NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	569-64-2
Chemical Name	N-[4-[[4-(dimethylamino)phenyl]phenylmethylene]-2,5-cyclohexadien-1-ylidene]-N-methylmethanaminium, chloride [Malachite green]
Substance ID	m-nite-569-64-2_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)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
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.	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 self-reactive properties (ethylene 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	- -	-	-	No data 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	Not classified (Not applicable)	- -	-	-	It is an organic compound which does not contain fluorine or oxygen but contains chlorine, and the chlorine is ionically bonded to the element other than carbon or hydrogen (N) and does not contribute to oxidation.	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)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Based on a report of an LD50 value of 80 mg/kg (HSDB (Access on August 2017)) for mice, it was classified in Category 3.	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	Category 1	Danger	H318	P305+P351+P338 P280 P310	There is a report that it is injurious to human eyes (NTP TOX71 (2004)). Based on the description that in an eye irritation test with rabbits (OECD TG 405 compliant), eye damage occurred and this did not resolve until after 8 days (ECHA registration dossier (Access on November 2017)), and the description of severe injury ranging from conjunctival edema, hyperemia, and purulence to total opacification and even necrosis of the cornea, and sloughing of the corneal stroma in another test with rabbits (HSDB (Access on August 2017)), it was classified in Category 1. Besides, this substance was classified as "Eye Dam. 1, H318" in EU CLP classification (ECHA CL Inventory (Access on August 2017)).	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	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	As for in vivo, this substance was negative in a micronucleus test with rat bone marrow cells, positive and negative in micronucleus tests with mouse bone marrow cells, negative in a micronucleus test with mouse peripheral blood, positive in chromosomal aberration tests with bone marrow cells and spermatocytes of mice, negative in gene mutation tests (hprt locus) with spleen lymphocytes and peripheral blood of mice and a gene mutation test (hepatic cII gene) with transgenic mice, and positive in DNA adduct formation tests with the liver of rats and mice (NICNAS (Access on September 2017), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2005), EFSA (2016), NTP TR527 (2005), NTP DB (Access on September 2017)). As for in vitro, there were mostly negative results in bacterial reverse mutation tests, and it was negative in a gene mutation test and a chromosomal aberration test with mammalian cultured cells (NICNAS (Access on September 2017), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2005), EFSA (2016), NTP TR527 (2005), NTP DB (Access on September 2017)). From the above, based on the positive results in the in-vivo germ cell mutagenicity test, the in-vivo somatic cell mutagenicity tests, and the in vivo somatic cell genotoxicity test, it was classified in Category 1B according to the GHS classification guidance for the Japanese government.	FY2017	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	In 2-year carcinogenicity studies with female rats and female mice dosed by feeding, it was concluded that there was equivocal evidence of carcinogenicity based on increased thyroid gland follicular cell adenoma and slight increases in hepatocellular adenoma and mammary gland carcinoma in female rats, but it was concluded that since there was no tumor development associated with the administration in the administration test with female mice, there was no evidence of carcinogenicity (NTP TR527 (2005)). Regarding these NTP test results, the Food Safety Commission concluded that carcinogenicity in the liver and mammary glands of female rats was suggested for this substance though it was weak (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2005)). On the other hand, CONTAM Panel of EFSA concluded that this substance did not show carcinogenicity in mice, but this substance had a carcinogenic potential in rats because slight increases in thyroid follicular tumors and mammary gland carcinoma were observed (EFSA (2016)). From the above, following the assessment results of Food Safety Commission and EFSA based on the NTP test results, it was judged as appropriate to classify this substance in Category 2 for carcinogenicity. Besides, the classification result was changed due to the use of new information sources.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, there is a report when pregnant rats were dosed orally at up to 500 mg/kg/day during the critical period, no effect on the incidence of skeletal malformations was observed (HSDB (Access on August 2017)).	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. There is no single exposure information on this substance in humans and experimental animals. Besides, there is a report that in a single oral dose test in which malachite green oxalate (CAS RN 2437-29-8) was administered to rats at 300, 450, 600, 750 mg/kg, an LD50 value was 520 mg/kg, and sedation, weakness, and coma were observed as symptoms (NTP TOX71 (2004), NICNAS IMAP (Access on March 2017)) (this was described in NICNAS IMAP as the data of this substance, but this was found to be the result from tests on the oxalate after the confirmation of the original source). Since, as also for oxalic acid (CAS RN 144-62-7), weakness and coma, etc. are reported as acute toxicity symptoms by oral ingestion (GHS Classification in FY2016), symptoms due to the ingestion of malachite green oxalate were not used as a reference for classification because the symptoms were possibly effects of oxalic acid.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (thyroid), Category 2 (blood system, liver)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	No information on humans is available. In 28-day tests with rats and mice dosed by feeding, in rats, within the guidance value range for Category 2, increased liver weight and decreased mean corpuscular hemoglobin content at or above 300 ppm (converted guidance value: 12.4 mg/kg/day), decreased mean corpuscular volume and increased gamma-GT activities at or above 600 ppm (converted guidance value: 21.8 mg/kg/day (male), 23.3 mg/kg/day (female)), and decreases in the erythrocyte count, hemoglobin concentration, hematocrit value and mean corpuscular hemoglobin concentration, and hepatocellular vacuolation at 1,200 ppm (converted guidance value: 54.4 mg/kg/day (male), 59.1 mg/kg/day (female)) were observed. In mice, decreased erythrocyte count at or above 100 ppm (converted guidance value: 6.2 mg/kg/day) within the guidance value range for Category 1, and decreases in hemoglobin concentration and hematocrit value, and increased reticulocyte count at or above 300 ppm (converted guidance value: 15.6 mg/kg/day (male), 20.2 mg/kg/day (female)) within the guidance value range for Category 2 were observed (NTP TOX71 (2004)). Other than these, in a 2-year test with rats dosed by feeding, cyst formation from the thyroid follicular epithelium at or above 100 ppm (converted guidance value: 7 mg/kg/day) within the guidance value range for Category 1, hyperplasia of the thyroid follicular epithelium at or above 300 ppm (converted guidance value: 21 mg/kg/day) within the guidance value range for Category 2 were observed, and increased liver weight and increased eosinophilic foci in the liver at or above 600 ppm (converted guidance value: 43 mg/kg/day) within the guidance value range for Category 2 were observed (NTP TR527 (2005), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2005)). Therefore, it was classified in Category 1 (thyroid), and Category 2 (haemal system, liver). Besides, the classification result was different from the previous classification due to the use of new information.	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 1	Warning	H400	P273 P391 P501	From 48-hour EC50 = 0.13 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)), it was classified in Category 1.	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 72-hour NOEC (rate method) = 0.049 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 due to being not rapidly degradable (BioWin), and 48-hour EC50 = 0.13 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)). 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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