NITE - Chemical Management Field

GHS Classification Result （Revision of the past classification result）

Chemical Name：m-Phenylenediamine
CAS：108-45-2

Result：


ID:	21B3165
Classifier:	Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified:	FY2009
Reference Manual:	GHS Classification Guidance by the Japanese Government （March, 2009）

PHYSICAL HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Explosives	Not applicable	-	-	-	-	There are no chemical groups associated with explosive properties present in the molecules.
2	Flammable gases （including chemically unstable gases）	Not applicable	-	-	-	-	Solid (GHS definition)
3	Aerosols	Not applicable	-	-	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	-	-	-	-	Solid (GHS definition)
5	Gases under pressure	Not applicable	-	-	-	-	Solid (GHS definition)
6	Flammable liquids	Not applicable	-	-	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	-	-	-	-	No data available.
8	Self-reactive substances and mixtures	Not applicable	-	-	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not applicable	-	-	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	-	-	-	-	Auto-ignition point is 560 degC (ICSC (1999)) exceeding 70 degC.
11	Self-heating substances and mixtures	Classification not possible	-	-	-	-	Test methods applicable to solid (melting point <= 140 degC) substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	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).
13	Oxidizing liquids	Not applicable	-	-	-	-	Solid (GHS definition)
14	Oxidizing solids	Not applicable	-	-	-	-	Organic compounds containing no oxygen, fluorine or chlorine
15	Organic peroxides	Not applicable	-	-	-	-	Organic compounds containing no bivalent -O-O- structure
16	Corrosive to metals	Classification not possible	-	-	-	-	Test methods applicable to solid substances are not available.

HEALTH HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Acute toxicity （Oral）	Category 3		Danger	H301: Toxic if swallowed	P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P321: Specific treatment （see ... on this label）. P330: Rinse mouth. P405: Store locked up. P501: Dispose of contents/container to ...	Based on rat LD50 values of 280 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 3 (2004)), 650 mg/kg (IARC vol. 16 (1978)), 204, 255, 260, 360 and 450 mg/kg (BUA (1995)), the substance was classified into Category 3 since most of the LD50 values are in this category.
1	Acute toxicity （Dermal）	Category 4		Warning	H312: Harmful in contact with skin	P302+P352: IF ON SKIN: Wash with plenty of soap and water. P280: Wear protective gloves/protective clothing/eye protection/face protection. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P322: Specific treatment （see ... on this label）. P363: Wash contaminated clothing before reuse. P501: Dispose of contents/container to ...	Based on a LD50 value of 1100 mg/kg for rats (Initial Risk Assessment Report (NITE, CERI, NEDO) vol. 54 (2008)), the substance was classified into Category 4.
1	Acute toxicity （Inhalation: Gases）	Not applicable	-	-	-	-	Solid (GHS definition)
1	Acute toxicity （Inhalation: Vapours）	Classification not possible	-	-	-	-	No data available.
1	Acute toxicity （Inhalation: Dusts and mists）	Classification not possible	-	-	-	-	No data available.
2	Skin corrosion/irritation	Not classified	-	-	-	-	There are reports of two tests where the substance was tested by open application to human skin. In the first test, the substance was found to have no effect when the solid was rubbed into human skin but a 10% alcoholic solution applied to the skin caused slight burning and itching. In the second test, one human subject was applied 1%, 5% and 10% solutions of the substance in alcohol, lanolin or Vaseline, and no visible effect was observed within 24-hour (DFGOT vol. 6 (1994)). Results for animal tests involving 4-hour applications are not reported. There is a result of "not irritating" following an occlusive application to rabbits for 24-hour (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). In three rabbit tests (application periods are unknown), no effect was noted when the substance was applied in solid form. However, application of a 10% alcoholic solution resulted in slight erythema (DFGOT vol. 6 (1994)). In two tests, following application of a 2.5% solution, results were "no irritation" (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)) and slight erythema and edema, which disappeared within 24-hour (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). Based on the reports, the substance was classified as "Not classified" in JIS Classification (correspond to Category 3 in GHS classification). As relevant information, in a rabbit test (application period is unknown), irritation was judged to be "local and moderate" (ACGIH (2001)). However, it is reported for the same test that direct application of the substance to rabbit skin resulted in no effects but application of a 10% alcoholic solution resulted in slight erythema (DFGOT vol. 6 (1994)).
3	Serious eye damage/eye irritation	Category 2		Warning	H319: Causes serious eye irritation	P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P337+P313: If eye irritation persists: Get medical advice/attention. P264: Wash ... thoroughly after handling. P280: Wear protective gloves/protective clothing/eye protection/face protection.	There is a report of "irritating to eyes" in human (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 3 (2004)). 3 rabbit tests have been conducted. In the first test, no irritation was noted following application of a 2.5% solution of the substance. In the second test, following application of a 20% solution, conjunctival erythema and corneal cloudiness were observed and disappeared within 7 days. In the third test, when 50 mg of the substance was applied, corneal cloudiness occurred and persisted more than 7 days (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). Based on these reports, the substance was classified into Category 2.
4	Respiratory sensitization	Classification not possible	-	-	-	-	No data available.
4	Skin sensitization	Category 1		Warning	H317: May cause an allergic skin reaction	P302+P352: IF ON SKIN: Wash with plenty of soap and water. P333+P313: If skin irritation or rash occurs: Get medical advice/attention. P261: Avoid breathing dust/fume/gas/mist/vapours/spray. P272: Contaminated work clothing should not be allowed out of the workplace. P280: Wear protective gloves/protective clothing/eye protection/face protection. P321: Specific treatment （see ... on this label）. P363: Wash contaminated clothing before reuse. P501: Dispose of contents/container to ...	In a scratch test of workers from a facility manufacturing this substance (exposure duration: 5 - 10 years), allergic positive response was observed in 9/112 persons (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). In a patch test of 19 female patients with eczema after use of hair color, positive rate was 21% at 0.1% application and 53% at 1% application (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). The substance is classified into Category 1 for skin sensitizer in Japan Society For Occupational Health (JSOH) (Recommendations for allowable concentrations (2008)) and R43 in EU classification (EU-Annex I (access on Jul. 2009)). The substance was classified into Category 1.
5	Germ cell mutagenicity	Category 2		Warning	H341: Suspected of causing genetic defects	P308+P313: IF exposed or concerned: Get medical advice/attention. P201: Obtain special instructions before use. P202: Do not handle until all safety precautions have been read and understood. P281: Use personal protective equipment as required. P405: Store locked up. P501: Dispose of contents/container to ...	Based on a positive result in a mouse bone marrow micronucleus test (in vivo test) (IUCLID (2000)), the substance was classified into Category 2. Although there is a weakly positive result in 1 of 3 dominant lethal tests, technical grade substance (purity: 98%) was used in the weakly positive test and there is no reproducibility in the other two tests using >99% purity substance (BUA No. 97 (1992)). From other in vivo tests, there are reports of negative mouse bone marrow micronucleus test (test substance: m-phenylenediamine hydrochloride) (BUA No. 97 (1992)), positive mouse testis unscheduled DNA synthesis test (BUA No. 97 (1992)), and negative mouse germ cell unscheduled DNA synthesis test (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). From in vitro mutagenicity tests, there are reports of positive CHO cell and CHL cell chromosomal aberration tests, Ames tests, CHL cell micronucleus tests as well as mouse lymphoma cell forward mutation tests (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008), NTP DB (access on Jul. 2009)). As relevant information, the substance is classified into Category 3; R68 in EU classification (EU-Annex I (access on Jul. 2009)).
6	Carcinogenicity	Not classified	-	-	-	-	Based on the classifications of "Group 3" in IARC (IARC suppl. 7 (1987)) and "A4" in ACGIH (1988) (ACGIH-TLV (2009)), the substance was classified as "Not classified". In 2-year oral (drinking) tests of m-phenylenediamine dihydrochloride, increased incidences of tumors were not observed in either sex of rats or mice, and carcinogenic activity of m-phenylenediamine dihydrochloride in F344/DuCrj (Fischer) rats and Crj:BDF1 mice was not indicated (Results from Carcinogenicity tests (Ministry of Health, Labour and Welfare) (1988)).
7	Reproductive toxicity	Category 2		Warning	H361: Suspected of damaging fertility or the unborn child	P308+P313: IF exposed or concerned: Get medical advice/attention. P201: Obtain special instructions before use. P202: Do not handle until all safety precautions have been read and understood. P281: Use personal protective equipment as required. P405: Store locked up. P501: Dispose of contents/container to ...	Since in an oral developmental toxicity test in rats, increased number of embryo resorptions was observed at dose levels at which decreased body weight gain was noted in the parental animals (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 3 (2004)), the substance was classified into Category 2. As relevant information, decreased number of sternal ossification centers was observed in fetuses (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, blood)		Danger	H370: Causes damage to organs (central nervous system, blood)	P307+P311: IF exposed: Call a POISON CENTER or doctor/physician. P260: Do not breathe dust/fume/gas/mist/vapours/spray. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P321: Specific treatment （see ... on this label）. P405: Store locked up. P501: Dispose of contents/container to ...	Reported effects on the central nervous system include a convulsion observed at 200 mg/kg following oral exposure to rats (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). Reported effects on the blood system include cyanosis observed at 100 - 200 mg/kg following oral exposure in mice (IUCLID (2000)). Oral exposure in cats at a dose level of 10 mg/kg and higher concentrations resulted in an increased methemoglobin concentration in blood (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)). Based on the data, the substance was classified into Category 1 (central nervous system, blood system). There is a report of "acute pulmonary edema following dermal exposure" (RTECS (2004)), however, this information regarding the respiratory system is on a document in List 3, therefore, the data was not used for this classification.
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, liver, kidney, urinary bladder), Category 2 (blood)		Danger Warning	H372: Cause damage to organs through prolonged or repeated exposure (nervous system, liver, kidney, urinary bladder) H373: May cause damage to organs through prolonged or repeated exposure (blood)	P260: Do not breathe dust/fume/gas/mist/vapours/spray. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P314: Get medical advice/attention if you feel unwell. P501: Dispose of contents/container to ...	In humans, there is a report of "abnormal reflex, cutaneous hyperesthesia and pathological changes in the kidney and liver" (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 3 (2004)). In workers, following long-term exposure to the substance "dysuria, edema of mucosa, polypous swellings and (eosinophilic) infiltration of the area of the triangle and cervix of the urinary bladder" were reported as effects (ACGIH (2001)). In animals, reported effects are as follows; "an abundance of degenerative lesions with a significant increase in the numbers of pyknotic hepatocytes in the livers" at 18 mg/kg following a 13-week oral exposure in rats (ACGIH (2001)); "methemoglobinemia" at 100 mg/kg (90-day equivalence: 31.1 mg/kg) following a 4-week oral exposure in rats; "chronic renal disease" at 40 mg/kg following a 104-week oral exposure in rats (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 3 (2004)); and "impairment of liver and central nervous system" at 5.6 mg/kg and higher dose levels following a 4-month oral exposure in rats (IUCLID (2000)). The nervous system, liver, kidney, urinary bladder and blood system are considered to be target organs. Since the findings in animals were noted at dose levels within the guidance value range for Category 1 and 2, the substance was classified into Category 1 (nervous system, liver, kidney, urinary bladder) and Category 2 (blood system). Additionally, there are reports of "pulmonary fibrosis, skin thickening of fingers" and "reflux esophagitis, pedal oedema, bradycardia, heart block, sclerodactyly, teleangiectasis over the fingers, pulmonary fibrosis, and dilation of oesophagus" (IUCLID (2000)), however, these effects were derived from exposure data for amine mixtures which contained the substance as the main component (Initial Risk Assessment Report (NITE, CERI, NEDO) No. 54 (2008)).The substance was not classified into Category 2 (cardiovascular system, respiratory system) since these effects may were induced by exposure to a mixture of the substance with other substances.
10	Aspiration hazard	Classification not possible	-	-	-	-	No data available.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
11	Hazardous to the aquatic environment （Acute）	Category 2	-	-	H401: Toxic to aquatic life	P273: Avoid release to the environment. P501: Dispose of contents/container to ...	Classified into Category 2 from its 48h-EC50 = 2.0 mg/L for Crustacea (Daphnia magna) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 2001), etc.).
11	Hazardous to the aquatic environment （Long-term）	Category 2		-	H411: Toxic to aquatic life with long lasting effects	P273: Avoid release to the environment. P391: Collect spillage. P501: Dispose of contents/container to ...	Classified into Category 2 since its acute toxicity is Category 2 and it is not rapidly degradable (BOD degradation rate: 2% (Biodegradation and Bioconcentration of Existing Chemical Substances under the Chemical Substances Control Law, 1985)).
12	Hazardous to the ozone layer	Classification not possible	-	-	-	-	This substance is not listed in Annexes to the Montreal Protocol.

NOTE:

* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.

Reference：

Reference Manual
Definitions / Abbreviations
Model Label by MHLW	MHLW Website （in Japanese Only）
Model SDS by MHLW	MHLW Website （in Japanese Only）