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EC number: 604-314-4 | CAS number: 142844-00-6
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on OECD421
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25th January 2010 to June 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with no deviations
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- oxo[(oxoalumanyl)oxy]alumane; silanedione
- EC Number:
- 604-314-4
- Cas Number:
- 142844-00-6
- Molecular formula:
- amorphous glass Si(n)O(3n+1) polymeric anions bonded to Zr and Al(3+)
- IUPAC Name:
- oxo[(oxoalumanyl)oxy]alumane; silanedione
- Details on test material:
- Name of test material( as cited in study report): RCF Covance
Substance type: Inorganic
- Physical state: solid
- Analytical purity: 100%
- Purity test date: 14.12.09
- Lot/batch No.: BG-10-X99-2982
- Expiration date of the lot/batch: 31.1.2020
- Stability under test conditions: stable
- Storage condition of test material: sealed container room temp
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River laboratories ,Margate ,UK
- Age at study initiation: 10-12weeks old
- Weight at study initiation: (P) Males: 286.2- 353.2 g; Females: 186.0-208.6 g
- Fasting period before study: No
- Housing:Cages conforming to "code of practice for the housing and care of animals used in scientific procedures" (home office,Lndon 1989)
- Diet - SQC rat and mouse breeder diet number 3 (special diet services' limited, Witham)
- Water:ad libitum
- Acclimation period:2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 10th February 2010 To:6th April 2010
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: methyl cellulose
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Daily
VEHICLE
- Justification for use and choice of vehicle (if other than water): Viscous solution to maintain suspension of test article
- Concentration in vehicle: see table 1
- Amount of vehicle (if gavage): 10ml/kg
Formulations of the test article in the vehicle were prepared daily.
The test article was formulated as a suspension in 1% (w/v) methylcellulose following dispensary SOPs and the formulation method 8215_686_O_01D as maintained in the study data - Details on mating procedure:
- - M/F ratio per cage:1:1
- Length of cohabitation: 15 days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged : individually
- Any other deviations from standard protocol:none - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- XRF
- Duration of treatment / exposure:
- 12weeks
- Frequency of treatment:
- daily
Doses / concentrations
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- Basis:
nominal conc.
- No. of animals per sex per dose:
- 10 per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The test and control articles were administered orally, by gavage, daily to the males for two weeks prior to pairing, during the pairing period and until the day before necropsy and daily to the females for two weeks prior to pairing, during the pairing period and until Day 4 post-partum, inclusive. The females were allowed to litter and rear their offspring to Day 4 post-partum. The males were treated for eight weeks prior to necropsy.
The dose levels were based on the results of previous inhalation studies and the physical properties of the test articles. Due to the potential risk of physical interference with gut motility, a high dose of between 50 and 100 mg/rat/day (250 mg/kg/day) was considered to be the limiting dose for this study
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE AND CLINICAL OBSERVATIONS : Yes
- Time schedule: Twice daily: beginning and end (nominal) of the working day
- Cage side observations checked
All animals were examined at least once daily for signs of ill health or overt toxicity. Any abnormalities of appearance or behaviour or other signs of reaction to treatment or ill health were recorded and a detailed individual record was maintained of the clinical condition of each animal on the days of body weight recording. Clinical signs for females during the gestation and lactation periods, were recorded more frequently that weekly due to days of body weight recording. This deviation was considered not to have affected the outcome or integrity of the study.
In addition, the animals were observed immediately on return to the home cage after dosing and at 0.5, 1, 2 and 4 hours post dose for signs of reaction to treatment for the first two weeks of dosing. As no signs were observed the animals were observed immediately on return to the home cage after dosing and at 0.5 and 1 hour post dose only from the start of the pairing period until the end of dosing.
On Days 4 and 13 of dosing, the 2 hour post-dose observations were recorded approximately 24 minutes late in error. This deviation did not affect the outcome or integrity of the study.
BODY WEIGHT: Yes
- Time schedule for examinations:males :Day -7 (randomisation body weight check)
Weekly .Day of (prior to) necropsy
females -Day -7 (randomisation body weight check)
Weekly prior to pairing and until confirmation of mating
Days 0, 7, 14 and 20 of gestation
Days 1 and 4 post partum
FOOD CONSUMPTION
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Pre-pairing: Over the same intervals as the body weights prior to pairing (males and females)
Gestation:
Day 0 to 4, 4 to 7, 7 to 10, 10 to 14, 14 to 17 and 17 to 20 of gestation (females only)
Post-partum:
Day 1 to 4 post-partum (females only)
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:
OTHER: - Oestrous cyclicity (parental animals):
- During the pairing procedure one male was housed with one female. Mating was confirmed by the presence of a vaginal plug in situ or sperm in a vaginal washing. On confirmation of mating vaginal washing was discontinued and the male was removed and rehoused as detailed in the section Environment. The day on which mating was confirmed was designated Day 0 of gestation.
- Litter observations:
- The females were allowed to litter and the date of parturition and the duration of gestation were recorded.
The following data were recorded for each litter to Day 4 post partum:
• number of pups born (live and dead)
• daily live litter size and sex (reported on Days 1 and 4)
• daily clinical observations
• individual pup weights on Days 1 and 4 post partum
• necropsy findings of dead pups where condition permitted - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals [after assessment of females
- Maternal animals: All females with live pups were sent to necropsy on Day 5 post-partum,
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGHTS
Organ weights
Animals were weighed before being sent to necropsy. Testes and epidiymides and ovaries were dissected free from fat and other contiguous tissues and weighed before fixation.
Tissue retention
The following tissues from all terminal adult animals were retained, where appropriate:
ovaries (with oviducts) testes
uterus epididymides
cervix seminal vesicles
vagina prostate
pituitary coagulating gland
gross lesions animal identification
All tissues were preserved in relevant preservatives.
Histopathology
Testes and epididymides from all terminal adult animals, as appropriate, were embedded in paraffin wax and sectioned at a nominal thickness of 5 μm. Sections allocated for testicular staging were stained with periodic acid Schiff (PAS); all other sections were stained with haemotoxylin and eosin.
Tissues from Groups 1, 2 and 3 were microscopically examined by the study pathologist.
- Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at 5 days of age.
- These animals were subjected to postmortem examinations macroscopic examination .
The following data were recorded for each litter to Day 4 post partum:
• number of pups born (live and dead)
• daily live litter size and sex (reported on Days 1 and 4)
• daily clinical observations
• individual pup weights on Days 1 and 4 post partum
• necropsy findings of dead pups where condition permitted
GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]
- Statistics:
- Statistical analysis: Data were processed, where appropriate, to give litter mean values, group mean values and standard deviations
- Reproductive indices:
- Mating Index, Female and Male Fecundity indices, male and female fertility indices, Median precoital time
- Offspring viability indices:
- Post implantation survival index, viability index, gestation index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 250 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other:
- Remarks:
- no effect observed
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- not specified
Details on results (F1)
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- no NOAEL identified Generation: P and F1
- Generation:
- F1
- Effect level:
- 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- Remarks on result:
- other:
- Remarks:
- no NOAEL identified Generation: P and F1
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
A selection of results on health , reproduction and litter condition are given below.
Table 2 Summary of female performance
Test article |
Control |
AES Covance |
RCF Covance |
Group |
1 |
2 |
3 |
Level (mg/kg/day) |
0 |
250 |
250 |
Number of animals: |
Group 1 |
Group 2 |
Group 3 |
|
|
|
|
Males |
|
|
|
Number in group |
10 |
10 |
10 |
Number died/killed after pairing |
0 |
0 |
0 |
Number inducing pregnancy |
9 |
10 |
9 |
|
|
|
|
Females |
|
|
|
Number in group |
10 |
10 |
10 |
Number died/killed |
0 |
0 |
0 |
Number not pregnant |
1 |
0 |
1 |
Number pregnant (%) |
9 (90.0) |
10 (100.0) |
9 (90.0) |
Number with total embryo/foetal loss |
0 |
0 |
0 |
Gestation index (%) |
90.0 |
100.0 |
90.0 |
Number with total litter loss |
0 |
1 |
0 |
Number with live pups on Day 4post-partum |
9 |
9 |
9 |
|
|
|
|
Table3 Summary of clinical observations
Clinical observations |
|||||||||||
Observation |
Group |
Number of animals with sign in Week: |
Total |
||||||||
|
Number |
1 |
2 |
3# |
4# |
5 |
6 |
7 |
8T |
affected |
|
|
|
|
|
|
|
|
|
|
|
|
|
Number of animals examined |
1 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
|
|
2 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
|
|
3 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Skin and hair: |
|
|
|
|
|
|
|
|
|
|
|
Sores/lesions |
1 |
|
|
|
|
|
|
|
|
|
|
|
2 |
1 |
1 |
|
|
|
|
|
|
1 |
|
|
3 |
|
|
|
1 |
1 |
1 |
1 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Thinning fur |
1 |
|
|
|
|
|
|
|
|
|
|
|
2 |
1 |
2 |
2 |
2 |
|
|
|
1 |
2 |
|
|
3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
# pairing period T = terminal week |
|
Table 4 Clinical observations females pre pairing
Clinical observations |
|||||
Observation |
Group |
Number of animals with sign in Week: |
Total |
||
1 |
2 |
||||
|
|
|
|
|
|
Number of animals examined |
1 |
10 |
10 |
|
|
|
2 |
10 |
10 |
|
|
|
3 |
10 |
10 |
|
|
|
|
|
|
|
|
Skin and hair: |
|
|
|
|
|
Thinning fur |
1 |
1 |
2 |
2 |
|
|
2 |
|
|
|
|
|
3 |
1 |
2 |
2 |
|
|
|
|
|
|
|
|
Table 5 - Clinical observations female gestation
Clinical observations Females |
||||||||||||||||||
Observation |
Group |
Number of animals with sign on Day of gestation: |
Total |
|||||||||||||||
0 |
7 |
14 |
20 |
21 |
22 |
23 |
||||||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
Number of animals examined+ |
1 |
9 |
9 |
9 |
9 |
9 |
3 |
0 |
|
|
||||||||
|
2 |
10 |
10 |
10 |
10 |
10 |
2 |
1 |
|
|
||||||||
|
3 |
9 |
9 |
9 |
9 |
9 |
3 |
0 |
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
Littered |
1 |
|
|
|
|
6 |
3 |
|
|
|
||||||||
|
2 |
|
|
|
|
8 |
1 |
1 |
|
|
||||||||
|
3 |
|
|
|
|
6 |
3 |
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
Skin and hair: |
|
|
|
|
|
|
|
|
|
|
||||||||
Hairloss |
1 |
|
|
|
|
|
|
|
|
|
||||||||
|
2 |
|
|
|
|
|
|
|
|
|
||||||||
|
3 |
|
1 |
1 |
1 |
|
|
|
1 |
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
Staining |
1 |
|
|
|
|
|
|
|
|
|
||||||||
|
2 |
|
|
1 |
1 |
|
|
|
1 |
|
||||||||
|
3 |
|
1 |
1 |
1 |
|
|
|
1 |
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
Thinning fur |
1 |
|
|
|
|
|
|
|
|
|
||||||||
|
2 |
1 |
1 |
1 |
1 |
|
|
|
1 |
|
||||||||
|
3 |
1 |
1 |
1 |
|
|
|
|
1 |
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
||||||||
+ excludes non-pregnant females |
|
Table 6 Group Mating Data
Mating indices |
|||
|
Group 1 |
Group 2 |
Group 3 |
|
|
|
|
Number of paired males |
10 |
10 |
10 |
Number of paired females |
10 |
10 |
10 |
|
|
|
|
Number of mated males |
10 |
10 |
10 |
Number of mated females |
10 |
10 |
10 |
|
|
|
|
Number of males inducing pregnancy |
9 |
10 |
9 |
Number of pregnant females |
9 |
10 |
9 |
|
|
|
|
Mating index % |
100.0 |
100.0 |
90.9 |
|
|
|
|
Fertility index % : male |
90.0 |
100.0 |
90.0 |
: female |
90.0 |
100.0 |
90.0 |
|
|
|
|
Fecundity index % : male |
90.0 |
100.0 |
90.0 |
: female |
90.0 |
100.0 |
90.0 |
|
|
|
|
Table 7 Group mean litter data
Pup numbers – females with live pups at Day 4post-partum |
|||
|
Group 1 |
Group 2 |
Group 3 |
|
|
|
|
Number of females with live pups at Day 4post-partum |
9 |
9 |
9 |
|
|
|
|
Mean duration of gestation (days) |
22.3 |
22.1 |
22.3 |
|
|
|
|
Mean number of implantation sites |
11.8 |
12.4 |
12.7 |
|
|
|
|
Mean number of pups born |
10.8 |
12.1 |
11.4 |
|
|
|
|
Mean number of pups alive Day 1 |
10.8 |
12.1 |
11.4 |
|
|
|
|
Mean % male pups Day 1 |
42.4 |
42.8 |
47.3 |
|
|
|
|
Mean number of pups alive Day 4 |
10.4 |
12.0 |
11.4 |
|
|
|
|
Table 8 - Group Litter Data - Necropsy
Summary necropsy data – pups surviving to Day 5 necropsy |
|||
|
Group 1 |
Group 2 |
Group 3 |
|
|
|
|
Number of animals examined |
93 |
108 |
103 |
Number of animals with finding: |
|
|
|
Not remarkable (%) |
78 (83.9) |
100 (92.6) |
90 (87.4) |
|
|
|
|
Animal - cannibalised |
|
|
1 |
Kidney - small |
1 |
|
|
Liver - pale |
|
|
1 |
- pale area |
1 |
|
1 |
- large |
|
|
1 |
- small |
|
|
1 |
Lung – red focus |
1 |
|
|
Testis - dark |
|
|
1 |
Ureter - distension |
1 |
|
2 |
Urinary bladder - distension |
11 |
8 |
9 |
- abnormal contents |
|
1 |
|
|
|
|
|
Applicant's summary and conclusion
- Conclusions:
- At what was regarded as the maximum usable dose there were no adverse reproductive effects seen with RCF administered by gavage.
- Executive summary:
There are two possible activities of fibres , those mediated by their chemistry and those due to their morphology. When inhaled most fibres are cleared to the gut by the mucocilliary escalator or macrophage activity. Thus any reproductive effects would have to mediated through adsorbtion via the gut. The most likely source of any toxic activity would be through the chemistry of the material.
Unsurprisingly orally administered fibres at many times any dose that would arrive from inhalation had no effect on the reproductive efficiency or health of rats.
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.