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EC number: 245-442-7 | CAS number: 23128-74-7
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- (1981-05-12)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-hexane-1,6-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenylpropionamide]
- EC Number:
- 245-442-7
- EC Name:
- N,N'-hexane-1,6-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenylpropionamide]
- Cas Number:
- 23128-74-7
- Molecular formula:
- C40H64N2O4
- IUPAC Name:
- N,N'-hexane-1,6-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanamide]
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Cheshire Rabbit Farms (Dudden Lodge, Nr. Tarporley, Cheshire), Ranch Rabbits (Crawley Down, Sussex), Buxted Rabbit Co. Ltd. (Gt. Totease Fram, Buxted, Sussex)
- Weight at study initiation: 3.5 to 4.6 kg (pretest); 2.8 to 3.6 kg (females only, main study)
- Age at study initiation: 12 - 20 weeks
- Housing: individual housing in metal cages equipped with sheet stainless steel sides, stainless steel wire front and an aluminated perforated floor panel. Individual undercage plastic trays were lined with absorbent paper.
- Diet (e.g. ad libitum): SDS rabbit diet SQC, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 10/14
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: methylcellulose (1%)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The highest required concentration of suspension was prepared by trituration of weighed compound with vehicle using a mortar and pestle to form a smooth mixture, then addition of further vehicle to required volume. Further mixing was carried out using a "Silverson" Laboratory mixer. The lower concentrations were prepared by serial dilution with the vehicle.
VEHICLE
- Concentration in vehicle: 5 % (dose: 500 mg/kg bw/d), 10% (dose: 1000 mg/kg bw/d), 20% (dose: 2000 mg/kg bw/d)
- Amount of vehicle (if gavage): 10mL/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1
- Length of cohabitation: at least 1 hour after coitus was observed - Duration of treatment / exposure:
- day 7-19 of gestation
- Frequency of treatment:
- daily, 7 days/week
- Duration of test:
- 29 days after gestation
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 2 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 18 (female rabbits)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dosages were based on a prior preliminary study in which animals were orally exposed to test substance with doses of 500, 1000 and 2000 mg/kg bw over a period of 13 days and sacrifice after 21 days. At 2000 mg/kg bw/d majority of animals showed pale discoloration of the faeces during the treatment period.
- Rationale for animal assignment (if not random):
rabbits were weighed and 24 within the bodyweight range 3.5 to 4.6 kg allocated to four groups, such that mean bodyweight and source of animals were similar for all groups.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: day 1, 7, 9, 11, 15, 20, 24 and 29 of gestation
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (g/rabbit/day)
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of pre-implantation loss: Yes
- Number of post-implantation loss: Yes
- Other:
- number and distribution of live young
- number and distribution of embryonic/foetal deaths
- individual foetal weights
- foetal abnormalities
- Embryonic/foetal deaths were classified as:
- Early: only placenta visible at termination
- Late: both placenta and embryonic remnants visible at termination
Abortion: only implantation site scars visible at termination - Fetal examinations:
- - External examinations: Yes [all per litter]
- Soft tissue examinations: Yes [all per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: Yes: [all per litter ]
OTHER:
Live young were examined externally then killed by intrathoracic injection of Pentobarbitone Sodium. They were weighed; dissected and examined for visceral abnormalities, and sexed. Where appropriate young showing suspected abnormalities were examined by alternative procedures (eg. micro-dissection, histopathology) to clarify initial observations. Young were skinned, eviscerated and fixed in 740P industrial methylated spirit; after fixation the heads were sliced through the line of the frontoparietal suture and the brain examined for visible abnormalities (eg.hydrocephaly, hydranencephaly) prior to clearing and staining (modified Dawson technique) of the carcasses for skeletal examination. - Statistics:
- Statistical analyses were performed routinely on litter data and incidences of skeletal anomalies and skeletal variants using the litter as the basic sample unit. Non-parametric methods (Kruskal-Wallis and Jonckheere tests) were employed since these values rarely follow a normal distribution.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The majority of animals at 2000 mg/kg/day showed pale discolouration of faeces throughout the treatment period. At 1000 mg/kg/day approximately half of the animals occasionally showed pale discolouration of faeces during the treatment period. There were no other signs of reaction considered attributable to treatment.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Single dosed animals at 500 and 2000 mg/kg/day, and one in the control group died or were killed. No treatment relationship was considered to be indicated.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Intergroup variation in bodyweight gain generally appeared unrelated to dosage, although at all dosages mean gain during the first two days of treatment was slightly lower than among control animals. Overall weight gain at 1000 and at 2000 mg/kg/day was greater than that of control animals. At 1000 mg/kg/day weight gain was higher than in the high dose group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- At all dosages mean food consumption during the first four days of the dosing period was similar to that of control animals. Thereafter individual mean test group values tended to be higher than, or similar to, those of control animals.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no macroscopic findings at terminal autopsy that were considered attributable to treatment.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Details on maternal toxic effects:
- Pregnancy rate as judged by the numbers of animals pregnant at termination, was high in all groups.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects at this dose level
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Mean foetal weights were essentially similar for all groups and intergroup differences- among mean values for litter weight were not statistically significant (P >0.05).
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- Intergroup differences among mean values for litter size,and pre- and post implantation loss were not statistically significant (p >0.05).
- Changes in postnatal survival:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A single animal, from the control group, showed total litter loss. For the following intergroup comparisons control values calculated excluding this animal (i.e. Mean B values) were employed.
- External malformations:
- no effects observed
- Description (incidence and severity):
- The incidence of malformed foetuses appeared unaffected by treatment; although the incidence at 500 mg/kg/day was higher than in the control group, the incidence at 1000 mg/kg/day was lower, and at 2000 mg/kg/day no malformations were observed.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Incidences of skeletal anomalies were not adversely affected at any dosage and the only differences to be statistically significantly (P <0.05) related to lower incidences of skeletal anomalies at 500 and 2000 mg/kg/day. At all dosages the incidence of foetuses with extra thoracolumbar rib and of foetuses with variant sternebrae tended to be similar to the control incidence; there were no statistically significant differences (p >0.05).
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- Incidences of visceral anomalies were not adversely affected at any dosage.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: no adverse effects observed
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
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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