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EC number: 202-849-4 | CAS number: 100-41-4
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline dose range finding study
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Reference Type:
- publication
- Title:
- Ethylbenzene: 4- and 13-week rat oral toxicity
- Author:
- Mellert, W., Deckardt, K., Kaufmann, W., van Ravenzwaay, B.
- Year:
- 2 007
- Bibliographic source:
- Arch. Toxicol. 81:361-370
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- none
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Ethylbenzene
- EC Number:
- 202-849-4
- EC Name:
- Ethylbenzene
- Cas Number:
- 100-41-4
- Molecular formula:
- C8H10
- IUPAC Name:
- ethylbenzene
- Details on test material:
- - Name of test material (as cited in study report): Ethylbenzene
- Physical state: liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS
- Species/strain: Rat Wistar (CrlGlxBrlHan:WI) (Charles River, Sulzfeld, Germany)
- Age at study initiation: 42 days +- 1 day
- Weight at study initiation:
- Number of animals: 5M+5F treated and controls.
- Housing: individually housed in suspended stainless-steel wire mesh cages
- Diet: ground Kliba maintenance diet mouse/rat (Provimi Kliba SA, Kaiseraugst, Switzerland), access ad libitum except during fasting period
- Water: access ad libitum expect during fasting period
- Environment: Temperature averaged 20-24 ºC; Relative Humidity averaged 30-70%
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- ADMINISTRATION / EXPOSURE
- Duration of test/exposure: 28 days
- Type of exposure: gavage
- Post exposure period: none
- Vehicle: cornoil
- Concentration in vehicle: 0, 0.75, 2.5 and 7.5 g/100ml.
- Total volume applied: 5 ml/kg
- Doses: 0, 37.5, 125 and 375 mg/kg administered twice daily to give the total daily doses of 75, 250 and 750 mg/kg/day bw. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Doses: 0, 37.5, 125 and 375 mg/kg administered twice daily to give the total daily doses of 75, 250 and 750 mg/kg/day bw
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- twice daily 8 hours apart
Doses / concentrations
- Remarks:
- Doses / Concentrations:
75, 250 and 750 mg/kg bw/day
Basis:
other: nominal concentration
- No. of animals per sex per dose:
- 5/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment: Random
- Post-exposure recovery period in satellite groups: None - Positive control:
- Not applicable
Examinations
- Observations and examinations performed and frequency:
- - Clinical signs: twice daily weekdays, once a day a weekends, plus daily after each treatment.
- Mortality: as above
- Body weight: Prior to treatment, treatment day 0 an weekly thereafter
- Food consumption: Weekly
- Water consumption: Weekly (over 4 days)
- Ophthalmoscopic examination: no
- Haematology: leucocytes, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, platelets, differential blood count, reticulocytes.
- Biochemistry: ALT, AST, ALP, GGT, Na, K, Cl, inorganic phopsphate, Ca, urea, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, Mg
- Urinalysis: Day 26 - Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: liver, kidneys, adrenals, testes, epididymes, ovaries, uterus, spleen, brain, heart, thymus
- Macroscopic: major organs, all gross lesions
- Microscopic: a range of major organs were fixed, liver and kidneys were examined microscopically. In addition to H&E staining the kidneys were stained with Mallory-Heidenhein stain to visualise hyaline droplet nephropathy. - Other examinations:
- None
- Statistics:
- Analysis of body weight, body weight change, food and water consumption, and food efficiency was preformed by comparing treatment group results with the control group using Dunnett's test (two-sided) for the hypothesis of equal means. Clinical pathology except reticulocytes and differential blood count and organ weights were evaluated by nonparametric one-way analysis using two-sided Kruskal-Wallis test in combination with Wilcoxon test if resulting p value was <= 0.05. For urinalysis except volume, colour, specific gravity and turbidity a pair-wise comparison using Fischers exact test was used.
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
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality and time to death: No deaths.
- Clinical signs: Salivation was observed in high and mid dose rats of both sexes.
- Body weight gain: Significantly reduced in high dose males at day 7 (17.6% below control value)
- Food consumption: No treatment related changes.
- Food efficiency: Significant decrease in high dose males and females on day 28.
- Water consumption: Increased in high and mid dose rats of both sexes, attaining statistical significance over several time periods.
See the attachment-1 for details of water consumption.
- Clinical chemistry: Slight increase in serum ALT in high dose animals of both sexes. Increased bilirubin and cholesterol in high dose animals of each sex. Increase in bilirubin not statistically significant in males. Increased serum urea was observed in high dose males and reduced sodium levels in high dose females
- Hematology: No treatment related changes in hematological and clotting parameters.
- Urinalysis: Increased incidence of granular and epithelial cell casts in top and mid dose males together with an increased number of degenerated transitional epithelial cells in high dose males.
- Organ weights: Increased absolute and relative liver weights in both sexes at the high and mid dose levels. Increased relative kidney weights in top and mid dose males.
See the attachment-1 for details of and organ weight data.
Significant differences in epididymal and spleen weights were regarded as incidental.
- Gross pathology: No treatment related changes.
- Histopathology: Liver-centrilobular hepatocellular hypertrophy in top dose males and females and mid dose males. Hyaline droplet nephropathy (HDN) in the male kidney at all dose levels. Incidence: At top and mid dose levels HDN occurs in all males’ vs. 1 in control and at 75 mg/kg the incidence was 3 males treated vs. 1 in controls.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 75 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL in this range finding study was 75 mg/kg/day based on increased liver weight and hepatocellular hypertrophy at higher dose levels.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
None
Applicant's summary and conclusion
- Conclusions:
- The NOAEL in this range finding study was 75 mg/kg based on increased liver weight and hepatocellular hypertrophy at higher dose levels. There was evidence of male rat specific nephropathy in high and mid dose groups which is not considered of relevance to man.
- Executive summary:
Four matched groups of five male Wistar rats each were given by intubation repeated oral doses, 0,75, 250 and 750 mg/kg/day body weight of ethyl benzene in corn oil solutions for a period of 28 days twice daily 8 hours apart. Rats were housed individually in stainless steel cages with wire bottoms. Ground Kliba maintenance diet rat (Provimi Kliba SA,) was supplied to rats and tap water supplied to rats adlibitum except during fasting period.
Monitored for effects included clinical observations, body weights, opthalmoscopy, food consumption, hematology, clinical chemistry, urinalysis, necropsy, organ weights, gross pathology and histopathology.
There were no mortalities were observed during 28 day administration period. Salivation was observed in high and mid dose rats of both sexes. In body weights significantly reduction in high dose males at day 7 (17.6% below control value). There were no treatment related changes in feed consumption.
Food efficiency shows significant decrease in high dose males and females on day 28. Water consumption is increased in high and mid dose rats of both sexes, attaining statistical significance over several time periods.
No treatment related changes in hematological and clotting parameters. Slight increase in serum ALT in high dose animals of both sexes. Increased bilirubin and cholesterol in high dose animals of each sex. Increase in bilirubin not statistically significant in males. Increased serum urea was observed in high dose males and reduced sodium levels in high dose females.Urinalysis shows increased incidence of granular and epithelial cell casts in top and mid dose males together with an increased number of degenerated transitional epithelial cells in high dose males.
Increased absolute and relative liver weights in both sexes at the high and mid dose levels...Increased relative kidney weights in top and mid dose males. Significant differences in epididymal and spleen weights were regarded as incidental
There were no treatment-related gross pathology findings in either sex of rat. Liver-centrilobular hepatocellular hypertrophy in top dose males and females and mid dose males. Hyaline droplet nephropathy (HDN) in the male kidney at all dose levels. Incidence: At top and mid dose levels HDN occurs in all males’ vs. 1 in control and at 75 mg/kg the incidence was 3 males treated vs. 1 in controls.The NOAEL in this range finding study was 75 mg/kg based on increased liver weight and hepatocellular hypertrophy at higher dose levels. There was evidence of male rat specific nephropathy in high and mid dose groups which is not considered of relevance to man.
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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