Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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: 245-904-8 | CAS number: 23843-64-3
- 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:
- 05 Sep - 08 Nov 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
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, Schwabach, Germany
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 449-160-7
- EC Name:
- -
- Cas Number:
- 116912-64-2
- IUPAC Name:
- ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, 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: at least 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:
Dose volume of test item (mL/kg) was calculated as follows:
Test item volume = mL/kg = Dose (g/kg) / density of test item (1.1 g/mL).
Thus, test item volume for the 100, 300 and 1000 mg/kg bw/day dose groups were 0.091, 0.27 and 0.91 mL/kg bw, respectively.
For each animal the individual dosing volume was calculated on the basis of the body weight most recently measured. - 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; twice daily for mobidity and mortality except on weekends and public holidays when observations were made once daily
- 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
BODY WEIGHT: Yes
- Time schedule for examinations: Mean body weights were recorded on gestation days 0, 5, 8, 11, 14, 17, and 20 except for one female of the control group (no. 23), which was weighed on GDs 0, 6, 9, 12, 15, 17 and 20.
FOOD CONSUMPTION: Yes
- Food consumption was measued on gestation days 5, 8, 11, 14, 17 and 20.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #20
- Organs examined: The uteri were removed 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. Each gravid uterus with the cervix was weighed. 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 - Blood sampling:
- - Plasma: No
- Serum: No - 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 or internal structure including the eyes,
brain, nasal passage and tongue by razor blade serial sectioning technique - 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.
- Historical control data:
- Historical control data were included for uterine data, litter weight data, and external, visceral, skeletal, and cranofacial fetal findings.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Low incidences of alopecia on various body parts were noted in isolated females of thel dose groups and the control group (2 control, 1 each from LD (low dose) and HD (high dose) and 2 from MD (mid dose). There was also crust on snout in one female of the LD and abnormal breathing observed in one female of the MD group. Moving the bedding in one MD and 2 HD and increased salivation in 2 HD group females on a few treatment days were observed. As the moving the bedding was noted mainly immediately after administration and just for a short period, this transient sign was considered to be a sign of 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.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the treatment period of this study and all animals survived until terminal sacrifice.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The mean body weight remained unaffected and increased with the progress of the study in the control, LD, MD and HD groups. There was no effect on body weight gain (GDs 0-20) observed in the treatment groups when compared to the controls. The group mean body weight and body weight gain of the treatment groups was comparable to the control group throughout the study period and was within the normal range of variation for this strain.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- In correlation to the body weight and body weight gain, food consumption in the LD, MD and HD groups was comparable to the controls. There was no statistically significant effect observed on food consumption in treatment groups throughout the study period when compared with the controls.
- 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
- Endocrine 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
- Description (incidence and severity):
- No gross pathological changes of toxicological relevance were observed during the macroscopic examination of the females of the control, LD, MD and HD groups.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- None of the females showed signs of abortion prior to the scheduled sacrifice.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- No test item-related effects of toxicological relevance or statistical significance were noted for percent pre-and post-implantation loss.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- No test item-related effects of toxicological relevance or statistical significance were noted for early and late resorptions.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- No dead foetuses were noted in any of the groups.
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- Successful mating resulted in 24/25 pregnancies in the MD and HD group compared to 25/25 pregnancies in the control and LD group. The marginally low pregnancy rates (no.of pregnancies / no. of females mated or sperm-positive x 100) of 96% in the MD and HD
group compared to 100% in the LD and control group was considered to be a biological variation and well above standard pregnancy rate of minimum 80% in rat. - Details on maternal toxic effects:
- No test item-related effects of toxicological relevance or statistical significance were noted for any of prenatal data parameters like terminal body weight, gravid uterus weight, adjusted maternal weights, number of corpora lutea and implantation sites.
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:
- other: no adverse clinical signs, no treatment-related effect on body weight, food consumption, prenatal data parameters and gross pathology
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- There were no test item-related effects of toxicological relevance or statistical significance observed for any litter data parameters like mean foetus weight (individual and litter basis), male and female foetus weight (individual basis), the total, male and female litter weight (litter basis) in any of the treatment groups when compared with the controls.
- Reduction in number of live offspring:
- not examined
- Description (incidence and severity):
- No test item-related effects of toxicological relevance or statistical significance were noted for live foetuses and number of male and female foetuses.
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- No test item-related effects of toxicological relevance or statistical significance were noted for sex ratio.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- There were no test item-related effects of toxicological relevance or statistical significance observed for any litter data parameters like mean foetus weight (individual and litter basis), the total, male and female litter weight (litter basis) in any of the treatment groups when compared with the controls.
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no external abnormalities considered to be of toxicological relevance in any of the dose groups. Statistical analysis of data revealed no significant differences compared to the control group.
Low incidences of red spot on snout and lower mandible (1 in Control) and haematoma on tail (1 in MD) were noted in isolated females of the control group and MD group without dose dependency. As these findings were observed in single foetuses, they were considered to be incidental in nature and unrelated to the treatment. - Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Skeletal examination of the Alcian blue and Alizarin red stained foetuses revealed a range of findings which occurred at an incidence generally comparable to or slightly lower or higher in the dose groups when compared to the control group. Most of the skeletal
findings observed in HD group were within the historical control data range.
A statistically significant decrease in litter incidence for supernumerary rib cartilage (14th) (L) and 14th full rib (L) in LD, hindlimb phalanges increased ossification in LD and HD, compared to the control group 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.
Slightly higher litter incidences, but without achieving statistical significance 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) were observed in the HD group when compared to the concurrent control group.
The observed reduced ossification without achieving statistical significance of few bones in the HD group that normally exhibit rapid ossification at the last days of gestation indicates a generalised skeletal delay in the HD group. 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.
Rudimentary/short ribs are considered as transient abnormalities. In contrast, full/long ribs are considered permanent and may cause health effects in humans; however, postnatal consequences in rats are unknown but are assumed to be minimal.This finding
was not considered to be treatment-related but spontaneous in nature.
Wavy ribs and bent scapulae are common findings in rodent studies and are considered to be postnatally reversible. Thus, wavy ribs are classified as variations and were not considered as an adverse effect of the treatment with the test item.
There was no statistical significance and no indication of a test item-related trend in the type and/or incidences of other skeletal findings and they were therefore considered to be spontaneous in nature. - Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Visceral findings observed in the dose groups were at frequencies generally comparable to or in some cases slightly higher or lower in frequency compared to controls. As observed findings were either minor variations and/or due to a lack of dose dependency
and consistency, no toxicological significance can be attributed to these findings and they were considered to be spontaneous in nature.
There was statistically significantly higher litter incidence of umbilical artery transposed in LD and HD groups when compared to the control group. However, values were well within historical control data range (85.71%).
Few visceral findings like renal pelvis dilated (R) in HD, ureter (L) convoluted in all treatment groups and ureter (B) dilated in LD and HD group litter and or individual incidences were observed in higher numbers without achieving statistical significance when compared to controls but well 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.
Dilated/convoluted ureter and dilated renal pelvis are common finding in rodent studies and is classified as a variation as it is transient and likely to be postnatally reversible. Furthermore, values were within the historical control data so that no toxicological relevance was attributed to it. - 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. Statistical analysis of the data revealed no statistical significance of any of the findings.
Effect levels (fetuses)
- Key result
- 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
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In an OECD 414 study conducted in compliance with GLP, no treatment-related effect on body weight, food consumption, prenatal data parameters and gross pathology of terminally sacrificed females was observed up to highest dose tested (1000 mg/kg bw/day). No mortality occurred during the treatment period of this study and all clinical signs observed in terminally sacrificed females were incidental or non adverse in nature. Furthermore, no treatment-related and toxicologically relevant effects on litter weight data, external, visceral or craniofacial foetal findings were observed in the high dose group. The NOAEL for both maternal toxicity and foetal toxicity of the test substance in this study is considered to be >=1000 mg/kg bw/day.
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.