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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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 002
- Reference Type:
- secondary source
- Title:
- 4-Nitrotoluene - CAS N°: 99-99-0 - SIDS Initial Assessment Report.
- Author:
- OECD
- Year:
- 2 003
- Bibliographic source:
- UNEP Publications
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- no interim kill was performed and no hematology data or clinical chemistry data were noted
- GLP compliance:
- yes
Test material
- Reference substance name:
- 4-nitrotoluene
- EC Number:
- 202-808-0
- EC Name:
- 4-nitrotoluene
- Cas Number:
- 99-99-0
- Molecular formula:
- C7H7NO2
- IUPAC Name:
- 1-methyl-4-nitrobenzene
- Details on test material:
- - Name of test material (as cited in study report): p-nitrotoluene
- Physical state: clear, pale yellow, crystalline solid
- Analytical purity: > 99%
- Lot/batch No.: 338297/1495
- Stability under test conditions: Stability studies of bulk chemical were performed by Midwest Research Institute (Kansans City, MO, USA) using gas chromatography. No degradation of the bulk chemical was observed after storage for two weeks, protected from light, at temperature up to 60°C
- Storage condition of test material: To ensure stability, the bulk chemical was stored at approximately 5°C in sealed containers. Stability was monitored during the 2-year studies using gas chromatography. No degradation of the bulk chemical was detected.
- Source: St.Louis, MO, USA
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: F344/N
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- ANIMALS PER CAGE: 2 or 3 (males) or 5 (females)
TIME HELD BEFORE STUDIES: 12 days AVERAGE AGE WHEN STUDY BEGAN: 5-6 weeks
DURATION OF EXPOSURE: 105-106 weeks AVERAGE AGE AT NECROPSY: 111 to 112 weeks
DIET: NTP-2000 Open Formula meal, available ad libitum; rats received nonirridiated feed from the beginning of the studies for 8 months and irradiated feed to the end of the studies. WATER: tap water, available ad libitum
ANIMAL ROOM ENVIRONMENT: temperature: 72°F; relative humidity: 50% ± 15%; room fluorescent light: 12 hours/day; room air changes: 10 hour
Administration / exposure
- Route of administration:
- oral: feed
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 105 -106 weeks
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 1250, 2500, 5000 ppm |(males: approx. 0, 55, 110, 240 mg/kg bw)|(females: approx. 0, 60, 125, 265 mg/kg bw)
Basis:
nominal in diet
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, plain diet
- Details on study design:
- Post-exposure period: no
Examinations
- Observations and examinations performed and frequency:
- TYPE AND FREQUENCY OF OBSERVATION: Observed twice daily, rats were weight initially, during week 4, and every 4 weeks thereafter; clinical findings were recorded at 4-week intervals, feed consumption was measured over a 1-week period every 4 weeks
METHOD OF SACRIFICE: Carbon dioxide asphyxisation
URINALYSIS: Urine was collected during a 24-hour period from 5 male and 5 female rats from each group at 2 weeks and 3, 12, and 18 months. Parameters evaluated included urine volume, creatinine, p-acetamidobenzoic acid and p-nitrobenzoic acid. - Sacrifice and pathology:
- NECROPSY: Necropsy was performed on all animals
HISTOPATHOLOGY: Complete histopathology was performed on all animals. In addition to gross lesions and tissue masses, the following tissues were examined: adrenal gland, bone, brain, clitoral gland, esophagus, heart and aorta, large intestine (cecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, liver, lung and mainstem bronchi, lymph nodes (mandibular and mesenteric), mammary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis with epididymis and seminal vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus
URINALYSIS: Urine was collected during a 24-hour period from 5 male and 5 female rats from each group at 2 weeks and 3, 12, and 18 months. Parameters evaluated included urine volume, creatinine, p-acetamidobenzoic acid and p-nitrobenzoic acid.
Haematology or clinical chemistry was not performed. - Statistics:
- Poly-k test, continuity corrected Poly-3 test, Fisher's least significant difference test, Mann-Whitney U test
Results and discussion
Any other information on results incl. tables
Survival rate (0 ppm, 1250 ppm, 2500 ppm, 5000 ppm):
males: 31/50, 38/50, 38/50, 40/50;females: 39/50, 37/50, 39/50, 41/50
Mean body weights at the end of the study (control, low, mid, high dose):
males: 402 g, 409 g, 402 g, 366 g (91 % of controls);females294 g, 272 g, 262 g, 210 g.
Clinical signs of toxicity:
all exposed male and female rats showed nasal- and eye discharge
Haematology data or clinical chemistry data were not reported
Non-Neoplastic effects (control, low, mid, high dose):
Kidney:
renal tubule hyaline droplet, m: 2/50, 23/50, 27/50, 18/50 f: 8/50, 41/50, 49/50, 46/50; renal tubule pigmentation, m: 10/50, 28/50, 47/50, 46/50 f: 9/50, 43/50, 49/50, 50/50; mineralization, f: 15/50, 21/50, 32/50, 40/50; oncocytic renal tubule hyperplasia, f: 0/50, 2/50, 4/50, 6/50
Spleen: hemapoietic cell proliferation, m: 9/50, 13/50, 19/50, 25/50 f: 26/50, 26/50, 45/50, 43/50; pigmentation, m: 10/50, 12/50, 24/50, 38/50 f: 24/50, 32/50, 45/50, 48/50;
Liver:
basophilic focus, m: 31/50, 39/50, 42/50, 45/50; clear cell focus, m: 20/50, 27/50, 30/50, 32/50; eosinophilic focus, m: 5/50, 5/50, 5/50, 9/50 f: 1/50, 2/50, 7/50, 9/50;
Testis:
germinal epithelial atrophy, m: 7/50, 11/50, 8/50, 30/50
Neoplastic effects (control, low, mid, high dose):
Clitoral gland:
adenoma or carcinoma, f: 8/50, 12/50, 20/50 (sign.), 8/50
(historical control: 84/636 = 13.2 %, range: 2-24 %)
Skin (subcutaneous):
fibroma, m: 1/50, 2/50, 7/50, 1/50 (historical control: 33/609 = 5.4 %, range: 0-12%);
fibroma or fibrosarcoma, m: 1/50, 2/50, 9/50, 1/50 (historical control: 41/609 =m 6.7 %, range: 2-14%)
Mononuclear cell leukemia:
m: 24/50, 12/50, 5/50, 4/50 f: 13/50, 12/50, 3/50, 1/50
Testis
interstitial cell adenoma, m: 49/50, 46/50 45/50 34/50
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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