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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 442-070-9 | CAS number: 329039-38-5
- 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 test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 442-070-9
- EC Name:
- -
- Cas Number:
- 329039-38-5
- Molecular formula:
- Hill formula: C8 H16 O5 Si CAS formula: C8 H16 O5 Si
- IUPAC Name:
- (acetyloxy)(methyl)(propan-2-yloxy)silyl acetate
- Details on test material:
- - Name of test material (as cited in study report): methyldiacetoxyisopropoxysilane
- Physical state: clear, colorless liquid
- Analytical purity: 85.8 %
- Impurities (identity and concentrations): 12.9 % Acetoxydiisopropoxymethtylsilane, 1.3 % hydrolisis product (siloxane)
- Purity test date: 04.10.2001
- Batch No.: AA001 (04.10.01)
- Storage condition of test material: Below 30 °C in an airtight container under nitrogen under the hood
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: albino CD® (Sprague-Dawley) rats ( CrI:CD®[SD] IGS BR)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, NC
- Age at study initiation: approximately ten weeks
- Weight at study initiation: males: 315.3 to 362.6 g; females: 212.9 to 255.2 g
- Housing: individually housed during the quarantine period and upon the initiation of the treatment period in solid-bottom polycarbonate cages with stainless-steel wire lids (LaboratoryProducts, Rochelle Park, NJ) with Sani-Chip® cage litter (p.J. Murphy Forest Products Corp., Montville, NJ);study animals two per cage (one male:one female from the same dose) during mating period; females separately and individually post mating; selected F1 male and female weanlings singly housed during the postwean period.
- Diet: Purina Certified Rodent Chow (No. 5002, PMI Feed), ad libitum.
- Water: tap water, ad libitum
- Acclimation period: quarantined for approx. one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared at the morning of each dosing day by adding vehicle to a precalibrated tared beaker containing the test material
VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil with 0.1 % water, because acetoxysilane decomposes rapidly in water
- Concentration in vehicle: 5, 15 and 45 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw
- Lot/batch no. (if required): Mazola®
- Purity: 99.9 % with 0.1 % water - Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as Day 0 of pregnancy
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): individually - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For analysis of the dosed formulations, content was based on the analysis of the major breakdown product, methylacetoxydiisopropoxy silane. Each sampIe was analyzed by single injection using capillary gas chromatography. The concentration of acetoxysilane was calculated in the dose formulation sampIes (mg/mI) from the peak area ratio for each sampIe and the linear regression equation.
For stability studies, the doses mixed for the low and high homogeneity studies were removed from the storage condition on the day of sampling (2, 4, and 7 days) and brought to ambient conditions. The formulations were stirred prior to sampling. Triplicate 1 g aliquots were removed and analyzed as described above. Dose formulations were not stable for two days when stored in the refrigerator (80.9% recovery for low dose; 131% recovery for high dose). Recovery values for days 4 and 7 were 37.1% and 43.3% for the low dose, respectively. Vehicle control formulations contained no acetoxysilane, with an estimated detection limit of 0.4 mg/mL. - Duration of treatment / exposure:
- F0 females: 10 weeks throughout the whole study
F0 males: 6 weeks
F1 females: 7 weeks from postnatal Day 21
F1 males: 7 weeks from postnatal Day 21 - Frequency of treatment:
- once daily, 7 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
25, 75, and 225 mg/kg bw/day
Basis:
other: calculated doses
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses were chosen based on a range-finding study, employing doses of 0, 100, 300, and 1000 mg/kg bw/day, administered by oral gavage at 5 mL/kg for ten days. There was profound toxicity (including morbidity) in both sexes at 1000 mg/kg bw/day, evidence of toxicity at 300 mg/kg bw/day, and the possibility of effects on ovarian weights at 100 mg/kg bw/day in the range-finding study.
- Rationale for animal assignment (if not random): by means of randomization stratified by body weight
- Rationale for selecting satellite groups: 5 males from control and high dose group
- Post-exposure recovery period in satellite groups: 2 weeks
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes, including, but not limited to, changes in: skin and fur, eyes, mucous membranes, respiratora and circulatory system, autonomic and central nervous system, somatomator activity and behavior pattern.
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: Initially and then weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necropsy
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, overnight
- How many animals: 5 / sex
- Parameters red blood cell (RBC), white blood cell (WBC), and platelet (PLT) counts; hemoglobin concentration (HGB); hematoerit (HCT); red cell
distribution width (RDW); mean platelet volume (MPV); the red blood cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC); and prothrombin time (PT) were analysed.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: Yes, overnight
- How many animals: 5 / sex
- Parameters albumin, asparatate aminotransferase (AST), alanine aminotransferase (ALT), urea nitrogen (BUN), total cholesterol, creatinine, glucose, total protein and the electrolytes sodium, potassium, and chloride were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Prior to necropsy, five parental males per group (selected randomly) were housed in metaboism cages overnight and urine was collected.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No
- Parameters glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocytes were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: weekly
- Dose groups that were examined: all
- Battery of functions tested: sensory and neuromuscular activity - Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight, epididymis weight, sperm count in testes, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm morphology - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 10 pups/litter (5/sex/litter as nearly as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioral abnormalities
F1 post weaning observations and procedures for each retained female included examination for vaginal patency (VP; from pnd 22 until acquisition of VP) and determination of estrus cyclicity and normality evaluated by vaginal smears taken daily the last three weeks of the postwean exposure period prior to scheduled sacrifice.
GROSS EXAMINATION OF DEAD PUPS:
Yes, All pups dying during lactation were necropsied, when possible, to investigate the cause of death. - Postmortem examinations (parental animals):
- GROSS PATHOLOGY: Yes, Ovaries (pair), Prostate, Epididymides (pair), Uterus with cervix and vagina, Testes (pair), Seminal vesicles with coagulating glands and their fluids (pair), Spinal cord, Thyroid, Stomach, Urinary bladder, Peripheral nerve (sciatic nerve), Bone marrow (femur), Small and large intestines (including Peyer's patches), Trachea and lungs (preserved by inflation with fixative and then immersion fixed), Lymph nodes (one cervical, near route of administration; and one mesentric, distant from the route of administration), All gross lesions,
HISTOPATHOLOGY: Yes - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at 70 days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:
GROSS NECROPSY
- hematology, clinical biochemistry, and urinalysis (males only) assays at necropsy for five F1 adult males and five F1 females per dose group.
- Ovaries (pair), Prostate, Epididymides (pair), Uterus with cervix and vagina, Testes (pair), Seminal vesicles with coagulating glands and their fluids (pair), Spinal cord, Thyroid, Stomach, Urinary bladder, Peripheral nerve (sciatic nerve), Bone marrow (femur), Small and large intestines (including Peyer's patches), Trachea and lungs (preserved by inflation with fixative and then immersion fixed), Lymph nodes (one cervical, near route of administration; and one mesentric, distant from the route of administration), All gross lesions
- Sperm motility (motile and progressively motile) was assessed immediately after necropsy for all males; number and morphology (at least 200 sperm per male, if possible) was evaluated using appropriately retained sperm sampIes initially from the high dose and control males.
HISTOPATHOLOGY: Yes - Statistics:
- Treatment groups were compared to the concurrent control group using either parametric ANOVA under the standard assumptions or robust regression methods (Zeger and Liang, 1986; RoyalI, 1986; Huber, 1967) that do not assume homogeneity of variance or normality. The homogenity of variance assumption was examined via Levene's Test (Levene, 1960), which is much more robust to the underlying distribution of the data than the traditional Bartlett's Test. If Levene's Test indicated lack of homogeneity of variance (p<0.05), robust regression methods were used to test all treatment effects.
Frequency data such as reproductive indices (e.g., mating and fertility indices) were not transformed. All indices were analyzed by Chi-Square Test for Independence for differences among treatment groups (Snedecor and Cochran, 1967) and by the Cochran-Armitage Test for Linear Trend on Proportions (Cochran, 1954; Armitage, 1955; Agresti et al., 1990). If Chi-Square revea1ed significant (p<0.05) differences among groups, then a Fisher's Exact Probability Test, with appropriate adjustments for multiple comparisons, was used for pairwise comparisons between each treatment group and the control group. - Reproductive indices:
- Mating index, Fertility index, Gestational index (females), Pregnancy index (males), Pereent Postimplantation Loss per Dam and Arcsine Root Transformation, Stillbirth Index per Dam and Arcsine Root Transformation, Live Birth index per Dam and Arcsine Root Transformation, Four-Day Survival index per Dam and Arcsine Root Transformation, Percent Males per Litter and Arcsine Root Transformation, Average Pup Body Weight per Litter, Average Male Pup Body Weight per Litter, Average Female Pup Body Weight per Litter
- Offspring viability indices:
- Live birth index, 4-Day survival index, 7-Day survival index, 14-Day survival index, 21-Day survival index, Lactation index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- at 225 mg/kg/day
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 225 mg/kg/bw: effects on stomach
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
audible breathing in two females, found dead or euthanized moribund in three females, rooting postdosing in ten females, and gasping, rough coat, and rooting prior to dosing in one female each at 225 mg/kg/day
NEUROBEHAVIOUR
During week 3 (the first week of the mating period), average muscle tone score per animal and average tail pinch response score per animal were significantly reduced at 225 mg/ kg/day. The percent animals with abnormal (depressed) arousal was significantly higher at 225 mg/kg/day during week 3.
HISTOPATHOLOGY:
In the stomach at 225 mg/kg/day: epithelial degeneration (five of five males) and acute inflammation of the forestomach (one of five), and acute inflammation of the glandular portion of the stomach (one of five).
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- Parental toxicity
- Effect level:
- 75 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: clinical signs, histopathology, neurobehavior
- Dose descriptor:
- NOAEL
- Remarks:
- Reproductive Toxicity
- Effect level:
- 225 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Remarks:
- Offspring toxicity
- Generation:
- F1
- Effect level:
- 225 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In this study the no observable adverse effect level (NOAEL) for systemic parental toxicity was 75 mg/kg/day; for reproductive and offspring toxicity, the NOAEL was >=225 mg/kg/day. Therefore, methyldiacetoxyisopropoxy silane has not to be classified for reproduction toxicity according to DSD and CLP.
- Executive summary:
In a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test according to OECD guideline 422 (Tyl, 2002) male and female rats were treated with 25, 75 and 225 mg/kg bw/day methyldiacetoxyisopropoxysilane. Female rats were treated daily for 10 weeks, male rats daily for 6 weeks. Furthermore the F1 generation was treated from weaning (pnd 21), for approximately seven more weeks (dosing for F1 selected pups began on pnd 22 and continued until all pups were at least 70 days of age). Only mild systemic toxicity in F0 parental males at 225 mg/kg/day was observed, expressed as sporadic effects on hematologic and neurobehavioral parameters and histopathologic lesions in the stomachs of F0 (but not Fl) males. There were no treatment- or dose-related effects on absolute organ weights or organ weights relative to terminal body or brain weights, or on gross findings, clinical chemistry, or urinalysis. There was no evidence of F0 reproductive toxicity in either sex at any dose. However, there were no effects on Fl male reproductive system histopathology or andrology at any dose. There was no other evidence of Fl offspring toxicity, either pre- or postnatally. There were no effects of treatment on acquisition of puberty in either sex and no changes in Fl adult male reproductive tract histopathology or andrology. In conclusion, administration of methyldiacetoxyisopropoxysilane by gavage once daily at 0, 25, 75, or 225 mg/kg bw/day to parental F0 rats, ten/sex/group, through prebreed, mating, gestation, and lactation, and direct dosing to F1 offspring from weaning to scheduled sacrifice on or about pnd 70, resulted only in minimal adult F0 parental toxicity at 225 mg/kg/day. Therefore, under the conditions of this study, the no observable adverse effect level (NOAEL) for systemic parental toxicity is 75 mg/kg/day; for reproductive and offspring toxicity, the NOAEL is >=225 mg/kg/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.