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EC number: 215-311-9 | CAS number: 1321-12-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
There is no acute toxicity study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4 -nitrotoluene (CAS 99-99-0):
LD50, oral, rat: > 2250
mg/kg bw;
LD50, dermal, rat: > 750 mg/kg bw;
LC50, inhalation, rat: > 4200 mg/m³/1h.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given (No OECD guideline or GLP defined; no necropsy and no histopathological examinations were performed)
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- No GLP study. Analytical purity not reported. Animals were not fasted before the treatment. Enviromental conditions not reported. Acclimation period not reported. Body weights not reported. No necropsy and no histopathological examinations were performed
- GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time of the study
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-nitrotoluene
- Physical state: solid
- Analytical purity: not reported - Species:
- rat
- Strain:
- other: Wistar-II-R
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 160-245 g
- Housing: animals were housed in Makrolon cages, type 3
- Diet (e.g. ad libitum): Altromin-Standarddiät (Altromin GmbH, Lage/Lippe, Germany) ad libitum
- Water (e.g. ad libitum): ad libitum - Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- Polyethylenglycol 400
- Doses:
- 100, 250, 500, 1000, 2250 mg/kg bw
- No. of animals per sex per dose:
- 15
- Control animals:
- other: not applicable
- Details on study design:
- - Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 250 mg/kg bw
- Remarks on result:
- other: No mortality occured
- Mortality:
- Deaths did not occur at the doses specified.
See "Remarks on results tables and figures". - Clinical signs:
- other: Symptoms of poisoning began in rat from 4 to 40 minutes after application in the form of disordered breathing and a reduced general condition. The respiratory disturbances were observed until 3 days after application, and the general condition was to be r
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- LD50 (oral, rat) > 2250 mg/kg bw.
- Executive summary:
In an acute oral toxicity study male rats received the test substance in a dose of 100, 250, 500, 1000 or 2250 mg/kg bw in Polyethylenglycol 400. Symptoms of poisoning began in rat from 4 to 40 minutes after application in the form of disordered breathing and a reduced general condition. The respiratory disturbances were observed until 3 days after application, and the general condition was to be reduced to 6 days. No mortalities were observed. Therefore the LD 50 was >2250 mg/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 250 mg/kg bw
Referenceopen allclose all
|
|
Symptoms of poisoning
|
Appereance ofdeath |
|
Dosis mg/kg |
Toxicological results |
Start |
End |
|
Male rats |
||||
100 |
0/0/15 |
- |
- |
- |
250 |
0/15/15 |
29´ |
2d |
- |
500 |
0/15/15 |
21´ |
4d |
- |
1000 |
0/15/15 |
18´ |
4d |
- |
2250 |
0/15/15 |
4´ |
6d |
- |
Female rats |
||||
100 |
0/0/15 |
- |
- |
- |
250 |
0/15/15 |
40´ |
3d |
- |
500 |
0/15/15 |
35´ |
4d |
- |
1000 |
0/15/15 |
20´ |
5d |
- |
2250 |
0/15/15 |
12´ |
5d |
- |
In this table in the column "Toxicological results" the numbers have the following meaning:
1stnumber= amount of dead animals
2ndnumber = amount of animals with symptoms
3rdnumber = amount of animals used
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- see "Any other information on material and method incl. tables"
- GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time of the study
- Test type:
- other: acute toxicity inhalation study, rats
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-Nitrotoluene
- Physical state: solid (yellow crystalline substance)
- Analytical purity: no data - Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: air
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 1 h
- Concentrations:
- 4167 mg/m³ air.
- No. of animals per sex per dose:
- 5
- Control animals:
- not specified
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- > 4 167 mg/m³ air
- Exp. duration:
- 1 h
- Remarks on result:
- other: No mortality occurred.
- Mortality:
- No martality occurred.
- Clinical signs:
- other: No signs of intoxication during the one hour exposure time or the 7 days post exposure observation period could be observed.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- LC50 (rat, inhaltion, 1h) > 4167 mg/m³ air.
- Executive summary:
In an acute inhalation toxicity study male Wistar rats were exposed to the test-substance in a dose of 4167 mg/m³ air.
No signs of intoxication during the one hour exposure time or the 7 days post exposure observation period could be observed.
Therefore the LC 50 was > 4167 mg/m³ air/1h.
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 851 mg/m³ air
- Exp. duration:
- 4 h
- Remarks on result:
- other: No mortality occurred.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented study report which meets basic scientific principles
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- Method: other: 5 rats/sex/dose group, 1 dose only as 30 % emulsion covered by aluminium foil fixed by broad stripes of adhesive plaster to back and belly for a 24 hour-exposure period: cleaning with soap and water, observation period: 1 week
- GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time of the study
- Test type:
- other: Acute dermal toxicity study in rats
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-Nitrotoluene
- Physical state: solid (yellow crystal)
- Analytical purity: no data - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Type of coverage:
- occlusive
- Vehicle:
- polyethylene glycol
- Remarks:
- polyethylene glycol 400
- Duration of exposure:
- 24 h
- Doses:
- 750 mg/kg bw in polyethylene glycol 400
- No. of animals per sex per dose:
- 10
- Control animals:
- not specified
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 750 mg/kg bw
- Remarks on result:
- other: No mortality occurred.
- Mortality:
- No mortalities could be observed.
- Clinical signs:
- other: After 18 hours after application of the test substance a decrease of general behavior could be observed in the animals. This condition persisted 5 days.
- Interpretation of results:
- Category 3 based on GHS criteria
- Conclusions:
- LD50 (dermal, rat, occlusive, 24h) >750 mg/kg bw.
- Executive summary:
When applied as an emulsion in polyethylene glycol 400 at a dose level of 750 mg/kg bw to the back of 5 rats/sex/group, no deaths during the 24 hour treatment period and during the one week observation period were noted, but the rats showed poor general condition from 18 hours post application up to 4 days after application.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 20 000 mg/kg bw
- Remarks on result:
- other: No mortality occurred.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Additional information
Mononitrotoluene is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene. Key data and classification is derived from the isomer with the most critical hazard identified for each specific end point. For completeness key data of the other isomer is added as supporting information, if available.
Regarding acute toxicity classification is driven by 4-nitrotoluene.
Acute Toxicity
Oral
Groups of rats received different doses of 4-nitrotoluene ranging from 100 to 2250 mg/kg bw in polyethylene glycol 400. The LD50 was determined as > 2250 mg/kg bw (Bayer AG, 1976).
Similar oral toxicity was observed with 2 -nitrotoluene e.g. oral LD50 value of 890 mg/kg bw (Vernot et al., 1977) and approx. 2100 mg/kg b.w. (Ciss et al., 1980) in rats. Clinical signs of toxicity were related with methaemoglobin formation.
Dermal
Neat 4-nitrotoluene (up to 20,000 mg/kg bw) was applied to the clipped back of 3 rabbits and kept in place by occlusive dressing for 24 hours. No rabbit died. No local or systemic effects were reported during treatment or after removal of the dressing and the following 14-day period (Kinkead et al., 1977). When applied as an emulsion in polyethylene glycol 400 at a dose level of 750 mg/kg bw to the back of 5 rats/sex/group, no deaths during the 24 hour treatment period and during the one week observation period were noted, but the rats showed poor general condition from 18 hours post application up to 4 days after application (Bayer AG, 1976).
Inhalation
Five male rats and 10 male mice were exposed to 4-nitrotoluene dust for one hour and then observed for 7 days to determine LC50-values. At the highest exposure level of 4167 mg/m³, no animal died and no signs of intoxication were noted during or post exposure (Bayer AG, 1976). In other studies 10 rats and 10 mice were exposed to an atmosphere essentially saturated with 4-nitrotoluene for four hours (rat: 152 ppm = 851 mg/m³; mouse: 228 ppm = 1,277 mg/m³). No death occurred during exposure or during the subsequent 14 day post exposure observation period. No lesions attributable to exposure could be discovered during gross pathological evaluation, neither in rats nor in mice (Kinkead et al., 1977). For none of the studies was information on particle size available.
Conclusion
4-Nitrotoluene is a methemoglobin forming chemical. Tachypnea, wheezing, somnolence and cyanosis were the predominant clinical signs following oral doses near to or exceeding the LD50 value. Methemoglobinemia was reported in rats after dermal exposure to high dose levels (LD50, oral, rat: > 2250mg/kg bw; LD50, dermal, rat: > 750 mg/kg bw; LD50, dermal, rabbit: > 20000 mg/kg bw;
LC50, inhalation, rat: > 4167 mg/m³/1h, LC50 inhalation, rat > 851 mg/m3/1h; no information on particle size available).
Justification for classification or non-classification
- Acute toxicity - oral Cat. 3 (H301: toxic if swallowed)
- Acute toxicity - dermal Cat. 3 (H311: toxic in contact with skin)
- Acute toxicity - inhalation Cat 3 (H331: toxic if inhaled).
Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There is no acute toxicity study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4-nitrotoluene (CAS 99-99-0). Like other nitrotoluenes, a primary toxic effect of 4-nitrotoluene is methaemoglobin formation. Taking into account that humans are much more sensitive to methaemoglobin producing substances than rats, 4-nitrotoluene is classified for acute oral toxicity Cat. 3 (H301: Toxic if swallowed.), acute inhalation toxicity Cat. 3 (H331: Toxic if inhaled.) and acute dermal toxicity Cat. 3 (H311: Toxic in contact with skin.) under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.
Furthermore, 4-nitrotoluene (CAS 99-99-0) is included in Annex VI of Regulation (EC) No. 1272/2008 with the following classification:
Therefore, nitrotoluene (CAS 1321-12-6) is also classified for acute oral, acute dermal and acute inhalation toxicity Cat. 3 (H301, H311, H331).
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