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EC number: 202-808-0 | CAS number: 99-99-0
- 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
Acute oral toxicity: LD50, oral, rat: > 2250 mg/kg bw (key, rel.2, OECD 401 eq, pre-GLP);
Acute dermal toxicity: LD50, dermal, rat: > 750 mg/kg bw; LD50, dermal, rabbit: > 20,000 mg/kg bw
Acute inhalation toxicity: LC50, inhalation, rat: > 851 mg/m³/4h
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
- 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
- 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:
- other: Polyethylene glycol 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
- Mortality:
- see "Remarks on results tables and figures"
- Clinical signs:
- other: 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
- 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 (Bayer AG, 1976).
Reference
|
|
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
- Dose descriptor:
- LD50
- Value:
- > 2 250 mg/kg bw
- Quality of whole database:
- A Klimisch rating of 2 has been applied. The study is pre-GLP but conducted to a relevant OECD test guideline using well-defined scientific procedures, therefore fulfilling the endpoint requirement.
Additional information
OECD SIDS 2003
Acute Toxicity
Oral
Groups of rats received different doses of 4-nitrotoluene ranging from 100 to 2,250 mg/kg bw in polyethylene glycol 400. The LD50 was determined as > 2,250 mg/kg bw (Bayer AG, 1976). In other rat studies, in which 4-nitrotoluene was administered in 1% aqueous methylcellulose, an LD50 value of 3,200 mg/kg bw was found in females, and a value of 4,700 mg/kg bw in males (Ciss, 1978; Ciss et al., 1980b). Clinical signs included poor condition, tachypnea, somnolence, atony, convulsions and wheezing for up to 24 hours. Survivors appeared normal one week after administration of the test substance. In a further study, an LD50 of 2,144 mg/kg bw was determined in male rats, with cyanogenic effects reported at 3,400 mg/kg bw and above (DuPont Chem, 1972).
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, 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). In a poorly documented study with rats, application of up to 16,000 mg/kg bw caused methemoglobinemia of up to 25 % within 72 hours which was reported to be reversible; no deaths occurred. No further details were described (Sisa et al., 1959).
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 4,167 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, 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: 2,144 - 4,700 mg/kg bw; LD50, dermal, rat: > 750 mg/kg bw; LD50, dermal, rabbit: > 20,000 mg/kg bw; LC50, inhalation, rat: > 851 mg/m³/4h; no information on particle size available).
Justification for classification or non-classification
Harmonised classification:
The substance is classified in Category 3 (H301 – Toxic if swallowed) according to the Regulation (EC) No. 1272/2008 (CLP).
The substance is classified in Category 3 (H311 – Toxic in contact with skin) according to the Regulation (EC) No. 1272/2008 (CLP).
The substance is classified in Category 3 (H331 – Toxic if inhaled) according to the Regulation (EC) No. 1272/2008 (CLP).
Self-Classification:
The oral LD50 value of the test item was established to exceed 2250 mg/kg body weight. Based on the conditions of this test, the test item would not be classified for acute oral toxicity, in accordance with CLP Regulation No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures. Since p-nitrotoluene has a harmonised classification, the substance will be classified accordingly even though the LD50 suggest otherwise.
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