Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 271-846-8 | CAS number: 68609-97-2
- 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:
- 11 December 2018 - 06 January 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- The study was not designed to meet any particular regulatory requirement. No claim for compliance with Good Laboratory Practice was made, although the work performed generally followed Good Laboratory Practice principles.
- GLP compliance:
- no
- Remarks:
- Not Required, Preliminary study used to inform main testing.
- Limit test:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Test material form:
- liquid
- Details on test material:
- Batch number: AAF1453400
Purity: UVCB
- Specific details on test material used for the study:
- Batch number: AAF1453400
Purity: UVCB
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Strain/Species: New Zealand White rabbit.
Supplier: Envigo RMS.
Number of animals ordered: 28 time mated females (delivered as two batches of 14 females).
Day of delivery: Gestation Day 1.
Duration of acclimatization: Five days from arrival on GD1 to start of treatment on GD6.
Age of the animals at the start of the study (Day 1 of gestation): 18 to 22 weeks old
Weight range of the animals at the start of the study (Day 1 of gestation): 2.50 to 4.44 kg
ENVIRONMENTAL CONDITIONS
Temperature and relative humidity: Monitored and maintained within the range of 15-21°C and 45-70%.
Air changes (per hr): Filtered fresh air which was passed to atmosphere and not recirculated.
Photoperiod (hrs dark / hrs light): Artificial lighting, 14 hours light : 10 hours dark.
Administration / exposure
- Route of administration:
- oral: gavage
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Weekly.
DIET PREPARATION
Diet: Teklad 2930 Diet. The diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
Availability: Restricted 200 g/animal/day.
In addition to this diet, a small supplement of autoclaved hay was given on a daily basis to promote gastric motility and a small amount (approximately 20 g) of chopped fresh vegetables was offered twice weekly. Consumption of hay was monitored qualitatively but not quantitatively.
VEHICLE
- Choice of vehicle (if other than water): Aqueous 1% w/v methylcellulose
- Amount of vehicle (if gavage): 5 mL/kg - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- none specified
- Details on mating procedure:
- Natural mating with New Zealand white bucks of established fertility at the supplier’s facility. Males and females not closely related. After mating each female injected intravenously with 25 i.u. luteinising hormone.
- Duration of treatment / exposure:
- Females were treated from Day 6 to Day 28 (inclusive) after mating.
- Frequency of treatment:
- Once daily at approximately the same time each day.
- Duration of test:
- 28 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 90 mg/kg bw/day (nominal)
- Dose / conc.:
- 180 mg/kg bw/day (nominal)
- Dose / conc.:
- 375 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 7 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A previous pilot study
- Rationale for animal assignment (if not random): Random
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Animals were inspected visually at least twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: The weight of each adult was recorded on the day of arrival (Day 1 after mating) and on Days 3, 6-29 after mating.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
The weight of food supplied to each animal, that remaining and an estimate of any spilled was recorded daily from Day 2 after mating.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Animals surviving until the end of the scheduled study period were killed on Day 29 after mating.
- Ovaries and uterine content:
- For females surviving to term, the following was recorded:
Uterus - Gravid uterine weight (including cervix and ovaries).
The following were recorded for all animals:
For each ovary/uterine horn: Number of Corpora lutea, Implantation sites, Intrauterine deaths (classified as early or late), Fetuses (live and dead).
Apparently non-pregnant animals and for apparently empty uterine horns: The absence or number of uterine implantation sites was confirmed. - Fetal examinations:
- All fetuses and placentae were dissected from the uterus and weighed individually. Fetuses were individually identified within the litter, using a coding system based on their position in the uterus. Each placenta and fetus was externally examined and an internal examination of the neck and the contents of the thoracic and abdominal cavities of each fetus was performed and any abnormalities were recorded, sampled as appropriate and retained in appropriate fixative. The sex of each fetus was recorded. Grossly normal fetuses were discarded.
- Statistics:
- Where appropriate, group mean values, each with standard deviation (SD), were calculated from individual data.
- Indices:
- Not specified
- Historical control data:
- Not specified
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- At 375 mg/kg/day mean bodyweight loss of 0.05 kg was recorded during Days 6-10 of gestation compared with a mean weight gain of 0.07 kg in controls; this resulted in a lower than control overall bodyweight gain.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was no effect of treatment on food consumption following treatment of with 90 or 180 mg/kg/day; reduced food intake was evident in animals treated at 375 mg/kg/day during the second week of treatment (GD12-16). Overall food consumption for animals at 375 mg/kg/day was 87% of the control group.
- 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:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- not examined
- Pre- and post-implantation loss:
- no effects observed
- 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 examined
- Changes in number of pregnant:
- not examined
- Other effects:
- no effects observed
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- dose level: suitable for main study
- Effect level:
- ca. 375 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- gross pathology
- organ weights and organ / body weight ratios
- pre and post implantation loss
- total litter losses by resorption
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- not examined
- Visceral malformations:
- not examined
- Other effects:
- not examined
- Details on embryotoxic / teratogenic effects:
- Litter data as assessed by the number of implantations, resorptions, live young, sex ratio and the extent of the pre- and post-implantation loss was unaffected by maternal treatment. Macropathological examination of the fetuses showed no treatment related abnormality.
There was no effect of treatment on placental and litter weights; overall fetal weights from Dams treated at 375 mg/kg/day were slightly less than control, however, this was considered to be due to the slightly larger litter size in these animals.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- dose level: for main study
- Effect level:
- ca. 375 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
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
- Lowest effective dose / conc.:
- 375 mg/kg bw/day (nominal)
- Treatment related:
- no
Applicant's summary and conclusion
- Conclusions:
- Based on the findings in this study a dose level of 375 mg/kg/day was considered suitable for use as the high dose level on the forthcoming main embryo-fetal development study.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

Route: .live2