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EC number: 449-160-7 | CAS number: -
- 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:
- 2 018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- 22 January, 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 449-160-7
- EC Name:
- -
- Cas Number:
- 116912-64-2
- Molecular formula:
- C7H18N2O4Si C8H20N2O4Si C9H22N2O4Si C10H24N2O4Si
- IUPAC Name:
- [3-(ethoxydimethoxysilyl)propyl]urea; [3-(trimethoxysilyl)propyl]urea; {3-[diethoxy(methoxy)silyl]propyl}urea
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 11-12 weeks old
- Weight at study initiation: males: 318 - 361 g; females: 194 - 238 g
- Housing: The animals were kept individually in IVC cages (type III H, polysulphone cages) on Altromin saw fibre bedding (except during the pre-mating period when females were kept in groups of two animals and during mating period when two females were paired with one male). During the pre-mating period and after mating, males were housed in groups (2 animals / cage) in IVC cages.
- Diet: Altromin 1324 maintenance diet for rats and mice provided ad libitum
- Water: tap water, sulphur acidified to a pH of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals) provided ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- - PREPARATION OF DOSING SOLUTIONS:
A dose formulation analysis was not performed in this study as test item was administered as it is. - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- A dose formulation analysis was not performed in this study as test item was administered as it is.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: Mating was performed using a ratio of 1:2 (male to female).
- Further matings after two unsuccessful attempts: no; after getting 100 sperm positive females, the remaining females and males were discarded without any observations.
- Proof of pregnancy: sperm in vaginal smear referred to as gestation day (GD) 0 - Duration of treatment / exposure:
- The female animals were treated with the test item or control item between gestation day 5 until gestation day 19.
- Frequency of treatment:
- daily
- Duration of test:
- 15 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 25 females/group
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Doses were selected based on a dose-range finding study. The highest dose level was chosen with the aim of inducing toxic effects, but not death or severe suffering. Thereafter, a descending sequence of dose levels was selected with a view to demonstrate any dose-related response and a NOAEL.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once a day, preferably at the same time each day
- Cage side observations included: spontaneous activity, lethargy, recumbent position, convulsions, tremors, apnoea, asphyxia, vocalisation, diarrhoea, changes in the skin and fur, eyes and mucous membranes (salivation, discharge), piloerection and pupil size. Changes in gait, posture, response to handling as well as the presence of clonic or tonic movements, stereotypes, difficult or prolonged parturition or bizarre behaviour
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least once a day, preferably at the same time each day
BODY WEIGHT: Yes
- Time schedule for examinations: Mean body weights were recorded on gestation days 0, 5, 8, 11, 14, 17, and 20.
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: The uteri were removed, weighed with the cervix, and the pregnancy status of the dams was confirmed. Uteri that appeared non-gravid were further examined by staining with 10% ammonium sulphide solution to confirm the non-pregnant status. The number of corpora lutea was counted for pregnant animals. The uterine contents were examined for embryonic or foetal deaths as well as the number of viable foetuses. The degree of resorption (late and early) was confirmed in order to help estimate the relative time of death of the conceptus. The position and number of foetuses in each uterine horn was also recorded. - 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 - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: Craniofacial examination of the heads of the foetuses used for the soft tissue examination of the first 20 litters per group were performed - Statistics:
- A statistical assessment of the results of the body weight, food consumption was performed by comparing values of dosed with control animals using a one-way ANOVA and a post-hoc Dunnett Test. Foetal evaluation parameters like external, visceral, craniofacial and skeletal parameters were analysed using Fisher’s exact test.
- Indices:
- Pre-implantation loss (%); post-implantation loss (%); early, late, and total resorptions
- Historical control data:
- Historical control data were included for uterine data, litter weight, and external, visceral, skeletal, and cranofacial fetal findings.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Low incidences of alopecia were noted in isolated females from all dose groups including the control group (2 controls, 1 each from low- and high-dose group and 2 from the mid-dose group). There was also crust on snout and abnormal breathing observed in one each mid- and high-dose group female. Moving the bedding in one low-dose, 2 high-dose and increased salivation in 2 high-dose group females on a few treatment days were observed. Moving the bedding was a transient sign and was considered to be a local reaction to the test item rather than a systemic adverse effect. All clinical signs observed in terminally sacrificed females were incidental or non adverse in nature.
- Mortality:
- no mortality 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
- Description (incidence and severity):
- No test item-related effects of toxicological relevance or statistical significance were noted for gravid uterus weight.
- 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:
- no effects observed
- 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:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- not examined
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: no treatment-related effect on body weight, food consumption, prenatal data parameters and gross pathology
Maternal abnormalities
- 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:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The following statistically significant findings were noted in litter indicence: decreased supernumerary rib cartilage (14th) (L) and 14th full rib (L) at 100 mg/kg bw/day; and increased hindlimb phalanges ossification at 100 and 1000 mg/kg bw/day. These changes were considered to be incidental as frequencies were even less in numbers compared to the controls. Therefore, these findings are not to be considered as treatment-related and solely spontaneous in nature.
In the high-dose group, slightly higher litter incidences, but without achieving statistical significance were noted for: incomplete ossification of frontal (B) (25% compared to 15% in controls), interparietal (85% compared to 65% in controls), parietal (B) (55% compared to 30% in controls), squamosal (B and R) (15-25% compared to 0-5% in controls), zygomatic arch (B) (15% compared to 5% in controls), femur (B) (15% compared to 5% in controls), basioccipital with small hole (15% compared to 5% in controls), scapula bent (B) (5% compared to 0% in control), scapula bent (R) (20% compared to 0% in control), branched xiphoid cartilage (65% compared to 55% in control), left 14th rudimentary rib (65% compared to 50% in control), wavy ribs (65% compared to 55% in controls), rudimentary 7th cervical rib (5-15% compared to 0% in control) misshapen humerus (20% compared to 5% in controls), unossified forelimb metacarpals (55% compared to 30% in controls) and pelvic girdle (B) caudal shift (20% compared to 10% in control).
The observed reduced ossification without achieving statistical significance of few bones at 1000 mg/kg bw/day that normally exhibit rapid ossification during the last days of gestation indicates a slight generalised skeletal delay at 1000 mg/kg bw/day. Generally slightly delayed ossification is not regarded to persist postnatally and not associated with long-term consequences on survival, general growth and development and therefore is not considered to be adverse. - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was statistically significantly higher litter incidence of umbilical artery transposed in low- and high-dose groups when compared to the control group; however, values were well within historical control data range. An increased incidence either for litters and/or for individuals were observed for a few of the visceral findings including renal pelvis dilated (R) at the high dose, ureter (L) convoluted at all doses, and ureter (B) dilated at the low and high dose; these increases occurred at high numbers but did not achieve statistical significance when compared to controls and were within historical control data range (renal pelvis dilated (R)- 47.37%, ureter (L) convoluted- 73.91%, ureter (B) dilated- 87.50%). There was discolouration of organs like liver and adrenal gland observed in few foetuses of treatment and control group without dose dependency. Discolouration of organs was considered likely to reflect the consequence of a functional disorder and thus not strictly as developmental anomalies. Due to lack of dose dependency and consistency, these discolouration findings were not considered as toxicologically relevant.
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Craniofacial examination by razor blade serial sectioning technique revealed few predominant findings (subcutaneous edema of head, retinal fold, slightly dilated 3rd ventricle and dilated lateral ventricle) at low frequencies generally comparable to or in some cases slightly higher or lower in frequency in the dose groups compared to the controls. These findings were considered to be spontaneous in nature and not related to the treatment with the test item.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no treatment-related and toxicologically relevant effect on litter weight data, external, skeletal, visceral or craniofacial foetal findings
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In an OECD 414 study conducted in compliance with GLP, no effects of ureidopropyltrialkoxysilane on females were found at dose levels up to 1000 mg/kg body weight/day. Regarding developmental toxicity no adverse effects were observed in foetuses up to the highest dose tested. The NOAEL for maternal toxicity and embryo-foetal toxicity of ureidopropyltrialkoxysilane in this study is considered to be 1000 mg/kg body weight/day.
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