NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	119-93-7
Chemical Name	3,3'-Dimethylbenzidine (o-Tolidine)
Substance ID	m-nite-119-93-7_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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	There is the information that it is combustible (ICSC (J) (2009)), but the classification is not possible due to no data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 526 deg C (ICSC (J) (2009)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) substances are not available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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 the report of an LD50 value of 404 mg/kg for rats (DFGOT Vol. 5 (1993)), it was classified in Category 4. Besides, Chemical Substance Hazard Data (CERI, 2002) used in the previous classification was not used since it is currently an information source in List 3.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Not classified	- -	-	-	Based on a description that skin irritation was not observed by occupational exposures to this substance (ACGIH (7th, 2001)), it was classified as "Not classified."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	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	As for in vivo, a micronucleus assay with rat bone marrow cells was positive, a sister chromatid exchange test with mouse bone marrow cells was positive (ACGIH (7th, 2001), DFGOT Vol. 5 (1993)), and as for in vitro, a bacterial reverse mutation test, a mouse lymphoma assay, a chromosomal aberration test, and a sister chromatid exchange test with cultured mammalian cells were all positive (DFGOT Vol. 5 (1993), ACGIH (7th, 2001), PATTY (6th, 2012), NTP DB (Access on August 2017)). From the above, it was classified in Category 2 according to the classification guidance for the Japanese government.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	As for humans, there are no epidemiological studies which evaluated the association between specific exposures to this substance and human carcinogenesis. However, one study found that occupational exposure to a mixture of arylamine products including this substance was associated with an increased incidence of urinary-bladder cancer (NTP RoC (14th, 2016)). As for experimental animals, in the carcinogenicity test in which the dihydrochloride salt of this substance (CAS RN 612-82-8) was administered to rats by drinking water (30-150 ppm) for 14 months, a dose-related increase of skin basal-cell adenoma, squamous-cell carcinoma, Zymbal's gland tumor, tumors of the oral cavity, liver, small intestine, large intestine and lungs in both sexes, tumors of the preputial gland in males, and tumors of the clitoral glands in females were observed (NTP TR390 (1991), NTP RoC (14th, 2016), PATTY (6th, 2012), ACGIH (7th, 2001)). NTP concluded that there was clear evidence of carcinogenic activity for both male and female rats (NTP TR390 (1991)). Other than these, it was reported that in a 2-year administration test with mice dosed by drinking water (5-140 ppm), incidence of lung tumors (bronchiolar alveolar adenoma, bronchiolar alveolar carcinoma, or combination of these) significantly increased after 78 weeks in the male 140 ppm administered group (ACGIH (7th, 2001), HSDB (Access on August 2017)), and that in multiple tests in which rats were dosed by subcutaneous injection for the long term, the incidence of tumors of the Zymbal's gland and external auditory canal increased (IARC 1 (1972), ACGIH (7th, 2001), NTP RoC (14th, 2016)). As classification results by other organizations, it was classified in Group 2B by IARC (IARC Suppl. 7 (1987)), in A3 by ACGIH (ACGIH (7th, 2001)), in R by NTP (NTP RoC (14th, 2016)), in Carc. 1B by EU (ECHA CL Inventory (Access on August 2017)), in 2B by Japan Society For Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (2017): proposed in 1991) respectively. From the above, although Category 2 is supported by the classification results by organizations other than EU, based on the fact that in the test report, an increased incidence of tumors including malignant tumors was shown in two species of experimental animals and the classification result by EU, it was judged appropriate to classify it in Category 1B for this hazard class. Besides, the category was changed from the previous classification of Category 2.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Classification not possible	- -	-	-	There is no information on reproductive effects in humans. As for experimental animals, it was reported that doses of 1 mL of a 1% aqueous solution of this substance were given by drinking water to pregnant rats on days 7-9 of gestation (total dose 30 mg) but no teratogenicity was found in fetuses, and that in a test in which this substance was subcutaneously administered at 0.26 mmol/kg (ca. 55.2 mg/kg) to pregnant rats on the day 7 of gestation, but fetotoxicity was not detected (DFGOT Vol. 9 (1993)). From the above, as for experimental animals, although there are reports to deny the developmental effect of administration of this substance, there is no test report evaluating the effect on fertility, therefore, classification was not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it was reported that inhalation of even small amounts of 3,3'-dimethyl benzidine dihydrochloride (CAS RN 612-82-8), which is a hydrochloride salt of this substance, caused sneezing spasms and subsequent irritation of the upper respiratory tract (DFGOT Vol. 5 (1993), Environmental Risk Assessment for Chemical Substances Vol.4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)). Based on this information, 3,3'-dimethyl benzidine dihydrochloride was classified in Category 3 (respiratory tract irritation) in FY 2007 classification.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver, kidney), Category 2 (blood system)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Effects on the liver and kidney were found within a range of Category 1 or above as written in (1), and effects on the haemal system were observed within a range of Category 2 as written in (2). Therefore, it was classified in Category 1 (liver, kidney), Category 2 (haemal system). Besides, findings in the Zymbal's gland in (1) are thought to be preneoplastic lesions. However, the Zymbal's gland was not adopted as a target organ because humans do not have the organ. Findings in the thymus, testis and thyroid-related ones in (2) were not adopted as evidence of the classification because they were not accompanied by histopathological changes. The category for part of organs was revised from the previous classification as the result of confirming doses of test substance this time. [Evidence Data] (1) It is reported that in a 14-month drinking water administration test in rats given 3,3'-dimethylbenzidine dihydrochloride (CAS: 612-82-8), that is the hydrochloride of this substance, increases in foci of cellular alteration in the liver and cystic degeneration in the liver, increased nephropathy, focal hyperplasia and diffuse swelling in the Zymbal's gland were observed at 30 ppm (0.003%) (males 1.8 mg/kg/day, females 3.0 mg/kg/day: a converted value equivalent to this substance, about 1.3-2.2 mg/kg/day, within a range of Category 1) or above (NTP TR390 (1991), Environmental Risk Assessment for Chemical Substances Vol. 4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)). (2) It is reported that in a 13-week drinking water administration test in rats given 3,3'-dimethylbenzidine dihydrochloride (CAS: 612-82-8), that is the hydrochloride of this substance this substance, decreased thymus weight, decreased thyroid hormone levels (T3, T4), and decreased relative testis weight at or above 300 ppm (0.03%) (converted guidance value: 37.5 mg/kg/day, a converted value equivalent to this substance: 28 mg/kg/day, within a range of Category 2) and decreases in erythrocyte count and hematocrit value, increased hepatocyte necrosis, increased nephrosis at or above 500 ppm (0.05%) (converted guidance value: 62.5 mg/kg/day, a converted value equivalent to this substance: 47 mg/kg/day, within a range of Category 2) were observed (NTP TR390 (1991), Environmental Risk Assessment for Chemical Substances Vol. 4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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	From 48-hour EC50 = 4.5 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, 2017)), it was classified in Category 2.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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 (non-biodegradable, a degradation rate by BOD: 3% (J-CHECK, 1984)), and 21-day NOEC (reproduction inhibition) = 0.26 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, 2017)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 due to being not rapidly degradable (non-biodegradable, a degradation rate by BOD: 3% (J-CHECK, 1984)), and 96-hour LC50 = 13 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, 2017)). From the above results, it was classified in Category 2.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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