GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 99-66-1 |
| Chemical Name | 2-Propan-1-ylpentanoic acid [Valproic acid] |
| Substance ID | H29-A-004 |
| Classification year (FY) | FY2017 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | New |
| Classification result in other fiscal year | |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| UN GHS document (External link) | UN GHS document |
| Definitions/Abbreviations (Excel file) | Definitions/Abbreviations |
| Model Label by MHLW (External link) | |
| Model SDS by MHLW (External link) | |
| OECD/eChemPortal (External link) | eChemPortal |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
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 |
- |
- | - | Liquid (GHS definition) |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 5 | Gases under pressure | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 6 | Flammable liquids | Classification not possible |
- |
- | - | No data available. |
| 7 | Flammable solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 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 | Classification not possible |
- |
- | - | No data available. |
| 10 | Pyrophoric solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | 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). |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 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. |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 2 | Skin corrosion/irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 3 | Serious eye damage/eye irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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). |
| 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)). |
| 7 | Reproductive toxicity | Category 1A, Additional category: Effects on or via lactation |
 Danger |
H360
H362 |
P308+P313
P201 P202 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. |
| 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). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, haemal 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). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Classification not possible |
- |
- | - | No data available. |
| 11 | Hazardous to the aquatic environment (Long-term) | Classification not possible |
- |
- | - | No data available. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_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. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |