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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	14047-09-7
Chemical Name	Bis(3,4-dichlorophenyl)diazene
Substance ID	R02-A-003-MHLW, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are neighboring nitrogen atoms present in the molecule, but it is an aromatic azo compound, which does not contain a chemical group associated with explosive properties (aliphatic azo compounds). It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available.
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. It was classified as "Not classified." Neighboring nitrogen atoms are not from aliphatic azo compounds.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.
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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine (but not fluorine or oxygen) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified."
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: 5,000 mg/kg (HSDB (Access on May 2020))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. [Evidence Data] (1) As for in vivo, in a micronucleus test using the bone marrow cells of mice (intraperitoneal injection), negative results were reported, and in a micronucleus test using the peripheral blood erythrocytes of mice (dosed by gavage for 13 weeks), positive results were reported (IARC 117 (2019), NTP TR558 (2010), NTP TOX65 (1998), CEBS (Access on April 2020)). (2) As for in vitro, in bacterial reverse mutation tests, negative and positive results were reported; in a gene mutation test (Hgprt) using the ovary cells derived from Chinese hamsters (CHO), negative results were reported; and in unscheduled DNA synthesis tests using the primary hepatocytes of rats, negative and positive results were reported (IARC 117 (2019), NTP TR558 (2010), NTP TOX65 (1998), CEBS (Access on April 2020)). [Reference Data, etc.] (3) It was reported that as for the tumors (urethra and lung) generated in a test with mice orally dosed with this test substance for two years, it was positive in an assessment of mutations in Tp53 and Kras which were genes involved in human carcinogenicity (IARC 117 (2019)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Since the IARC classified this substance in Group 2A based on the animal study results in (2) and the evidence of AhR activation in (3), it was classified in Category 1B. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2A (IARC 117 (2019)). (2) In a two-year carcinogenicity study with male and female rats and mice dosed by gavage, there were significant increases in the incidence of cystic keratinizing epithelioma of the lung, gingival squamous cell carcinoma of the oral mucosa in male and female rats, and cholangiocarcinoma and follicular cell adenoma of the thyroid in male rats. There were significant increases in the incidence of transitional epithelial carcinoma of the urethra, alveolar/bronchiolar tumor (adenoma or carcinoma), and squamous cell carcinoma of the forestomach in male mice; and fibrosarcoma and fibrosarcoma or malignant schwannoma (combined) of the skin, alveolar/bronchiolar tumor (adenoma or carcinoma), and squamous cell carcinoma of the forestomach in female mice (IARC 117 (2019), NTP TR558 (2010)). Based on the above, it was concluded that there was clear evidence of carcinogenicity of this substance in both male and female rats and male and female mice (NTP TR558 (2010)). (3) The IARC determined that this substance activated the aryl hydrocarbon receptor (AhR) as is the case with dioxin, polychlorinated biphenyls, polybrominated biphenyls, etc. based on the following (1) to (3) as evidence. [1] As for in vitro, this substance was bound to the mouse AhR, and activated the rat and rainbow trout AhRs. [2] This substance induced a spectrum of tumors in rats and mice including those observed with other AhR agonists which are categorized in Group 1 such as dioxin and PCB. [3] This substance induced multiple non-neoplastic effects in mice, rats, rabbits, chickens, and zebrafish consistent with AhR activation including chloracne (AhR-mediated toxic response) in mice and rabbits (IARC 117 (2019)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. [Evidence Data] (1) In a two-generation reproduction toxicity (continuous pairing) study with rats dosed by gavage, a reduction in gestation rate (F1 only) and a reduction in the number of live offspring (all dosed groups of F1, and middle-or-higher dose groups of F2) were observed in all dosed groups in which a tendency or significance of lower body weight and lower food consumption was observed in F0 and F1 parent animals (NTP RACB20101 Abst (Access on April 2020), NTP TR558 (2010)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification was not possible due to lack of data.
9	Specific target organ toxicity - Repeated exposure	Category 1 (skin, oral cavity, thyroid, lung, digestive organ, liver, immune system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), there was information that effects on the skin were observed in humans, and based on (2) to (6), effects on the skin, oral cavity, thyroid, lung, digestive organs, liver, and immune system were observed in test animals at doses of Category 1. Based on (7), this substance might affect many other organs because it activated aryl hydrocarbon receptor (AhR). Therefore, it was classified in Category 1 (skin, oral cavity, thyroid, lung, digestive organs, liver, immune system). [Evidence Data] (1) It was reported that 38% of 102 workers in a Propanil manufacturing plant had chloracne that was attributed to the exposure to this substance. The highest incidence (61%) occurred among the production workers (NTP TR558 (2010)). (2) In a 3-month oral toxicity test with rats, at or above 0.1 mg/kg (within the range for Category 1), a reduction in the concentration of thyroxine (T) and triiodothyronine in the blood was observed; at or above 3 mg/kg (within the range for Category 1), an increase in liver weight and forestomach epithelial hyperplasia were observed; and at or above 10 mg/kg (within the range for Category 1), atrophy of the thymus, reactive anemia, a decrease in platelet count, and hematopoietic cell proliferation of the spleen were observed (NTP TR558 (2010)). (3) In a 3-month oral toxicity test with mice, at or above 1 mg/kg (within the range for Category 1), forestomach epithelial hyperplasia was observed; at or above 3 mg/kg (within the range for Category 1), hepatocyte hypertrophy, proliferation of hematopoietic cells of the spleen, and a decrease in epididymal spermatozoal concentration were observed; at or above 10 mg/kg (within the range for Category 1), increases in liver and spleen weight were observed; and at 30 mg/kg (within the range for Category 2), a decrease in thymus weight was observed (NTP TR558 (2010)). (4) In a 3-month oral toxicity test with rats, at or above 0.1 mg/kg (converted guidance value 0.0778 mg/kg, within the range for Category 1), increases in ALP activities and SDH activities, increases in bile acid concentration and serum cholesterol concentration, decreases in total thyroxine (T) and free T serum concentrations, an increase in spleen weight, and atrophy of the thymus were observed; at or above 1 mg/kg (converted guidance value 0.778 mg/kg, within the range for Category 1), hepatocyte hypertrophy was observed; at or above 3 mg/kg (2.33 mg/kg, within the range for Category 1), proliferation of hematopoietic cells of the liver, cytoplasmic fatty vacuolation of hepatocytes (males only), and a decrease in lung weight were observed; and at or above 10 mg/kg (converted guidance value 7.78 mg/kg, within the range for Category 1), an increase in liver weight, microcytic normochromic anemia (decreases in hemoglobin concentrations and hematocrit values, an increase in reticulocytes), a decrease in absolute thymus weight, bronchiolar metaplasia of the alveolar epithelium, and pigmentation of the spleen were observed (NTP TR558 (2010)). (5) In a two-year oral toxicity test with rats, at or above 10 mg/kg (within the range for Category 1), hepatocyte hypertrophy, centrilobular degeneration, hepatocellular necrosis, oval cell hyperplasia, bile duct hyperplasia, hematopoietic cell proliferation, mixed cell focus and acidophilic focus in the liver, cystic keratinizing epithelioma, squamous metaplasia and bronchiolar metaplasia of the alveolar epithelium in the lung, squamous hyperplasia of the gingival epithelium, cystic hyperkeratosis of the oral cavity, squamous hyperplasia of the forestomach epithelium, degeneration, cytoplasmic vacuolization, and hyperplasia of the adrenal cortex zona fasciculata, and pigmentation of the liver, lung, and spleen were observed; at or above 30 mg/kg (within the range for Category 2), toxic hepatopathy, nodular hyperplasia and focal fatty change of the liver, inflammation of the peridontal tissue, follicular cell adenoma of the thyroid, hypertrophy, hyperplasia, and inflammation of thyroid follicular cells, and hyperplasia and necrosis of adrenal cortex zona fasciculata were observed; and at 100 mg/kg (within the range for Category 2), bile duct cyst, cholangiofibrosis, multinucleated hepatocytes, and squamous papilloma and inflammation of the forestomach epithelium were observed (NTP TR558 (2010)). (6) In a two-year oral toxicity test with mice, at or above 3 mg/kg (within the range for Category 1), transitional epithelial hyperplasia of the urethra, ureter, and urinary bladder, hyperplasia of the forestomach epithelium, focal epithelial hyperplasia, epithelial cyst, mucosal lymphoid cell infiltration, and mineralization in the glandular stomach were observed; at or above 10 mg/kg (within the range for Category 1), cystic dilatation of the infundibular segment of the hair follicle, and sebaceous gland atrophy were observed; and at 30 mg/kg (within the range for Category 2), chronic active inflammation, dermal fibrosis, epidermal hyperplasia, and ulcers of the skin were observed. Furthermore, at or above 10 mg/kg (within the range for Category 1), dilatation and chronic active inflammation of the renal tubules were observed in male mice, and chronic active inflammation of the lung was observed in female mice (NTP TR558 (2010)). (7) It was considered that this substance activated the aryl hydrocarbon receptor (AhR) as in the case with dioxin, polychlorinated biphenyls, polybrominated biphenyls, etc. (IARC 117 (2019)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.
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.
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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