NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	13311-84-7
Chemical Name	2-Methyl-4'-nitro-3'-(trifluoromethyl)propananilide [Flutamide]
Substance ID	m-nite-13311-84-7_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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) in the molecule, and the calculated oxygen balance of -142 is above the criteria, -200. However, the classification is not possible due to no data on onset temperature and decomposition energy.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (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)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2017	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 explosive properties (nitro group) in the molecule, but the classification is not possible due to no data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	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 solid (melting point <= 140 deg C) 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)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Classification not possible	- -	-	-	It is an organic compound which does not contain chlorine but contains fluorine and oxygen, and the oxygen is chemically bonded to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.	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	- -	-	-	Test methods applicable to solid substances are not 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)	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 (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)	- -	-	-	Solid (GHS definition)	FY2017	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)	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.	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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	As for humans, it is reported that a major side effect of this substance when it is prescribed as a prostate-cancer treatment drug was gynecomastia (Ethical Pharmaceuticals 2017 (2016)). As for experimental animals, there is a report that in a test (pubertal assay) with male rats dosed by gavage on postnatal days 23-54 after weaning, delayed preputial separation, increased testicular weights, and decreased weights of accessory reproductive organs at or above 25 mg/kg/day, and histopathological lesions in the testis at 50 mg/kg/day were observed (NTP Abstract for RACB20103, RACB20104, RACB20105, RACB20106, and RACB20203 (Access on August 2017)). From the above, the gynecomastia in men is the adverse effect on the endocrine system. This is therefore a finding that is beyond the scope of evaluation of reproductive effects. Meanwhile, in experimental animals, although effects due to the antiandrogenic action of this substance (NTP Abstract for RACB 2010, RACB 2010, RACB 2010, RACB 2010, and RACB 20203 (Access on August 2017)) were observed, these did not include any severe developmental effects. Therefore, it was classified in Category 2 for this hazard class.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	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))
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver, endocrine system, blood system, reproductive organs (male))	Danger	H372	P260 P264 P270 P314 P501	This substance (synonyms: flutamide) is a nonsteroidal antiandrogen drug, which is used to treat prostate cancer (Ethical Pharmaceuticals 2017 (2016)). In humans, the incidence of side effects and abnormal laboratory values in 6,393 cases was 29.0%, gynecomastia 2.9%, loss of appetite 2.0%, diarrhea 1.7%, nausea and vomiting 1.1%, increased AST 13.2%, increased ALT 13.2%, increased gamma-GT 5.9%, increased LDH 3.8%, increased alkaline phosphatase 3.1%, reduced erythrocyte count 1.8%, reduced hemoglobin 1.5%, reduced hematocrit value 1.5%, etc. were main, and as severe side effects, fatal cases due to severe liver damage such as fulminant hepatitis were reported. It is also described that interstitial pneumonitis (less than 0.1%) and heart failure/myocardial infarction (incidences not specified) may occur (Ethical Pharmaceuticals 2017 (2016)). As for experimental animals, there is a report that decreases in the absolute and relative weights of the epididymis, and lobular atrophy of the mammary glands were observed at or above 1 mg/kg/day (converted guidance value: 0.31 mg/kg/day) which is within the guidance value range for Category 1, and increased blood testosterone and estradiol, decreases in the absolute and relative weights of the seminal vesicles, and an increased number of leptotene-stage spermatocytes during Stages IX-XI of the spermatogenesis cycle were seen at 4 mg/kg/day (converted guidance value: 1.24 mg/kg/day) in a 28-day toxicity test with rats orally dosed (Health Science Research Grants in FY 1998: Study report on a 28-Day Repeated Dose Study etc. (International Joint Validation Project for OECD Test Guideline), http://www.nihs.go.jp/edc/houkoku10/10-9/10-9-shunin.pdf). From the above, it was classified in Category 1 (liver, endocrine system, haemal system, genetic organs (men)). Besides, although loss of appetite, diarrhea, nausea and vomiting in humans are the side effects on the gastrointestinal system, these were insufficient as rationale for GHS classification, and among the severe side effects, the incidence of interstitial pneumonitis, heart failure and myocardial infarction were low. Therefore, it was not adopted as the target organs.	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)	Category 2	- -	H401	P273 P501	From 96-hour LC50 = 1.38 mg/L for crustacea (Neomysis integer) (EPA AQUIRE: 2017, Verslycke, T. et al. (2004)), it was classified in Category 2.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (BioWin), and 21-day NOEC (reproduction inhibition) = 0.1 mg/L for crustacea (Daphnia magna) (EPA AQUIRE: 2017, Haeba, M. H. et al. (2008)). Because acute toxicity data were not obtained for a trophic level (algae) for which chronic toxicity data were not obtained, it is classified as "Classification not possible." From the above results, it was classified in Category 1.	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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