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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	99-65-0
Chemical Name	m-Dinitrobenzene
Substance ID	R01-B-049
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	FY2008
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	*	- -	-	-	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 (2004)), 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	*	- -	-	-	Classification is not possible because 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	*	- -	-	-	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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 3. [Evidence Data] (1) LD50 for rats: 59 mg/kg (ATSDR (1995), HSDB (Access on July 2019)) (2) LD50 for rats: male: 91 mg/kg, female: 81 mg/kg (ATSDR (1995), HSDB (Access on July 2019)) (3) LD50 for rats: 83 mg/kg (DFGOT vol.1 (1990), OEL Documentations (Japan Society For Occupational Health (JSOH), 1994), HSDB (Access on July 2019))
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P362+P364 P280 P312 P321 P501	[Rationale for the Classification] Based on (1), it was classified in Category 4. [Evidence Data] (1) LD50 for rabbits: 1,990 mg/kg (ATSDR (1995), HSDB (Access on July 2019))
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) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test with rabbits according to OECD TG 404, it revealed no irritation (GESTIS (Access on July 2019)). (2) Although details were unknown, there is a report that no irritation was observed in a skin irritation test with rabbits (ATSDR (1995)). [Reference Data, etc.] (3) In a skin irritation test with guinea pigs applied with a formulation containing 0.5% of this substance, no irritation was observed (ATSDR (1995)).
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. [Evidence Data] (1) This substance is slightly irritating to the eyes of rabbits (ATSDR (1995)). (2) This substance is mildly irritating to the eyes and is sensitizing to the skin (GESTIS (Access on July 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. [Evidence Data] (1) It was reported as positive in a skin sensitization test (maximization method) with guinea pigs according to OECD TG 406 (GESTIS (Access on July 2019)). [Reference Data, etc.] (2) This substance was not sensitizing to the skin of rabbits (ATSDR (1995)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] There were no in vivo data. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vitro, there were positive and negative results reported for bacterial reverse mutation tests, and a negative report in an unscheduled DNA synthesis test with cultured mammalian cells (ATSDR (1995), DFGOT vol. 1 (1990), IRIS (1998)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Based on classification results by other organizations shown in (1), it was classified as "Classification not possible" in accordance with to the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for the classification results by domestic and international organizations, it was 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] Based on (1) and (2), effects on spermatogenesis and effects on fertility in males were seen. Therefore, it was classified in Category 2. [Evidence Data] (1) In a test in which weaned male rats were dosed by gavage for 12 weeks and mated with untreated females, no sperm in the testis and cauda epididymis, decreased weight of the testis and epididymis, and infertility were observed (ATSDR (1995), HSDB (Access on July 2019)). (2) As a result of oral administration 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)-(3), it was classified in Category 1 (central nervous system, blood system, liver, reproductive organs (men)). The category was changed from the previous classification by the use of the new information sources. [Evidence Data] (1) One female employee in an electrical parts manufacturing factory was admitted to the hospital with cyanosis, generalized indisposition, and lack of appetite 3 days after the start of work handling parts immersed in a solution containing 0.5% (w/w) of this substance, and the developed icterus, palpable liver hypertrophy, and anemia. 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 session. This substance was detected from the inner surface of the gloves worn during the task, and it was concluded that the poisoning was due to percutaneous absorption of this substance (DFGOT vol.1 (1990), OEL Documentations (Japan Society For Occupational Health (JSOH), 1994), ATSDR (1995)). (2) It was described that the major acute toxic effects of this substance and technical dinitrobenzene were effects on the blood system (formation of methemoglobin), central nervous system (dyspnea, vertigo, paresthesia) and liver (liver enlargement, icterus) (DFGOT vol.1 (1990), GESTIS (Access on July 2019)). (3) In a single oral administration test with rats, splayed hind limbs and flaccid paralysis of the forelimbs were observed at 20 mg/kg of this substance, and blood methemoglobin formation (28%) and cyanosis at 25 mg/kg (ATSDR (1995), DFGOT vol.1 (1990)). In another single oral administration test with rats, cyanosis at 16 mg/kg and ataxia and loss of equilibrium at 48 mg/kg were observed (ATSDR (1995)). In addition, in another single oral administration test with rats, Sertoli cell vacuolation and degeneration and exfoliation of the germ cells were observed at 25 mg/kg (DFGOT vol.1 (1990)). The doses at which these effects were observed correspond to Category 1. [Reference Data, etc.] (4) Technical grade dinitrobenzene is comprised mostly of this substance with traces of o-dinitrobenzene (CAS RN 528-29-0) and p-dinitrobenzene (CAS RN 100-25-4) (DFGOT vol.1 (1990)).
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] Based on (1)-(4), in dermal and inhalation exposure to humans, effects on the central nervous system, visual organs, blood system, liver, and kidney were observed. Based on (5) and (6), effects on the central nervous system, blood system, spleen, and testis were observed within the range of Category 1 in oral administration to rats. 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 the previous classification was changed. [Evidence Data] (1) There were reports 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)). (2) Dinitrobenzene (CAS RN 25154-54-5) was rapidly absorbed from the lungs and skin to form methemoglobin. As for early symptoms of exposure, cyanosis, headache, nausea, fatigue, etc. developed and the formed methemoglobin was considered to be difficult to remove, resulting in liver damage. Nitroaniline, an in vivo metabolite, had a hemolytic effect and it was also considered to be highly hepatotoxic. Acute yellow liver atrophy occurred along with liver damage, as well as renal degeneration and central nervous system damage (OEL Documentations (Japan Society For Occupational Health (JSOH), 1994)). (3) 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)). (4) Chronic exposure of dinitrobenzene (CAS RN 25154-54-5) to workers caused anemia, and liver injury has been reported in a few cases. Visual impairment (reduced visual acuity, central scotomas) occurred (ACGIH (7th, 2019)). (5) When rats were given this substance in their 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)). (6) As a result of gavage administration of this substance 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, loss of 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)). [Reference Data, etc.] (7) Technical grade dinitrobenzene is comprised mostly of m-dinitrobenzene with traces of o-dinitrobenzene (CAS RN 528-29-0) and p-dinitrobenzene (DFGOT vol.1 (1990)). (8) The toxicity of technical dinitrobenzene was not significantly different from that 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 testis were also observed (DFGOT vol.1 (1990)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour EC50 = 0.1 mg/L for algae (Chlamydomonas reinhardtii) (ECETOC, 2003).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (BIOWIN), and 72-hour NOEC = 0.063 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2012)). 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 (BIOWIN), 96-hour LC50 = 12 mg/L for fish (Oryzias latipes), and 48-hour EC50 = 35 mg/L for crustacea (Daphnia magna) (both, Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2005)). By drawing a comparison between the above results, it was classified in Category 1.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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