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Diss Factsheets
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EC number: 203-625-9 | CAS number: 108-88-3
- 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
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Neurotoxicity
Administrative data
Description of key information
Although there are a number of repeated dose inhalation studies in rats investigating neurotoxic effects, weaknesses in study design (i.e. only one sex evaluated, lack of dose response information, non-standard methods, lack of GLP) hinders any definitive conclusions on reliable NOAEC and LOAEC levels. Neuropsychological effects in humans are reported to occur with high occupational exposure. The LOAEC for psychological and cognitive effects in human above 59 ppm (222 mg/m3). The availability of a great deal of human data indicated to SCOEL no reliable evidence of neurological effects at or below toluene concentrations of 50 ppm (192 mg/m3). It can be concluded that long-term occupational exposure of toluene at concentrations below the occupational exposure limit of 50 ppm (192 mg/m3) has no effect on psychological performance.
Key value for chemical safety assessment
Effect on neurotoxicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Effect on neurotoxicity: via inhalation route
Link to relevant study records
- Endpoint:
- neurotoxicity: inhalation
- Remarks:
- other: regulatory review
- Type of information:
- other: Recommendation from the Scientific Committee on Occupational Exposure Limits
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Science position underpinning EU occupational exposure limit for toluene
- Qualifier:
- no guideline required
- GLP compliance:
- no
- Species:
- other: human
- Route of administration:
- inhalation: vapour
- Dose descriptor:
- other: 8 hr IOELV
- Effect level:
- 50 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: SCOEL concluded there was a great deal of human data demonstrating no reliable evidence of neurological effects at or below 50 ppm (192 mg/m3), hence 50 ppm was an appropriate level for an 8 hr TWA
- Remarks on result:
- other:
- Executive summary:
SCOEL noted that toluene exposures in the range 90-150 ppm (345-575 mg/m3) for several hours lead to decrements in neurological test results although some of the findings were difficult to interpret due to uncertainties regarding the relationship between the effects monitored and contemporary / past levels of exposure. However the availability of a great deal of human data indicated no reliable evidence of effects at or below toluene concentrations of 50 ppm (192 mg/m3). SCOEL therefore concluded that 50 ppm (8 hour TWA) was an appropriate level for an IOELV.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEC
- 222 mg/m³
- Species:
- other: human
- Quality of whole database:
- The available data provide information that is adequate for the purpose of hazard assessment
Effect on neurotoxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Non-human information
Repeated dose inhalation studies in rats have shown that toluene may cause a possibly transient reduction in the volume of hippocampal structures during postnatal development, neuron loss in the regio inferior of the hippocampus, reduction in the weight of the hippocampus, transient cognitive impairment in Morris maze, and changes in neurotransmitters and other neurochemical parameters. However, weaknesses in study design (i.e. only one sex evaluated, lack of dose response information, non-standard methods, lack of GLP) hinder any definitive conclusions on reliable NOAEC and LOAEC levels. More recent studies (Beasley et al., 2010) showed very limited evidence for persistent effects of repeated inhaled toluene exposure on cognitive function in rats. Consequently human data will be used for DNEL determination.
Human information
Acute exposures to toluene have been shown to produce neurological effects such as sleepiness, ataxia, confusion and neurobehavioural and neuropsychological effects. There are data from human toluene abusers that serious neurological effects such as tremor, ataxia, and memory impairment may occur with repeated extremely high level exposures. Several occupational exposure studies have also reported neurological effects as a consequence of occupational exposures although accurate data characterising exposures and hence allowing determination of NOAEC are generally lacking. The recent study by Seeber et al (2004) is considered to be the key study for risk characterisation. In that investigation, employees (total of 192) from 14 magazine rotary printing plants were classified into groups of "high" (printing area) vs "low" (end-processing) and "short" vs "long" exposure. Attention (symbol digit substitution, switching attention, simple reaction), memory (digit span forward and backwards, immediate and delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board) were measured as dependent variables. There was no evidence that long-term exposure to toluene at 59 ppm for 21 years had any effects on cognitive function. Evidence for psychological performance effects due to long-term toluene exposure below 50 ppm could not be proved. A human NOAEC was not determined and the LOAEC was considered to be above 59 ppm (222 mg/m3).
SCOEL noted that toluene exposures in the range 90-150 ppm (345-575 mg/m3) for several hours lead to decrements in neurological test results although some of the findings were difficult to interpret due to uncertainties regarding the relationship between the effects monitored and contemporary / past levels of exposure. However the availability of a great deal of human data indicated no reliable evidence of neurological effects at or below toluene concentrations of 50 ppm (192 mg/m3).
Justification for selection of effect on neurotoxicity via
inhalation route endpoint:
Studies on human toluene abusers have shown that serious
neurological effects (tremor, ataxia, memory impairment) may occur
following repeated extremely high level exposures, however no comparable
deficits were present in workers exposed to average toluene levels of 59
ppm for an average of 21 years. A human NOAEC was not determined for
this occupational population, however the long-term LOAEC was considered
to be above 59 ppm (222 mg/m3)
Justification for classification or non-classification
After repeated dose exposure, toluene causes a number of adverse neurological effects including neuron loss in the central nervous system of animals and neuropsychological effects in humans. Consequently, toluene is classified as Category 2 (H373), according to GHS / CLP.
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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