NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	62-53-3
Chemical Name	Aniline
Substance ID	m-nite-62-53-3_v2
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)	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)

PHYSICAL HAZARDS

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.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	From a flash point of 70 deg C (closed-cup) (ICSC (2004)), it was classified in Category 4.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	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 present in the molecule associated with explosive or self-reactive properties.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 630 deg C (ICSC (2014)).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2016	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).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	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	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

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	Six LD50 values of 250 mg/kg (HSDB (Access on June 2016)), 440 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), IARC 27 (1982), ACGIH (7th, 2001), PATTY (6th, 2012), DFGOT Vol.26 (2010), 442mg/kg (EU-RAR (2004), DFGOT Vol.26 (2010)), 780 mg/kg (EU-RAR (2004), DFGOT Vol.26 (2010)), 930 mg/kg (EU-RAR (2004), DFGOT Vol.26 (2010)), and 440-1072 mg/kg (CEPA (1994)) were reported for rats. Since one value corresponds to Category 3 and 5 values correspond to Category 4, this substance was classified in Category 4 to which the larger number of value corresponds.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	Two LD50 values of 670 mg/kg (DFGOT vol.26 (2010)) and 1,400 mg/kg (HSDB (Access on June 2016)) were reported for rats. One value corresponds to Category 3, and one corresponds to Category 4. 　Three LD 50 values of 820 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), EU-RAR (2004), DFGOT Vol.26 (2010)), 840 mg/kg (IARC 27 (1982)) and 1,540 mg/kg (EU-RAR (2004), DFGOT Vol.26 (2010)) were reported for rabbits. Two values correspond to Category 3, and one value corresponds to Category 4. This substance was classified in Category 3 to which the larger number of value corresponds.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	Based on the LC50 value (4 hours) of 250 ppm for rats (Converted value; 0.95 mg/L) (EU-RAR (2004), IARC 27 (1982), PATTY (6th, 2012)), it was classified in Category 2. 　Additionally, since the LC50 value was lower than 90% of the saturated vapor pressure concentration (405.94 ppm (1.55 mg/L)), a reference value in the unit of ppm was applied as vapour without mist.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Based on the 4 reports that rat LC50 values (4 hours) were 478 ppm (Converted value: 1.82 mg/L) (EU-RAR (2004)), 479 ppm (Converted value: 1.82 mg/L) (DFGOT Vol.26 (2010)), 2,100 mg/m3 (Converted value: 551.3 ppm (2.10 mg/L)) (CEPA (1994)) and 839 ppm (Converted value: 3.19 mg/L) (DFGOT Vol.26 (2010), EU-RAR (2004)), this substance was classified in Category 4. 　Besides, since these LC50 values were higher than the saturated vapor pressure concentration (405.94 ppm (1.55 mg/L)), the reference value for mist with units of mg/L was applied.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Not classified	- -	-	-	In a rabbit skin irritation test, erythema was observed for three days or more, but no edema occurred (EU-RAR (2004)). In addition, slight erythema was observed in rabbit skin but it resolved within 8 days (EU-RAR (2004)). From the above, this substance was classified as "Not classified"(Category 3 in UN GHS classification).	FY2016	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	Several test results on eye irritation have been reported. In a Draize test using rabbits, severe corneal opacity and severe conjunctival erythema and edema were observed and were not reversible within 8 days after application; eight days after application pannus formation was determined (EU-RAR (2004)). Mean scores for effects on the cornea, iris and conjunctiva in 6 rabbits were ca. 52/110 within the first 3 days after application (EU-RAR (2004)). In another Draize test applied to rabbits, corneal opacity was reversible within 2 days, conjunctival irritation reached a maximum within 2 days after application and did not reverse within an 4-day observation period (EU - RAR (2004)). Taken together, the eyes of rabbits showed severe irritation; the average score for the cornea, iris and conjunctiva is 52 (maximum 110); and there were findings that did not resolve within 7 days. Therefore, this substance was classified in Category 2A.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2016	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	The Japan Society for Occupational Health recommended Group 1 of skin sensitization (JSOH 55 (2013)). A single injection adjuvant test (SIAT), a skin sensitization test using guinea pigs, showed a positive rate of 50%, and a Magnusson Kligman test had the positive rate of 10% (EU-RAR (2004)). Therefore, this substance was classified in Category 1.	FY2016	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	Data on aniline hydrochloride (CAS RN 142-04-1) are also used in the classification of this substance. As for in vivo, several test results on genotoxicity were reported: negative or equivocal results in a dominant lethal test by intraperitoneal administration to rats, positive or negative results in bone marrow cell micronucleus tests by intraperitoneal or oral administration to mice or oral administration to rats, positive in a micronucleus test on peripheral blood by feeding to mice, negative in a chromosomal aberration test in bone marrow cells by intraperitoneal administration to mice, positive or negative results in bone marrow cell chromosomal aberration tests by oral administration to rats, positive in a sister chromatid exchanging test using bone marrow cells by intraperitoneal administration to mice, and positive or negative results in DNA strand break tests and Comet Assays using the liver, kidneys, spleen and so on by intraperitoneal administration to mice or rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2004), CEPA (1994), DFGOT Vol. 26 (2010), IRIS (1990), NTP DB (Access on June 2016)). As for in vitro, negative in bacterial reverse mutation tests, positive in many of gene mutation tests using mammalian cultured cells and mouse lymphoma tests, and positive in many of micronucleus tests, chromosomal aberration tests and sister chromatid exchange tests of mammalian cultured cells were noted (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2004), IRIS (1990), ACGIH (7th, 2001), DFGOT Vol. 26 (2010), CEPA (1994), NTP DB (Access on June 2016)). From the above, this substance was classified in Category 2 according to the GHS Classification Guidance for the Japanese Government.	FY2016	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 (6), it was classified in Category 1B. [Evidence Data] (1) As for the classification results by international organizations, the IARC changed the category from the previous Group 3 (IARC (1987)) to Group 2A based on the data in (2) to (6) (IARC 127 (2021)). (2) It was reported that, in a carcinogenicity study for aniline hydrochloride (CAS RN 142-04-1) used as a test substance with rats dosed by feeding for two years, at 3,000 to 6,000 ppm, an increase in the incidence of fibrosarcoma or sarcoma (not otherwise specified) and hemangiosarcoma of the spleen or of multiple organs other than spleen within the body cavities was observed in males. It was also reported that a trend towards increased incidences of pheochromocytoma of the adrenal gland in males and fibrosarcoma or sarcoma (not otherwise specified) of the spleen or of multiple organs other than spleen within the body cavities in females was observed (IARC 127 (2021), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2013), EU RAR (2004), IRIS (1990), NTP TR130 (1978)). (3) It was reported that, in a carcinogenicity study for aniline hydrochloride used as a test substance with rats dosed by feeding for two years, at 10 to 100 mg/kg/day, increased incidences of stromal sarcoma and hemangiosarcoma of the spleen and mesothelioma of the tunica vaginalis of the testis (only at 30 mg/kg/day) were observed in males. Besides, it was reported that no increase in the incidence of tumors was observed in females (IARC 127 (2021), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2013), EU RAR (2004), IRIS (1990)). (4) It was reported that, in a carcinogenicity study for aniline hydrochloride used as a test substance with mice dosed by feeding for two years, at 6,000 to 12,000 ppm, no increase in the incidence of tumors was observed (IARC 127 (2021), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2013), EU RAR (2004), IRIS (1990), NTP TR130 (1978)). (5) This substance and its hydrochloride salt achieve a pH-dependent acid-base equilibrium in the body. Therefore, the classification of carcinogenic hazard may apply to both this substance and aniline hydrochloride (IARC 127 (2021)). (6) The IARC concluded that since there was inadequate evidence in humans but sufficient evidence in experimental animals regarding the carcinogenicity of this substance and its hydrochloride salt, and since this substance also belongs, based on mechanistic considerations, to a class of aromatic amines which have been classified as carcinogenic to humans, it was classified in Group 2A (IARC 127 (2021)). [Reference Data, etc.] (7) This substance belongs, based on mechanistic consideration, to a class of aromatic amines, for which several members (such as 4-aminobiphenyl (para-phenylaniline), 2-naphthylamine, ortho-toluidine (ortho-methylaniline)) had been classified in Group 1 (carcinogenic to humans) (IARC 127 (2021)). (8) As for epidemiological studies of this substance for the carcinogenicity in humans, several cohort studies and case-control studies reported concerns about induction of bladder cancer, but the finding was obtained from studies conducted under co-exposure to other bladder cancer-causing substances, such as ortho-toluidine, rather than exposure to this substance alone (IARC 127 (2021), DFG MAK (2018), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU RAR (2004), IRIS (1990)).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	There was no information on the reproductive effects in humans. There was also no data on this substance itself in experimental animals, but test results using aniline hydrochloride (CAS RN 142-04-1) are considered to be available for classification of this substance. In a developmental toxicity test in which aniline hydrochloride was administered to pregnant rats by gavage, increases in relative liver weight and red blood cell volume (MCV) in the fetus and increases in MCV on postnatal Day 0 and weight loss in females on postnatal Day 2 in pups were noted at the dose where methemoglobinemia was observed in dams (Hazardous evaluation report of Aniline by the Ministry of Health, Labor and Welfare (Access on August 2016)). Also in a study in which aniline hydrochloride was administered subcutaneously to rats, methemoglobinemia (25-42% methemoglobin) was observed in the dams, and cleft palate and malformations of the heart and ribs in the fetus were observed. While these are secondary effects due to maternal toxicity, they are considered to be non-negligible effects of developmental toxicity (Hazardous evaluation report of Aniline by the Ministry of Health, Labor and Welfare (Access on August 2016)). From the above, because aniline hydrochloride was classified in Category 2 in reproductive toxicity on the basis of developmental effects in experimental animals using aniline hydrochloride, this substance was also classified in Category 2 for this hazard class.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 1 (blood system, nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	It is stated that acute poisoning of this substance is caused by methemoglobin formation and may cause cyanosis, disturbance of consciousness, dyspnea, convulsions and so on, leading to possibility of death (ACGIH (7th, 2001), EU-RAR (2004), Risk Assessment Report (NITE, CERI, NEDO, 2007)). In humans, symptoms such as dizziness, coma, confusion, pallor, cyanosis, and dyspnoea have actually been reported due to accidental ingestion, suicidal intake, or occupational exposure; and it is described that its symptoms depend on the amount of methemoglobin in the total hemoglobin (EU-RAR (2004)), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). Based on the above, this substance was classified as Category 1 (haemal system, nervous system). Also in laboratory animals, in acute oral or inhalation exposure to rats, tremors, cyanosis, prostration, etc. (EU-RAR (2004)), and in acute oral exposure to cats, symptoms such as panting, cyanosis and methemoglobin formation have been reported (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2004)).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood system, nervous system)	Danger	H372	P260 P264 P270 P314 P501	In humans, many workers in aniline manufacturing factories revealed cyanosis as well as headaches, dizziness, dysphasia, nausea, vomiting, chest and abdominal pain or convulsions, weakness, palpitations, irregular respiration, pupillary constriction (reactivity to light), abnormal body temperature, aniline odor on the breath and sweat and dark urine were seen. Pulmonary edema and involuntary urination and defecation were also noted in severe cases (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). 　In experimental animals, multiple tests have been conducted for both the oral and inhalation routes, and in both of these routes, effects on the haemal system (methemoglobinemia, hemolysis) and secondary effects related to them in the range of Category 1 were observed. 　As mentioned above, the haemal system and the nervous system were mainly affected. 　Therefore, this substance was classified in Category 1 (haemal system, nervous system).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data. Additionally, from the numerical data (Viscosity: 4.35 mPa*s (20 deg C), density (specific gravity): 1.0217 (20/20 deg C)) listed in HSDB (Access on May 2016), the kinematic viscosity is calculated as 4.26 mm2/sec (20/20 deg C).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

ENVIRONMENTAL HAZARDS

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	From 48-hour EC50 = 0.1 mg/L for crustacea (Daphnia pulex) (CEPA, 1994; EU-RAR, 2004), it was classified in Category 1.	FY2016	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	Due to being rapidly degradable (a degradation rate by BOD: 85 % (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1993)), and 21-dayNOEC (reproduction) = 0.004 mg/L for crustacea (Daphnia magna) (ECETOC TR91, 2003; Initial Risk Assessment (NITE, CERI, NEDO, 2007); Environmental Risk Assessment for Chemical Substances vol. 1 (Ministry of the Environment, 2002)), it was classified in Category 1.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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