GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTES:
Updated date:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS number | 1069-66-5 |
| Chemical name | Sodium valproate |
| Substance ID | 23A5046 |
| Fiscal year of classification conducted | FY2011 |
| Classifier(s) (Ministries) | Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE） |
| New/Revised | New |
| Download in Excel format | Excel file |
| Item | Information |
|---|---|
| Guidance used for classification (External link) |
Physical Hazards & Health Hazards: GHS Classification Guidance by the Japanese Government （July, 2010）
Environmental Hazards: UN GHS Document （4th revised edition） |
| Definitions / Abbreviations (Excel file) | Definitions / Abbreviations |
| Model Label by MHLW (External link) | MHLW Website （in Japanese Only） |
| Model SDS by MHLW (External link) | MHLW Website （in Japanese Only） |
| OECD/eChemPortal (External link) | eChemPortal |
| Hazard class | Classification |
Pictogram (Code: symbol) Signal word |
Code (Hazard statement) |
Code (Precautionary statement) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not applicable | - | - | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 2 | Flammable gases （including chemically unstable gases） | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 3 | Aerosols | Not applicable | - | - | - | Not an aerosol product. |
| 4 | Oxidizing gases | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 5 | Gases under pressure | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 6 | Flammable liquids | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 7 | Flammable solids | Classification not possible | - | - | - | No data. |
| 8 | Self-reactive substances and mixtures | Not applicable | - | - | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. |
| 9 | Pyrophoric liquids | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 10 | Pyrophoric solids | Classification not possible | - | - | - | No data. |
| 11 | Self-heating substances and mixtures | Classification not possible | - | - | - | No data. |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not applicable | - | - | - | Not containing metals or semimetals (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). |
| 13 | Oxidizing liquids | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 14 | Oxidizing solids | 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. |
| 15 | Organic peroxides | Not applicable | - | - | - | An organic compound that does not contain -O-O- structure. |
| 16 | Corrosive to metals | Classification not possible | - | - | - | No established test method suitable for solid substances. |
| Hazard class | Classification |
Pictogram (Code: symbol) Signal word |
Code (Hazard statement) |
Code (Precautionary statement) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity （Oral） | Category 4 |  |
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. |
| 1 | Acute toxicity （Dermal） | Classification not possible | - | - | - | No data. |
| 1 | Acute toxicity （Inhalation: Gases） | Not applicable | - | - | - | "Solids" according to GHS definition. |
| 1 | Acute toxicity （Inhalation: Vapours） | Classification not possible | - | - | - | No data. |
| 1 | Acute toxicity （Inhalation: Dusts and mists） | Classification not possible | - | - | - | No data. |
| 2 | Skin corrosion/irritation | Classification not possible | - | - | - | No data. |
| 3 | Serious eye damage/eye irritation | Classification not possible | - | - | - | No data. |
| 4 | Respiratory sensitization | Classification not possible | - | - | - | No data. |
| 4 | Skin sensitization | Classification not possible | - | - | - | No data. |
| 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)) |
| 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)) |
| 7 | Reproductive toxicity | Category 1A, Additional category: Effects on or via lactation |  |
H360 H362 |
P308+P313 P201 P202 P281 P405 P501 P260 P263 P264 P270 |
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)). |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system) | |
H370 |
P307+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). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, liver, blood system) | |
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). |
| 10 | Aspiration hazard | Classification not possible | - | - | - | No data. |
| Hazard class | Classification |
Pictogram (Code: symbol) Signal word |
Code (Hazard statement) |
Code (Precautionary statement) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment （Acute） | Classification not possible | - | - | - | No data. |
| 11 | Hazardous to the aquatic environment （Long-term） | Classification not possible | - | - | - | No data. |
| 12 | Hazardous to the ozone layer | Classification not possible | - | - | - | This substance is not listed in Annexes to the Montreal Protocol. |
NOTES:
|
* Hazard statement or Precautionary statement will show when hovering the mouse over a code of Hazard statement or Precautionary statement. Hazard statement and Precautionary statement are also provided in the Excel file. * Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users. * This is a provisional English translation of classification results and is subject to revision without notice. * The responsibility for any resulting GHS labelling and SDS referenced from this site is with users. |
Updated date:
|
2017/1/30 Addition of Rationale for the classification |