NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	62-53-3
Chemical Name	Aniline
Substance ID	H28-B-024, C-035B
Classification year (FY)	FY2016
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	FY2009 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 (Ver. 1.1))
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	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P403+P235 P210 P280 P501	From a flash point of 70 deg C (closed-cup) (ICSC (2004)), it was classified in Category 4.
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
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 classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 630 deg C (ICSC (2014)).
10	Pyrophoric solids	Not applicable	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid 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	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine
14	Oxidizing solids	Not applicable	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
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.
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.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
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.
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.
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).
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.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
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.
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.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	In epidemiological studies on workers exposed to multiple chemicals including this substance in UK or US rubber chemical manufacturing plants, increased bladder cancer incidence was suggested. However, it is thought that it is attributed to effects of o-toluidine, not those of this substance. There have been no reports of carcinogenic effects due to exposure to this substance alone in humans (Sorahan, T. et al., Occup. Environ. Med., 57, 106- 115 (2000), Carreon, T. et al., Occup. Environ. Med., 71, 175-182. (2014)). In experimental animals, in three experiments where the hydrochloride of this substance was administered to rats or mice for 2 years, spleen tumors (sarcoma, fibrosarcoma, hemangiosarcoma, etc.) increased in males in the two experiments using rats. However, neither female rats nor male and female mice showed an increase in tumor incidence (EU-RAR (2004), IRIS (1990)). As for classifications by other organizations, IARC classified this substance in Group 3 (IARC Suppl. 7 (1987)), the EPA in B2 (IRIS (1990)), ACGIH in A3 (ACGIH (7th, 2001)), and the EU in Carc 2 (Carc. 3 of DSD-classification by EU-RAR (2004)). From the classification results other than that by IARC, it was judged that Category 2 was appropriate for this item.
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.
8	Specific target organ toxicity - Single exposure	Category 1 (haemal 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)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (haemal 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).
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).

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	From 48-hour EC50 = 0.1 mg/L for crustacea (Daphnia pulex) (CEPA, 1994; EU-RAR, 2004), it was classified in Category 1.
11	Hazardous to the aquatic environment (Long-term)	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.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

NOTE:

* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* 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.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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