GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 97240-79-4 |
| Chemical Name | Topiramate |
| Substance ID | H28-A-020, C-063A |
| Classification year (FY) | FY2016 |
| 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) | 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 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 |
- |
- | - | Solid (GHS definition). |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | Solid (GHS definition). |
| 5 | Gases under pressure | Not applicable |
- |
- | - | Solid (GHS definition). |
| 6 | Flammable liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 7 | Flammable solids | Classification not possible |
- |
- | - | No data available. |
| 8 | Self-reactive substances and mixtures | Classification not possible |
- |
- | - | There is a chemical group associated with self-reactive properties (S=O) present in the molecule, but the classification is not possible due to no data. |
| 9 | Pyrophoric liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 10 | Pyrophoric solids | Classification not possible |
- |
- | - | No data available. |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to solid (melting point <= 140 deg C) 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 |
- |
- | - | Solid (GHS definition). |
| 14 | Oxidizing solids | Classification not possible |
- |
- | - | No data available. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Additionally, in Pharmaceutical Interview Forms (Antiepileptic drug (Revised in February 2015)) and Report on the Deliberation Results (May 21, 2007), there is a description that the minimum lethal dose for rats (both sexes) is > 2,000 mg/kg, which corresponds to "Not classified." |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 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 |
- |
- | - |
As for in vivo, a chromosomal aberration test using rat bone marrow is negative (HSDB (Access on June 2016)). As for in vitro, a bacterial reverse mutation test, a mouse lymphoma assay and a chromosomal aberration test using cultured mammalian cells are all negative (HSDB (Access on June 2016)). From the above, this substance was classified as "Classification not possible" according to the GHS Classification Guidance for the Japanese Government. |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 |
P308+P313
P201 P202 P280 P405 P501 |
There is no information on human carcinogenicity. As for experimental animals, it is described that in carcinogenicity studies by oral administration (in the diet) for 2 years to rats, and 21 months to mice, in rats, no evidence of carcinogenicity was seen at doses of up to 120 mg/kg, but in the high dose (300 mg/kg/day) group of mice, bladder tumors (mainly smooth muscle tumors) were observed. Also it is described that the concentration of this substance in the plasma of mice receiving 300 mg/kg was approximately 0.5 to 1 times the steady state plasma exposures measured in humans receiving this substance at the recommended human dose of 400 mg (HSDB (Access on June 2015)). From the above, it was judged as appropriate to classify this substance in Category 2. |
| 7 | Reproductive toxicity | Category 1A |
Danger |
H360 |
P308+P313
P201 P202 P280 P405 P501 |
There is a report that a patient who was given this substance during pregnancy was delivered of a baby with malformations (cleft lip, cleft palate, hypospadias). Also there are qualifying statements that for pregnant women or women who may be pregnant, this substance should be administered only when it is judged that the therapeutic benefit (preventing frequent occurrence of maternal epileptic seizures and protecting the fetus from hypoxia) exceeds the risk (Ethical Pharmaceuticals 2017 (2016)). Also in experimental animals, as the results of oral administration using pregnant rats or pregnant rabbits during the period of organogenesis, increases in malformation frequency (rib and vertebral skeletal malformations and limb malformations (ectrodactyly, micromelia, and amelia)) were observed mainly at doses where maternal toxicity was observed (HSDB (Access on June 2016), Ethical Pharmaceuticals 2017 (2016)). Therefore, this substance was classified in Category 1A. |
| 8 | Specific target organ toxicity - Single exposure | Category 2 (central nervous system) |
Warning |
H371 |
P308+P311
P260 P264 P270 P405 P501 |
In humans, there are several reports that due to single oral ingestion of this substance by mistake or with suicidal intent, symptoms including confusion, hallucination, slurred speech, ataxia of gait and disorientation, etc. were seen (HSDB (Access on June 2016)). Since these are described in the information sources listed in List 2, this substance was classified in Category 2 (central nervous system). Additionally, it is described that in humans, somnolence and dizziness may appear as side effects after administration of this substance (Ethical Pharmaceuticals 2017 (2016)). However, since it is unclear whether these symptoms occur after a single dose, this was not adopted as rationale for classification. In addition, it is described that in a single oral dose study using rats, ataxia, reduced reflex and reduced muscle tones were observed (Pharmaceutical Interview Forms (Antiepileptic drug (Revised in February)) 2015), however, this information was not adopted as rationale for classification because the source is not listed as an information source available for classification in the GHS Classification Guidance for the Japanese government. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, eye, liver, urinary system, systemic toxicity) |
Danger |
H372 |
P260
P264 P270 P314 P501 |
As information on side effects in humans, in adults, side effects were observed in 228 cases (75.2%) out of 303 cases that were subjected to safety analysis. The main side effects were as follows: 90 cases (29.7%) of somnolence, 75 cases (24.8%) of decreased body weight, 44 (14.5%) cases of free-floating and 32 cases (10.6%) of anorexia and bulimia, etc. In addition, major abnormal laboratory values were 24 cases (7.9%) of increased gamma-GT, 22 cases (7.3%) of increased blood chloride, 19 cases (6.3%) of decreased blood bicarbonate and 16 cases (5.3%) of decreased blood phosphorus, etc. In children, side effects were seen in 66 cases (76.7%) out of 86 cases subjected to safety analysis. The main side effects were 28 cases (32.6%) of somnolence, 13 cases (15.1%) of hypohidrosis, 12 (14.0%) cases of decreased appetite, 11 cases (12.8%) of dyshidrosis and 8 cases (9.3%) of decreased body weight, etc. In addition, major abnormal laboratory values were 26 cases (30.2%) of decreased blood bicarbonate. Moreover, as serious side effects, secondary angle closure glaucoma and associated acute myopia (frequency unknown), calculus in the kidney and urinary tract (2.3%), metabolic acidosis (1.8%) and hypohidrosis and associated high fever (0.3%) were reported (Ethical Pharmaceuticals 2017 (2016)). In addition, this substance is an epilepsy treatment drug and is used for therapy by the oral route. Therefore, this substance was classified in Category 1 (central nervous system, eye, liver, urinary system, systemic toxicity). |
| 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. |