NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	95-53-4
Chemical Name	o-Toluidine
Substance ID	23B5507
Classification year (FY)	FY2011
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	FY2006
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	Physical Hazards & Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010) Environmental Hazards: UN GHS Document (4th revised edition)
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	It corresponds to Category 4 from a flash point of 85 deg C [closed-cup] (Merck (14th, 2006)), which is > 60 deg C and <= 93 deg C.
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 482 deg C (900 deg F) (HSDB (2011)).
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	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	Among seven LD50 values for rats [900 mg/kg, 670 mg/kg, 940 mg/kg, 750 mg/kg, 635 mg/kg, 2,951 mg/kg (the above, SIDS (2005)), 2,217 mg/kg (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008))], five correspond to Category 4, and two correspond to "Not classified." It was classified in Category 4, to which most corresponded.
1	Acute toxicity (Dermal)	Not classified	- -	-	-	It was classified as "Not classified" in the Classification JIS (Category 5 in UN GHS classification) based on an LD50 value of 3,250 mg/kg for rabbits (SIDS (2005)).
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	It was classified in Category 4 based on an LC50 value of 3.827 mg/L/4 hours for rats (SIDS (2005)). Besides, because the LC50 value (3.827 mg/L) was higher than the saturated vapour pressure concentration (1.50 mg/L), a reference value of mists was applied.
2	Skin corrosion/irritation	Not classified	- -	-	-	In a test by 24-hour occlusive application of the undiluted substance to the skin of six rabbits, the mean erythema scores were 2.3 (24 hours), 2.0 (48 hours), 1.7 (72 hours), and those for edema were 2.0 (24 hours), 0.3 (48 hours), 0.3 (72 hours) (SIDS (2005)). From the above, the 3 consecutive day average score was < 1.5 for edema but >= 1.5, < 2.3 for erythema. Therefore, it was classified as "Not classified" in the Classification JIS (Category 3 in UN GHS classification). Besides, there is another report that it was not irritating in a test by 24-hour semi-occlusive application of 0.5 mL of the undiluted substance to the skin of two rabbits.
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	In a test in which 0.1 mL of undiluted this substance was applied to the conjunctival sac of rabbits, slight corneal opacity and slight to moderate conjunctival edema and redness were observed, which were not reversible within the 8-day observation period, it was judged as highly irritating, with a primary irritation score (equivalent to AOI) of 31.3/110 (SIDS (2005)). Therefore, it was classified in Category 2A. Besides, it was reported to be slightly irritating in another test by application of 0.1 mL of undiluted this substance to the conjunctival sac of rabbits (SIDS (2005)).
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.
4	Skin sensitization	Classification not possible	- -	-	-	Data are lacking. Besides, it is reported that 40 patients who were hypersensitive to p-phenylenediamine were patch tested with this substance, and 25% of the patients showed positive reactions (SIDS (2005)).
5	Germ cell mutagenicity	Not classified	- -	-	-	It was classified as "Not classified" because negative results were reported in all of the multiple micronucleus tests with bone marrow after intraperitoneal or oral administration to mice and a chromosomal aberration test by intraperitoneal administration to mice (in vivo somatic cell mutagenicity tests) (SIDS (2005), NTP DB (Access on Aug. 2011), Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)). Besides, it was reported to be positive in sister chromatid exchange tests with bone marrow after intraperitoneal or oral administration to mice and a DNA damage test and an unscheduled DNA synthesis test with liver or kidney cells after oral administration to mice (in vivo somatic cell genotoxicity tests) (SIDS (2005), Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)). Furthermore, as for in vitro tests, many Ames tests gave mostly negative results (SIDS (2005), Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)), but positive results were also reported in a chromosomal aberration test with cultured mammal cells and a mouse lymphoma test (SIDS (2005)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 1A because IARC classified it in Group 1 for carcinogenicity (IARC 99 (2010)). Also, it was classified in A3 by ACGIH (ACGIH (2001)), 2A by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2010)), and Cat.2; R45 by the EU (EC-JRC (ESIS) (Access on Aug. 2011)). Besides, in humans, in epidemiological surveys in Italy, Germany, and the United States, there are reports of results suggesting a relationship between the occurrence of bladder cancer and occupational exposure (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)). As for experimental animals, in long-term diet administration tests, there are reports of significantly increased incidences of hemangioma, hemangiosarcoma, hepatocellular adenoma and carcinoma in mice, and increased incidences of dermatofibroma, spleen fibroma, hepatocellular carcinoma, bladder papilloma, and bladder transitional cell carcinoma in rats (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)).
7	Reproductive toxicity	Classification not possible	- -	-	-	No data available. Besides, there is no valid study on reproductive or developmental toxicity available, and there are no specific studies according to the current standard (SIDS (2005)).
8	Specific target organ toxicity - Single exposure	Category 1 (urinary bladder, kidney, blood)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	As effects in humans, it is mentioned that it causes methemoglobin formation, headache, fatigue, dyspnea, nerve damage, irritation pf the kidney and urinary bladder, resulting in hematuria (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)), acutely exposed workers developed strangury, oliguria, hematuria, cystitis, degeneration of the bladder epithelium, etc. (DFGMAK-Doc. 3 (1992)). Also, there is a case report in which accidental exposure caused methemoglobinemia, dyspnea, cyanosis, and hematuria (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)). As for experimental animals, it is reported that a methemoglobin level was 11.6% 8 hours after oral administration of 200 mg/kg to rats (SIDS (2005)), and oral administration of 50 mg/kg to cats resulted in about a 60-70% methemoglobin level within 4 hours and signs of vomiting, cyanosis, mydriasis, and apathy (SIDS (2005)). Based on information in humans and findings in animals above (corresponding to the guidance values for Category 1), it was classified in Category 1 (kidney, urinary bladder, blood). Besides, because neurological symptoms such as headache, fatigue, dizziness, and nausea were those seen with increasing blood methemoglobin levels, these were not used for classification for target organs.
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood)	Danger	H372	P260 P264 P270 P314 P501	It is reported that as a result of examining 81 workers exposed occupationally to this substance and/or p-toluidine for several months to over ten years, 20 persons had methemoglobinemia (DFGMAK-Doc. 3 (1992)). As for animal tests, there are reports on methemoglobinemia, erythrocytopenia, and reticulocytosis in a test by 2.5-month oral administration of 35 mg/kg/day to rats (converted guidance value; 42 mg/kg/day) (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)), and histopathological findings of congestion, increased extramedullary hematopoiesis, and hemosiderin deposit in the spleen and increased bone marrow cells in a test by gavage administration of 225 mg/kg/day to rats for 5, 10, or 20 days (converted guidance value; 50 mg/kg/day) (Initial Risk Assessment Report 202 (NITE, CERI, NEDO, 2008)). From the above, the doses were within the guidance value range for Category 2 in animal tests, but from information in humans, it was classified in Category 1 (blood). Besides, a statistically significant and dose-related increase in methemoglobin production was reported in a 14-day diet administration test with rats (37.5, 225, 450 mg/kg bw/day), although no toxic signs or histological changes were mentioned (SIDS (2005)).
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.

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	It was classified in Category 1 from 48-hour EC50 = 0.52 mg/L for crustacea (Daphnia magna) (SIDS, 2006).
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to being not rapidly degradable (a 4-week 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) (SIDS, 2006, etc.)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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.

To GHS Information