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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	95-54-5
Chemical Name	o-Phenylenediamine
Substance ID	R01-B-008
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2009 FY2006
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

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	No data available.
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 540 deg C (GESTIS (Access on May 2019)).
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because 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	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine. It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

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	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 660-1,284 mg/kg (ACGIH (7th, 2001)) (2) LD50 for rats: 500-1,300 mg/kg (DFGOT vol.21 (2005))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (ACGIH (7th, 2001)) (2) LD50 for rabbits: > 5,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014)) (3) There were dead animals in rabbits after percutaneous application at 5,000 mg/kg (ACGIH (7th, 2001))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Neither (1) nor (2) could specify the classification, therefore, it was classified as "Classification not possible." [Evidence Data] (1) LC50 value (1 hour) for rats: > 0.056 mg/L (converted 4-hour equivalent value: > 0.014 mg/L) (ACGIH (7th, 2001)) (2) LC50 value (4 hours) for mice: > 0.091 mg/L (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test with rabbits according to OECD TG 404, it is reported to show no irritation (DFGOT vol.13 (1999)). (2) It is reported that in a skin irritation test with 3 rabbits according to OECD TG 404, very light erythema was observed after 48 hours. This was reversible after 72 hours, and that the mean scores at 24/48/72 hours for erythema and edema were 0.6 and 0, respectively (REACH registration dossier (Access on June 2019)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1), it was classified in Category 2A. [Evidence Data] (1) In an eye irritation test according to OECD TG 405, irritation was seen, and the average scores were 2.1 for cornea, 1 for iris, 3 for conjunctival redness and 2.9 for conjunctival edema, but they were reversible within 14 days (REACH registration dossier (Access on June 2019)). [Reference Data, etc.] (2) In an eye irritation test according to OECD TG 405, it caused conjunctival redness and edema, corneal opacity, and inflammation of the iris, but these were reversible within 14 days (DFGOT vol.13 (1999)). (3) It was classified as "Eye Irrit. 2 (H31)" in the EU CLP classification (EU CLP classification (Access on May 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. [Evidence Data] (1) It was classified as occupational skin sensitizers Group 3 (OEL Documentations (Occupational Sensitizer classification) (Japan Society For Occupational Health (JSOH)) (2010)). (2) In a skin sensitization test with guinea pigs, mild to moderate sensitization was observed in 3-7 out of 10 animals (with positive rate 30-70%) (REACH registration dossier (Access on June 2019)). [Reference Data, etc.] (3) It was classified as "Skin Sens. 1 (H317)" in the EU-CLP classification (EU CLP classification (Access on May 2019)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for in vivo, it is reported to be negative in a dominant lethal test with rats and a mouse spot test, and positive in a micronucleus test and chromosomal aberration tests with bone marrow of mice, etc. (DFGOT vol.6 (1994), DFGOT vol.13 (1999), OEL Documentations (Japan Society For Occupational Health (JSOH), 1999), ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014)). (2) As for in vitro, it is reported to be positive in a mouse lymphoma test, and positive in many mammalian cell chromosomal aberration tests and bacterial reverse mutation tests (DFGOT vol.6 (1994), DFGOT vol.13 (1999), OEL Documentations (Japan Society For Occupational Health (JSOH), 1999), ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014)). (3) It was classified in Category 2 in the EU CLP harmonized classification.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on classification results by other organizations in (1), it was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In classification results by domestic and international organizations, it was classified as Group 2B by IARC (IARC 123 (In prep.)), A3 by ACGIH (ACGIH (7th, 2001)), in Carc.2 in the EU-CLP classification (EU CLP classification (Access on May 2019)). [Reference Data, etc.] (2) In a carcinogenicity study with rats dosed with the dihydrochloride salt (CAS RN 615-28-1) of this substance in drinking water for 2 years, increased incidences were observed in liver tumors in both sexes and urinary bladder tumors in males (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)). (3) In a carcinogenicity study with mice dosed with the dihydrochloride salt of this substance in drinking water for 2 years, increased incidences of liver tumor and gallbladder tumor were observed in both sexes (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] There was not enough information to evaluate and classify the reproductive and developmental toxicity of this substance. Therefore, classification was not possible due to lack of data. [Reference Data, etc.] (1) There is a report that as a result of oral administration of this substance at 0.8 mg/kg/day to rats, effects on fetuses were seen. However, details were unknown (Initial Risk Assessment Report (Ministry of Health, Labour and Welfare, 2014)). (2) As a result of a mouse spot test dosed intraperitoneally to female mice on Day 10 of gestation, a decreased ongoing pregnancy rate and increased prenatal and postnatal mortality were seen (Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014), DFGOT vol.13 (1999)). (3) As a result of a dominant lethal test with male rats administered intraperitoneally and then mated with untreated females, there were no effects on the numbers of implantations, fetal resorptions, and live fetuses (Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014), DFGOT vol.13 (1999)). (4) As a result of applying a hair dye containing this substance to female rats on gestation Days 1, 4, 7, 10, 13, 16 and 19, there were no significant effects on the numbers of corpora lutea, implantations, live fetuses and fetal resorptions, and there was also no incidence of malformations (OEL Documentations (Japan Society For Occupational Health (JSOH), 1999), PATTY (6th, 2012), Initial Risk Assessment Report (Ministry of Health, Labour and Welfare, 2014)).
8	Specific target organ toxicity - Single exposure	Category 1 (blood system), Category 2 (central nervous system), Category 3 (respiratory tract irritation)	Danger Warning	H370 H371 H335	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] There is no report on single exposure to this substance in humans. From the information in (1) to (3) in the experimental animals, it was classified in Category 1 (blood system), Category 2 (central nervous system), Category 3 (respiratory tract irritation). The previous classification also included respiratory organs among target organs, but the only supporting information was dyspnea seen in the oral dose test, and histological findings provided no information on injury to the respiratory organs. Therefore, the classification result was changed. [Evidence Data] (1) In a single oral dose test with cats, an increase in the blood methemoglobin level was seen at doses of 25-50 mg/kg (corresponding to Category 1) of this substance (DFGOT vol.13 (1999), ACGIH (7th, 2001), BUA 97 (1992)). (2) In a single oral dose test with rats, impairment of general condition, excitability, depression, breathing difficulties, tremor, convulsions and paralysis were observed at doses of 500-2,000 mg/kg/day (corresponding to Category 2) of this substance (DFGOT vol.13 (1999), BUA 97 (1992)). (3) In a test with rats and mice exposed to a mixture of the vapor and dust of this substance by inhalation at 0.0905 mg/L for 4 hours, mild irritation to the nasal mucosa was seen (DFGOT vol.13 (1999)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (nasal cavity, kidney, urinary bladder, blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) and (2), effects on the nasal cavity, kidney, urinary bladder and blood system were observed in experimental animals dosed orally with the dihydrochloride salt (CAS RN 615-28-1) of this substance within the dose range of Category 2. Therefore, it was classified in Category 2 (nasal cavity, kidney, urinary bladder, blood system). The Harderian gland was not adopted as a target organ because extrapolation to humans would be impossible for this. Besides, the classification result was changed from the previous classification by the use of new information sources. [Evidence Data] (1) As a result of administrating the dihydrochloride salt of this substance in drinking water to rats at doses of 250-3,000 ppm (within the range of Category 2) for 13 weeks, inflammation of the Harderian gland, and effects on the blood system (decreased erythrocyte counts and hematocrit, etc.), kidney (papillary degeneration, increased urea nitrogen, etc.), nasal cavity (ductal dilation and necrosis of the olfactory epithelium) and urinary bladder (simple hyperplasia of transitional epithelial cells) were observed (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)). (2) As a result of administrating the dihydrochloride salt of this substance in drinking water to mice at doses of 500-5,000 ppm for 13 weeks, effects on the blood system (increases in MCV and platelet counts) and kidney (increased urea nitrogen, etc.) were observed at or above 1,000 ppm (within the range of Category 2) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)). [Reference Data, etc.] (3) As a result of administrating the dihydrochloride salt in drinking water to rats or mice for 104 weeks, non-neoplastic lesions of the nasal cavity and kidney, which were considered to be treatment-related, were observed above the range of Category 2 (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour EC50 = 0.821 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, 2001), Environmental Risk Assessment for Chemical Substances Vol. 12 (Ministry of the Environment, 2014)).
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 (not readily degradable, a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2001)), and 21-day NOEC = 0.083 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, 2001), Environmental Risk Assessment for Chemical Substances Vol. 12 (Ministry of the Environment, 2014)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 due to being not rapidly degradable (not readily degradable, a degradation rate by BOD: 2% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2001)), and 96-hour LC50 = 4.6 mg/L for fish (Oryzias latipes) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2001), Environmental Risk Assessment for Chemical Substances Vol. 12 (Ministry of the Environment, 2014)). By drawing a comparison between the above results, it was classified in Category 1.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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