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EC number: 239-816-9 | CAS number: 15721-78-5
- 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:
- key study
- Study period:
- 08 June 2015 to February 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- see results
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine
- EC Number:
- 239-816-9
- EC Name:
- Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine
- Cas Number:
- 15721-78-5
- Molecular formula:
- C28H43N
- IUPAC Name:
- 4-(2,4,4-trimethylpentan-2-yl)-N-[4-(2,4,4-trimethylpentan-2-yl)phenyl]aniline
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Batch No.: not specified
- Purity: not specified
Constituent 1
- Specific details on test material used for the study:
- - CAS RN: CAS RN 15721-78-5
- Physical State/Appearance: Off white powder
- Purity: 93.2%
- Batch Number: HY14KSV07
- Date Received: 11 October 2015
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- - Ninety-six time-mated female Sprague-Dawley Crl:CD (SD) IGS BR strain rats were used
- Animals were delivered in one batch prior to Day 3 of gestation
- The day that positive evidence of mating was observed was designated Day 0 of gestation
- At the start of treatment, the females weighed 205 to 280g
- Housed individually
- Solid-floor polypropylene cages with stainless steel mesh lids furnished with softwood flakes color coded cage cards were prepared with details of test item, study number, dose level, sex, number of animals, route of administration and Study Director responsible for the study
- Free access to food and water
- Pelleted diet rodent feed (Rodent 2018C)
- Mains drinking water was supplied from polycarbonate bottles attached to the cage
- Environmental enrichment - wooden chew blocks and cardboard fun tunnels
- The animals were housed in a single air-conditioned room within the laboratory
- Air exchange was at least fifteen air changes per hour
- 12 hours continuous light, 12 hours darkness
- Target ranges for temperature and relative humidity were 22 ± 3 ºC and 50 ± 20% respectively. Short term deviations from these targets were considered not to have affected the purpose or integrity of the study; see deviations from Study Plan.
- Animals were randomly allocated to treatment groups based on stratified body weight
- Animals were identified by an ear punching system
Schedule
Experimental Starting Date: 08 June 2015
Experimental Completion Date: 16 July 2015
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- The test item was prepared at the appropriate concentrations as a suspension in Arachis oil BP.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability and homogeneity of the test item formulations were determined as part of another study and showed the formulations to be stable for up to twenty five days when stored refrigerated (approximately 4°C) in the dark. Formulations were prepared twice during the study, divided into daily aliquots and stored as above prior to use. Samples were taken of each test item formulation and were analyzed for concentration of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (CAS RN 15721-78-5 The formulations investigated during the study were found to comprise test item in the range of the required content limit of ±10% with reference to the nominal content.
- Duration of treatment / exposure:
- The test item was administered by gavage to three groups each of twenty-four time-mated Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, between Days 3 and 19 of gestation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- The test item was administered by gavage to three groups each of twenty-four time-mated Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, between Days 3 and 19 of gestation inclusive at dose levels 100, 300, and 1000 mg/kg bw/day.
- Control animals:
- yes
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- The test item was administered by gavage to three groups each of twenty-four time-mated Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, between Days 3 and 19 of gestation. Clinical signs, body weight change, food and water consumptions were monitored during the study.
- Ovaries and uterine content:
- All surviving females were terminated on Day 20 of gestation and subjected to gross necropsy, including examination of the uterine contents. The number of corpora lutea, number, position and type of implantation, placental weights, fetal weight, sex and external and internal macroscopic appearance were recorded.
- Fetal examinations:
- Half of each litter was examined for detailed skeletal development and the remaining half was subjected to detailed visceral examination.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No clinical signs for any of the animals considered to be related to treatment with the test item.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- There were no treatment-related deaths during the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There was no effect of treatment at any dose level on body weight development.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Dietary intake across all groups of females receiving the test item remained similar to controls throughout the treatment period.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Visual inspection of water bottles did not indicate any intergroup differences in water consumption when compared with controls.
- 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:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related macroscopic findings for any of the females sent to the scheduled necropsy on Day 20 of gestation.
- 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:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- 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): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were detected in the uterine parameters examined, in fetal viability or in fetal growth and development. No treatment-related effects were detected on external development or in the type and incidence of skeletal or visceral findings.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- changes in number of pregnant
- changes in pregnancy duration
- clinical biochemistry
- clinical signs
- dead fetuses
- early or late resorptions
- effects on pregnancy duration
- food efficiency
- gross pathology
- maternal abnormalities
- mortality
- necropsy findings
- number of abortions
- organ weights and organ / body weight ratios
- pre and post implantation loss
- total litter losses by resorption
- water consumption and compound intake
Maternal abnormalities
- Key result
- Abnormalities:
- effects observed, non-treatment-related
Results (fetuses)
- Fetal body weight changes:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified - Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were detected on external development.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were detected iin the type and incidence of skeletal findings.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were detected regarding visceral findings.
- Other effects:
- not specified
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- fetal/pup body weight changes
- changes in litter size and weights
- changes in postnatal survival
- external malformations
- skeletal malformations
- visceral malformations
Fetal abnormalities
- Key result
- Abnormalities:
- effects observed, non-treatment-related
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Deviation No. 1
According to the Study Plan, target ranges for relative humidity were to be between 30 to 70%. Instances of higher relative humidity were noted for this study on 20 June 2015. During these episodes, the relative humidity ranged between 72.58 to 83.20% RH. Although these instances of higher relative humidity were less than ideal, they were seen on one day only and were of short duration with each lasting up to a maximum of two hours. The clinical condition of the animals was unaffected and this deviation from the Study Plan was therefore considered not to have any impact on the scientific integrity of the study or the results obtained.
See attachment for Tables.
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the study, the oral administration of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (CAS RN 15721-78-5) to pregnant rats by oral gavage during gestation at dose levels of 100, 300 and 1000 mg/kg bw/day was well tolerated. The ‘No Observed Effect Level’ (NOEL) for maternal toxicity was considered to be 1000 mg/kg bw/day. No treatment-related changes were detected in the offspring parameters measured. The ‘No Observed Effect Level’ (NOEL) for developmental toxicity, was, therefore, considered to be 1000 mg/kg bw/day.
- Executive summary:
The study was designed to investigate the effects of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (CAS RN 15721-78-5):on embryonic and fetal development following repeated administration by gavage to the pregnant female during gestation including the period of organogenesis. The study was performed to OECD 414 Test Guidelines under GLP conditions.
The test item was administered by gavage to three groups each of twenty-four time-mated Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, between Days 3 and 19 of gestation inclusive at dose levels 100, 300, and 1000 mg/kg bw/day. A group of twenty-four time-mated females was treated with the vehicle only (Arachis oil BP) to serve as a control. Clinical signs, body weight change, food and water consumptions were monitored during the study.
All surviving females were terminated on Day 20 of gestation and subjected to gross necropsy, including examination of the uterine contents. The number of corpora lutea, number, position and type of implantation, placental weights, fetal weight, sex and external and internal macroscopic appearance were recorded. Half of each litter was examined for detailed skeletal development and the remaining half was subjected to detailed visceral examination.
There were no treatment-related deaths during the study. No clinical signs for any of the animals considered to be related to treatment with the test item. There was no effect of treatment at any dose level on body weight development. Dietary intake across all groups of females receiving the test item remained similar to controls throughout the treatment period. Visual inspection of water bottles did not indicate any intergroup differences in water consumption when compared with controls. There were no treatment-related macroscopic findings for any of the females sent to the scheduled necropsy on Day 20 of gestation. No treatment-related effects were detected in the uterine parameters examined, in fetal viability or in fetal growth and development. No treatment-related effects were detected on external development or in the type and incidence of skeletal or visceral findings.
The oral administration of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (CAS RN 15721-78-5) to pregnant rats by oral gavage during gestation at dose levels of 100, 300 and 1000 mg/kg bw/day was well tolerated. The ‘No Observed Effect Level’ (NOEL) for maternal toxicity was considered to be 1000 mg/kg bw/day.
No treatment-related changes were detected in the offspring parameters measured. The ‘No Observed Effect Level’ (NOEL) for developmental toxicity was, therefore, considered to be 1000 mg/kg bw/day.
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