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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	615-28-1
Chemical Name	Benzene-1,2-diamine dihydrochloride
Substance ID	R01-A-001
Classification year (FY)	FY2019
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)
Model SDS by MHLW (External link)
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	*	- -	-	-	Because it is classified in Division 6.1 (toxic substances), PG III in UNRTDG (UN1673), and it is considered to be not applicable to pyrophoric solids, hazards of the highest precedence, it was classified as "Not classified."
11	Self-heating substances and mixtures	*	- -	-	-	No data 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	*	- -	-	-	It is an organic compound which does not contain fluorine or oxygen but contains chlorine, which is ionically bonded to amine and does not contribute to oxidization of other substances. 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)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, there was information of reference data in (1), but an oral LD50 value could not be confirmed. [Reference Data, etc.] (1) It is described that the LD50 values for rats via the oral and parenteral routes of this substance were within the range of 300-1,600 mg/kg (GESTIS (Access on June 2019)).
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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] Classification not possible due to lack of data.
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), since o-phenylenediamine (CAS RN 95-54-5), a free base of this substance, was judged to be classified as "Not classified," this substance was classified as "Not classified." [Evidence Data] (1) It was reported that o-phenylenediamine was non-irritating in a skin irritation test according to OECD TG 404 with rabbits (DFGOT vol.13 (1999)). (2) A skin irritation test on o-phenylenediamine with 3 rabbits according to OECD TG 404, showed very slight erythema after 48 hours, which was reversible after 72 hours. The average scores for erythema and edema at 24/48/72 hours are reported to be 0.6 and 0 (REACH registration dossier (Access on June 2019)). [Reference Data, etc.] (3) To be on the safe side it should be assumed that the handling of this substance involves a pronounced irritative potential, particularly with regard to possible irritations to the eyes and respiratory tract (GESTIS (Access on May 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), since o-phenylenediamine (CAS RN 95-54-5), a free base of this substance, was judged to be Category 2A, this substance was classified in Category 2A. [Evidence Data] (1) In an eye irritation test with o-phenylenediamine according to OECD TG 405, it showed irritation, and the average scores for the cornea, the iris, conjunctival redness and conjunctival edema were 2.1, 1, 3 and 2.9, respectively, but these were reversible within 14 days (REACH registration dossier (Access on June 2019)). [Reference Data, etc.] (2) In an eye irritation test with o-phenylenediamine according to OECD TG 405, it caused reddening and swelling of the conjunctiva, corneal clouding and inflammation of the iris, but these were reversible within 14 days (DFGOT vol.13 (1999)). (3) o-Phenylenediamine was classified as Eye Irrit. 2 (H319) in the EU-CLP classification (EU CLP classification (Access on May 2019)). (4) To be on the safe side it should be assumed that the handling of this substance involves a pronounced irritative potential, particularly with regard to possible irritations to the eyes and respiratory tract (GESTIS (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), since o-phenylenediamine (CAS RN 95-54-5), a free base of this substance, was judged to be Category 1, this substance was classified in Category 1. [Evidence Data] (1) o-Phenylenediamine was classified in occupational skin sensitizers Group 3 by Japan Society For Occupational Health (OEL Documentations (Sensitization classification) (Japan Society For Occupational Health (JSOH), 2010)). (2) In a skin sensitization test on o-phenylenediamine with guinea pigs, mild to moderate sensitization was demonstrated in 3-7 out of 10 guinea pigs (with a positive rate, 30-70%) (REACH registration dossier (Access on June 2019)). [Reference Data, etc.] (3) o-Phenylenediamine was classified as Skin Sens. 1 (H317) in EU CLP (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] There were no in vivo or in vitro data on this substance, but there were reports in (1)-(3) for o-phenylenediamine (CAS RN 95-54-5), a free base of this substance. From the above, this substance was classified in Category 2. [Evidence Data] (1) Although there are no in vivo data of this substance, o-phenylenediamine is reported to be negative in a dominant lethal test in rats and mouse spot test, and positive in a micronucleus test/a chromosomal aberration test with mouse bone marrow and others (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) Although there are no in vitro data of this substance, o-phenylenediamine is reported to be positive in a mouse lymphoma test, and in many mammalian cell chromosome 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) o-Phenylenediamine was classified in Category 2 in EU CLP harmonized classification.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the 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 in Group 2B by IARC (IARC 123 (In prep.)), Carc.2 in EU CLP (EU CLP classification (Access on May 2019)). [Reference Data, etc.] (2) A carcinogenicity study with rats dosed with drinking water for 2 years showed increased incidences of 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) A carcinogenicity study with mice dosed with drinking water for 2 years showed increased incidences of liver tumors and gallbladder tumors 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 are no data on this substance itself. Besides, o-phenylenediamine, a free base of this substance, could not be classified due to lack of data (See classification results of o-phenylenediamine (CAS RN 95-54-5)). [Reference Data, etc.] (1) It is reported that effects on fetuses were observed in rats orally administered o-phenylenediamine at a dose of 0.8 mg/kg/day. The details, however, were unknown (Initial Risk Assessment Report (Ministry of Health, Labour and Welfare, 2014)). (2) In a mouse spot test with o-phenylenediamine dosed intraperitoneally to female mice on gestation Day 10, a decreased ongoing pregnancy rate and increased prenatal/postnatal mortality were observed (Environmental Risk Assessment for Chemical Substances Vol.12 (Ministry of the Environment, 2014), DFGOT vol.13 (1999)). (3) In a dominant lethal test in which male rats were intraperitoneally administered o-phenylenediamine and then mated with untreated females, no effects were seen on the numbers of implantations, 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 o-phenylenediamine 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 resorption, and there was also no development 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 are no reports of single exposure to this substance itself in humans and experimental animals. o-Phenylenediamine (CAS RN 95-54-5), a free base of this substance, showed effects on the blood system and central nervous system and irritation to the respiratory tract in experimental animals as shown in (1)-(3). Based on information in (4), it was classified in Category 1 (blood system), Category 2 (central nervous system), Category 3 (respiratory tract irritation) like o-phenylenediamine. [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 (a converted value equivalent to this substance: 42-84 mg/kg, corresponding to Category 1) of o-phenylenediamine (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, tremors, convulsions and paralysis were abserved at doses of 500-2,000 mg/kg/day (a converted value equivalent to this substance: 837-3,349 mg/kg, corresponding to or exceeding the range of Category 2) (DFGOT vol.13 (1999), BUA 97 (1992)). (3) In a test in which rats and mice were exposed to a mixture of o-phenylenediamine vapor and dust by inhalation at 0.0905 mg/L (a converted value equivalent to this substance: 0.1515 mg/L) for 4 hours, slight irritation to the nasal mucous membranes was seen (DFGOT vol.13 (1999)). (4) It is described that the acute toxicity of o-phenylenediamine and this substance are similar (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 within the 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 with it. Besides, the category was changed from the previous classification by using new information sources. [Evidence Data] (1) As a result of administrating this substance in drinking water to rats at doses of 250-3,000 ppm (almost within the range of Category 2) for 13 weeks, inflammation of the Harderian gland, effects on the blood system (decreased erythrocyte counts and hematocrit, etc.), kidney (papillary necrosis, increased urea nitrogen, etc.), nasal cavity (ductal dilation of the olfactory glands, necrosis of the olfactory epithelium) and urinary bladder (simple hyperplasia of the transitional epithelial cells) were seen (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2019)). (2) As a result of administrating 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 seen at or above 1,000 ppm (male: exceeding the range of Category 2, female: exceeding 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 this substance in drinking water to rats or mice for 104 weeks, non-neoplastic lesions of the nasal cavity and kidney which was considered to be due to administration of this substance 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)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
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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