NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	95-53-4
Chemical Name	o-Toluidine / Toluidines
Substance ID	m-nite-95-53-4_v1
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)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
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.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	It was classified in Category 4 based on a flash point of 85 deg C (closed cup) (ISCS (2009)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
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.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 480 deg C (ISCS (2009)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
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).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Organic substances containing no oxygen, fluorine or chlorine	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
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 multiple reports of LD50 values of 635 mg/kg (DFGOT vol. 3 (1992)), 670 mg/kg (DFGOT vol. 3 (1992), ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1991)), 750 mg/kg (SIDS (2006)), 900 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), CICAD 7 (1998), DFGOT vol. 3 (1992), OEL Documentations (Japan Society For Occupational Health (JSOH), 1991)), 940 mg/kg (ACGIH (7th, 2001), CICAD 7 (1998), DFGOT vol. 3 (1992)), 670-940 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), and 900-940 mg/kg (PATTY (6th, 2012)) for rats, it was classified in Category 4.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on a report of an LD50 value of 3,250 mg/kg for rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2006), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), DFGOT vol. 3 (1992), CICAD 7 (1998)), it was classified as "Not classified" (Category 5 in UN GHS classification).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Based on a report of an LC50 value (4 hours) of 3.827 mg/L for rats (SIDS (2006)), it was classified in Category 4. Besides, although there is a description that the test was conducted with vapour/aerosol (SIDS (2006)), the LC50 value was higher than the saturated vapour concentration (1.5 mg/L), therefore, the reference value of a mist was applied.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
2	Skin corrosion/irritation	Not classified	- -	-	-	There were 2 reports of application of this substance to rabbits for 24 hours (semi-occlusive application or occlusive application) (SIDS (2006)). No irritation was observed in the semi-occlusive application test. On the other hand, in the occlusive application test, although the mean erythema scores were 2.3 (24 hours), 2.0 (72 hours) and 1.7 (72 hours), and the mean edema scores were 2.0 (24 hours), 0.3 (48 hours) and 0.3 (72 hours), necrosis (1/6 animals) was observed 72 hours after application. From the above, since no irritation was observed in the semi-occlusive application test, it was classified as "Not classified." Besides, there is a description that this substance was moderately to severely irritating to the skin of rabbits (ACGIH (7th, 2001)), although the application time was unknown.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	Based on a result that in a test in which 0.1 mL undiluted liquid of this substance was applied to rabbits, mild corneal opacity and mild to moderate conjunctival edema and redness were observed and these did not disappear within the observation period of 8 days, and it was severely irritating with a primary irritation score (corresponding to AOI) of 31.3/110 (SIDS (2006)), it was classified in Category 2A. In addition, there is another report that when 0.1 mL undiluted liquid of this substance was applied to the conjunctival sac of rabbits, mild irritation was observed (SIDS (2006)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	Numerous mutagenicity data have been collected for this substance. As for in vivo, it was negative in micronucleus tests and chromosomal aberration tests with mouse bone marrow cells, positive in micronucleus tests with mouse bone marrow cells and peripheral blood erythrocytes, positive in a sister chromatid exchange test with mouse bone marrow cells, positive in a DNA damage test with mice and comet assay with mice and rats, and positive in an unscheduled DNA synthesis test with rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, Quantitative risk assessment of carcinogenicity, 2003), ACGIH (7th, 2001), CICAD 7 (1998), DFGOT vol. 3 (1992), SIDS (2006), IARC 100F (2012), NTP DB (Access on September 2014)). As for in vitro, although many data showed negative results in bacterial reverse mutation tests and gene mutation tests with cultured mammalian cells, there were also multiple positive data. Moreover, positive results were predominant in chromosomal aberration tests and micronucleus tests with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2001), CICAD 7 (1998), DFGOT vol. 3 (1992), SIDS (2006), IARC 100F (2012), Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, Quantitative risk assessment of carcinogenicity, 2003), NTP (2014), NTP DB (Access on September 2014)). From the above, it was classified in Category 2.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	It was classified in Group 1 in IARC 100F (2012), in A3 in ACGIH (7th, 2001), in Group 2A in Japan Society For Occupational Health (JSOH) (2001), as K in NTP (2011), as Carc. Cat. 2 in the CLP classification (Access on September 2014). Although these classification results were different, giving priority to IARC and NTP, it was classified in Category 1A. Besides, in humans, many epidemiological studies were conducted, and the association between occupational exposure and the onset of bladder cancer is suggested (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, blood system, urinary bladder), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	Toxic symptoms due to inhalation or dermal exposure in humans, from multiple cases, were reported as headache, dizziness, nausea, dyspnea, loss of consciousness, nervous system disorder, sweating, cyanosis, methemoglobinemia and hematuria due to severe stimulation of the bladder (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2006), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), OEL Documentations (Japan Society For Occupational Health (JSOH), 1991), CICAD 7 (1998), DFGOT vol. 3 (1992)). Moreover, strangury, oliguria, hematuria, cystitis, degeneration of the bladder epithelium, etc. were observed in acutely exposed workers (DFGOT vol. 3 (1992)). As for experimental animals, by inhalation exposure at 492 ppm (2.16 mg/L) with rats, tremors, cyanosis, labored breathing, convulsions and dyspnea were observed, and by oral doses of 600-900 mg/kg with rats, narcotic effects, cyanosis and increased urinary volume were observed and by the oral dose at 50 mg/kg with cats, lateral position, tachypnea, cyanosis, mydriasis, apathy and salivation were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2001), PATTY (6th, 2012), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), SIDS (2006)). These effects on the central nervous system and hemal system were observed at concentrations within the guidance value range for Category 1. From the above, it was classified in Category 1 (central nervous system, hemal system, urinary bladder), Category 3 (narcotic effects). Although the central nervous system and narcotic effects were not adopted in the previous classification, in this classification, it was adopted to the Category. Additionally, although the kidney was adopted in the previous classification, it was not adopted owing to lack of information of effects on the kidney.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood system, urinary bladder)	Danger	H372	P260 P264 P270 P314 P501	Since there is a description that methemoglobinemia was developed in 20 of 81 workers who were exposed to o-toluidine and p-toluidine by the repeated inhalation at a production factory of both substances (DFGOT vol. 3 (1992)), and methemoglobinemia was known as one of the acute effects from this substance, it was considered that methemoglobinemia will also occur by the repeated exposure to this substance alone. In addition, in this report, non-neoplastic changes in the bladder mucosa (details unknown) were observed in several out of 81 workers, and in another occupational exposure case, there is a description of a worker who developed hematuria, oliguria and strangury and was diagnosed as cystitis (degeneration in the bladder mucosa were observed histologically) (DFGOT vol. 3 (1992)). From the above, the bladder was also considered to be a target organ. As for experimental animals, there is a description that in a test in which rats were dosed by feeding for 14 days, methemoglobinemia was observed at doses corresponding to Category 1 (40.4-43.5 mg/kg/day: 6.3-6.8 mg/kg/day (converted guidance value)), urinary bladder epithelial cell proliferation and urothelial hyperplasia were observed at doses corresponding to Category 2 (236-481 mg/kg/day: 37.0-74.8 mg/kg/day (converted guidance value)) (SIDS (2006)). Moreover, when rats were dosed at 225 mg/kg/day (converted guidance value: 50 mg/kg/day (corresponding to Category 2)) by gavage for up to 20 days, cyanosis and methemoglobinemia were developed and 25/30 animals died within this period. Histopathological investigations showed secondary effects to compensate for hematotoxicity such as congestion, hemosiderosis, and an increase in extramedullary hematopoiesis in the spleen, hemosiderosis in the kidney and hypercellularity in the bone marrow (SIDS (2006), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above, it was classified in Category 1 (hemal system, urinary bladder). Besides, although the "urinary bladder" was not adopted as a target organ in the previous classification, in this classification, it was added to the target organs by judging based on the findings on humans and experimental animals.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))

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	It was classified in Category 1 from 48-hour EC50 = 0.52 mg/L for crustacea (Daphnia magna) (SIDS, 2008).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to not rapid degradability (a degradation rate by BOD = 5% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2000)), and 21-day NOEC = 0.0126 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Environment Agency in Japan (Environment Agency, 1995), Environmental Risk Assessment for Chemical Substances Vol. 1 (Ministry of the Environment, 2002), Initial Risk Assessment (NITE, CERI, NEDO, 2008), SIDS, 2008).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))

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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