GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 119-93-7
Chemical Name 3,3'-Dimethylbenzidine [o-Tolidine]
Substance ID H29-B-106
Classification year (FY) FY2017
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 FY2014   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 (Ver. 1.1))
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
-
-
- - There is the information that it is combustible (ICSC (J) (2009)), but the classification is not possible due to no data.
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 526 deg C (ICSC (J) (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
-
-
- - Test methods applicable to solid substances are not 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
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.
1 Acute toxicity (Dermal) Classification not possible
-
-
- - Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Not applicable
-
-
- - Solid (GHS definition)
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - Classification not possible due to lack of data.
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."
3 Serious eye damage/eye irritation Classification not possible
-
-
- - Classification not possible due to lack of data.
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
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.
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.
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.
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.
9 Specific target organ toxicity - Repeated exposure Category 2 (haemal system, liver, kidney)


Warning
H373 P260
P314
P501
There is no data for this substance, but as for 3,3'-dimethylbenzidine dihydrochloride (CAS RN 612-82-7) which is a hydrochloride salt of this substance, a test with rats dosed by drinking water was conducted by NTP.
In a 13-week test with rats dosed by drinking water, at or above 0.03% (converted guidance value: 37.5 mg/kg/day, a converted value equivalent to this substance: 28 mg/kg/day) which is within a guidance value range for Category 2, depressions in body weight increase, decreases in absolute and relative weight of the thymus, decreases in serum triiodothyronine (T3) and thyroxin (T4) levels, an increase in pigment deposit in the sinusoidal lining cells in the liver, increases in relative weight of testes were observed, at or above 0.05% (converted guidance value: 62.5 mg/kg/day, a converted value equivalent to this substance: 47 mg/kg/day) decreases in the number of erythrocytes and hematocrit value, increases of hepatocellular necrosis, and increases of nephropathy were observed. In a 14-month drinking water administration test with rats, at or above 0.03% (converted guidance value: 37.5 mg/kg/day, a converted value equivalent to this substance: 65 mg/kg/day) which is within the guidance value range for Category 2, increases in foci of cellular alteration and cystic degeneration in the liver, exacerbation of nephropathy, and focal hyperplasia and diffuse enlargement of the Zymbal's gland were observed, and at doses of 0.07% (converted guidance value: 87.5 mg/kg/day, a converted value equivalent to this substance: 65 mg/kg/day) or more, decreases in survival rates, proliferation of hematopoietic cells in the liver were observed (NTP TR390 (1991), Environmental Risk Assessment for Chemical Substances Vol.4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)).
Of the above, proliferation of hematopoietic cells in the liver and an increase in pigment deposit in the sinusoidal lining cells in the liver are findings related to anemia. In addition, focal hyperplasia and diffuse enlargement of the Zymbal's gland can be considered as a pre-cancerous lesion, but Zymbal's glands are not adopted as a target organ because they don't exist in humans. Therefore, it was classified in Category 2 (haemal system, liver, kidney).
Besides, this substance was classified as "Classification not possible" due to no data in the previous classification, however, the classification result was different by using the data of 3,3'-dimethylbenzidine dihydrochloride (CAS RN 612-82-7). In addition, hydrochloride salt of this substance was classified in Category 1 (liver, kidney, lymph node, pancreas, thyroid, bone marrow) in FY2007 GHS classification by the Japanese Government, but as a result of review, findings in the pancreas and lymph nodes were observed at doses exceeding the range of Category 2. Therefore, the classification result was different from the previous one.
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 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.
11 Hazardous to the aquatic environment (Long-term) 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.
12 Hazardous to the ozone layer Classification not possible
-
-
- - No data available.


NOTE:
* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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