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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	25154-54-5
Chemical Name	Dinitrobenzene (isomer mixture)
Substance ID	R01-B-051
Classification year (FY)	FY2019
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	FY2018 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)
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	*	- -	-	-	There is a nitro group, a chemical group associated with explosive properties, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN3443), and it was considered to be not applicable to explosives, hazards of the highest precedence, it was classified as "Not classified."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	There is information that it is combustible (ICSC (2001)), but the classification is not possible due to no data.
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a nitro group, a chemical group associated with explosive properties, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN3443), and it was considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, it was classified as Type G.
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" because it is classified in Division 6.1 in UNRTDG (UN3443), and it was considered to be not applicable to pyrophoric solids, hazards of the highest precedence.
11	Self-heating substances and mixtures	*	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	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 (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to an element (N) other than carbon or hydrogen. However, the classification is not possible due to no data.
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	It was classified as "Not classified" because it is not desensitized by wetting, dilution, etc.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. [Evidence Data] (1) LD50 for rats: 5-60 mg/kg (ACGIH (7th, 2019))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Though there are no data on this substance, the category was changed by inferring from the information on m-dinitrobenzene (CAS RN 99-65-0), which is a constituent of this substance. [Evidence Data] (1) m-Dinitrobenzene (CAS RN 99-65-0), a constituent of this substance, is slightly irritating to the eyes but not to the skin (GESTIS (Access on July 2019)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. The category was changed because no information for sub-categorization could be obtained. [Evidence Data] (1) It is slightly irritating to the mucous membranes (GESTIS (Access on July 2019)). (2) m-Dinitrobenzene (CAS RN 99-65-0), a constituent of this substance, is slightly irritating to the eyes but not to the skin (GESTIS (Access on July 2019), REACH registration dossier (Access on September 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. However, it was assumed that the content of m-dinitrobenzene (CAS RN 99-65-0) in this substance was 0.1% or more. [Evidence Data] (1) It was reported that the result was positive in a skin sensitization test with guinea pigs according to OECD TG 406 (maximization test) using m-dinitrobenzene, a constituent of this substance (GESTIS (Access on July 2019)). [Reference Data, etc.] (2) This substance was not a skin sensitizer in rabbits (ATSDR (1995)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] There was no in vivo data, therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vitro, there were reports on positive or negative results in bacterial reverse mutation tests and a negative result in an unscheduled DNA synthesis test with cultured mammalian cells (ATSDR (1995), DFGOT vol. 1 (1990), IRIS (1998)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) o-Dinitrobenzene (CAS RN 528-29-0) and m-dinitrobenzene (CAS RN 99-65-0) were classified as D by EPA (IRIS (1991)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Though there was no data on this substance, since this substance was a mixture of three isomers (m-dinitrobenzene (CAS RN 99-65-0), o-dinitrobenzene (CAS RN 528-29-0), p-dinitrobenzene (CAS RN 100-25-4)), and it was judged that it could be classified using the data for m-dinitrobenzene (CAS RN: 99-65-0) based on (1) and (2). Based on (3) and (4), since m-dinitrobenzene showed effects on spermatogenesis and male fertility, this substance was classified in Category 2. Besides, refer to the classification result for m-dinitrobenzene in FY 2019. [Evidence Data] (1) The technical grade of this substance was comprised mostly of m-dinitrobenzene with traces of o-dinitrobenzene and p-dinitrobenzene (DFGOT vol.1 (1990)). (2) Toxic effects of this chemical for industrial use were said not to be significantly different from those of pure m-dinitrobenzene (DFGOT vol.1 (1990)). (3) In a test in which weaned male rats were given m-dinitrobenzene by gavage for 12 weeks and mated with untreated females, no sperm in the testes and cauda epididymis, reduced weight of the testis and epididymis, and infertility were observed (ATSDR (1995), HSDB (Access on July 2019)). (4) As a result of oral administration of m-dinitrobenzene to male rats, decreased fertilizing ability of spermatids was observed at 5 weeks, and 91% of treated rats lost their fertilizing capability. However, only 18% of rats had not recovered their reproductive capability after 5 months of treatment discontinuation, therefore, it was considered that these changes were partially reversible (ATSDR (1995)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, blood system, liver, reproductive organs (male))	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1)-(4), it was classified in Category 1 (central nervous system, blood system, liver, reproductive organs (men)). The information on respiratory tract irritation which was adopted as the evidence in the previous classification was not adopted since ICSC (J) was a document in List 3 and details of the descriptions in HSDB (Access on Jury 2019) were unknown. The classification result was changed from the previous classification by the use of the new information sources. [Evidence Data] (1) The technical grade of this substance was comprised mostly of m-dinitrobenzene (CAS RN 99-65-0) with traces of o-dinitrobenzene (CAS RN 528-29-0) and p-dinitrobenzene (CAS RN 100-25-4) (DFGOT vol.1 (1990)). (2) It was described that the toxic effects of the technical grade of this substance were not significantly different from those of m-dinitrobenzene, and the major acute toxicity was effects on the blood system (methemoglobin formation), central nervous system (dyspnea, vertigo, paresthesia) and liver (liver enlargement, icterus) (DFGOT vol.1 (1990), GESTIS (Access on July 2019)). (3) One female employee who was handling a solution containing m-dinitrobenzene in an electrical parts manufacturing factory showed cyanosis, icterus, liver hypertrophy, and anemia. Also in one male volunteer who performed the same work for the purpose of investigating this case, an increased blood methemoglobin concentration (about 11%) was observed immediately after one use. As a result of the investigation, it was concluded that the poisoning was due to percutaneous absorption of m-dinitrobenzene (DFGOT vol.1 (1990), OEL Documentations (Japan Society For Occupational Health (JSOH), 1994), ATSDR (1995)). (4) In two single oral administration tests with rats using m-dinitrobenzene, cyanosis and blood methemoglobin formation were observed at 16-25 mg/kg, splayed hind limbs and flaccid paralysis of the forelimbs, ataxia and loss of equilibrium at 20-48 mg/kg (ATSDR (1995)). In addition, in another single oral dose test with rats, Sertoli cell vacuolation and degeneration and exfoliation of the germ cells were observed in the testes at 25 mg/kg (DFGOT vol.1 (1990)). The doses at which these effects were observed correspond to Category 1.
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, visual organs, blood system, liver, reproductive organs (male))	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Though there were no data on this substance, since this substance is a mixture of 3 isomers (m-dinitrobenzene (CAS RN 99-65-0), o-dinitrobenzene (CAS RN 528-29-0), p-dinitrobenzene (CAS RN 100-25-4)), and it was judged that it could be classified by the data of m-dinitrobenzene based on (1) and (2). Based on (3)-(6), effects on the central nervous system, visual organs, blood system, liver, and kidney were observed in dermal and inhalation exposure to humans. Based on (7) and (8), in oral administration to rats, effects on the central nervous system, blood system, spleen, and testes were observed within the range of Category 1. Of these, the effects on the kidney and spleen were considered to be secondary changes associated with hematotoxicity. Therefore, it was classified in Category 1 (central nervous system, visual organs, blood system, liver, reproductive organs (men)). New information sources were added and reviewed, and it was changed from the previous classification. [Evidence Data] (1) The technical grade of this substance was comprised mostly of m-dinitrobenzene with traces of o-dinitrobenzene and p-dinitrobenzene (DFGOT vol.1 (1990)). (2) The toxic effects of the technical grade of this substance were not significantly different from those of m-dinitrobenzene. In humans and experimental animals, the blood, liver, and central nervous system were most affected, and effects on the spleen, and in experimental animals, effects on the testes were also observed (DFGOT vol.1 (1990)). (3) Dinitrobenzene was rapidly absorbed from the lungs and skin to form methemoglobin. As early symptoms of exposure, cyanosis, headache, nausea, fatigue, etc. were developed and the formed methemoglobin was considered difficult to remove and caused liver damage. Nitroaniline, an in vivo metabolite, had a hemolytic effect and it was also considered to be highly hepatotoxicity. During liver injury, acute yellow atrophy of the liver occurred along witih degeneration of the kidney and damage of the central nervous system (OEL Documentations (Japan Society For Occupational Health (JSOH), 1994)). (4) Cyanosis is known as a subchronic/chronic toxicity of dinitrobenzene (CAS RN 25154-54-5), sometimes accompanied by icterus and visus impairment (DFGOT vol.1 (1990)). (5) Chronic exposure to dinitrobenzene caused anemia, and liver injury was reported in several cases. Visual impairment (reduced visual acuity, central scotomas) occurred (ACGIH (7th, 2019)). (6) It was reported that visus disorders developed in 3 cases with exposure to this substance for 1-6 months, 3 cases for 6-12 months, and 8 cases for 1-3 years (DFGOT vol.1 (1990)). (7) When rats were given m-dinitrobenzene in drinking water for 16 weeks, increased spleen weight at 1.13/1.32 mg/kg/day (males/females) (within the range of Category 1) and decreased hemoglobin, decreased testes weight, and decreased spermatogenesis in males at 2.64/3.1 mg/kg/day (males/females) (within the range of Category 1) were observed (ATSDR (1995)). (8) As a result of gavage administration of m-dinitrobenzene to male rats for 12 weeks (5 days/week), an increase in splenic hemosiderosis was observed at or above 0.75 mg/kg/day (within the range of Category 1), an increased spleen weight, reduced spermatogenesis were observed at or above 1.5 mg/kg/day (within the range of Category 1), and ataxia, paresis equilibrium, muscle rigidity, decreased epididymal sperm counts, increased nonmotile spermatozoa and atypical sperm morphology, seminiferous tubular atrophy, incomplete spermatogenesis were seen at or above 3 mg/kg/day (within the range of Category 1) (ATSDR (1995), HSDB (Access on July 2019)).
10	Aspiration hazard	*	- -	-	-	[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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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