NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	122-39-4
Chemical Name	Diphenylamine
Substance ID	H26-B-049, R-021
Classification year (FY)	FY2014
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	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)
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	Not applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
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	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 634 deg C (ICSC (2006)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data 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 in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
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.
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.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
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.
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.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
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.
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)).
6	Carcinogenicity	Classification not possible	- -	-	-	This substance was classified in A4 in ACGIH (7th, 2001), and as "Not Likely to be Carcinogenic to Humans" in EPA (2006). In these classifications by these other international organizations, it was corresponding to "Classification not possible" by ACGIH, and to "Not classified" by EPA, therefore, the category was divided. In addition, it was concluded in EU-RAR (2007) that no carcinogenicity was shown in rats, mice and dogs by citing the JMPR (1998). From the above, among classification by the other international organizations, by giving priority to that by ACGIH, which is newer, it was classified as "Classification not possible." Besides, in 2-year carcinogenicity studies with male/female F344 rats and male/female B6D2F1 mice administered by feeding, which were conducted according to OECD TG 451 under GLP in Japan in 2011 (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (Access on May 2014)), a tendency to increase the incidence of vascular system tumors in the spleen, and an increased incidence of vascular system tumors in all organs including the spleen and subcutis in male rats, a tendency to increase the incidence of adenocarcinoma in the uterus in female rats, and an increased incidence of vascular system tumors in all organs including the spleen and liver in male mice were observed.
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.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, haemal 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.
9	Specific target organ toxicity - Repeated exposure	Category 2 (haemal 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.
10	Aspiration hazard	Classification not possible	- -	-	-	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 (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).
11	Hazardous to the aquatic environment (Long-term)	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)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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.

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