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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: other routes
Administrative data
- Endpoint:
- sub-chronic toxicity: other route
- Adequacy of study:
- supporting study
- Study period:
- 1991
- 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:
- Possible Involvement of 1,2-Diacetylbenzene in Diethylbenzene-Induced Neuropathy in Rats
- Author:
- Gagnaire, F., Ensminger, A., Marignac, B., and De Ceaurriz, J.
- Year:
- 1 991
- Bibliographic source:
- Journal Appl. Tox. 11: 261-268.
Materials and methods
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 1,2-diacetylbenzene
- IUPAC Name:
- 1,2-diacetylbenzene
- Details on test material:
- IUCLID4 Test substance: A01-03:1,2-Diacetylbenzene (98%) and diethylether (uvasol)
1,2-Diacetylbenzene [DAB] (98%) and diethylether (uvasol) were obtained from Merck-Schuchardt, Darmstadt, Germany.
1,2-Diethylbenzene (95%) was supplied by Aldrich, Steinheim, Germany. Gas chromatography-mass spectrometry showed that 1,2-DEB was free from 1,2-DAB.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
Administration / exposure
- Route of administration:
- other: ip and oral
- Details on exposure:
- Experiment A
In experiment A, 34 rats were assigned to two treatment groups (12 rats each) and one control group (10 rats). Treated groups were given intraperitoneally either 10 mg/kg 1,2-diacetylbenzene(DAB), 4 days per week for 11 weeks, or 20 mg/kg 1,2-DAB, 4 days per week for 6 weeks. Controls received vehicle (a mixture of saline and 2% acetone) only.
Experiment B
In experiment B, four rats were administered orally 165 mg/kg 1,2-DEB in olive oil, on four consecutive days. Controls received vehicle (olive oil) only. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 6 or 11 weeks
Experiment A
In experiment A, 34 rats were assigned to two treatment groups (12 rats each) and one control group (10 rats). Treated groups were given intraperitoneally either 10 mg/kg 1,2-diacetylbenzene(DAB), 4 days per week for 11 weeks, or 20 mg/kg 1,2-DAB, 4 days per week for 6 weeks. Controls received vehicle (a mixture of saline and 2% acetone) only.
Experiment B
In experiment B, four rats were administered orally 165 mg/kg 1,2-DEB in olive oil, on four consecutive days. Controls received vehicle (olive oil) only. - Frequency of treatment:
- 4 days/week
Experiment A
In experiment A, 34 rats were assigned to two treatment groups (12 rats each) and one control group (10 rats). Treated groups were given intraperitoneally either 10 mg/kg 1,2-diacetylbenzene(DAB), 4 days per week for 11 weeks, or 20 mg/kg 1,2-DAB, 4 days per week for 6 weeks. Controls received vehicle (a mixture of saline and 2% acetone) only.
Experiment B
In experiment B, four rats were administered orally 165 mg/kg 1,2-DEB in olive oil, on four consecutive days. Controls received vehicle (olive oil) only.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
i.p. - 10 or 20 mg/kg 1,2-DAB; orally - 165 mg/kg
- No. of animals per sex per dose:
- Experiment A
In experiment A, 34 rats were assigned to two treatment groups (12 rats each) and one control group (10 rats). Treated groups were given intraperitoneally either 10 mg/kg 1,2-diacetylbenzene(DAB), 4 days per week for 11 weeks, or 20 mg/kg 1,2-DAB, 4 days per week for 6 weeks. Controls received vehicle (a mixture of saline and 2% acetone) only.
Experiment B
In experiment B, four rats were administered orally 165 mg/kg 1,2-DEB in olive oil, on four consecutive days. Controls received vehicle (olive oil) only. - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: 5 weeks
Examinations
- Observations and examinations performed and frequency:
- Neurophysiological measurements
Neurophysiological measurements were conducted in a room maintained at 25 - 26°C. The motor conduction velocity (MCV) and sensory conduction velocity (SCV) of the tail nerve and the amplitude of the sensory action potential (ASAP) were measured.
Experiment A
Rats were observed daily, weighed weekly and subjected to electrophysiological measurements every 2 weeks during the course of treatment and through the recovery period of 5 weeks. After the recovery period, they were sacrificed for post-mortem examination.
Experiment B
Urine from each animal was collected for 24 h after the end of the treatment. The 24-h urine samples then were pooled and stored at -20°C for further gas chromatography-mass spectrometry analysis.
- Statistics:
- Differences in mean body weight, MCV, SCV and ASAP between experimental and control groups were analysed using Students's t-test for independent data. Differences were considered to be statistically significant at the P<0.05 level.
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
- Behaviour (functional findings):
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Details on results:
- Rats treated with 10 or 20 mg/kg 1,2-DAB developed hyperactivity after each injection, with stereotyped behavour (sniffing and rummaging in the sawdust). They exhibited a blue discoloration of skin and urine. Hair was also discolored at the i.p. injection point. A general discoloration of skin appeared between the 3rd and 5th days of treatment.
Significant reduction in weight gain was observed from the 1st week of treatment in the group treated with 20 mg/kg. In the high-dose group, two animals died during the 3rd week of treatment; there were nine, eight and seven surviving rats at weeks 4, 5, and 6, respectively. One more rat died in the 2nd week of the recovery period. No animal died in the low-dose group. One rat died in the control group during the 2nd week due to a bad injection. Rats treated with 20 mg/kg 1,2-DAB developed severe weakness in hind limbs and disturbance in gait from the 4th week of the experiment. At the 5th week of treatment, four rats showed evidence of foot drop and muscle atrophy. The three other rats in this group showed an awkward gait. Soon the hind limbs became so weak that animals crawled. At the 6th week, rats developed complete paralysis of the hind limbs and treatment was stopped because of the excessive poor condition. During the first week of the excessively poor condition, they were fed by oral gavage with a nutritive solution.
In the low-dose group, rats exhibited decreased weight gain. Weakness developed after 6 weeks of treatment, but no paralysis was seen.
During the recovery period, the 1,2-DAB treated rats regained weight. Two weeks after the last treatment, the high-dose treated rats became more mobile although they dragged their hind limbs. On the 5th week they were able to stand up but had an awkard gait. Low dose treated rats, except for body weight, were indistinguishable from controls at the end of the recovery period.
At necropsy, internal organs appeared bluish and brain and nerves showed a blue-grey color.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The findings in this study support the hypothesis that the formation of 1,2-diacetylbenzene derivatives contributes to the neurotoxicity of 1,2-DEB.
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