NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	97240-79-4
Chemical Name	Topiramate
Substance ID	m-nite-97240-79-4_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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2016	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 solid (melting point <= 140 deg C) substances are not available.	FY2016	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).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Classification not possible	- -	-	-	No data available.	FY2016	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	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2016	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)	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."	FY2016	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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2016	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.	FY2016	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.	FY2016	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.	FY2016	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.	FY2016	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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2016	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, eye, liver, urinary system, systemic)	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).	FY2016	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.	FY2016	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.	FY2016	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.	FY2016	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.	FY2016	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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