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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	106-50-3
Chemical Name	p-Phenylenediamine
Substance ID	R01-B-006
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	FY2011 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 400 deg C (ICSC (1997)).
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	*	- -	-	-	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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 3. [Evidence Data] (1) LD50 for rats: 80 mg/kg (DFGOT vol.6 (1994), PATTY (6th, 2012), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004)) (2) LD50 for rats: 98 mg/kg (DFGOT vol.6 (1994))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. The classification result was changed due to the revised JIS for classification and the revision of information sources. [Reference Data, etc.] (1) There is a report that death was observed by application of 5,000 mg/kg of this substance to rabbits for 24 hours (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)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 3. [Evidence Data] (1) LC50 for rats (4 hours, aerosol): 0.92 mg/L (Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), REACH registration dossier (Access on June 2019))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." In the previous classification, it was classified based on the results of preparations such as solutions, not the undiluted substance. Therefore, since this was judged to be inappropriate, the classification result was changed. [Evidence Data] (1) There is a report that it was non-irritant in a test in which 500 mg of undiluted substance was administered to rabbits (applied for 24 hours) (BUA 97 (1992)). [Reference Data, etc.] (2) It is reported that slight irritation was observed when this substance in a 50% aqueous ointment was applied to 6 volunteers (DFGOT vol.6 (1994)). (3) As for findings on the skin, the result was from none up to moderately irritating, dependent on the concentration and duration of contact. A test on rabbits' skin with 50% emulsion of this substance revealed distinct reactions. However, irritation to human skin was minor. Based on these findings, this substance was assessed to be moderately irritating to the eyes and slightly irritating to the skin (GESTIS (Access on May 2019)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] Based on (1), it was classified in Category 2B. [Evidence Data] (1) It was reported to be slightly irritant in a Draize test in which the undiluted substance was applied to rabbits (BUA 97 (1992)). [Reference Data, etc.] (2) It was reported that in a test in which 30 mg was applied to rabbits, though redness and edema of the conjunctiva and corneal clouding were observed, these were reversible within 7 days (BUA 97 (1992)). (3) It was classified as "Eye Irrit. 2 (H319) " in the EU CLP classification (EU CLP classification (Access on July 2019)). (4) Though application of the solid matter or saturated solutions on the rabbits' eyes caused distinct irritation, diluted solutions (2.5%) did not (GESTIS (Access on May 2019)).
4	Respiratory sensitization	Category 1	Danger	H334	P304+P340 P342+P311 P261 P284 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. [Evidence Data] (1) There is a report that this substance is a potent sensitizer of the skin and respiratory tract and may cause asthma (PATTY (6th. 2012)).
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1)-(4), it was classified in Category 1A. [Evidence Data] (1) It was classified as occupational skin sensitizers Group 1 by Japan Society For Occupational Health (JSOH) (OEL Documentations vol.52 (Japan Society For Occupational Health (JSOH), 2010)). (2) It is reported that in a repeated insult patch test with humans, the positive rate was 100% (DFGOT vol.14 (2000)). (3) It is reported that in various guinea pig skin sensitization tests, the positive rate was 100% (DFGOT vol.6 (1994)). (4) It is reported that EC3 values were 2 or under (0.06% and 0.20%) in a mouse Local Lymph Node Assay (LLNA) (SCCS (2012)). [Reference Data, etc.] (5) It was classified as "Skin Sens. 1 (H317) " in the EU CLP classification (EU CLP classification (Access on July 2019)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1), according to the weight of evidence, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there are reports of negative results in dominant lethal tests with rats and mice, a reciprocal translocation test with rats, micronucleus tests with rats and mice and an unscheduled DNA synthesis test with rat liver (DFGOT vol.6 (1994), ACGIH (7th, 2001), IARC 16 (1978), SCCS (2012)). (2) As for in vitro, there are reports of positive results in a bacterial reverse mutation test, a mouse lymphoma TK test, a chromosomal aberration test and a DNA damage test, and negative results in a mammalian cell HPRT test and a micronucleus test with human peripheral blood lymphocytes (IARC 16 (1978), ACGIH (7th, 2001), DFGOT vol.6 (1994), SCCS (2012), PATTY (6th, 2012), OEL Documentations (Japan Society For Occupational Health (JSOH), 1997)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Based on classification results by other organizations in (1), it was classified as "Classification not possible" 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 3 by IARC (IARC Suppl.7 (1987)), and in A4 by ACGIH (ACGIH (7th, 2001)). [Reference Data, etc.] (2) In a carcinogenicity test in which a dihydrochloride salt of this substance (CAS RN 624-18-0) was administered to rats and mice by feeding for 2 years, no statistically significant tumor incidence was observed in rats or mice of either sex (NTP TR174 (1979)). (3) No tumor incidence was observed in a test in which this substance was orally administered to rats for 8 months (IARC 16 (1978)). (4) No tumor was observed in a test in which this substance in acetone solution was dermally administered to mice for 120-130 weeks (DFGOT vol.6 (1994), ACGIH (7th, 2001)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), only slight effects were observed on developmental toxicity, and it corresponds as "Not classified." However, since there is no information for sexual function and fertility, the classification was not possible due to lack of data. [Evidence Data] (1) In a developmental toxicity test (OECD TG 414) in which female rats were dosed by gavage on gestational Days 6-19, delayed ossification was observed (SCCS (2012)). (2) In a developmental toxicity test in which female rats were dosed by gavage on gestational Days 6-15, though maternal toxicity (reduced body weight gain, decreased food consumption, death) was observed, no teratogenic or embryo/fetotoxicity was observed (SCCS (2012), ACGIH (7th, 2001)). [Reference Data, etc.] (3) No teratogenic effect was observed in tests in which female mice were dosed subcutaneously on gestational Days 5-7, 8-10 or 11-14 (SCCS (2012)).
8	Specific target organ toxicity - Single exposure	Category 1 (heart, kidney, muscle)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] As for humans, as represented in (1) and (2), several cases are reported in which single oral ingestion of this substance caused rhabdomyolysis and renal failure. Moreover, in (3), there are cases in which myocarditis was observed in persons who accidentally or intentionally ingested hair dye containing this substance as the main component. As for also experimental animals, in a test with mice described in (4), effects on the muscle and increased blood creatine phosphokinase (CPK) were observed at doses within the range of Category 1. From the above, it was classified in Category 1 (heart, kidney, muscle). [Evidence Data] (1) A 40-year-old man who ingested 5,000 mg (70 mg/kg) of this substance showed dyspnea, and edema of the face and tongue, followed by rhabdomyolysis, increases in LDH, AST and ALT in blood, acute kidney failure and red-brown urine (DFGOT vol.6 (1994)). (2) A 50-year-old man who accidentally ingested a cup of an aqueous solution of this substance showed abdominal pain, facial edema and dyspnea, followed by rhabdomyolysis, increases in LDH, AST, CPK and aldolase in blood, acute kidney failure and dark-brown urine (DFGOT vol.6 (1994)). (3) As for humans, after accidental or intentional ingestion of hair dyes containing this substance as the main component, persons who developed angioneurotic edema, rhabdomyolysis and renal failure, and persons who developed myocarditis are reported (SCCS (2012)). (4) In a test in which 35 or 70 mg/kg of this substance was administered to mice by nasogastric tube, a significant increase in blood CPK and necrosis of microfibres in the skeletal muscles were observed (DFGOT vol.6 (1994)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (heart, muscle)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1)-(3), in experimental animals, since effects on heart and muscle were observed within the range of Category 1, it was classified in Category 1 (heart, muscle). Besides, among rationales for the previous classification, the one in which causal substance was unclear (mixture) was removed, the information sources were reviewed after adding the new ones, and the classification result was changed from the previous classification. [Evidence Data] (1) As a result of oral administration of 5-40 mg/kg/day of this substance to rats for 14 days, increased LDH was observed at or above 5 mg/kg/day (converted guidance value: 0.8 mg/kg/day, within the range of Category 1), increases in ALT, AST and creatinine phosphokinase in blood, and increased weight of the thyroid were observed at or above 10 mg/kg/day (converted guidance value: 1.6 mg/kg/day, within the range of Category 1), and increased liver weight and slight myodegeneration in the skeletal muscle were observed at 40 mg/kg/day (converted guidance value: 6.2 mg/kg/day, within the range of Category 1) (SCCS (2012)). (2) As a result of oral administration of 2-16 mg/kg/day of this substance to rats for 13 weeks, increases in liver weight and kidney weight were observed at or above 8 mg/kg/day (within the range of Category 1), slight myodegeneration on the skeletal muscle was observed at 16 mg/kg/day (within the range of Category 2) (Environmental Risk Assessment for Chemical Substances Vol.3, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2004), SCCS (2012)). (3) As a result of oral administration of 10 mg/kg/day (within the range of Category 1) of this substance to rabbits for 90 days, alterations of the myocardial parenchyma (edema, swelling of the muscular fibers, cytoplasmic homogenization, disappearance of cross-striation) were observed (ACGIH (7th, 2001)). [Reference Data, etc.] (4) It is well known that this substance and its derivatives can induce myotoxicity (SCCS (2012)). (5) As for information on humans, there is a report that a 51-year-old woman who had regularly used a commercial hair dye including this substance developed hepatomegaly and spleen enlargement, followed by progressive neurological symptoms prior to her death 11 weeks after hospital admission (IARC 16 (1978), ACGIH (7th, 2001)). In addition, there is a report that gastrointestinal and nervous symptoms were observed after using a hair dye containing this substance (ACGIH (7th, 2001)). Moreover, there is a report that a worker with occupational exposure to a hair dye containing this substance for 5 years died of jaundice and subacute atrophy of the liver (ACGIH (7th, 2001)).
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 96-hour LC50 = 0.066 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)).
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: 5% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2002)), and 72-hour NOEC = 0.01 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)). 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 (not readily degradable, a degradation rate by BOD: 5% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2002)), and 96-hour LC50 = 0.066 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)). From 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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