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EC number: 246-874-9 | CAS number: 25340-17-4
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well-documented and acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Diethylbenzene-induced sensorimotor neuropathy in rats
- Author:
- Gagnaire, F., Marignac, B., and de Ceaurriz, J
- Year:
- 1 990
- Bibliographic source:
- J. Applied Toxicology 10(2): 105-112.
Materials and methods
- Principles of method if other than guideline:
- Method: similar to repeated dose oral study with focus on assessing neurotoxicity
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Diethylbenzene
- EC Number:
- 246-874-9
- EC Name:
- Diethylbenzene
- Cas Number:
- 25340-17-4
- Molecular formula:
- C10H14
- IUPAC Name:
- diethylbenzene
- Details on test material:
- IUCLID4 Test substance: other TS: as prescribed by 1.1-1.4 and individual isomers
Diethylbenzene (DEB) mixture (approx. 7% 1,2-diethylbenzene, 58% 1,3-diethylbenzene, and 35% 1,4-diethylbenzene)
Purity of isomers:95% 1,2-diethylbenzene, 99% 1,3-diethylbenzene, 96% 1,4-diethylbenzene
Supplied by Aldrich Chemie, Steinhein, FRG.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- not specified
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: olive oil
- Details on oral exposure:
- 500 or 750 mg/kg (in olive oil) for DEB mixture; 100 mg/kg for 1,2-diethylbenzene; and 500 mg/kg for 1,3- and 1,4-diethybenzene
Control group and treatment: Concurrent, given olive oil vehicle - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 8 weeks (1,2-DEB isomers) and 10 weeks (1,3-DEB; 1,4-DEB mixed isomers)
- Frequency of treatment:
- 5 days/week (mixture, 1,3- or 1,4-diethylbenzene isomers); 4 days/week (1,2-diethylbenzene)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
500 or 750 mg/kg (in olive oil) for DEB mixture
Basis:
other: nominal
- Remarks:
- Doses / Concentrations:
100 mg/kg for 1,2-diethylbenzene
Basis:
other: nominal
- Remarks:
- Doses / Concentrations:
500 mg/kg for 1,3- and 1,4-diethybenzene
Basis:
other: nominal
- No. of animals per sex per dose:
- There were 12 rats/group.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: Postexposure observation period: 8 weeks (isomer study only)
Examinations
- Observations and examinations performed and frequency:
- Rats were subjected to neurophysiological measurements every week during the treatment period. The survivors were kept for observation and neurophysiological measurements during the post-exposure period. The motor conduction velocity (MCV) and sensory conduction velocity (SCV) of the tail nerve and the amplitude of the sensory action potential (ASAP) were adopted as parameters for testing peripheral nerve function in rats.
- Statistics:
- Statistical methods: Differences in mean body weight, motor and sensory conduction velocities, and amplitude of the sensory action potential between experimental and control groups were analyzed using Student's t-test for independent data. Mean electrophysiological deficits in the tail nerve were also analyzed, as a function of the length of treatment, by least-squares regression.
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
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, treatment-related
- Details on results:
- Diethylbenzene mixture
Rats given diethylbenzene (DEB) mixture with either 500 or 750 mg/kg exhibited a blue discoloration of the skin and urine as soon as the 3rd day of treatment. These doses exceeded the maximum tolerated dose (MTD). A significant reduction in weight gain was observed from the first week of treatment in the group treated with 750 mg/kg. Two animals died in the 750 mg/kg dose group during the first week of treatment. Two rats died in the 500 mg/kg group during the 4th and 7th weeks of treatment. No animals died in the control group. Rats in the DEB-dosed groups developed severe weakness in hind limbs and disturbances in gait from the 4th week of treatment. This weakness got worse in the following weeks, resulting in a complete paralysis of the hind limbs for some rats. There was a time-dependent decrease in MCV, SCV, and ASAP.
Diethylbenzene isomers
1,3- and 1,4-Diethylbenzene-treated rats (500 mg/kg) did not display any signs of neurotoxicity or any other signs of systemic toxicity.
Rats given 1,2-diethylbenzene 100 mg/kg developed the same symptoms (decreased body weight, blue discoloration of skin and urine, weakness of hind limbs, paralysis) as those described for the diethylbenzene mixture. The MTD was exceeded. One rat died in the first week of treatment and another died in the 5th week of treatment. During the recovery period, the 1,2-diethylbenzene treated rats regained weight, became more mobile but presented trailing hind limbs, when attempting to walk. On the 4th week of recovery, all animals treated with 1,2-diethylbenzene succeeded in standing up.
A time-dependent decrease in MCV, SCV, and ASAP was observed in animals dosed with 1,2-diethylbenzene, but no changes were seen with 1,3- or 1,4-diethylbenzene.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- other: DEB mixture
- Dose descriptor:
- LOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- other: 1,2-diethylbenzene
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- other: 1,3-diethylbenzene
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- other: 1,4-diethylbenzene
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Repeated oral exposure to diethylbenzene mixture and 1,2-diethylbenzene at doses exceeding the MTD resulted in some lethality and produced adverse effects on the peripheral nervous system whereas 1,3- and 1,4-diethylbenzene did not cause any systemic or neurotoxic effects at doses of 500 mg/kg.
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