Latest GHS Classification Results by the Japanese Government (edited by NITE)
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 122-39-4 |
| Chemical Name | Diphenylamine |
| Substance ID | m-nite-122-39-4_v1 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| 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) | To Workplace Safety Site (MHLW) |
| Sample SDS by MHLW (External link) | To Workplace Safety Site (MHLW) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 7 | Flammable solids | Classification not possible |
- |
- | - | No data available. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 8 | Self-reactive substances and mixtures | Not classified (Not applicable) |
- |
- | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 9 | Pyrophoric liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 10 | Pyrophoric solids | Not classified |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 634 deg C (ICSC (2006)). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | No data available. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 17 | Desensitized explosives | - |
- |
- | - | - | - | - |
| 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) | Not classified |
- |
- | - | There are 11 reports of LD50 values within the range of >800 mg/kg->15,000 mg/kg for rats (PATTY (6th, 2012), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2004), JMPR 949 (1998), JMPR 701 (1984), JMPR 157 (1969)). It was classified as "Not classified" (Category 5 in UN GHS classification) to which the most data (4 data) (2,960 mg/kg (male), 2,480 mg/kg (female) (EU-RAR (2007), JMPR 701 (1984)), 3,000 mg/kg (male), 2,700 mg/kg (female) (JMPR 949 (1998)), 3,000 mg/kg (EU-RAR (2007)), 3,200 mg/kg (JMPR 157 (1969))) corresponded. By adding the new information sources (PATTY (6th, 2012), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2004), JMPR 949 (1998), JMPR 701 (1984), JMPR 157 (1969)), the category was revised. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | Based on reports of LD50 values of >2,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), JMPR 949 (1998)) and >5,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) for rabbits, and of >5,000 mg/kg for rats (EU-RAR (2007), JMPR 701 (1984)), it was classified as "Not classified." By adding the new information sources (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), JMPR 949 (1998)), the category was revised. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | There are multiple reports of skin irritation tests with rabbits, in which it was not irritating, or mild irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), JMPR 701_ Diphenylamine (Pesticide residues in food 1984 evaluations)). From the above results, it was classified as "Not classified" (Category 3 in UN GHS classification). By adding the information sources in List 1, the category was changed. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 3 | Serious eye damage/eye irritation | Category 1 |
 Danger |
H318 | P305+P351+P338 P280 P310 |
In an eye irritation test in which 0.1 g of this substance was applied to 3 rabbits (EU TG and OECD TG compliant), since irritation and eye damage including the corneal persisted longer than 21 days after application, it was judged to be a "corrosive" substance (EU-RAR (2007)). Additionally, in a test in which 0.1 g of this substance was applied to 1 rabbit for 7 days, corrosivity and corneal opacity were observed (JMPR 949_ Diphenylamine (addendum) (JMPR Evaluations 1998 Part II Toxicological)). On the other hand, there are reports in other eye irritation tests with rabbits, that slight iritis and moderate conjunctivitis were observed but these cleared within 10 days (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), JMPR701_ Diphenylamine (Pesticide residues in food 1984 evaluations)), and that mild redness and edema (1/2 animals) were observed but they disappeared within 3 days (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Moreover, there is a report that this substance was slightly irritating in an eye irritation test with rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above results, although there were conflicting data on corrosivity and mild irritation, corrosivity was observed in the test according to the guidelines, therefore, considering of possibility of serious effects on the eyes, it was classified in Category 1. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, although there is a report that it was negative in a sensitization test with guinea pigs (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), JMPR 949_ Diphenylamine (addendum) (JMPR Evaluations 1998 Part II Toxicological)), these data were judged as insufficient for classification since details such as the test methods were unknown. In addition, although there is a report that 3 of 1,012 people showed a positive response in a human patch test (Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004)), it is considered that "this substance was considered not to be sensitizing" in the Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), and details such as the test conditions were unknown, therefore, it was judged to be insufficient data for classification. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | It was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, it was all negative in micronucleus tests with bone marrow cells of rats and mice, in a chromosomal aberration test with bone marrow cells of rats (this test was to evaluate chromosomal aberrations of bone marrow cells in a chronic toxicity test), and in a sister chromatid exchange test with bone marrow cells of mice (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), IRIS (1987), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), IUCLID (2000), BUA 15 (1991)). As for in vitro, although a positive result is reported only in a chromosomal aberration test with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), in other information, it was all negative in bacterial reverse mutation tests, a mouse lymphoma test with cultured mammalian cells, a sister chromatid exchange test with cultured human lymphocyte cells and an unscheduled DNA synthesis test with primary hepatocytes of rats (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), IRIS (1987), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), BUA 15 (1991), NTP DB (Access on July 2014), IUCLID (2000)). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] As for carcinogenicity, there is no available report in humans. After classification results by domestic and international organizations in (3), in tests conducted according to appropriate test guidelines and GLP standards, (1) and (2), increased incidences of tumors were reported in two animal species. However, incidences of malignant tumors were not clear. Moreover, the substance was judged to be not applicable to guidelines after discussions in the risk evaluation meeting for chemical substances in FY2011 (the 4th small committee of hazard evaluation). Therefore, it was classified in Category 2 by judging that the results are insufficient to constitute evidence of carcinogenicity. [Evidence Data] (1) In a 2-year carcinogenicity test in rats dosed by feeding, a trend toward an increase in vascular tumors in the spleen and increased incidences of vascular tumors in all organs including the spleen and subcutis were observed in males, and a trend toward an increase in uterus adenocarcinoma was found in females (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2011)). (2) In a 2-year carcinogenicity test in mice dosed by feeding, increased incidences of vascular tumors in all organs including the spleen and liver were observed in males (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2011)). (3) As for classification results by domestic and international organizations, EPA classified it in NL (EPA OPP Annual Cancer Report (2017): classification in 1997), ACGIH classified it in A4 (ACGIH (7th, 2001)), but the results of (1) and (2) were not used in the evaluation. [Reference Data, etc.] (4) In two tests in which mice were orally administered (by feeding, by gavage) for 18 months, dose-related tumors were not observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2008), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006), JMPR (1998), EPA Pesticide RED (1998)). (5) In two 2-year diet administration tests in rats, dose-related tumors were not observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2008), ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), JMPR (1998)). (6) In a 2-year diet administration test in beagle dogs, dose-related tumors were not observed (EU-RAR (2008), ACGIH (7th, 2001)). (7) It is reported that it exhibited a promoter activity in tumors induced by N-ethyl-N-hydroxyethylnitrosamine (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), JMPR (1998)). (8) It is described in an EU Risk Assessment Report that a guideline-compliant long-term test is not available, but neoplastic alterations related to this substance are not reported in a number of older investigations in several strains of rats and mice, and dogs (EU-RAR (2008)). |
FY2018 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Reproductive toxicity | Category 2 |
Warning |
H361 | P308+P313 P201 P202 P280 P405 P501 |
In a two-generation reproduction toxicity study with rats by the oral route, a decreased number of implantation scars and a decreased number of litter size were observed at a dose (corresponding to 450 mg/kg bw/day) where parental toxicity (decreased body weight, blackish-purple colored spleen, congestion and hemosiderosis of the spleen, enlarged spleen, increased relative liver weight, hepatocytic hypertrophy, brown pigment in the proximal convoluted tubules of the kidney, brown pigments in the Kupffer cells of the liver, swelling of mammary gland and palpable lateral-ventral masses (without histopathological examination)) was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), JMPR (1998)). In teratogenicity tests with rats and rabbits by the oral route, no developmental toxicity was observed even at doses where maternal toxicity was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), JMPR (1998)). From the above, since a decreased number in litter size was observed at the dose where parental toxicity was observed in the two-generation reproduction toxicity study, it was classified in Category 2 according to the GHS classification guidance for the Japanese government. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system, blood system), Category 3 (respiratory tract irritation) |
 Danger Warning |
H370 H335 |
P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
In humans, it was irritating to the respiratory tract (mucosa) by inhalation exposure (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), ACGIH (7th, 2001), HSDB (Access on June 2014), PATTY (6th, 2012)). In addition, there are reports that it caused effects on the blood leading to methemoglobinemia and on the urinary organs (details unknown), and it caused coughing, sore throat, cyanosis, headache, dizziness, nausea, confusion, convulsions, loss of consciousness by the inhalation exposure or oral ingestion. Additionally, it may cause cyanosis after being absorbed through the dermal route (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), ACGIH (7th, 2001), HSDB (Access on June 2014), PATTY (6th, 2012)). From the above, it was classified in Category 1 (central nervous system, blood system), Category 3 (respiratory tract irritation). Besides, since the effect on the urinary organs was considered to be that secondary to the effects on the blood system, it was not included the target for the category. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (blood system, kidney) |
Warning |
H373 | P260 P314 P501 |
Although there is a description that bladder symptoms, tachycardia, hypertension and eczema occurred in humans as poisoning symptoms by the occupational exposure to this substance (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), details of exposure were unknown, and it was difficult to confirm the original source (ACGIH quoted descriptions in the document published in 1957. The other information sources re-quoted ACGIH), therefore, it was judged as inappropriate findings for classification from the viewpoint of reliability too. There was no other available information, and there were no findings on humans available for classification. As for experimental animals, in tests in which rats were dosed by feeding for 90 days or 2 years, and in a test in which dogs (beagle) were dosed by gavage (capsule) for 1 year, at doses (15-93 mg/kg/day) corresponding to Category 2, the anemia-like findings (decreases in erythrocyte counts, hemoglobin values and hematocrit values. etc.) were observed, and the findings (hemosiderosis, extramedullary hematopoiesis, pigmentation, congestion) considered as secondary effects due to hemal toxicity were observed in the spleen, liver and kidney (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007)). In 90-day or 78-week feeding tests with mice, similar findings were observed from doses within the range for Category 2 to a high dose corresponding to "Not classified" (73- >110 mg/kg/day) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007)). Moreover, in 13-week or 2-year feeding tests with rats and mice delegated by Health, Labour and Welfare Ministry, at doses within the range for Category 2 (12-93 mg/kg/day), findings of anemia and secondary effects on the spleen, liver and kidney were also observed (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2014)). On the other hand, based on a description that in a test in which rats were dosed by gavage for 28 days, at a dose near the upper limit (333 mg/kg/day: converted guidance value (103 mg/kg/day)) of Category 2, degeneration of the renal tubules was observed in the kidney with increased kidney weight (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EU-RAR (2007)), "kidney" was added as a target organ. From the above, it was classified in Category 2 (blood system, kidney). Besides, the previous classification was based mainly on the effects due to occupational exposures in humans described at the front. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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 48-hour EC50 = 0.31 mg/L for crustacea (Daphnia magna) (Initial Risk Assessment (NITE, CERI, NEDO, 2008), EU-RAR, 2008). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 1 |
Warning |
H410 | P273 P391 P501 |
It was classified in Category 1 due to being not rapidly degradable (a degradation rate by BOD = 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1977)), and 72-hour NOEC (growth inhibition) = 0.0273 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Environment Agency in Japan (Environment Agency, 1995), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
NOTE:
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