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EC number: 270-735-1 | CAS number: 68477-50-9 A complex combination of hydrocarbons obtained from the distillation of polymerized steam-cracked petroleum distillate. It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C5 through C12.
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- specific investigations: other studies
- 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, fully adequate for assessment of ototoxicity but not other repeat-dose end-points.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 984
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The rats were exposed to toluene at different concentrations and for varying exposure times. Hearing loss was assessed by behavioural and electrophysiological methods.
- GLP compliance:
- not specified
- Type of method:
- in vivo
- Endpoint addressed:
- repeated dose toxicity: inhalation
Test material
- Details on test material:
- Industrial grade toluene was purchased from Van Waters and Rogers. The material contained over 99% toluene, with less than 1.0% contamination by other hydrocarbons, including benzene (0.1%), octanes, and xylenes as measured by gas chromatography-mass spectroscopy.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Fischer
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Madison, WI, USA (Experiment 1-3), Simonsen Laboratories, Gilroy, CA, USA (Experiments 4-7).
- Age at arrival: 23 or 35 days
- Weight at study initiation: not reported
- Housing: 2-3 rats/cage in standard plastic rat cages or directly in exposure chambers (12/cage).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not reported
ENVIRONMENTAL CONDITIONS
- Temperature: 23±1°C
- Humidity: 40-60%
- Photoperiod: 14 hrs dark / 10 hrs light
IN-LIFE DATES: not reported
Administration / exposure
- Route of administration:
- inhalation: vapour
- Vehicle:
- other: air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 4-chamber system constructed of clear Plexiglas, the interior of each chamber measured 50x50x25 cm and had a volume of 62.5 L.
- System of generation: Toluene concentration in each chamber was controlled by bubbling filtered air through the solvent and diluting it with the main air flow (15 - 20 L/min). Control rats were exposed to filtered air, at the same flow rate.
TEST ATMOSPHERE
- Brief description of analytical method used: monitored daily by gas chromatography - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were monitored daily by gas chromatography but no detail provided of analytical concentrations and refers to target concentrations only
- Duration of treatment / exposure:
- Variety of durations from 4-14 h/day or intermittent
- Frequency of treatment:
- Variety from single exposure to 7d/week for up to 16 weeks
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
Expt 1:0, 400/850, 700/1000, 100/1000 ppm (1507/3203, 2638/3768, 377/3768 mg/m3)
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
Expt 2: 0, 1000, 2000, 4000 ppm (0, 3768, 7537, 15074 mg/m3)
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
Expt 3: 0, 1500, 3000 ppm (0, 5653, 11306 mg/m3)
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
Expt 4: 0, 1000 ppm (0, 3768 mg/m3); Expt 5: 0, 1500, 2000, 4000 ppm (0, 5625, 7500, 15000 mg/m3)
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
Expts 6 and 7: 0, 2000, 4000 ppm (0, 7537, 15074 mg/m3)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, sham-exposed
Examinations
- Examinations:
- Test methodology included:
Multisensory conditioned avoidance response (CAR): Rats learn to pull or climb a pole suspended from the ceiling of the test chamber to avoid an electric shock through the grill floor. Shocks are preceded by an increase in light intensity, a non-aversive shock or a sound. All rats were trained on all three stimuli which were presented randomly (one per trial) during each session. A response during the warning signal ended the trial and was scored as a successful avoidance. A response during the aversive shock was scored as an escape. Absence of any response was scored as a failure. training was in 3 phases. First rats were trained in a 30 trial session to escape aversive shock presented randomly and 20 seconds duration in the absence of a response). Then the rats were given four daily 60 trial sessions to learn to avoid the shock with each of the warning stimuli. The warning stimulus lasted 10 seconds and shock 20 seconds. During the third phase, the rats were given several 80 trial sessions in which the warning stimulus was reduced to 5 seconds and aversive shock reduced to 10 seconds.
Behavioural audiometry: Auditory response thresholds were estimated by giving the rats a series of test sessions during which only the warning used was the sound. Each session consisted of 60 trials, 10 at each of five tone intensities and 10 blank trials. The different tone intensities and blank trials were presented randomly and only one frequency (4, 8, 12, 16 or 20 kHz) was tested in a given 60 trial session. The auditory response threshold was defined as the estimated intensity at which 50% avoidance was expected for each rat at each frequency.
Electrophysiological audiometry: Brainstem auditory-evoked responses (BAERs) were recorded from sub-dural scalp electrodes in awake or anaesthetised, restrained rats. The BAERs were elicited by tone pips of 4, 8 and 16 kHz and 25 to 95 dB in 10 dB steps.
Results and discussion
- Details on results:
- Seven experiments examined concentration and exposure parameters necessary to cause toluene-induced ototoxicity. Hearing loss, measured by behavioural and electrophysiological methods, was observed after as few as 2 weeks. 3000 ppm (11306 mg/m3) 4 h/day for 9 weeks is a NOAEC for ototoxicity.
Any other information on results incl. tables
Hearing loss, measured by behavioural and electrophysiological methods, was repeatedly observed after as few as 2 weeks of exposure to 1000 ppm toluene for 14 hours per day, but lower concentrations (400 and 700 ppm) were without effect even after 16 weeks of exposure. Three-day exposures to 1500 ppm for 14 hours per day or 2000 ppm for 8 hours per day were ototoxic, whereas single exposures to 4000 ppm for 4 hours or 2000 ppm for 8 hours were without effect. Intermittent exposure to 3000 ppm for 30 minutes every hour for 8 hours per day caused hearing loss within 2 weeks, but a similar exposure schedule for 4 hours per day was ineffective even after 9 weeks.
Exposure Schedule |
LOAEC |
NOAEC |
14 h/day, 16 weeks |
1000 ppm |
700 ppm |
8 h/day, 3 days |
2000 ppm |
|
Intermittent 8 h/day, 2 weeks |
3000 ppm |
|
Intermittent 4 h/day 9 weeks |
|
3000 ppm |
Applicant's summary and conclusion
- Conclusions:
- Toluene is ototoxic in rats at relatively intense schedules of exposure. The toluene concentration and the duration of exposure must be above certain levels before hearing loss will occur.
- Executive summary:
The relationship between toluene concentration, exposure pattern, and hearing loss in rats was investigated in a series of experiments in male Fischer rats. Hearing loss was measured by conditioned avoidance response to tone frequencies of 4, 8, 12, 16 or 20 kHz, and brainstem auditory-evoked response to tone pips of 4, 8, and 16 kHz.
Two weeks of exposure to 1000 ppm (3768 mg/m3) toluene 14 h/day caused hearing loss. Lower concentrations (400 (1507 mg/m3) and 700 ppm (2638 mg/m3)) were without effect even after 16 weeks of exposure. Three-day exposures to 1500 ppm (5653 mg/m3) for 14 h/day or to 2000 ppm (7537 mg/m3) for 8 h/day were ototoxic. Single exposures to 4000 ppm (15074 mg/m3) for 4 h or to 2000 ppm for 8 h were without effect. Intermittent exposure to 3000 ppm (11306 mg/m3) for 30 minutes every hour for 8 h/day caused hearing loss within 2 weeks, but a similar exposure schedule for 4 h/day was ineffective even after 9 weeks. Seven experiments with young male Fischer rats were done to examine concentration and exposure parameters necessary and sufficient to cause toluene-induced ototoxicity. Hearing loss, measured by behavioural and electrophysiological methods, was observed after as few as 2 weeks.
It is concluded that 3000 ppm (11306 mg/m3) 4h/day for 9 weeks is a NOAEC for ototoxicity.
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