during the first pregnancy trimester had more cases of having offspring with spina bifida than women in a control group in an epidemiological study, and that infants born from treated women had heart anomalies such as ventricular septal defect and external malformations including polydactyly and cleft palate, and other abnormalities, the package insert stated that pregnant women or women anticipating pregnancy may be administered only when the benefit exceeds the risk. (Ethical pharmaceuticals (2010), corresponding to List 1): From the above, it was classified in Category 1A due to evidence of adverse reproductive effect in human despite no general toxicity information in parent animals in a result of mouse test. In addition, "additional category: Effects on or via lactation" was adopted because the package insert states that breastfeeding should be avoided if a patient is receiving this substance due to its breast milk transfer (Ethical pharmaceuticals (2010)).	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	It is reported that a 16-year-old epileptic female who developed somnolence after ingested 30 g of tablets of this substance recovered by treatment after 12 hours (PIM 551 (1997)), and that a 15-year-old girl took an unknown amount of this one became comatose and died of cardiopulmonary arrest (PIM 551 (1997)). Other cases such as onsciousness disorder (somnolence, coma), convulsions, respiratory depression, hyperammonemia, and brain edema caused by accidental take or excess ingestion for suicide attempt were reported. (Ethical pharmaceuticals (2010)) Furthermore, there is the information that antiepileptic action of this substance is estimated to be based on an activating effect of an inhibitory system in the brain via neurotransmitter. Therefore it was classified in Category 1 (central nervous system).	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, liver, blood system)	Danger	H372	P260 P264 P270 P314 P501	In an epidemiological study of 88 pediatric patients receiving monotherapy of this substance, 71 patients with adverse effects including neurological changes had a higher average dose than 17 patients without adverse effects. (PIM 551 (1997)) In addition, a case of a 24-year-old female dosed with this substance developed stupor and confusion followed by visual hallucinations (PIM 551 (1997)), and a case of a 15-year-old boy who received antiepileptic medications including this one for more than five years was hospitalized with cerebral coma and died (HSDB (2009)) were reported. As other adverse effects, the package insert lists somnolence, ataxia, headache, allesthesia, visual impairment, tremor, and dizziness (Ethical pharmaceuticals (2010)). Therefore it was classified in Category 1 (central nervous system). On the other hand, a case of a patient receiving valproic acid and its derivatives died of hepatic failure (HSDB (2009)), and identifying toxic hepatitis and microvesicular steatosis consistent with valproate hepatotoxicity in a liver biopsy by finding out lichenoid dermatitis in another patient who showed nonspecific polymorphous eruptions, fulminant hepatitis, and jaundice (HSDB (2009)) were reported. From a possibility of critical liver damage such as fulminant hepatitis, jaundice, and fatty liver as serious adverse effects described in the package insert (Ethical pharmaceuticals (2010)), it was classified in Category 1 (liver). Furthermore, it is reported that an infant administrated this substance showed severe anemia and thrombopenia and was diagnosed with promyelocytic leukemia from bone marrow aspirate, and dyshematopoiesia disappeared by stopping a dose of this drug. From descriptions of hemolytic anemia, pure red cell aplasia, pancytopenia, severe thrombopenia, and granulocytopenia listed as possible serious adverse effects in the package insert (Ethical pharmaceuticals (2010)), it was classified in Category 1 (blood system).	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
10	Aspiration hazard	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）

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.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in Annexes to the Montreal Protocol.	FY2011	GHS Classification Guidance by the Japanese Government （July, 2010）

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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