Item | Information |
---|---|
CAS RN | 95-54-5 |
Chemical Name | o-Phenylenediamine |
Substance ID | m-nite-95-54-5_v2 |
Download of Excel format | Excel file |
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) |
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. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
7 | Flammable solids | Classification not possible |
- |
- | - | No data available. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
8 | Self-reactive substances and mixtures | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
9 | Pyrophoric liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
10 | Pyrophoric solids | Not classified |
- |
- | - | 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)). | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available. | FY2019 | 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). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine. It was classified as "Not classified (Not applicable)." | FY2019 | 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. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
16 | Corrosive to metals | Classification not possible |
- |
- | - | Classification is not possible because test methods applicable to solid substances are not available. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
17 | Desensitized explosives | Not classified |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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 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)) |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | [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)) |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | [Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)." |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | [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)) |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
2 | Skin corrosion/irritation | Not classified |
- |
- | - | [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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
6 | Carcinogenicity | Category 1B |
Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Based on (1) to (4), clear evidence of carcinogenicity including malignant tumors was observed in two animal species, and based on (4), this substance is a target substance in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act, and emphasizing these, it was classified in Category 1B. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) In a carcinogenicity study (OECD TG 451, GLP) with rats dosed by drinking water for two years using o-phenylenediamine dihydrochloride (CAS RN 615-28-1) as the test substance, marked increases in the incidences of hepatocellular adenoma and hepatocellular carcinoma were observed in the liver in males and females, and in addition, an increase in the incidence of transitional cell papilloma and transitional cell papilloma or carcinoma (combined) was observed in the urinary bladder of males. It was concluded that these results were clear evidence of carcinogenicity of o-phenylenediamine dihydrochloride in male and female rats (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2004), IARC 123 (2020)). (2) In a carcinogenicity study (OECD TG 451, GLP) with mice dosed by drinking water for two years using o-phenylenediamine dihydrochloride as the test substance, an increase in the incidence of hepatocellular adenoma in the liver was observed in males, a marked increase in the incidence of hepatocellular adenoma and hepatocellular carcinoma was observed in females, and an increase in the incidence of papillary adenoma was also observed in the gall bladder of males and females. It was concluded that these results were evidence of carcinogenicity of o-phenylenediamine dihydrochloride in male mice and clear evidence of carcinogenicity in female mice (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2004), IARC 123 (2020)). (3) This substance is a basic compound and will undergo acid-base reactions. Since this substance and its dihydrochloride are expected to undergo a pH-dependent acid-base equilibrium in the body, the results of carcinogenicity study for one compound can be used as information on the carcinogenicity assessment for the other (IARC 123 (2020)). (4) This substance is a target substance in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act (guidelines in order to prevent the impairment of worker's health, announcement No. 27 on February 7, 2020). (5) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 123 (2020)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (2020): Classification in 2019), the ACGIH classified it in A3 (ACGIH (7th, 2001)), the EU classified it in Carc. 2 (EU-CLP Classification Results (Accessed Sep. 2021)) and the DFG classified it in Category 3 (List of MAK and BAT values 2020 (Accessed Sep. 2021)). [Reference Data, etc.] (6) Also in a carcinogenicity study with male rats and male and female mice dosed by feeding for 18 months (rats were necropsied 6 months later) using dihydrochloride of this substance as the test substance, an increase in the incidence of hepatocellular carcinoma was observed (IARC 123 (2020), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2014), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2014), AICIS (previous NICNAS) IMAP (2013), ACGIH (7th, 2001), Patty (6th, 2012)). (7) As for the assessment of carcinogenicity of this substance, no human data were available (IARC 123 (2020)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
7 | Reproductive toxicity | Classification not possible |
- |
- | - | [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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
10 | Aspiration hazard | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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 |
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)). | FY2019 | 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 (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. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
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