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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	119-90-4
Chemical Name	3,3'-Dimethoxybenzidine [Dianisidine]
Substance ID	H29-B-107
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	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) (2005)), 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	Classification not possible	- -	-	-	No data available.
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	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
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 reports of LD50 values of 1,001 mg/kg and 1,920 mg/kg for rats (HSDB (Access on August 2017)), it was classified in Category 4.
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	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is described that in the skin irritation test with rabbits, skin irritation was not observed even when 0.02 mL of a solution containing 9.8% of this substance and 0.2% of pentaethylene glycol dodecyl ether (CAS RN 3055-95-6) was intradermally administered (BUA 27 (1988)). It is also described that, as an effect on humans, it may cause skin irritation (HSDB (Access on August 2017)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it was described that in the eye irritation test with rabbits, eye irritation was not observed even when 0.1 mL of a solution containing 9.8% of this substance and 0.2% of pentaethylene glycol dodecyl ether (CAS RN 3055-95-6) was applied (BUA 27 (1988)).
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is described that there is no case of workers who showed sensitization in chemical plants in which this substance had been manufactured for about 100 years (BUA 27 (1988)).
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is described that among 26 workers who developed dermatitis at the textile dyeing factory, one worker showed a positive reaction to this substance and skin sensitization was suspected, and that there was no case of workers who showed sensitization in any chemical plant in which this substance had been manufactured for about 100 years (both from BUA 27 (1988)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	As for in vivo, a sister chromatid exchange analysis with mouse bone marrow cells was positive, and an unscheduled DNA synthesis test with rat liver cells was negative (DFGOT vol. 5 (1993)). Also, it is reported that an in-vivo chromosomal aberration test was positive (Mutat Res., 319, 19-30, 1993), and a micronucleus assay with mice was weak positive (Mutat Res., 389, 1-122, 1997). As for in vitro, a bacterial reverse mutation test was positive, mammalian cultured cell chromosomal aberration tests were positive and negative, and a sister chromatid exchange analysis was positive (DFGOT vol. 5 (1993), NTP DB (Access on August 2017)). From the above, it was classified in Category 2 according to the GHS classification guidance for the Japanese government.
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	As for humans, epidemiological studies available to evaluate the association between specific exposures to this substance and human carcinogenesis were inadequate. Most of the workers exposed to this substance were also concurrently exposed to benzidine or other related amine compounds which are strongly associated with urinary bladder cancer in humans (NTP RoC (14th, 2016)). As for experimental animals, in the carcinogenicity test in which the dihydrochloride salt of this substance (CAS RN 20325-40-0) was administered to rats by drinking water (80-330 ppm) for 21 months, increased incidences of tumors were observed in multiple organs as follows: at the low dose (80 ppm) or higher, tumors of the Zymbal's glands in males and females, tumors of the basal cells or sebaceous glands in the skin, squamous cell neoplasm of the skin, oral tumors, tumors of the preputial gland, and tumors of the small intestine, large intestine, and liver in males, tumors of the clitoral gland, and adenocarcinoma of the mammary gland in females; at middle dose (170 ppm) or higher, mesothelioma in males and oral tumors in females; and at high dose (330 ppm), tumor in the large intestine and liver. (NTP TR372 (1990), DFGOT vol. 5 (1993), PATTY (6th, 2012), NTP RoC (14th, 2016)). It is concluded in NTP that there was clear evidence of carcinogenicity for both male and female rats (NTP TR372 (1990)). In addition, it is reported that in a test with rats dosed by gavage for 13 months/52 weeks, tumors in the Zymbal's gland, ovary, and mammary gland were observed in the surviving group, in a test with rats dosed by gavage for 13 months/52 weeks, tumors in the urinary bladder, intestine, skin, and Zymbal's gland were observed, and in a dietary study with hamsters, carcinomas in the urinary bladder and forestomach papilloma were observed (IARC 4 (1974), DFGOT vol. 5 (1993)). As for classification results by other organizations, IARC classified it in Group 2B (IARC Suppl. 7 (1987)), NTP classified it in R (NTP RoC (14th, 2016)), EU classified it in Carc. 1B (ECHA CL Inventory (Access on August 2017)), Japan Society For Occupational Health (JSOH) classified it in 2B (Recommendation of Occupational Exposure Limits (2017): proposal in 1991). From the above, the classification results by other organizations supported Category 2 or Category 1B. However, with regard to this substance (dianisidine), based on the public notice on Article 35 of the Ordinance for Enforcement of the Labor Standards Act (December 3, 1988: No. 735, Labour Standards Bureau, MHLW: https://www.jaish.gr.jp/anzen/hor/hombun/hor1-29/hor1-29-56-1-0.htm), which stated "Tumor of urinary tract due to work involving exposure to dianisidine is designated as illness in the course of employment," it was classified in Category 1A for this hazard class. Besides, category was changed from the previous classification of Category 2.
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification 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. As for humans, it is described that exposure to this substance by inhalation, causes sneezing even in very small amounts and may cause nose and upper respiratory tract catarrh (DFGOT vol. 5 (1993), BUA 27 (1988)), as for dogs, it was reported that a single oral administration of 275 mg/kg of this substance caused death with clonic-tonic spasms after 3.5 hours (DFGOT vol. 5 (1993), BUA 27 (1988)). However, both these were the old information in 1908 and there is only one case reported for the experiment with dog, therefore these were not used as evidence. Therefore, it was classified as "Classification not possible."
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver, haemal system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	There is no information regarding this substance, but a drinking water administration test of 3,3-dimethoxy benzidine dihydrochloride (CAS RN 20325-40-0), which is a hydrochloride of this substance was performed by NTP. In the 21-month drinking water administration test with rats, at or above 80 ppm (converted guidance value: 10 mg/kg/day, a converted value equivalent to this substance: 7.7 mg/kg/day), which is within the range of the guidance value of Category 1, death, cystic and centrilobular degeneration and necrosis of the liver, hematopoietic cell proliferation of the liver and spleen, reticular cell hyperplasia of the mesenteric lymph nodes, increased incidences of atrial thrombosis in the heart, histiocytic cellular infiltration in the lungs, and hyperplasia of the myeloid cells in the bone marrow were observed (NTP TR372 (1990)). Of the above, hematopoietic cell proliferation of the liver and spleen, hyperplasia of the myeloid cells in the bone marrow are thought to be secondary effects of anemia, and it seems that the blood system was affected. In addition, as for thrombosis of the atrium, since it was described in NTP TR372 (1990) that, "Related to compound-caused morbidity, blood circulation was impaired and sludging of blood occurred in the atrial chambers," it was considered to be a secondary effect. As for reticulum cell hyperplasia of the lymph nodes, it is described in NTP TR372 (1990) that, "Although this effect may be related to compound, it is probably a nonspecific reaction." Therefore, it was classified in Category 1 (liver, haemal system, respiratory organs). Besides, the kidney was considered to be the target organ in the previous classification, but since there was only a change in the weight, it was not adopted as evidence of the classification. Furthermore, by the use of a new information source, the classification result was changed 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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment (Long-term)	Classification not possible	- -	-	-	No data available.
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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