NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	90-04-0
Chemical Name	o-Anisidine
Substance ID	m-nite-90-04-0_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 molecules.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Flammable liquids	Not classified	- -	-	-	It is judged that flash point is >93 degC under closed-cup test method since data are available that flash point is 118 degC (open-cup) (ICSC (1999)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Pyrophoric liquids	Not classified	- -	-	-	Auto-ignition point is 415 degC (ICSC (1999)) exceeding 70 degC.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	The substance contains oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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 LD50 values of 2000 mg/kg (ACGIH (2001)), 1890 mg/kg (EU-RAR (2002)) and 1150 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 4 (2005)) for rats, the substance was classified into Category 4.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on no mortality at 2000 mg/kg in rats (EU-RAR (2002)), the substance was classified as "Not classified".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	A LC50 (aerosol) value was >3.87 mg/L (EU-RAR (2002)). Classification was not possible since determination of the category was impossible.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (OECD TG404, GLP-compliant, n = 3), after 4-hour semi-occlusive application of undiluted this substance, erythema scores: 1 (2/3) and 0.7 (1/3) and a edema score: 0 were obtained after 72 hours, and animals fully recovered within 72 hours (DFGOT Vol.10 (1998), EU-RAR (2002), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). [Reference Data, etc.] (2) It is reported that in a skin irritation test with rabbits (n = 5), after 5-day open application of undiluted this substance, no irritation effects were seen after five days (REACH registration dossier (Accessed Dec. 2018)).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	In a rabbit eye irritation test (OECD TG405), chemosis, reddening of the conjunctivae, iritis and keratitis were observed and disappeared within 7 days after application (EU-RAR (2002)). Based on the report, the substance was classified into Category 2B.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[[Rationale for the Classification] It was classified in Category 1 from (1), (2). The category was revised from the previous classification by using new information sources. [Evidence Data] (1) It is reported: in an LLNA test with mice (OECD TG429, GLP-compliant, n = 4/group), after application of 25, 50, 100% solutions (DMSO) of this substance, SI values of 2.26 (25%), 3.43 (50%), 1.27 (100%) were obtained without dose-response relationship; one out of four animals died in a high-dose group, meaning that it is the dose where toxicity occurred; because an SI value was above 3 in a mid-dose group, the substance is regarded as sensitizing (REACH registration dossier (Accessed Dec. 2018)). (2) It is reported that in a maximization test with guinea pigs, after this substance was dosed at 0.5 and 2.5 mg/kg/week, it was weekly sensitizing (EU-RAR (2002), REACH registration dossier (Accessed Dec. 2018)). [Reference Data, etc.] (3) In the announcement No. 33 of the Ministry of Labour (1996) (revised by the announcement No. 316 of the Ministry of Health, Labour and Welfare, 2013), this substance was designated as "anisidine" in Simple chemical substances or compounds designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and a disease principally having specific symptoms and disorders (subjective symptoms such as headaches, dizziness, and vomiting, and skin disorders, hemolytic anemia, or methemoglobinemia) due to work involving exposure to this substance was designated as an occupational disease by the Minister of Health, Labour and Welfare. (4) In the notice No. 0811001 issued by Director of Labour Standards Bureau, the Ministry of Labour (2003), this substance was designated as "anisidine" among hazardous substances for which installation of protective equipment to prevent skin disorders is mandated in Article 594 in the Industrial Safety and Health Regulations.	FY2018	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	Although there are negative results in a mouse bone marrow micronucleus test and a rat hepatic cell micronucleus test (in vivo somatic cell mutagenicity tests) (DFGOT vol. 10 (1998)), the substance was classified into Category 2 based on positive result in a Big Blue transgenic mouse mutagenicity test (EU-RAR (2002)). Positive results are also reported from other in vivo tests including DNA synthesis test, DNA adduct formation test and host-mediated test (DFGOT vol. 10 (1998)). As relevant information, from in vitro mutagenicity tests, there are reports of both positive and negative results in Ames tests and chromosomal aberration tests using CHO cells and human lymphocytes (with or without S9). In addition, the substance is classified into Category 3 for Mutagenicity; R68 in EU classification.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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 domestic and international organizations, the IARC changed the category from the previous Group 2B (IARC 73 (1999)) to Group 2A (IARC 127 (2021)) based on the data in (2) to (5). The NTP classified it in R (NTP RoC (14th, 2016)) and the EU classified it in Carc. 1B (EU-CLP Classification Results (Accessed Sep. 2021)). Also, the ACGIH classified it in A3 (ACGIH (7th, 2001)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH) (1997) and the DFG classified it in Carc. 2 (DFG MAK (2021)). (2) It was reported that, in a carcinogenicity study for hydrochloride of this substance (o-anisidine hydrochloride: CAS RN 134-29-2) used as a test substance with rats dosed by feeding for two years, bladder tumors (transitional cell carcinoma, transitional cell papilloma + carcinoma) in males and females and renal pelvis tumors (transitional cell carcinoma) and thyroid tumors (follicular cell adenoma + cystadenoma + papillary cystadenoma + follicular cell carcinoma + papillary cystadenocarcinoma) in males were observed (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), IARC 127 (2021), EU RAR (2002), ACGIH (2001), Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH) (1996), NTP TR89 (1978)). (3) It was reported that, in a carcinogenicity study for o-anisidine hydrochloride used as a test substance with mice dosed by feeding for two years, bladder tumors (transitional cell carcinoma, transitional cell papilloma + carcinoma) in males and females were observed (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), IARC 127 (2021), EU RAR (2002), ACGIH (2001), Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH) (1996), NTP TR89 (1978)). (4) This substance, which is a parent compound of o-anisidine hydrochloride, is a basic compound and will undergo acid-base reactions, and o-anisidine and its hydrochloride salt will achieve a pH-dependent acid-base equilibrium in the body. Therefore, the classification of carcinogenic hazard applies to both o-anisidine and its hydrochloride salt (IARC 127 (2021)). (5) As a result of consideration of the mechanism of action of this substance, there was strong evidence that this substance had a mechanism of action common to a class of aromatic amines for which several member compounds had been classified as known human carcinogens. This substance had structural similarity to other member compounds of this class, and there was concordance with respect to the bioactivation mechanism to DNA-reactive moieties, genotoxicity and target organs of carcinogenicity in long-term animal tests (IARC 127 (2021)). (6) Although there was inadequate evidence in humans regarding the carcinogenicity of this substance, The IARC concluded that both this substance and its hydrochloride were classified in Group 2A for carcinogenicity based on (2) to (5) (IARC 127 (2021)).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7	Reproductive toxicity	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 2 (blood, central nervous system)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	In rats, the single oral application via gavage of 690 mg/kg or more resulted in significantly elevated methaemoglobin levels (EU-RAR (2002)). In another oral test with rats (DFGOT vol. 10 (1998), EU-RAR (2002)), neurologic symptoms such as squatting, staggering gait, reduced spontaneous activity and dizziness were noted at dose levels of 1250 - 2000 mg/kg. In addition, slight impairment in the breathing and reflexes was seen after inhalation exposure of rats to concentration of 3.87 mg/L. (DFGOT vol. 10 (1998)). Based on the data, the substance was classified into Category 2 (blood system, central nervous system).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood)	Warning	H373	P260 P314 P501	Based on a report of a 4-week oral test with rats where hemolytic anemia was observed at dose levels of 80 mg/kg (90-day equivalence: 24.8 mg/kg) or higher (EU-RAR (2002), DFGOT vol. 10 (1998)), the substance was classified into Category 2 (blood system). For humans, there is a report that no anaemia occurred in workers exposed for 6 months to o-anisidine concentrations of 0.4 mg/m3 for 3.5-hour/day but increased sulfhaemoglobin and methaemoglobin values and Heinz bodies in the erythrocytes were detected (DFGOT vol. 10 (1998)). However, this data was not used as the basis of classification because of the availability of only one report.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

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 2	- -	H401	P273 P501	It was classified in Category 2 from 48-hour EC50 = 2.18 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021)).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 2 due to being not rapidly degradable (BIOWIN) and 21-day NOEC = 0.25 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 1996), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2003), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (fish), then it is classified as "Not classified" due to being not rapidly degradable and 96-hour LC50 = 196 mg/L for fish (Oryzias latipes) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 1996), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2003), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021)). By drawing a comparison between the above results, it was classified in Category 2. The classification result was revised from the previous classification by changing how to classify it in chronic toxicity and using new information.	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))

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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