GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 95-53-4
Chemical Name o-Toluidine / Toluidines
Substance ID H26-B-069, R-028
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 FY2011   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
-
-
- - 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 was classified in Category 4 based on a flash point of 85 deg C (closed cup) (ISCS (2009)).
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 480 deg C (ISCS (2009)).
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 substances 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 in the molecule
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
P362+P364
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.
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).
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - Classification not possible due to lack of data.
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.
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.
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)).
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
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.
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)).

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, 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.
9 Specific target organ toxicity - Repeated exposure Category 1 (haemal 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.
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 = 0.52 mg/L for crustacea (Daphnia magna) (SIDS, 2008).
11 Hazardous to the aquatic environment (Long-term) 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).
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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