NITE - Chemical Management Field

GHS Classification Result （Revision of the past classification result）

Chemical Name：Aniline
CAS：62-53-3

Result：


ID:	21B3074
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	-	-	-	-	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: Combustible liquid	P370+P378: In case of fire: Use ... for extinction. P403+P235: Store in a well-ventilated place. Keep cool. P210: Keep away from heat/sparks/open flames/hot surfaces. - No smoking. P280: Wear protective gloves/protective clothing/eye protection/face protection. P501: Dispose of contents/container to ...	Flash point 70 degC (ICSC (2004)), 76 degC (Merck (13th, 2001)) are >60 degC and <=93 degC.
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	-	-	-	-	Auto-ignition point is 615 degC (ICSC (2004)) exceeding 70 degC.
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
16	Corrosive to metals	Classification not possible	-	-	-	-	No data available.

HEALTH HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Acute toxicity （Oral）	Category 4		Warning	H302: Harmful if swallowed	P301+P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P330: Rinse mouth. P501: Dispose of contents/container to ...	LD50 values of 930 mg/kg (male), 780 mg/kg (female) (EU-RAR (2004)), 442 mg/kg (EU-RAR (2004)) and 440 mg/kg (ACGIH (7th, 2001)) for rats correspond to Category 4.
1	Acute toxicity （Dermal）	Category 3		Danger	H311: Toxic 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）. P361: Remove/Take off immediately all contaminated clothing. P363: Wash contaminated clothing before reuse. P405: Store locked up. P501: Dispose of contents/container to ...	LD50 values of 1540 mg/kg and 820 mg/kg for rabbits (EU-RAR (2004)) correspond to Category 3 with higher hazard. A LD50 value of 670 mg/kg for rats (DFGOT vol. 6 (1994)) corresponds to Category 3. Therefore, the substance was classified into Category 3.
1	Acute toxicity （Inhalation: Gases）	Not applicable	-	-	-	-	Liquid (GHS definition)
1	Acute toxicity （Inhalation: Vapours）	Category 2		Danger	H330: Fatal if inhaled	P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P403+P233: Store in a well-ventilated place. Keep container tightly closed. P260: Do not breathe dust/fume/gas/mist/vapours/spray. P271: Use only outdoors or in a well-ventilated area. P284: Wear respiratory protection. P310: Immediately call a POISON CENTER or doctor/physician. P320: Specific treatment is urgent （see ... on this label）. P405: Store locked up. P501: Dispose of contents/container to ...	Based on a LC50 value of 300 ppm/4h (1 mg/L/4h) for rats (EU-RAR No. 50 (2004)), the substance was classified into Category 2. Since saturated vapour pressure concentration of the substance is 400 ppm (1.5 mg/L) at saturated vapour pressure of 0.04 kPa (20 degC) (ICSC (2004)), the test was considered to be conducted for vapour with almost no included mists and classification criteria for gas (ppmV) were adopted.
1	Acute toxicity （Inhalation: Dusts and mists）	Category 4		Warning	H332: Harmful if inhaled	P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P261: Avoid breathing dust/fume/gas/mist/vapours/spray. P271: Use only outdoors or in a well-ventilated area. P312: Call a POISON CENTER or doctor/physician if you feel unwell.	LC50 values of 3.27 mg/L/4h (839 ppm/4h), 1.86 mg/L/4h (478 ppm/4h) (EU-RAR (2004)) and 2.1 mg/L/4h (552 ppm/4h) (CaPSAR (1994)) for rats correspond to Category 4. Since the saturated vapour pressure concentration of the substance was 1.5 mg/L (400 ppm) at a saturated vapour pressure of 0.04 kPa (20 degC) (ICSC (2004)), the test was considered to be conducted for mists.
2	Skin corrosion/irritation	Not classified	-	-	-	-	Although there is a report that skin irritation after application of undiluted substance revealed erythema grade 1 in 6/6 rabbits for more than 3 days, no oedema was detected (EU-RAR (2004)). In addition, application of undiluted substance to the skin of rabbits revealed slight erythema which was reversible within 8 days (EU-RAR (2004)). Based on these reports, the substance was classified as "Not classified" in JIS Classification (correspond to Category 3 in GHS classification). As relevant information, following a 24-hour application of the substance (20 mg), moderate irritation was observed in rabbits (Hazard Assessment Report (CERI, NITE) No. 63 (2004)).
3	Serious eye damage/eye irritation	Category 2A		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.	In a Draize test after instillation into the eyes of rabbits, severe corneal opacity and severe conjunctival erythema and oedema were detected which were not reversible within 8 days, and pannus formation was determined 8 days after the instillation (EU-RAR (2004)). In an eye irritation test using 6 rabbits, mean scores of ca. 52/110 for effects on cornea, iris and conjunctivae were detected within the first 3 days after instillation (EU-RAR (2004)). In another rabbit Draize test, corneal opacity was reversible within 2 days, maximal conjunctival irritation was reached within 2 days after instillation, and conjunctival irritation did not reverse within an observation period of 4 days (EU-RAR (2004)). Based on these data (severe irritation to rabbit eyes, mean score of 52/110 for effects on cornea, iris and conjunctivae), and a sign of recovery (though not full recovery) during observation period of few days), the substance was classified into Category 2A. As relevant information, in EU classification, the substance is classified into Xi; R41 (EU-Annex I (access on May 2009)).
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 ...	With the use of the maximization test, 7/25 volunteers showed positive reactions to the substance (EU-RAR (2004)). 24/181 persons with sensitization to aromatic amino compounds showed mild to moderate positive reactions (13%) (EU-RAR (2004)). Patients of a dermatological hospital showed reaction rates between 5.1% and 13% in patch tests (EU-RAR (2004)). In a Single Injection Adjuvant test in guinea pigs, skin sensitization was reported (positive rate: 50%) (EU-RAR (2004)). In addition to these findings, the substance is classified into R43 in EU classification (EU-Annex I (access on May 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 positive results in bone marrow micronucleus tests by intraperitoneal or oral administration to mice and a bone marrow micronucleus test by oral administration to rats (in vivo somatic cell mutagenicity tests) (Hazard Assessment Report (CERI, NITE) No. 63 (2004)), the substance was classified into Category 2. As relevant information, in other in vivo tests, no definitive conclusion were obtained in a rat dominant lethal test, and negative results were reported in a mouse bone marrow micronucleus test and a chromosomal aberration test (EU-RAR (2004), Hazard Assessment Report (CERI, NITE) No. 63 (2004)). From in vitro mutagenicity tests, there is a report of a negative Ames test (Hazard Assessment Report (CERI, NITE) No. 63 (2004)) and a positive mouse lymphoma test and a positive CHO cell chromosomal aberration test (Hazard Assessment Report (CERI, NITE) No. 63 (2004)). In addition, the substance is classified into Category 3 for Mutagenicity; R68 in EU classification.
6	Carcinogenicity	Category 2		Warning	H351: Suspected of causing cancer	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 ...	The substance is classified into "Group 3" in IARC (IARC Supplement 7 (1987)), into Category 3 in EU classification (EU-RAR (2004)), into "A3" in ACGIH (ACGIH (2001)), and into "B2" in EPA (IRIS (2005)). The classification in IARC corresponds to "Not classified" but the classifications by other organizations correspond to Category 2. Since the classification in IARC is the earliest, the substance was classified into Category 2 in accordance with the classification by the other 3 organizations. In 2-year feeding tests with aniline hydrochloride in rats and mice, increased incidence of splenic tumours (haemangiosarcoma, fibrosarcoma and stromal sarcoma) in male rats was characteristic (DFGOT vol. 6 (1994)), but there were no increases in tumor incidence or no proliferative lesion in mice (DFGOT vol. 6 (1994)). In epidemiological tests for humans exposed occupationally, increased urinary bladder cancer was reported (IARC vol. 27 (1982), EU-RAR (2004), PATTY (5th, 2001)), however, the reports do not show clear evidence for the relationship with exposure of aniline.
7	Reproductive toxicity	Classification not possible	-	-	-	-	In a test where rats were treated with aniline hydrochloride by gavage from day 7 to day 20 of gestation or from day 7 of gestation until the birth, some rats were examined before the delivery and the rest were allowed to deliver their pups (DFGOT vol. 6 (1994)). Maternal general toxicity such as decreased body weight gain and increased spleen weights was observed. There were, however, no signs of foetotoxic or teratogenic effects. In the foetuses of the high dose group an increase in relative liver weights was found and changes in some haematological parameters indicative of slightly increased haematopoietic activity observed. Toxicologically relevant effects were not reported for nursing and lactation of the pups during postnatal period. Since there was no data for effects on sexual function and fertility by exposure before mating, classification was not possible.
8	Specific target organ toxicity - Single exposure	Category 1 (blood system, systemic toxicity)		Danger	H370: Causes damage to organs (blood system, systemic toxicity)	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 ...	Acute intoxication due to the formation of methemoglobin, resulting in cyanosis and possible death from asphyxiation, was the most frequent consequence of overexposure to the substance (ACGIH (2001)). In humans, dizziness, coma, miosis, confusion, pallor, cyanosis, dyspnea, degeneration in the heart, liver and kidney, edemas in the lung and brain, and hemorrhage in the medulla oblongata are reported following accidental ingestions, suicide attempts or occupational exposures. The type of symptom depends on the methemoglobin content of total hemoglobin (Hazard Assessment Report (CERI, NITE) No. 63 (2004)). Formation of methemoglobin was confirmed in suicide cases and human volunteers. In humans, the main effect of analine exposure is formation of methemoglobin in blood, and the subsequent systemic symptoms reported above. The substance was classified into Category 1 (blood system). In acute exposure animal tests, clinical signs included tremors, cyanosis and lethargy in rats (EU-RAR (2004)) and formation of methaemoglobin leading to cyanosis in cats (EU-RAR (2004)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood system, systemic toxicity)		Danger	H372: Cause damage to organs through prolonged or repeated exposure (blood system, systemic toxicity)	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 a 2-week inhalation test with rats, congestion of spleen, hemosiderin deposition and extramedullary hematopoiesis were induced at dose levels of 17 - 30 ppm (0.066 - 0.116 mg/L) and higher (EU-RAR (2004)). Decreases in erythrocyte count, hemoglobin concentration and hematocrit and an increase in methemoglobin were observed at 45 ppm (174.2 mg/m3) and higher levels (Hazard Assessment Report (CERI, NITE) (2004)). In a 4-week oral test with rats, onset of erythrotoxicity at 10 mg/kg/day (aniline 4 mg/kg/day) and dose related onset of macrocytic hemolytic anemia and methaemoglobinemia were observed (EU-RAR (2004)). These findings were noted at dose levels within the guidance value range for Category 1. Systemic effects observed in occupationally exposure cases are reported to be cyanosis, headache, dizziness, aphagia, nausea, vomiting, thoracic and abdominal pain, convulsion, weakness, palpitation, irregular respiration, miosis (with response to light), abnormal body temperature and dark urine. Severe cases exhibited pulmonary edema and urinary and fecal incontinence. (Hazard Assessment Report (CERI, NITE) No. 63 (2004)) Increased methemoglobin is also reported (DFGOT vol. 6 (1994)). Based on the data, the substance was classified into Category 1 (blood system, systemic toxicity).
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 1		Warning	H400: Very toxic to aquatic life	P273: Avoid release to the environment. P391: Collect spillage. P501: Dispose of contents/container to ...	Classified into Category 1 from its 48h-LC50 = 80 microg/L for Crustacea (Daphnia magna) (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment), Vol. 1, 2002).
11	Hazardous to the aquatic environment （Long-term）	Not classified	-	-	-	-	Classified into Not classified since it is rapidly degradable (BOD degradation rate: 85% (Biodegradation and Bioconcentration of Existing Chemical Substances under the Chemical Substances Control Law, 1993)) and low bioaccumulative potential is estimated (log Kow = 0.9 (PHYSPROP Database, 2009)).
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）