NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	106-49-0
Chemical Name	p-Toluidine
Substance ID	H26-B-147, R-115
Classification year (FY)	FY2014
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)	GHS Classification Guidance for the Japanese Government (FY2013 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	- -	-	-	Solid (GHS definition).
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition).
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition).
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition).
7	Flammable solids	Classification not possible	- -	-	-	No data available.
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 applicable	- -	-	-	Solid (GHS definition).
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 480 deg C (ICSC (2009)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) 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	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Not applicable	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	A melting point is lower than 55 deg C, but the classification is not possible due to no data.

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 P362+P364 P264 P270 P330 P501	Based on reports of LD50 values of 336 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006)), 620 mg/kg (SIDS (2006)), 656 mg/kg (SIDS (2006), ACGIH (7th, 2001), DFGOT vol. 3 (1992), 760 mg/kg (DFGOT vol. 3 (1992))), 656-760 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) for rats, it was classified in Category 4.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P280 P312 P321 P361 P364 P405 P501	Based on a report of an LD50 value of 890 mg/kg for rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2006), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), DFGOT vol. 3 (1992)), it was classified in Category 3.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, although there is a report of an LC50 value (1 hour) of >0.64 mg/L (converted 4-hour equivalent value: >0.32 mg/L) for rats (SIDS (2006), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), ACGIH (7th, 2001), DFGOT vol. 3 (1992)), it is impossible to identify the category based on this value only. Besides, since the LC50 value was lower than 90% of the saturated vapour concentration (376 ppm), the reference value in units of ppm was applied as a vapour without a mist.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Not classified	- -	-	-	There is a report that in a test in which this substance was applied to rabbits for 4 hours, the primary irritation score was 0.15, and there was no irritation (SIDS (2006)). Additionally, there is a report that after occlusive application of this substance for 24 hours, no irritation was observed (SIDS (2006)). From the above, it was classified as "Not classified." Besides, although there is a report that in another test in which this substance was applied for 24 hours, moderate to severe irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), it was not adopted for classification because it was a result of 24-hour application.
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	In an eye irritation test with rabbits, the average scores 24, 48 and 72 hours after application were 56.2/110, 52.0/110, 43.3/110, respectively (SIDS (2006)). In addition, there is a report that when 20 mg of this substance was applied to rabbits' eyes, moderate irritation was observed, and after application of 100 mg, severe irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). On the other hand, there is a report that in another test in which this substance was applied to rabbits, no irritation was observed (SIDS (2006)). From the above, based on the irritation scores and a description that it was severely irritating, it was classified in Category 2A. Besides, this substance was classified as "Xi; R36" in the EU DSD classification, and as "Eye Irrit. 2 H319" in the CLP classification.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	There is a report that in a sensitization test with guinea pigs (Buehler method), sensitization was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2006), DFGOT vol. 3 (1992)). From the above, it was classified in Category 1. Besides, this substance was classified as "R43" in the EU DSD classification, and as "Skin Sens. 1" in the EU CLP classification.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	As for in vivo, there were positive results in a DNA damage test with the kidney and the liver of mice (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), SIDS (2006), ACGIH (7th, 2001), DFGOT vol. 3 (1992)). As for in vitro, it was negative in bacterial reverse mutation tests, positive in a chromosomal aberration test with cultured mammalian cells and negative in a DNA damage test (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), ACGIH (7th, 2001), DFGOT vol. 3 (1992), SIDS (2006)). The positive result of the DNA damage test in vivo was a result obtained only with 1 dose, and it was evaluated in SIDS (2006) that it was unknown whether it was correct or not, therefore, it was classified as "Classification not possible" due to lack of data.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	Since it was classified in A3 by ACGIH (ACGIH (2001)) and in 3 by the EU (EU (Access on Dec. 2014)), it was classified in Category 2.
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, haemal system, kidney, urinary bladder), Category 3 (respiratory tract irritation)	Danger Warning	H370 H335	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	This substance was irritating to the respiratory tract (ACGIH (7th, 2001)). In humans, there are reports of headache, fatigue, dizziness, a feeling of sickness, shortness of breath, nausea, confusion, dizziness, loss of consciousness, methemoglobinemia, hematuria, strangury, anemia, and cyanosis of the lips, nail and skin by the inhalation, oral and dermal exposure. Additionally, there is a description that it caused damage to the kidneys and bladder by exposure at high concentrations (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.5 (Ministry of the Environment, 2006), SIDS (2006), ACGIH (7th, 2001), PATTY (6th, 2012), DFGOT vol. 3 (1992)). As for experimental animals, hypoactivity, an increase in the urinary excretion, emaciation, cyanosis, anorexia and narcosis were observed in rats orally dosed at 100-900 mg/kg, and generalized inactivity, muscular weakness, convulsions, methemoglobinemia, cyanosis and coma were observed in rats by the inhalation exposure at or above 0.64 mg/L (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2006), ACGIH (7th, 2001)). From the above, since this substance affected the central nervous system, hemal system, kidney and urinary bladder in addition to respiratory tract irritation, it was classified in Category 1 (central nervous system, hemal system, kidney, urinary bladder), Category 3 (respiratory tract irritation).
9	Specific target organ toxicity - Repeated exposure	Category 1 (haemal system, urinary bladder)	Danger	H372	P260 P264 P270 P314 P501	It is reported that poisoning symptoms from exposure to this substance were methemoglobinemia and hematuria (ACGIH (7th, 2001), PATTY (6th, 2012)). Moreover, among 81 workers who were exposed to this substance and o-toluidine by repeated inhalation in a production plant for both substances, bladder papilloma was observed in 2 out of 75 workers who underwent the cystoscopy examination. One out of the subjects was exposed only to this substance for 1 year and 8 months, and the other was exposed to both substances for 23 years. In addition, it is reported that methemoglobinemia was observed in 20 out of 81 workers (DFGOT vol. 3 (1992)). As for experimental animals, there is a report that in a test in which this substance, mixed in a low protein diet, was administrated to rats by feeding for 6 months, dose-related methemoglobinemia was observed at or above 40 mg/kg/day (SIDS (2006)). On the other hand, in a test in which rats were fed for 28 days, increased relative liver weight was observed at or above 66.8 mg/kg/day (converted guidance value: equivalent to 20.8 mg/kg/day), but there were no available results for classification since no histopathological examination was conducted, and it was unknown whether histological disorders exist or not (SIDS (2006), ACGIH (7th, 2001)). There were no other data available for classification. From the above, it was classified in Category 1 (hemal system, urinary bladder) because methemoglobinemia was observed in humans and experimental animals, and the possibility to cause changes in the bladder tissues by long-term exposure was suggested although the causal correlation between hemoglobinuria and effects on the bladder was unclear. Besides, o-toluidine (CAS RN: 95-53-4), the isomer of this substance was similarly also classified in Category 1 (hemal system, urinary bladder).
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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 = 0.12 mg/L for crustacea (Daphnia magna) (SIDS, 2005).
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 degradation rate by BOD: 97%, 0%, 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2001)), and 21-day NOEC = 0.011 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. 5 (Ministry of the Environment, 2006)).
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.

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