NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	142-04-1
Chemical Name	anilinium chloride
Substance ID	m-nite-142-04-1_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)	- -	-	-	Solid (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)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	It is combustible, but the classification is not possible due to no data.	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 (Not applicable)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data 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)	- -	-	-	Solid (GHS definition).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Classification not possible	- -	-	-	The substance is an organic compound containing chlorine, but the classification is not possible due to no data.	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	- -	-	-	Test methods applicable to solid substances are not 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	Based on reports that the LD50 values of this substance for rats were 840 - 1,070 mg/kg (CEPA (1994)), it was classified in Category 4. Please see also the related substance, aniline (CAS RN 62-53-3) for the following health hazards.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	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))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	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))
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, GESTIS (Access on May 2016) adopted in the previous classification is an information source in List 3, and the exposure time is longer than that of the test guidelines; ICSC (2001) is also an information source in List 3, and the original literature is not described, so these were not used for classification.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, GESTIS (Access on May 2016), which was adopted in the previous classification, is an information source in List 3. The original document is RTECS in List 3, and the reliability of its data cannot be confirmed. ICSC (2001) is likewise in List 3, and the original literature is not described. Therefore, these were not used for classification.	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	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))
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	Data on aniline (CAS RN 62-53-3) 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 of 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 on 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 2-year carcinogenicity study with rats dosed by feeding, 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 2-year carcinogenicity study with rats dosed by feeding, 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 2-year carcinogenicity study with mice dosed by feeding, 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 aniline (CAS RN 62-53-3), which is a basic compound, achieve a pH-dependent acid-base equilibrium in the body. Therefore, the classification of carcinogenic hazard may apply to both aniline and this substance (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 aniline and this substance, 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) Aniline (CAS RN 62-53-3) 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 aniline (CAS RN 62-53-3) 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 data on reproductive effects in humans. In experimental animals, in a study in which this substance was administered to pregnant rats by gavage on gestational days 7-20, in the dams, decreased weight gain and an increase in relative spleen weight were observed at 10 mg/kg/day or above; an increase in blood methaemoglobin concentration, reduction in red blood cell count, and an increase of reticulocytes at 100 mg/kg/day were observed. In the fetuses, however, only a mild increase in relative liver weight and slight change in blood parameters were observed at 100 mg/kg/day; no fetal toxicity or malformations were observed (EU-RAR (2004)). In addition, dams were dosed similarly from gestational day 7 to postnatal day 0, and the animals were allowed to spontaneously deliver. The dams and pups were examined up till Postnatal day 30 and Postnatal day 60, respectively, and then they were necropsied. As a result, the dams which had received 100 mg/kg/ day showed increased relative spleen weight, increased blood methemoglobin concentration, and increased MCV, but pups revealed no clear toxic effects up to 100 mg/kg/day (EU-RAR (2004)). On the other hand, with regard to the same data, according to the Ministry of Health, Labor and Welfare, increased relative liver weight and increased mean corpuscular volume (MCV) were seen in fetuses at 100 mg/kg/day; and an increase in MCV on Postnatal day 0 and weight loss in females on Postnatal day 2 were seen in the offspring at 100 mg/kg/day. These were deemed developmental effects (Hazards evaluation report by the Ministry of Health, Labor and Welfare (Access on August 2016)). Also, in a test in which this substance was administered subcutaneously at 195 mg/kg/ day in rats, methemoglobinemia (25-42% methemoglobin) in dams, and cleft palate and malformations in heart and ribs in fetuses, were observed. The frequency of heart abnormalities and cleft palates was decreased by the administration of methylene blue, so it is considered that the effect on the fetuses is due to hypoxia caused by methemoglobin formation (Hazards evaluation report on Aniline by the Ministry of Health, Labor and Welfare (Access on August 2016)). Based on the effects of developmental toxicity on laboratory animals described in the Hazards Evaluation Report on Aniline by the Ministry of Health, Labor and Welfare, it was judged as appropriate to classify this substance 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	There is no data on single exposure to this substance. It is stated that acute poisoning of this substance is caused by methemoglobin formation and causes cyanosis, disturbance of consciousness, dyspnea, and convulsions, possibly leading to death (ACGIH (7th, 2001), EU-RAR (2004), Risk Assessment Report (NITE, CERI, NEDO, 2007)). In humans, symptoms such as dizziness, coma, confusion, pallor, cyanosis, dyspnea, etc. 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)). From the above, it is considered that this substance may have the same toxicological effect as aniline, so this substance was classified in Category 1 (haemal system, nervous system). Besides, in the previous classification, this substance was classified in Category 3 (respiratory tract irritation) based on the descriptions in ICSC (2001) and HSFS (2003) that this substance is irritating to the respiratory tract in humans, but since these are information sources in the current GHS Classification Guidance for the Japanese Government, the category was revised.	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	This substance is considered to have the same effect as aniline. 　In humans, many workers at aniline manufacturing factories revealed cyanosis as well as headaches, dizziness, dysphasia, nausea, vomiting, chest and abdominal pains or convulsions, weakness, palpitations, irregular respiration, pupillary constriction (reactivity to light), abnormal body temperature, aniline odor on the breath and in the sweat and dark urine were seen. Also pulmonary edema and involuntary urination and defecation were 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 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), DFGOT vol.26 (2010)). 　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.	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)	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	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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