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EC number: 203-266-8 | CAS number: 105-06-6
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from secondary source
Data source
Reference
- Reference Type:
- secondary source
- Title:
- The Developmental toxicity study of test material
- Author:
- HPVIS
- Year:
- 2 018
- Bibliographic source:
- HPVIS ,2018
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Developmental toxicity study of test material was performed on Charles River COBS CD rats.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 4-ethyltoluene
- EC Number:
- 210-761-2
- EC Name:
- 4-ethyltoluene
- Cas Number:
- 622-96-8
- Molecular formula:
- C9H12
- IUPAC Name:
- 1-ethyl-4-methylbenzene
- Details on test material:
- - Name of test material (as cited in study report):1-ethyl-4-methylbenzene- Molecular formula:C9H12- Molecular weight :120.194 g/mol - Substance type:Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- Details on test animals and env. conditionsTEST ANIMALS- Source:- Age at study initiation: 12 weeks old- Acclimation period: 13 days
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Remarks:
- Mazola corn oil
- Details on exposure:
- Details on exposurePREPARATION OF DOSING SOLUTIONS:The appropriate amount of test material was added to 50 ml of the vehicle, Mazola corn oil, and mixed by hand to ensure a homogeneous mixture. The test substance was prepared fresh dailyDIET PREPARATION- Rate of preparation of diet (frequency):No data available- Mixing appropriate amounts with (Type of food )- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): test material dissolved in , Mazola corn oil- Concentration in vehicle: 0, 25, 100, and 200 mg/kg/day. - Amount of vehicle (if gavage): 5 ml/kg- Lot/batch no. (if required): No data available- Purity: No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: [artificial insemination / purchased timed pregnant / cohoused] - If cohoused: - M/F ratio per cage: 1::1 - Length of cohabitation: - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. - Further matings after two unsuccessful attempts: [no / yes (explain)] - Verification of same strain and source of both sexes: [yes / no (explain)] - Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:The day that evidence of mating was detected was designated day 0 of gestation - Any other deviations from standard protocol:
- Duration of treatment / exposure:
- 20 days ( from day 6 through day 19 )
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
Doses / concentrations
- Remarks:
- 0, 25, 100, 200mg/kg bw/day
- No. of animals per sex per dose:
- Total:1000 mg/kg bw/day:2525mg/kg bw/day:25100mg/kg bw/day:25200 mg/kg bw/day:25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
Examinations
- Maternal examinations:
- Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: They were observed daily for mortality and clinical signs of toxicityBODY WEIGHT: YesTime schedule for examinations: Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 16, and 20.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly. Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: : No data availableCompound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations:
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes Examinations included: - Gravid uterus weight: Yes - Number of corpora lutea: Yes - Number of implantations: Yes - Number of early resorptions: Yes - Number of late resorptions: Yes - Other:
- Fetal examinations:
- - External examinations: Yes:[all per litter - Soft tissue examinations: Yes: half per litter - Skeletal examinations: Yes: half per litter - Head examinations: No data
- Statistics:
- All statistical analyses compared the treatment groups to the control group with the level of significance at p<0.0l and p<0.05. The male to female fetal sex distribution and the number of litters with malformations were compared using the Chi-square test criterion with Yates' correction for 2 x 2 contingency tables and/or Fisher's exact probability tests to judge significance of differences. The number of early resorptions and postimplantation losses were compared by the Mann-Whitney U-test. The mean number of viable fetuses, total implantations, corpora lutea, and mean fetal body weights were compared by ANOVA, Bartlett's test for homogeneity of variances and Dunnett's multiple comparison tables to judge significance of differences.
- Indices:
- No data available
- Historical control data:
- No data available
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Hair loss (primarily of the limbs and abdomen) occurred with similar frequency in all treatment and control groups at various intervals throughout the treatment period.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- Survival was 100% in the control and all treated groups.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no biologically meaningful differences in mean maternal body weight gain throughout the entire gestation period in any treated group when compared to controls
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A slight increase in mean postimplantation loss was observed in the 25 mg/kg/day group when compared to controls. However, no dose-related trend was evident and this response was considered to be due to a random occurrence. Mean postimplantation loss number for 0, 25, 100, and 200 mg/kg/day was 13, 29, 19, and 19, respectively.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
- Other effects:
- not specified
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- dead fetuses
- early or late resorptions
- effects on pregnancy duration
- maternal abnormalities
- mortality
- number of abortions
- pre and post implantation loss
- total litter losses by resorption
- Remarks on result:
- other: overall no toxic effects observed
Maternal abnormalities
- Abnormalities:
- not specified
- Localisation:
- not specified
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): no effects observed in mean fetal body weight in any of the treated groups when compared to the control group. - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- no effects observed in the fetal sex distribution in any of the treated groups when compared to the control group
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- There were no biologically meaningful or statistically significant differences in the number of litters with malformations in any of the treated groups compared to controls. Microphthalmia and thoracoschisis each occurred in one fetus in one litter in the 25 and 200 mg/kg/day groups, respectively. Scoliosis was observed in one litter from both of the 200 mg/kg/day and control groups. The number of litters (and fetuses) with genetic and developmental variations in the treated groups was comparable to controls.
- Visceral malformations:
- no effects observed
- Other effects:
- not specified
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- changes in postnatal survival
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: No effects on developmental parameters
Fetal abnormalities
- Abnormalities:
- not specified
- Localisation:
- other: not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- No Observed Adverse Effect Level (NOAEL) for developmental was considered to be 200mg/kg/day. When female CD 1rats were treated with test material orally.
- Executive summary:
The developmental toxicity study of test material was performed inPregnant Charles River COBS CD rats. Dosage levels of 25, 100, and 200 mg/kg/day were administered orally by gavage as a single daily dose on days 6 through 19 of gestation at a constant volume of 5 ml/kg.The control group received the vehicle only, Mazola corn oil, on a comparable regimen.One female and one male rat of the same strain and source were placed together for mating. The occurrence of copulation was determined by daily inspection for a copulatory plug. The day that evidenice of mating was detected was designated day 0 of gestation and the female was returned to an individual cage.Dams were observed daily for mortality and clinical signs of toxicity .Individual maternal body weights were recorded on gestation days 0, 6, 9, 12, 16, and 20. A Cesarean section was performed on each female on gestation day 20 immediately following sacrifice by carbon dioxide inhalation. The uterus was excised and weighed prior to removal of the fetuses. The number and location of viable and nonviable fetuses, early and late resorptions, total implantations and corpora lutea were recorded. The thoracic and abdominal cavities and organs of the dams were examined for grossly evident morphological changes and the carcasses discarded. Uteri from females that appeared nongravid were opened and placed in 10% ammonium sulfide solution for confirmation of pregnancy status. All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was externally sexed and individually numbered and tagged for identification. Approximately one-half of the fetuses were placed in Bouin's fixative for subsequent visceral examination by razor blade sectioning. The remaining one-half of the fetuses were fixed in alcohol, macerated in potassium hydroxide, and stained with Alizarin Red S for subsequent skeletal examination.
There were no biologically meaningful differences in the appearance or behavior of the rats in the 25, 100, or 200 mg/kg/day groups when compared to controls. Hair loss (primarily of the limbs and abdomen) occurred with similar frequency in all treatment and control groups at various intervals throughout the treatment period. Survival was 100% in the control and all treated groups. There were no biologically meaningful differences in mean maternal body weight gain throughout the entire gestation period in any treated group when compared to controls. There were no biologically meaningful or statistically significant differences in the mean numbers of corpora lutea, total implantations, early resorptions, postimplantation loss, viable fetuses, the fetal sex distribution or mean fetal body weight in any of the treated groups when compared to the control group. Non viables and late resorptions were not observed in the control or in any of the treated groups. A slight increase in mean postimplantation loss was observed in the 25 mg/kg/day group when compared to controls. However, no dose-related trend was evident and this response was considered to be due to a random occurrence. Mean postimplantation loss number for 0, 25, 100, and 200 mg/kg/day was 13, 29, 19, and 19, respectively.
There were no biologically meaningful or statistically significant differences in the number of litters with malformations in any of the treated groups compared to controls. Microphthalmia and thoracoschisis each occurred in one fetus in one litter in the 25 and 200 mg/kg/day groups, respectively. Scoliosis was observed in one litter from both of the 200 mg/kg/day and control groups. The number of litters (and fetuses) with genetic and developmental variations in the treated groups was comparable to controls. Hence No Observed Adverse Effect Level (NOAEL) for developmental was considered to be 200mg/kg/day.When femaleCD 1rats were treated with test materialorally.
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