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EC number: 270-790-1 | CAS number: 68478-10-4 A complex combination of hydrocarbons obtained by the distillation of debenzenized light steam-cracked naphtha. It consists predominantly of cyclic olefinic and aromatic hydrocarbons having carbon numbers predominantly in the range of C8 through C16 and boiling in the range of approximately 130°C to 300°C (226°F to 572°F).
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Near guideline, GLP animal experimental study, available as published report, fully adequate for assessment
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- Cited as Directive 87/302/EEC, part B, p. 8
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Details on test material:
- Toluene was obtained in one lot (lot no. H-12-19-80) from Exxon Company, USA (Baytown, TX, USA) as a clear, colourless liquid. Purity was greater than 99% as determined by elemental analysis, Karl Fischer water analysis and gas chromatography (GC).
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI., USA
- Age at study initiation: approx. 6-7 weeks
- Housing: 5 per cage in polycarbonate cages with hardwood bedding
- Diet: IH 07 Rat and Mouse Ration (Zeigler Bros., Inc., Gardners, PA) ad libitum
- Water: ad libitum
- Acclimation period: 18days
ENVIRONMENTAL CONDITIONS:
- Temperature: mean temperature 72.4°F (~22.4°C), range 63-82°F (~17-28°C)
- Humidity: mean humidity 59.8%, range 44-82%
- Air changes (per hr): not reported
- Photoperiod: 12hrs dark / 12hrs light
IN-LIFE DATES: Not reported
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Toluene was dissolved in corn oil. Solutions at 20 mg/kg were stable for at least 2 weeks at room temperature
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: 31.2, 62.5, 126, 250 and 500 mg/mL
- Amount of vehicle (if gavage): dose volume of 10 mL/kg
- Lot/batch no. (if required): no data
- Purity: no data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Dose mixtures were analysed several times during the 13-week studies and found to be within 10% of the target concentrations
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily, 5 days/ week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
312, 625, 1250, 2500, 5000 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- Post-exposure period: none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes (for dead and moribund animals)
- Time schedule: twice/day
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: beginning of the study and weekly
FOOD CONSUMPTION: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to termination
- Anaesthetic used for blood collection: no data
- Animals fasted: yes
- How many animals: all
- Parameters examined: eosinophils, haematocrit, haemoglobin, lymphocytes, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, mean cell volume, methaemoglobin, monocytes, platelets, erythrocytes, reticulocytes, segmented neutrophils, leukocytes
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to termination
- Animals fasted: yes
- How many animals: all
- Parameters examined: blood urea nitrogen (BUN), albumin, calcium, lactate dehydrogenase, inorganic phosphorus, total protein.
URINALYSIS: Yes
- Time schedule for collection of urine: overnight prior to termination
- Animals fasted: yes
- How many animals: all
- Metabolism cage used for collection: yes
- Parameters examined: No data - Sacrifice and pathology:
- Necropsy was performed on all animals.
Tissues examined in control, 2500 and 5000 mg/kg/day groups: adrenal glands, aorta, brain, caecum, colon, duodenum, oesophagus, heart, ileum, jejunum, kidneys, liver, lungs, and bronchi, mammary gland, mesenteric lymph nodes, nasal cavity and turbinates, pancreas, parathyroid glands, pituitary gland, preputial or clitoral glands, prostate/testes or ovaries/uterus, rectum, salivary glands, spinal cord, spleen, sternebrae, including marrow, stomach, thymus, thyroid gland, tissue masses, trachea, urinary bladder and gross lesions. Tissues examined in other groups were: brain, kidneys, liver, and urinary bladder.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY
All rats in the 5000 mg/kg group died within the first week. In the 2500 mg/kg group 8 males and one female died before termination of the study. Clinical signs included prostration, hypoactivity, ataxia, piloerection, lachrymation, and excessive salivation in the 5000 and 2500 mg/kg groups.
BODY WEIGHT AND WEIGHT GAIN
The final mean body weight of males that received 2500 mg/kg was 19% lower than that of vehicle controls.
HAEMATOLOGY, CLINICAL CHEMISTRY AND URINALYSIS
A there were no treatment related effects in the haematological and serum chemical analyses or urinalyses.
ORGAN WEIGHTS
Absolute and relative kidney weight was increased in males at 625 mg/kg and higher, and in females at 1,250 mg/kg and higher. The differences in absolute and relative liver weights for female rats that received 2500 or 1250 mg/kg (22-62% relative liver weight increase) and for males that received 1250 or 625 mg/kg (8-78% relative liver weight increase) were statistically significant. Statistically significant increases were also seen in absolute and relative heart weight for male and female rats at 2500 and females at 1250 mg/kg. Absolute, but not relative brain weight was reduced in both sexes at 2500 mg/kg.
HISTOPATHOLOGY
Neuropathological changes in the brain, consisting of neuronal cell necrosis in the dentate gyrus and Ammons horn of the hippocampus, was seen in male and female rats that received 2500 or 1250 mg/kg. In addition to the hippocampal lesions, necrosis and/or mineralisation were present in the granular layer of the cerebellar cortex. Haemorrhage was present in the mucosa, submucosa, or muscularis of the urinary bladder of males and females of the two highest dose groups. A dose of 312 mg/kg/kg did not cause any effects.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 625 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: neuropathology (neuronal cell necrosis in hippocampus)
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 1 250 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: adverse clinical signs, differences in brain, liver, kidney and heart weight and neuropathology (neuronal cell necrosis in hippocampus).
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL considered to be 625 mg/Kg/day. Increased relative weights of liver and kidney are interpreted as toxicologically insignificant differences in liver and kidney weight unaccompanied by histological findings.
- Executive summary:
Groups of 10 male and 10 female F344N rats received 0, 312, 625, 1250, 2500, or 5000 mg toluene/Kg in corn oil by gavage for 13 weeks. All rats in the 5000 mg/Kg group died within the first week. In the 2500 mg/Kg group 8 males and one female died before termination of the study. The final mean body weight of males that received 2500 mg/Kg was 19% lower than that of vehicle controls. Clinical signs included prostration, hypoactivity, ataxia, piloerection, lachrymation, and excessive salivation in the 5000 and 2500 mg/Kg groups. Absolute and relative kidney weight was increased in males at 625 mg/Kg and higher, and in females at 1,250 mg/Kg and higher.
The differences in absolute and relative liver weights for female rats that received 2500 or 1250 mg/Kg (22-62% relative liver weight increase) and for males that received 1250 or 625 mg/Kg (8-78% relative liver weight increase) were statistically significant. Statistically significant increases were also seen in absolute and relative heart weight for male and female rats at 2500 and females at 1250 mg/Kg. Absolute, but not relative brain weight was reduced in both sexes at 2500 mg/Kg. There were no treatment related effects in the haematological and serum chemical analyses or urinalyses. Neuropathological changes in the brain, consisting of neuronal cell necrosis in the dentate gyrus and Ammons horn of the hippocampus, was seen in male and female rats that received 2500 or 1250 mg/Kg. In addition to the hippocampal lesions, necrosis and/or mineralisation were present in the granular layer of the cerebellar cortex. Haemorrhage was present in the mucosa, submucosa, or muscularis of the urinary bladder of males and females of the two highest dose groups. A dose of 312 mg/kg did not cause any effects.
The NOAEL for repeat dose oral toxicity is considered to be 625 mg/Kg. At this dose increased absolute and relative liver and kidney weight (up to 46% increase in relative kidney weight, up to 78% increase in relative liver weight) were unaccompanied by histopathological findings were present. Therefore, the increased relative weights of liver and kidney are interpreted as toxicologically non-significant signs of metabolic activity related to exposure.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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