NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	99-66-1
Chemical Name	2-Propan-1-ylpentanoic acid [Valproic acid]
Substance ID	m-nite-99-66-1_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)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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 report of an LD50 value of 670 mg/kg (IPCS, PIM 551 (1997), HSDB (Access on August 2017)) for rats, it was classified in Category 4.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. As for in vivo, there was information that it was negative in a dominant lethal test and a chromosomal aberration test (Brambilla and Martelli, Mutation Res., 209-229, 2009). As for in vitro, a bacterial reverse mutation test was negative (NTP DB (Access on August 2017)). The information on in-vivo tests is from the PDR (Physicians' Desk Reference).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, in 2-year administration tests with rats and mice (administration route: although not described, perhaps the oral route, dose: 80-170 mg/kg/day), an increased incidence of subcutaneous fibrosarcoma in male rats at the high dose, and a dose-related increase in incidence of benign pulmonary adenomas in male mice were observed. However, there is a description that the importance of these findings to humans is not known (IPCS, PIM 551 (1997)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 1A,	Danger	H360 H362	P308+P313 P201 P202 P260 P263 P264 P270 P280 P405 P501	The sodium salt of this substance (sodium valproate) is used as a therapeutic agent for epilepsy, mania, depressed condition, and migraine (Ethical Pharmaceuticals 2017 (2016)), and toxicity information on sodium valproate was considered available for the classification of this substance. Sodium valproate is in principle contraindicated for pregnant women or women who may be pregnant (Ethical Pharmaceuticals 2017 (2016)). There are multiple reports that there is an association between the use of this substance in pregnant epileptic women and congenital malformations in children born (particularly neural tube defects). As for experimental animals, it is described that in reproductive toxicity tests with rats and mice, adverse effects on fetuses were observed (IPCS, PIM 551 (1997)). In addition, it is written to avoid breast feeding when sodium valproate was administered to nursing women because it may transfer into human breast milk (Ethical Pharmaceuticals 2017 (2016)). From the above, it was classified in Category 1A for this hazard class, and "additional category for effects on or via lactation" was added to the classification.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	There is a description that this substance inhibits GABA transferase, and after increasing concentrations of the inhibitory neurotransmitter GABA in the brain, it inhibits neural excitation (IPCS, PIM 551 (1997)). As for humans, there is a description that although details such as the number of ingestions are unknown, ingestion of this substance causes gastrointestinal tract upset and central nervous system depression (confusion, disorientation, obtundation, and coma with respiratory failure) and may cause hypotension with tachycardia and a prolonged QT interval (HSDB (Access on August 2017)). There is no other information on the effect of a single exposure to this substance. However, the sodium salt of this substance (sodium valproate) (CAS RN. 1069-66-5) is used as a therapeutic agent for epilepsy, mania, depressed condition, and migraine, and cases are reported in which overdose due to accidental ingestion or suicide attempt caused consciousness disturbance (drowsiness, coma), convulsions, respiratory depression, hyperammonemia, and cerebral edema (Ethical Pharmaceuticals 2017 (2016)). In addition, there is a report that after a 16-year-old epileptic female patient ingested 30 g of sodium valproate tablets, she developed somnolence but recovered after 12 hours by treatment, and a report that after a 15-year-old girl ingested sodium valproate (unknown amount), she became comatose and died due to cardio-respiratory arrest (both in IPCS, PIM 551 (1997)). Based on these pieces of information, sodium valproate was classified in Category 1 (central nervous system) in GHS classification in FY2011. Although the above information seems to include information on the sodium salt of this substance rather than information on only this substance, it is considered that side effects were attributed to this substance. Therefore, based on the above information, this substance was classified in Category 1 (central nervous system), Category 3 (narcotic effects).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, blood system, liver)	Danger	H372	P260 P264 P270 P314 P501	The sodium salt of this substance (sodium valproate) is used as a therapeutic agent for epilepsy, mania, depressed condition, and migraine (Ethical Pharmaceuticals 2017 (2016)). As for humans, fatal hepatic failure is reported in patients in chronic use, and pancreatitis is also reported at normal therapeutic doses. The most commonly reported adverse effects on the gastrointestinal system are anorexia, nausea and vomiting. The effects on the central nervous system are drowsiness, and also include apathy, withdrawal, confusions, restlessness, and hyperactivity, and less frequently, seizures and coma may appear. Sedative effects are more pronounced when the drug is used together with other anti-epileptic agents. There is a description that the effects on the hematopoietic system are thrombocytopenia, abnormal bleeding time and partial thromboplastin time with decreased fibrinogen levels, prolonged prothrombin time, etc., leading to bruising, petechiae, haematoma, and epistaxis (IPCS, PIM 551 (1997), HSDB (Access on August 2017)). In addition, it is described in Ethical Pharmaceuticals 2017 (2016) that as serious side effects, severe liver damage such as fulminant hepatitis, consciousness disturbed accompanied with hyperammonemia, hemolytic anemia, pure red cell aplasia, pancytopenia, severe thrombocytopenia, granulocytopenia, acute pancreatitis, interstitial nephritis, Fanconi syndrome, toxic epidermal necrolysis, oculomucocutaneous syndrome (Stevens-Johnson syndrome), hypersensitivity syndrome, cerebral atrophy, dementia-like symptoms, Parkinsonian syndrome, rhabdomyolysis, inappropriate antidiuretic hormone secretion syndrome, interstitial pneumonia, and eosinophilic pneumonia may appear, and as for the incidence of side effects, many adverse effects on the haemal system, psychoneurotic system, gastrointestinal system, and liver, hypersensitivity and hyperammonemia are reported. The above information is considered to include information on the sodium salt of this substance rather than information on only this substance. However, since side effects are considered to be attributable to this substance, classification was conducted based on the above information, by taking into consideration the severity, incidence, etc. Therefore, it was classified in Category 1 (central nervous system, haemal system, liver). Besides, sodium valproate (CAS RN 1069-66-5), the sodium salt of this substance, was classified in Category 1 (central nervous system, liver, haemal system) in GHS classification by Japanese government (FY 2011).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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