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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://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- chronic toxicity: inhalation
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-guideline, non-GLP, animal experimental study, published in peer reviewed literature, notable limitations in design, but contributing to weight of evidence.
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 983
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- - only 5/sex/group examined for chronic toxicity at 1 year
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Details on test material:
- - Name of test material (as cited in study report): high purity toluene
- Supplier: Shell Oil Company, Oak Brook, IL, USA in two shipments. First shipment for the initial 21.5 months and the second for the final 2.5 months of exposure.
- Analytical purity: > 99.98%
- Impurities (identity and concentrations): benzene content was less than 0.01% and 0.004%, for the first and second lot respectively
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Fischer-344 rats [CDF(F-344)/CrIBr]
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA., USA
- Age at study initiation: approx. 6-7 weeks
- Housing: group housed, sexes separately, 10/cage in stainless steel suspended cages
- Diet: standard laboratory diet (Wayne Lab-Blox F6, Allied Mills Inc., Chicago, IL., USA) ad libitum (except during exposure)
- Water: ad libitum
- Acclimation period: quarantined for at least 10 days
ENVIRONMENTAL CONDITIONS: No details reported
IN-LIFE DATES: Not reported
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: rectangular stainless steel and glass chambers (nominal volume 8.0 m3)
- Source and rate of air: absolute and charcoal filtered air separate from the room air supply
- Temperature, humidity, pressure in air chamber: temperature 22°C / relative humidity 50%. The inhalation chambers containing toluene were maintained at slight sub-atmospheric pressure (0.1 in - 0.5 in H2O). Control chambers were under slight positive pressure (0.1 in - 0.5 in H20).
- Air flow rate: approx. 2000 L/min
- Generation: toluene vapour was generated by bubbling clean dry air (dew point -40°C) through liquid toluene. The rate of vapour generation was regulated by controlling airflow into the generator flask.
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: not reported - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The time weighted average concentration of toluene for each exposure group was 0.0, 30.1, 99.7, 299.0 ppm for target concentrations of 0, 30, 100 and 300 ppm, respectively.
- Duration of treatment / exposure:
- 6 h/day
- Frequency of treatment:
- 5 days/week, up to 24 months (interim kills at 6, 12 and 18 months)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 30, 100, 300 ppm
Basis:
other: target concentration
- Remarks:
- Doses / Concentrations:
0, 30.1, 99.7, 299.0 ppm
Basis:
other: time weighted average concentration
- Remarks:
- Doses / Concentrations:
0, 113, 377 or 1131 mg/m3
Basis:
nominal conc.
- No. of animals per sex per dose:
- 120
- Control animals:
- yes, sham-exposed
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes (for dead and moribund animals)
- Time schedule: once/day non-exposure days, twice/day exposure days
DETAILED CLINICAL OBSERVATIONS: Yes (including palpation and measurement of tissue masses)
- Time schedule: every 2 weeks
BODY WEIGHT: Yes
- Time schedule for examinations: beginning of the study (week 0), weekly for the first 6 months, every other week from 6 to 24 months and immediately prior to sacrifice
FOOD CONSUMPTION: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to sacrifice
- Dose groups that were examined: All
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 6, 12, 18 and 24 months (prior to termination)
- Anaesthetic used for blood collection: no data
- Animals fasted: yes
- How many animals: selected (no further detail reported)
- Parameters examined: haemoglobin concentrations, haematocrits, total erythrocyte counts and total and differential leukocyte count. Mean corpuscular volumes, mean corpuscular haemoglobins, and mean corpuscular haemoglobin concentrations were calculated.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 6, 12, 18 and 24 (months prior to termination)
- Animals fasted: yes
- How many animals: selected (no further detail reported)
- Parameters examined: blood urea nitrogen (BUN), serum glutamic pyruvic transaminase (SGPT) activity, and serum alkaline phosphatase (SAP) activity
URINALYSIS: Yes
- Time schedule for collection of urine: 16 hour period prior to blood collection (at 6, 12, 18 and 24 months)
- Metabolism cages used for collection of urine: yes
- Animals fasted: yes
- Parameters examined: appearance, specific gravity, protein, pH, ketones, glucose and microscopic particles - Sacrifice and pathology:
- SACRIFICE AND GROSS PATHOLOGY: Animals killed at each interval, and all survivors at 24 months, were exsanguinated following carbon dioxide anaesthesia. Each was examined grossly and the brain, heart, kidneys, liver, lungs and gonads weighed.
HISTOPATHOLOGY: The following tissues were examined histopathologically: brain, spinal cord, peripheral nerve, pituitary, parathyroid, salivary gland, heart, lungs, spleen, liver, pancreas, oesophagus, adrenals, lymph nodes, kidneys, bladder, prostate, ovaries, uterus, fallopian tubes, stomach, small intestine, large intestine, skeletal muscle, thymus, skin, mammary gland, bone marrow, adipose tissue, aorta, ear canal, nasal turbinate, trachea, tibial and plantar nerves, lumbar, sacral and dorsal ganglia, proximal and distal hind limb, eyes and testes. - Statistics:
- Analysis of variance (Kruskal-Wallis test for ratios): absolute body weight, total body weight change (surviving animals), organ weights, organ weight/body weight and organ weight/brain weight ratios. Other techniques for multiple comparisons: Tukey's for equal-sized groups, Scheffe's for groups of unequal sizes. Tests for homogeneity of variance, transformed (natural logarithm) as needed, and analysis of variance were used for haematology data.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- There were 140 unscheduled deaths (14.6% of 960 animals) over the 2-year course of the study. The distribution of spontaneous deaths among the treatment groups was not significantly different from controls.
There were no differences between control and toluene exposed groups with regard to clinical observations, blood chemistry analyses, urinalysis, ophthalmology, gross or histopathological findings.
The males in the toluene treatment groups were significantly heavier than the control males throughout the study although there was no clear cut dose response relationship. A similar finding was noted for the females but the effect disappeared during the final weeks of the study. Neither observation was considered to be adverse.
Female rats exposed to 100 and 300 ppm of toluene for 24 months had slightly, but significantly, reduced haematocrits and for the 300 ppm group only the mean corpuscular haemoglobin concentration was slightly, but significantly, increased. Other haematology parameters were not significantly different from controls.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- chronic toxicity
- Effect level:
- 300 ppm (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: no toxicologically significant effects at highest dose tested (300 ppm)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1 131 mg/m³ air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: no toxicologically significant effects at highest dose tested (1131 mg/m3)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
All statistically significant differences from control were considered to be of no toxicological significance.
Applicant's summary and conclusion
- Conclusions:
- Toluene does not cause adverse effects in the rat following inhalation exposure to 300 ppm for up to 24 months. The NOAEC for chronic systemic or local toxicity in this study was 300 ppm (1131 mg/m3).
- Executive summary:
Chronic toxicity of inhaled toluene was assessed in Fischer-344 rats exposed to 0, 30, 100 or 300 ppm 6 h/day, 5 days/week for 6, 12 or 18 months. There were no toxicologically significant effects on bodyweight, clinical signs, ophthalmoscopy, haematology, blood and urine clinical chemistry, organ weights or gross and microscopic pathology.
The NOAEC for chronic systemic and local toxicity from this study was 300 ppm (1131 mg/m3) for an exposure duration of 18 months.
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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