NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	98-95-3
Chemical Name	Nitrobenzene
Substance ID	m-nite-98-95-3_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, and calculated oxygen balance of -162 is higher than the criteria of -200, and it is possible to be classified as explosives. However, the classification is not possible due to no data.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	Based on a flash point of 88 deg C (closed cup) (ICSC (2006)), it was classified in Category 4.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (N-O) present in the molecule, but the classification is not possible due to no data.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 480 deg C (ICSC (2006)).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to the element other than carbon or hydrogen (N), but the classification is not possible due to no data.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	Based on the reports of LD50 values for rats of 349 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)), 588 mg/kg (EU-RAR (2007)), 600 mg/kg (EHC 230 (2003), ATSDR (1990), ACGIH (7th, 2001), IARC 65 (1996), HSDB (Access on May 2016)), 640 mg/kg (EHC (230, 2003), DFGOT vol.19 (2003), Hazard Assessment Report (CERI, NITE, 2008), BUA 59 (1991)), and 732 mg/kg (EU-RAR (2007)), this substance was classified in Category 4. Besides, it is classified in Division 6.1, PG II in the United Nations Recommendations on the Transport of Dangerous Goods (UN 1662).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	As LD50 values for rabbits, there is one report of 560–760 mg/kg (EU-RAR (2007)) and two reports of 760 mg/kg (EHC (230, 2003), HSDB (Access on May 2016)). As an LD50 value for rats, there are three reports of 2,100 mg/kg (EHC 230 (2003), EU-RAR (2007), DFGOT vol.19 (2003), Hazard Assessment Report (CERI, NITE) (2008), HSDB (Access on May 2016), BUA 59 (1991)). There are three reports corresponding to Category 3 and likewise three reports corresponding to "Not classified." Therefore, by adopting the more hazardous category, this substance was classified in Category 3.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Based on reports of an LC50 value of 556 ppm (4 hours) (converted value: 2.79 mg/L) (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003), EU-RAR (2007)) for rats, this substance was classified in Category 4. Besides, as this value is higher than the saturated vapor pressure concentration (1.62 mg/L), the reference value for mist was applied.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Not classified	- -	-	-	From a description in EHC 230 (2003)) that "A score of 1 (barely perceptible or very slight erythema at 24 hours with 0 scores at 48, 72 and 96 hours) was observed" in a skin irritation test (exposure time unspecified) using rabbits and a description on effects on human health in PATTY (4th, 1999) that this substance is "irritating to human eyes and skin," this substance is considered to be mildly irritating. Therefore, it was classified as "Not classified" (Category 3 in UN GHS classification).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on descriptions that 0.05 ml of this substance applied under the lower eyelid in an eye irritation test using rabbits resulted in minimal effects (EHC 230 (2003)), and that this substance is irritating to human eyes and skin (PATTY (6th, 2012)), this substance was classified in Category 2B.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is reported that sensitization was not observed in a skin sensitization test using guinea pigs (EHC 230 (2003)), but this data was judged insufficient to use for classification as details such as test method are not known.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo data, a chromosomal aberration test using rat peripheral blood, a micronucleus test using mouse bone marrow cells, sister chromatid exchanging tests using rat peripheral blood and spleen lymphocytes, and an unscheduled DNA synthesis test using rat liver were negative (Hazard Assessment Report (CERI, NITE, 2008), EHC 230 (2003), IRIS Tox. Review (2009), ACGIH (7th, 2001), DFGOT (2012), IARC 65 (1996), EU-RAR (2007), ECHA RAC Background Document (2012)). As for in vitro, bacterial reverse mutation tests and mammalian cell chromosomal aberration tests were negative, and a micronucleus test using cultured mammalian cells was weakly positive (Hazard Assessment Report (CERI, NITE, 2008), EHC 230 (2003), IRIS Tox. Review (2009), IARC 65 (1996), EU-RAR (2007), DFGOT (2012), NTP DB (Access on June 2016), ECHA RAC Background Document (2012)). Additionally, although there is a weak positive finding in a micronucleus test using cultured mammalian cells, it is evaluated in EU-RAR (2008) that this substance is not mutagenic.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	There is no information on the carcinogenicity of this substance in humans. As for experimental animals, in three carcinogenicity studies in which rats or mice were exposed by inhalation for 2 years, increases in the incidences of tumors in the liver, kidney, lung, mammary gland, etc. were found (Hazard Assessment Report (CERI, NITE, 2008), EU-RAR (2007)). Based on these results, this substance was classified in Group 2B by IARC (IARC 65 (1996)), A3 by ACGIH (ACGIH (7th, 2001)), L by EPA (IRIS Summary (2009)), R by NTP (Report on Carcinogens (13th, 2014)), 2B by Japan Society For Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (2015)), and Carc 2 H351: Suspected of causing cancer by EU (ECHA C&L Inventory (Access on May 2016)). Therefore, this substance was classified in Category 2 for this hazard class.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	In a 2-generation study in which rats were exposed by inhalation, at 40 ppm (200 mg/m3), parental animals in both the F0 and F1 generations showed decreased fertility indices and testicular toxicity (a reduction in the size of the testes, seminiferous tubule atrophy, spermatocyte degeneration and multinucleate giant cells, degenerated spermatocytes in the tubular lumina, and decreased numbers of spermatids in the epididymides, etc.) (Hazard Assessment Report (CERI, NITE, 2008), EU-RAR (2007)). Testicular toxicity (atrophy of seminiferous tubules and Leydig cell hyperplasia) was also observed in the parental animals in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test using rats by gavage administration (Hazard Assessment Report (CERI, NITE, 2008), EU-RAR (2007)). 　While it is said that the most sensitive toxicity is methemoglobin production, which is a hematotoxicity, it is concluded in a discussion by the Risk Assessment Committee (RAC) of the EU that testicular toxicity is an effect that is unrelated to methemoglobinemia, on the basis of observed atrophy and degeneration of the seminiferous tubular epithelium and reduced fertility under conditions in which methemoglobin concentrations were not so high (increases of about 10%) as to cause hypoxia in peripheral tissue (ECHA RAC Background Document (2012)). As a result, in the EU, this substance was classified in Category 1B (H365F: May damage fertility), and designated as an SVHC (ECHA ANNEX XV - IDENTIFICATION OF NITROBENZENE AS SVHC (2015)). As described above, marked testicular toxicity and reduced fertility were observed through two routes, oral and inhalation, in experimental animals. Based on this, and also considering the opinion of the EU, this substance was classified in Category 1B for this hazard class.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, blood system, liver, reproductive organs (male)), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	In humans, a few tens of minutes after accidental or intentional ingestion of this substance, severe disturbance of consciousness, and cyanosis are seen, followed by methemoglobin formation in the blood. In addition, anisocytic erythrocytes, polychromatic erythrocytes, and basophilic erythroblasts were confirmed in large numbers in blood morphology tests (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). Inhalation of vapors of this substance causes fatigue, dizziness, headache, nausea, etc., and symptoms such as gastric injury, tachycardia, loss of consciousness, and convulsions occur at high concentrations. Poisoning can also occur by absorption through the skin (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)). In experiments in which single oral dose within the guidance value range of Category 1 was given to rats, nucleolar enlargement and centrilobular necrosis of hepatocytes, and necrosis of spermatogenic cells, and multinucleation of germinal epithelial cells were observed (EHC 230 (2003)). From the above, this substance was classified in Category 1 (nervous system, haemal system, liver, genetic organs (men)) and Category 3 (narcotic effects). 　Additionally, in the previous classification, the basis for identifying the kidney as a target organ was a single dermal dose test using mice (EHC 230 (2003)), but this was not adopted because there was no detailed description of the dosage.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, respiratory organs, liver, kidney, reproductive organs (male))	Danger	H372	P260 P264 P270 P314 P501	In humans, it is reported that severe headache, vertigo, paralysis of legs, anorexia, cyanosis, methemoglobinemia, jaundice, liver damage, hypotension, hyperalgesia, and positives in urinary urobilinogen were seen as symptoms of a woman who used paint containing this substance during painting work for 17 months, and p-aminophenol and p-nitrophenol, which are metabolites, were detected in the urine for 2 weeks after hospitalization (Hazard Assessment Report (CERI, NITE, 2008)). 　As for experimental animals, with the inhalation route, in a 13-week inhalation exposure test using rats and mice, in rats, methemoglobin, toxic nephrosis, and hypertrophy and necrosis of hepatocytes were seen at or above 25 mg/m3 (converted guidance value: 0.018 mg/L), which is within the range of Category 1; hemolytic anemia was seen at 81 mg/m3 (converted guidance value: 0.059 mg/L); and testicular atrophy and increased degeneration of the spermatogenic epithelium were observed at (252 mg/m3 (0.18 mg/L). In mice, hepatocellular hyperplasia, methemoglobin, etc. were observed at the dose within the range of Category 1; and vacuolization in the reticular zone of the adrenal glands was observed in the females at 25 mg/m3 (converted guidance value: 0.018 mg/L), which is within the range of Category 1 (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)). In addition to these effects, in a 2-year inhalation exposure test using rats, effects on the thyroid (hyperplasia of follicular cells) and effects on the respiratory organs (inflammation of the nasal cavity) were seen at 125 mg/m3 (0.125 mg/L), which is within the range of Category 1; and in a 505-day inhalation toxicity test using mice, at 25 mg/m3 (0.025 mg/L) or 125 mg/m3 (0.125 mg/L), which are within the range of Category 1, effects on the respiratory organs (bronchiolization of alveolar walls in the lung, degeneration and inflammatory lesions in the nasal cavity, etc.) and effects on the thyroid (hyperplasia of follicular cells) were seen (Hazard Assessment Report (CERI, NITE) (2008)). 　As for the oral route, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test using rats by gavage administration, effects on the blood and liver were seen at doses within the range of Category 1 or above, and effects on the testes were seen at a dose within the range of Category 2. In addition, at 60 mg/kg/day (converted guidance value: 26.7 mg/kg/day) and 100 mg/kg/day (converted guidance value: 44.5 mg/kg/day), which are within the range of Category 2, effects on the nervous system (abnormal gait, head tilt, necrosis of the central nervous system/gliosis) were also observed (Hazard Assessment Report (CERI, NITE, 2008)). In addition, effects on the nervous system (ataxia, head tilt, lethargy, trembling, circling) were also seen in a 13-week repeated dose toxicity study using rats by gavage administration at or above 75 mg/kg/day, which is within the range of Category 2 (EHC 230 (2003)). 　As for the dermal route, in 13-week studies using mice and rats by dermal administration, at 50 mg/kg/day, which is within the range of Category 2, lung congestion and adrenal cortical fatty change in both mice and rats, as well as variations in the size of hepatocyte nuclei in the centrilobular zone of the liver in mice were seen (EHC 230 (2003)). 　As described above, effects mostly on the nervous system, haemal system, respiratory organs, liver, kidney, and testis were seen from doses equivalent to Category 1. 　Therefore, this substance was classified in Category 1 (nervous system, haemal system, respiratory organs, liver, kidney, genetic organs (men)).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, the kinematic viscosity is calculated as 1.548 mm2/sec (25/20degC) using numerical data (viscosity: 1.863 mPa*s (25 degC), density: 1.2037 g/cm3 (20 degC)) listed in HSDB (Access on May 2016).	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Category 2	- -	H401	P273 P501	From 96-hour LC50 = 6.68 mg/L for crustacea (Mysidopsis bahia) (Initial Risk Assessment (NITE, CERI, NEDO, 2005)), it was classified in Category 2.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 3	- -	H412	P273 P501	If chronic toxicity data are used, then it is classified as "Not classified" due to 21-day NOEC (reproduction) = 2.6 mg/L for crustacea (Daphnia magna) (ECETOC TR91, 2003; EHC 230, 2003; Initial Risk Assessment (NITE, CERI, NEDO, 2005); Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)), though it is not rapidly degradable (a degradation rate by BOD: 3.3 % (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1976)). 　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 because it is not rapidly degradable (a degradation rate by BOD: 3.3 % (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1976)), and 96-hour LC50 = 24 mg/L for fish (Oryzias latipes) (EHC 230, 2003). 　It was classified in Category 3 by drawing a comparison between the above results.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2016	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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