GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 541-69-5
Chemical Name meta-Phenylenediamine dihydrochloride
Substance ID R01-A-015
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. Besides, there is information that it is combustible (GESTIS (Access on July 2019)).
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 *
-
-
- - 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 *
-
-
- - 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) 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: 400-800 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008))
(2) Mortality in rats: male: 10/10 animals at 800 mg/kg, 9/10 animals at 471 mg/kg, 1/10 animal at 277 mg/kg, female: 10/10 animals at 800 mg/k and 471 mg/kg, 5/10 animals at 277 mg/kg, 1/10 animal at 163 mg/kg (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on July 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), m-phenylenediamine (CAS RN 108-45-2), a free base of this substance, was judged to correspond to "Not classified" (Category 3 in UN GHS classification) in the GHS classification guidance for the Japanese Government. This substance was also classified as "Not classified" (Category 3 in UN GHS classification).

[Evidence Data]
(1) In a skin irritation test (in accordance with EEC Directive 93/21, Annex VI) with rabbits of m-phenylenediamine, a free base of this substance, slight to mild erythema was observed in all animals 1 hour to 24 hours after removal of the test substance. There were slight erythema in 2/6 animals after 48 hours and only slight edema in 4 animals after 24 hours, and the mean score after 1, 24, and 48 hours was 1.39 (REACH registration dossier (Access on June 2019)).

[Reference Data, etc.]
(2) No irritation was observed in a 24-hour occlusive application test in which 500 mg of m-phenylenediamine, a free base of this substance, was applied to the auricles of rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008))
(3) m-Phenylenediamine, a free base of this substance, is irritating to the eyes and skin (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
[Rationale for the Classification]
Based on (1), since m-phenylenediamine, a free base of this substance, was classified in Category 2B, this substance was also classified in Category 2B.

[Evidence Data]
(1) In an eye irritation test compliant with OECD TG 405 with rabbits of m-phenylenediamine, a free base of this substance, severe conjunctival redness, moderate corneal opacity, moderate iritis, hemorrhaging, chemosis and damage of the cornea were produced. In addition, severe edema in the treated unwashed rabbit eye was observed, but both treated eyes were normal by 7 days. The mean scores for corneal opacity, iris, conjunctival redness and chemosis at 24/48/72 hours in the unwashed group were 0.67, 0, 2.7 and 2.0, respectively (REACH registration dossier (Access on June 2019)).

[Reference Data, etc.]
(2) There are reports that in a test in which 0.1 mL (equivalent to 20 mg) of a 20% aqueous solution of m-phenylenediamine, a free base of this substance, was instilled into the eyes of rabbits, conjunctival redness and corneal opacity were observed and these resolved within 7 days, and that in a test in which 50 mg was applied, corneal opacity was observed, which did not resolve within 7 days (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
(3) It was classified as "Eye Irrit. 2 (H319)" in the EU CLP classification (EU CLP classification (Access on July 2019)).
4 Respiratory sensitization *
-
-
- - [Rationale for the Classification]
There is data in (1). However, since it was impossible to determine the classification of "respiratory sensitization," it was classified as "Classification not possible."

[Reference Data, etc.]
(1) A worker who had been repeatedly exposed to this substance due to leakage accidents of m-phenylenediamine, a free base of this substance, in the United States developed a wet cough, fatigue, shortness of breath in addition to skin symptoms by inhalation exposure, and decreased vital capacity, chest X-ray findings and pulmonary fibrosis at open lung biopsy were observed, therefore, the person was diagnosed scleroderma. Since similar symptoms were observed in another worker in the same department, this substance was considered to be a causative agent (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).
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) and (2), since m-phenylenediamine, a free base of this substance, was classified in Category 1A, this substance was also classified in Category 1A.

[Evidence Data]
(1) In a mouse local lymph node test compliant with OECD TG 429 of m-phenylenediamine, a free base of this substance, it was positive, and EC3 was estimated to be 0.49 (REACH registration dossier (Access on June 2019)).
(2) m-Phenylenediamine, a free base of this substance, was classified as occupational skin sensitizers Group 3 (OEL Documentations (Japan Society For Occupational Health (JSOH), 2010)).

[Reference Data]
(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 *
-
-
- - [Rationale for the Classification]
There are no in vivo data on this substance. However, based on the findings and classification on m-phenylenediamine, a free base of this substance, it was classified as "Not classified."

[Evidence Data]
(1) As for in vitro, there were reports of a positive result in a bacterial reverse mutation test and a negative result in a mouse lymphoma test (Mutagenicity Test Data of Existing Chemical Substances based on the toxicity investigation system of the Industrial Safety and Health Law (Access on September 2019)).
(2) m-Phenylenediamine (CAS RN 108-45-2), a free base of this substance, was classified as "Not classified" (GHS classification result in FY 2019).
6 Carcinogenicity *
-
-
- - [Rationale for the Classification]
Based on classification results by other organizations for the free base of this substance in (1) and the test result in experimental animals in (2), it was classified as "Not classified."

[Evidence Data]
(1) As for classification results by domestic and international organizations, the free base (CAS RN 108-45-2) of this substance was classified in Group 3 by IARC (IARC Suppl.7 (1987)).
(2) In carcinogenicity tests with rats and mice dosed with drinking water for 104 weeks, neither male nor female animals of both rats and mice showed any carcinogenicity (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on July 2019)).
7 Reproductive toxicity *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data. Besides, m-phenylenediamine (CAS RN 108-45-2), a free base of this substance, was also considered to be "Classification not possible" due to lack of data. Besides, please refer to the classification result for m-phenylenediamine in FY 2019.

[Reference Data, etc.]
(1) In a developmental toxicity test in which m-phenylenediamine was orally administered to female rats on gestational Days 6-15, an increase in resorptions, a decrease in the number of viable fetuses, lower fetal body weight and delayed ossification of the sternum were observed at the dose where reduced body weight gain, or death (6/25 animals) was observed in maternal animals (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), ACGIH (7th, 2001), DFGOT vol.6 (1994)). This data was not adopted as evidence for classification because effects on embryos/fetuses were observed only at the dose where the maternal toxicity (deaths in 6/25 animals, 25% mortality) was observed.
(2) In a developmental toxicity test in which m-phenylenediamine was orally administered to female rats on gestational Days 6-15, reduced body weight gain was observed in maternal animals, but no effects on fetal development were observed (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2001), DFGOT vol.6 (1994)). The number of maternal animals is as small as the 7-9 animals/group in this data and is insufficient to evaluate effects.
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system, blood system)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
[Rationale for the Classification]
There are no reports on single exposure to this substance in humans. As for m-phenylenediamine (CAS RN 108-45-2), a free base of this substance, as shown in (1) and (2), effects on the central nervous system and blood system in experimental animals were observed at doses corresponding to Category 1. In (3), since the toxic effects of this substance are not essentially different from those of m-phenylenediamine, it was classified in Category 1 (central nervous system, blood system). The report in (4) was not adopted as evidence due to the findings in dead animals.

[Evidence Data]
(1) In a single oral administration test with cats, cyanosis, loss of appetite, respiratory disturbance, sedation, convulsions and methemoglobin production were observed at 10 and 25 mg/kg of m-phenylenediamine (a converted value equivalent to this substance: 16.7 and 41.9 mg/kg, corresponding to Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), BUA 97 (1992)).
(2) In a single oral administration test with rats, convulsions and inflammation of the gastrointestinal tract were observed at 200 mg/kg of m-phenylenediamine (a converted value equivalent to this substance: 335 mg/kg, corresponding to Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), BUA 97 (1992)).
(3) There is a description that the toxic effects of this substance are not essentially different from those of m-phenylenediamine (GESTIS (Access on July 2019)).

[Reference Data, etc.]
(4) In a test by single oral administration of 96-800 mg/kg of this substance to rats, pulmonary congestion and edema, proximal tubular necrosis and protein casts in the kidneys, necrosis of the small intestine, and nasal epithelium degeneration were observed in dead animals (at or above 277 mg/kg, corresponding to Category 2) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on July 2019)).
9 Specific target organ toxicity - Repeated exposure Category 1 (urinary bladder), Category 2 (kidney, blood system)


Danger
Warning
H372
H373
P260
P264
P270
P314
P501
[Rationale for the Classification]
Based on (1), effects on the urinary bladder were observed due to exposure to m-phenylenediamine (CAS RN 108-45-2), a free base of this substance, in humans, and based on (2)-(4), effects on the kidney and blood system were observed within the range of Category 2 by oral administration of this substance or m-phenylenediamine to rats and mice. Therefore, it was classified in Category 1 (urinary bladder), Category 2 (kidney, blood system). The classification result was different from that of m-phenylenediamine due to the molecular weight conversion.

[Evidence Data]
(1) One hundred twelve workers in their 30s to 50s in a Russian factory producing phenylenediamine were exposed to 1-2 mg/m3 of m-phenylenediamine for 5-10 years, 15 of them complained of dysuria. In a scratch test with m-phenylenediamine, 9 out of the 112 persons showed an allergy-positive reaction, and edema of the mucous membranes and polypous swellings were observed in the triangle and cervix of the urinary bladder in the cystoscopy of the persons who showed a positive reaction, and all of the 9 persons were diagnosed with eosinophilia. In addition, 0.003-0.40 mg/L of m-phenylenediamine was detected in the urine (DFGOT vol.6 (1994), ACGIH (7th, 2001), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).
(2) When rats were given 62.5-1,000 ppm of this substance in drinking water for 13 weeks, increased kidney weight and pigmentation in the kidneys in females at or above 250 ppm (23 mg/kg/day, within the range of Category 2), slight degeneration of the renal papilla, etc. in males and females at or above 500 ppm (male: 30 mg/kg/day, female: 32 mg/kg/day, within the range of Category 2), and decreased platelet count, etc. in males and females at 1,000 ppm (male: 54 mg/kg/day, female: 57 mg/kg/day, within the range of Category 2) were observed (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on July 2019)).
(3) When mice were given 24.4-2,000 ppm of this substance in drinking water for 13 weeks, increases in AST, ALP and total cholesterol, pigment granules in Kupffer cells in the liver and in the spleen at 222 ppm (male: 29 mg/kg/day, female: 52 mg/kg/day, within the range of Category 2), decreased red blood cell counts, hemoglobin and hematocrit, etc. at or above 667 ppm (male: 49 mg/kg/day, female: 67 mg/kg/day, within the range of Category 2), and deaths at 2,000 ppm (male: 108 mg/kg/day, female: 132 mg/kg/day, exceeding Category 2) were observed. Heart dilation and muscle necrosis, etc. were also observed in the dead or moribund animals (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on July 2019)).
(4) When m-phenylenediamine was orally administered to rats for 90 days, increased liver weight, pyknotic hepatocytes and increased kidney weight, etc. were observed at 18 mg/kg/day (a converted value equivalent to this substance: 30 mg/kg/day, within the range of Category 2) (IRIS (1987), DFGOT vol.6 (1994), ACGIH (7th, 2001), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).

[Reference Data, etc.]
(5) There is a report that 2 male chemical plant workers exposed to amines with m-phenylenediamine as the main ingredient suffered from systemic sclerosis (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).
(6) When mice were given 0.02 and 0.04% (within the range of Category 2) of m-phenylenediamine in drinking water for 78 weeks, increased organ weights and pigmentation, etc., but no toxicological effects on tissues were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)).
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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