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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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1999
- 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:
- Toxicokinetics of 1,2-diethylbenzene in Male Sprague-Dawley Rats-Part 1: Excretion and Metabolism of [14C]1,2-Diethylbenzene
- Author:
- Payan, J-P., Beydon, D., Cossec, B., Ensminger, A., Fabry, J-P., and Ferrari, E.
- Year:
- 1 999
- Bibliographic source:
- Drug Metabolism and Disposition Vol. 27, No. 12 pp 1470-1478.
Materials and methods
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- In a series of studies, 14C-labelled 1,2-DEB was administered by various routes (oral gavage, i.v., etc.) to male
Sprague-Dawley adult rats, and radioactivity was measured in excreta (feces, urine), exhaled air, and in some cases with cannulated animals, bile, collected over several days following dosing, to determine the disposition of 1,2-DEB. - GLP compliance:
- not specified
Test material
- Reference substance name:
- o-diethylbenzene
- EC Number:
- 205-170-1
- EC Name:
- o-diethylbenzene
- Cas Number:
- 135-01-3
- Molecular formula:
- C10H14
- IUPAC Name:
- 1.2-diethylbenzene
- Details on test material:
- IUCLID4 Test substance: other TS: 1,2-Diethylbenzene
1,2-Diethylbenzene
Radiolabeled 1,2-diethyl [U-14C]benzene. Radiochemical purity exceeding 95%.
Unlabelled 1,2-DEB (97%) pure
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
Administration / exposure
- Route of administration:
- other: oral gavage and intravenous
- Vehicle:
- other: oral gavage:T52-003:mineral oil; i.v.: water
- Details on exposure:
- 14C-radiolabelled 1,2-DEB was administered orally by gastric intubation (2 ml/kg) in mineral oil or i.v.(1 ml/kg; 50% aqueous suspension of polyethylene glycol 600 into the dorsal vein of the penis of lightly anesthetized rats, and animals were immediately place in individual metabolism cages for collection of excreta and exhaled air.
- Duration and frequency of treatment / exposure:
- Noncannulated Rats: Groups of 6 rats were given a single i.v. administration of [14C]1,2-DEB at 1 mg/kg or a single oral administration of [14C]1,2-DEB at 1 or 100 mg/kg. One group of 6 rats was given 100 mg/kg of [14C]1,2-DEB orally four times over 5 days (4 x 100 mg/kg).
Excretion of Radioactivity by Bile Duct-Cannulated Rats: One day before [14C]1,2-DEB administration, the common bileduct of 3 groups of 6-8 rats was cannulated near the hilum of the liver under pentobarbital (40 mg/kp i.p.) anesthesia. Except during i.v. injection of 1,2-DEB, the rats were not anesthetized or restrained at any time during the experiment. [14C]1,2-DEB solution was administered i.v. (1 mg/kg) or orally (1 or 100 mg/kg) 1 day after the surgical procedure.
Excreta of Radioactivity by Billiary Recycling Rats: Five pairs of rats were used as bile duct duodenum cannula-linked rats to determine the extent of enterohepatic recirculation.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Males: 1 or 100 mg/kg (2 ml/kg)
Noncannulated Rats: Groups of 6 rats were given a single i.v. administration of [14C]1,2-DEB at 1 mg/kg or a single oral administration of [14C]1,2-DEB at 1 or 100 mg/kg. One group of 6 rats was given 100 mg/kg of [14C]1,2-DEB orally four times over 5 days (4 x 100 mg/kg).
Excretion of Radioactivity by Bile Duct-Cannulated Rats: One day before [14C]1,2-DEB administration, the common bileduct of 3 groups of 6-8 rats was cannulated near the hilum of the liver under pentobarbital (40 mg/kp i.p.) anesthesia. Except during i.v. injection of 1,2-DEB, the rats were not anesthetized or restrained at any time during the experiment. [14C]1,2-DEB solution was administered i.v. (1 mg/kg) or orally (1 or 100 mg/kg) 1 day after the surgical procedure.
Excreta of Radioactivity by Billiary Recycling Rats: Five pairs of rats were used as bile duct duodenum cannula-linked rats to determine the extent of enterohepatic recirculation.
- No. of animals per sex per dose / concentration:
- Noncannulated Rats: Groups of 6 rats were given a single i.v. administration of [14C]1,2-DEB at 1 mg/kg or a single oral administration of [14C]1,2-DEB at 1 or 100 mg/kg. One group of 6 rats was given 100 mg/kg of [14C]1,2-DEB orally four times over 5 days (4 x 100 mg/kg).
Excretion of Radioactivity by Bile Duct-Cannulated Rats: One day before [14C]1,2-DEB administration, the common bileduct of 3 groups of 6-8 rats was cannulated near the hilum of the liver under pentobarbital (40 mg/kp i.p.) anesthesia. Except during i.v. injection of 1,2-DEB, the rats were not anesthetized or restrained at any time during the experiment. [14C]1,2-DEB solution was administered i.v. (1 mg/kg) or orally (1 or 100 mg/kg) 1 day after the surgical procedure.
Excreta of Radioactivity by Billiary Recycling Rats: Five pairs of rats were used as bile duct duodenum cannula-linked rats to determine the extent of enterohepatic recirculation. - Control animals:
- not specified
- Details on study design:
- In a series of studies, 14C-labelled 1,2-DEB was administered by various routes (oral gavage, i.v., etc.) to male Sprague-Dawley adult rats, and radioactivity was measured in excreta (feces, urine), exhaled air, and in some cases with cannulated animals, bile, collected over several days following dosing, to determine the disposition of 1,2-DEB.
Disposition of radiolabelled 1,2-DEB: Noncannulated Rats: Groups of 6 rats were given a single i.v. administration of [14C]1,2-DEB at 1 mg/kg or a single oral administration of [14C]1,2-DEB at 1 or 100 mg/kg. Exhaled air (volatiles and CO2) was collected every 24 h for 72 h, and urine and feces every 24 h for 7 days. One group of 6 rats was given 100 mg/kg of [14C]1,2-DEB orally four times over 5 days (4 x 100 mg/kg). The excreta were
collected over 24-h intervals during repeated administration period, and for 7 days after the last administration. [14C]1,2-DEB or its volatile [14C] metabolites and 14CO2 were collected by drawing the exhaled air from the individual metabolism glass cage through a series of three activated charcoal traps and two traps containing 100 ml of Carbosorb. At the end of the collection period, animals were sacrificed by exsanguination under light ether anesthesia. The carcass was solubilized in 20% aqueous potassium hydroxide solution. Excreta and certain tissues were analyzed for radioactivity to determine disposition of 1,2-DEB.
Excretion of Radioactivity by Bile Duct-Cannulated Rats: One day before [14C]1,2-DEB administration, the common bileduct of 3 groups of 6-8 rats was cannulated near the hilum of the liver under pentobarbital (40 mg/kg i.p.) anesthesia. Except during i.v. injection of 1,2-DEB, the rats were not anesthetized or restrained at any time during the experiment. [14C]1,2-DEB solution was administered i.v. (1 mg/kg) or orally (1 or 100 mg/kg) 1 day after the surgical procedure. Excreta (urine and feces) were collected at 24 and 48 h after administration. Bile was collected each hour for the first 8 h, and at 8-24, 25, 26, 27, 28, 29, 30-47, and 48 h post-dosing in preweighed tubes. Bile and urine were collected at 4°C and samples were analyzed using HPLC.
Excreta of Radioactivity by Billiary Recycling Rats: Five pairs of rats were used as bile duct duodenum cannula-linked rats to determine the extent of enterohepatic recirculation. Bile from donor rats was collected for exactly 2 min each hour in weighed scintillation minivials during two periods 0-8 and 8-30 h after i.v. [14C]1,2-DEB administration (1 mg/kg) to donor rats. Bile from recipient rats was collected at 4°C in weighed tubes each hour during the two periods 0-8 and 8-30 h. The bile excreted during the night (8-24 h) was collected in one tube. Urine and feces were collected over 30 h. At the end of the experiment, animals were sacrificed by exsanguination under light anesthesia. Kidneys, liver, brain, and gastrointestinal tract were removed for radioactivity analysis. - Details on dosing and sampling:
- See study design above.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
Disposition of i.v. and oral administered 1,2-DEB (1 mg/kg bw) were very similar, with ~75% of dose recovered in urine and 15-17% in feces; exhaled air accounted for only 2-3% of administered dose, similar to remaining carcass. The 100 mg/kg bw dose demonstrated a slight shift in excretion pattern, with 65% eliminated via urine and 23% in feces; 4 doses of 100 mg/ke bw resulted in a similar pattern with 71% recovered in urine and 17% in feces.
Biliary excretion was a major elimination route, demonstrated by 52-64% of administered radioactivity recovered in bile for i.v. or oral administration of 1 or 100 mg/kg bw; about 10% of the orally administered dose was recovered from feces in bile-cannulated animals, indicating that it was not absorbed. Urinary elimination was 23-30% of administered dose for these routes, similar to the non-cannulated rats.
The data from the bile-duct cannulated animals demonstrated that 1,2-DEB is highly absorbed and mainly excreted via bile
and then reabsorbed for several cycles of enterohepatic recirculation, and finally is eliminated via urine.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Hydroxylation of the alpha carbon of the sidechain, leading to formation of ethylphenolethanol (EPE), appears to be the first step in metabolism of 1,2-DEB. Urinary metabolites were enantiomers of ß-glucuronide conjugates of ethylphenolethanol (EPE); the major fecal metabolite was EPE, with a small amount of unchanged parent 1,2-DEB. The two main [14C]1,2-DEB metabolites accounted for 57 and 79% of urinary and biliary radioactivity, respectively.
Applicant's summary and conclusion
- Conclusions:
- 1,2-DEB is highly absorbed following oral administration, and primarily excreted in the urine following oral or i.v. exposure to the male rat. This study showed that in vivo hydroxylation of 1,2-DEB yields two enantiomers, which are mainly excreted, after glucuronide conjugation in the urine (65-76%), with the remaining radiolabelled material excreted in the feces (15-23%) or exhaled air (3-5%). Rats fitted with biliary cannula demonstrated 52 to 64% of the administered doses (1 or 100 mg/kg) was initially excreted in bile. However, the biliary metabolites were extensively reabsorbed from the gut and ultimately excreted in urine after several cycles of enterohepatic recirculation.
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