GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 98-95-3 |
| Chemical Name | Nitrobenzene |
| Substance ID | H28-B-022, C-030B |
| Classification year (FY) | FY2016 |
| 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 | FY2014 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 |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 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. |
| 2 | Flammable gases (including chemically unstable gases) | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 5 | Gases under pressure | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 |
P370+P378
P403+P235 P210 P280 P501 |
Based on a flash point of 88 deg C (closed cup) (ICSC (2006)), it was classified in Category 4. |
| 7 | Flammable solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 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. |
| 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)). |
| 10 | Pyrophoric solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid 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 | 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. |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. |
| 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 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). |
| 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. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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. |
| 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). |
| 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. |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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. |
| 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. |
| 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. |
| 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. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (nervous system, haemal system, liver, genetic organs (men)), 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. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (nervous system, haemal system, respiratory organs, liver, kidney, genetic organs (men)) |
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)). |
| 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). |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (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. |
| 11 | Hazardous to the aquatic environment (Long-term) | 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. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* 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. |