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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 220-449-8 | CAS number: 2768-02-7
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- 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:
- 2 005
- Report date:
- 2005
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)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Trimethoxyvinylsilane
- EC Number:
- 220-449-8
- EC Name:
- Trimethoxyvinylsilane
- Cas Number:
- 2768-02-7
- Molecular formula:
- C5H12O3Si
- IUPAC Name:
- ethenyltrimethoxysilane
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Yokohama, Japan
- Age at study initiation: 9 weeks
- Weight at study initiation: males: 317 - 423 g, females: 250 - 277 g
- Fasting period before study: no fasting period
- Housing: individual in stainless steel cages
- Diet (e.g. ad libitum): CRF-1, pelleted, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 17 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24 °C
- Humidity (%): 41 - 71%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared more than once a week. Concentration of stock solution was 200 mg/ml and stored at 4 °C in a refrigerator. The stock solution was diluted with corn oil to achieve the concentration of the dosing solutions.
VEHICLE
- Lot/batch no.: V3T0416 and V4K3008 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentration of dosing solution was verified by GC at the study initiation and at the end of the study. The range of concentration was acceptable because it was between 93.6 - 101.2%.
- Duration of treatment / exposure:
- Male: 14 days before mating, 28 days thereafter (42 days)
Females for repeated dose study: 42 days
Females in mating groups: 14 days before mating, during mating, during resulting pregnancies, 6 days during lactation (44 - 58 days) - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 62.5 mg/kg bw/day (nominal)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- (Males)
6 males/dose
for satellite group: 6 males/dose
(Females for satellite group)
Control, 250 mg/kg b.w., 1000 mg/kg b.w.: 6 females/dose - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels were based on the results of a foregoing range finding study, in which animals were orally exposed to 0, 250, 500 and 1000 mg/kg bw/day (Hashima, year not available, 401223P). No mortality was observed in all groups. Reddish urine, decrease in food consumption and occult blood was observed in administered groups. Therefore, 62.5, 250 and 1000 were selected as the dose levels for the main study.
Post-exposure period: Yes, for a sub group of males and females for 14 days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice a day during administration period, daily during recovery period, and once before necropsy
DETAILED CLINICAL OBSERVATIONS: Yes (including FOB)
- Time schedule: once before administration, Day 7, 14, 21, 28, 35 and 41 (males)
- Time schedule: once before administration, Day 8 and 15 of administration; Day 1, 8 and 15 of gestation; Day 3 of lactation
- Time schedule: once before administration, Day 8, 15, 22, 29, 36 and 42 (females for satellite group)
BODY WEIGHT: Yes
- Time schedule for examinations: twice a week
Males and satellite females: Day 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39 and 42 during administration period, Day 1, 4, 8, 11, 14 and 15 during recovery period
Pregnant females: Day 1, 4, 8, 11, 15 and 18, Day 0, 7, 11 and 21 during gestation, Day 0, 4, 6 and 7 during lactation
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day after last administration or after recovery period
- Anaesthetic used for blood collection: Yes (Pentobarbital-Na)
- Animals fasted: Yes
- How many animals: all administered animals
- Parameters checked: RBC, Haemoglobin, Haematocrit, MCV, MCH, MCHC, Platelets, Reticulocytes, PT, APTT, Fibrinogen, WBC, Differential leukocytes: Lymphocyte, Neutrophils, Eosinophils, Basophil, Monocyte
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day after last administration or after recovery period
- Animals fasted: Yes
- How many animals: all administered animals
- Parameters checked: AST, ALT, ALP, gamma-GTP, T-protein, Albumin, A/G, T-bilirubin, Urea nitrogen, Creatinine, Glucose, T-cholesterol, Triglycerides, Na, K, Cl, Ca, Inorganic-P
URINALYSIS: Yes
- Time schedule for collection of urine: on Day 2 and 37 in fasted males, Day 3 and 38 in non-fasted males, Day 2 during administration period and Day 5 of lactation in fasted females, Day 3 during administration period and Day 6 of lactation in non-fasted females, after recovery period in females
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes/No
- Parameters checked: Colour, pH, Protein, Glucose, Ketone body, Bilirubin, Occult blood, Urobilinogen, Urinary sediments, Epithelial cells, Erythrocytes, Leukocytes, Casts, Crystals - Sacrifice and pathology:
- ORGAN WEIGHT: Yes: Brain, pituitary, thyroids, thymus, heart, liver, spleen, kidney, adrenals, testes, epididymides, ovaries, uterus, lung
GROSS PATHOLOGY: Yes: heart, lung, trachea, liver, pancreas, sublingual gland, submandibular gland, oesophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, thymus, spleen, submandibuar lymph node, mesentric lympha node, kidney, urinary bladder, testis, epididymis, seminal vesicle, prostate, ovary, uterus, pituitary, adrenal, thyroid, parathyroid, cerebrum, cerebellum, medulla oblongata, spinal code, sciatic nerve, eyeball, Harderian gland, bone (sternum or femur), and mammary gland
HISTOPATHOLOGY: Yes: heart, lung, trachea, liver, pancreas, sublingual gland, submandibular gland, oesophagus, stomach, duodenum, jejunum, ileum. cecum. colon, rectum, thymus, spleen, submandibuar lymph node, mesentric lympha node, kidney, urinary bladder, urethra, ovary, uterus, pituitary, adrenal, thyroid, parathyroid, cerebrum, cerebellum, medulla oblongata, spinal code, sciatic nerve, eyeball, Harderian gland, bone (sternum or femur), bone marrow (sternum or femur), and mammary gland - Statistics:
- Bartlett test, Dunnett test, chi-square test, Cochran-Armitage test
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: mortality occurred
Transient salivation, soiled hair, a decrease in locomotor activity, reddish urine, hypothermia, perioral smudges, perianal soiling, diarrhoea, bradypnea, and piloerection were noted in the dying animals. Transient salivation, soiled hair and reddish urine were noted in the surviving males and females of the 1000 and 250 mg/kg groups. - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 1000 mg/kg bw/day: mortality occurred
Two males and 1 female from the 1000 mg/kg bw/day group died on Day 16 and 17 of males and Day 8 of female. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: reduced body weight
Low body weights were noted in males on Day 4 to 42 during administration period and Day 1 and 4 during recovery period. No changes were detected in females during administration period and recovery period. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption was decreased on Day 2 in males of 62.5 and 250 mg/kg bw/day group and on Day 2, 5 and 9 of males in 1000 mg/kg bw/day. Males in 62.5 mg/kg bw/day group and 250 mg/kg bw/day group showed more food consumption on Day 9 and 5, respectively. Increased food consumption was also observed in males of 1000 mg/kg bw/day on Day 5, 9 and 12 in recovery period. These increase was not observed as a toxicity effect of the test item, since no change was observed in body weight.
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: reduced Hb concentration
Decreased red blood cell counts, haemoglobin concentrations, hematocrit, MCV, and MCH and increased fibrinogen concentrations were noted in males of the 1000 mg/kg bw/day group after administration period. Prolonged APTT was observed in males of 62.5 mg/kg after recovery period. This change was no regarded as a tox effect of the test item due to lack of dose-responsibility. Red blood cell counts, haemoblobin, hematocrit were decreased and reticulocytes were increased in males administered with 1000 mg/kg bw/day. Besides, decreased fibrinogen were observed in 250 and 1000 mg/kg administered males. However, this change disappeared after recovery period. This change was not caused by the test item.
Lower hematocrit in females of the 1000 and 250 mg/kg bw/day groups, and decreased haemoglobin concentrations and prolonged APTT in females of the 1000 mg/kg bw/day group were also noted after administration period. Decreased MCV and MCH was detected in females of 250 mg/kg bw/day after recovery period. Decreased MCV, MCH, MCHC and RBC were also observed in females of 1000 mg/kg bw/day group. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: TP reduced in males/females
Increased CL was observed in males of 62.5 mg/kg bw/day after administration period. However, dose- responsibility was not noted. Low total protein, albumin, A/G ratios, and potassium, and high g-GTP, urea nitrogen, and creatinine were noted in males of the 1000 mg/kg bw/day group after administration period. The change of g-GTP was not caused by the test item because no changes of liver was detected by the histopathological findings. Lower AST was detected in males of 250 and 1000 mg/kg bw/day after administration period but this was not regarded as a tox effect of the test item.
Decreased total protein and increased A/G ratio was detected in males of 1000 mg/kg bw/day after recovery period. Increased chloride was noted in males of 1000 mg/kg bw/day after recovery period but this was not caused by the test item due to the range of background data (106.4 ± 1.9 mEq/l). Inorganic phosphate was increased in same group. This change was not considered as a tox effect of the test item, since this was not observed after administration period.
Low total protein and triglycerides in females of the 1000 mg/kg bw/day group were noted after administration period, and a tendency for high g-GTP in females of the 1000 and 250 mg/kg bw/day groups was observed. The decrease in t-bilirubin was not considered as a tox effect of the test item in females of 1000 mg/kg after administration period. Decreased in total protein was observed in females of 1000 mg/kg bw/day after recovery period. Increased ALP and Cl observed in females of 1000 mg/kg bw/day was not caused by the test item, since this data was similar to the background data of this test facility (ALP: 242.7 ± 1012.4 IU/l, Cl: 107.7 ± 2.1 mEq/l). - Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: occurrence of blood and epithelial cells
Males on Day 2 before administration: increased volume and decreased specific gravity, occult blood positive, epithelial cells and erythrocytes were noted in 1000 mg/kg bw/day. 250 mg/kg bw/day groups showed occult blood and erythrocytes.
Females on Day 2 before administration: increased volume and decreased specific gravity, occult blood positive, erythrocytes and leukocytes were noted in 1000 mg/kg bw/day. 250 mg/kg bw/day groups showed occult blood and erythrocytes.
Males on Day 3 after administration: 250 mg/kg bw/day groups showed white turbidity, occult blood and erythrocytes. White turbidity, occult blood, erythrocytes and leukocytes were observed in 1000 mg/kg bw/day.
Females on Day 3 after administration: 250 mg/kg bw/day groups showed white turbidity, occult blood and erythrocytes. White turbidity, occult blood, erythrocytes and epithelial cells were observed in 1000 mg/kg bw/day.
Males on Day 37 before administration: Decreased specific gravity, occult blood, epithelial cells, erythrocytes and leucocytes were observed in 1000 mg/kg bw/day.
Females on last day before administration: Epithelial cells were observed in 250 mg/kg bw/day and erythrocytes and leucocytes were observed in 1000 mg/kg bw/day.
Males on Day 37 after administration: 250 mg/kg bw/day groups showed white turbidity, erythrocytes and leucocytes. White turbidity, occult blood, erythrocytes and leucocytes were observed in 1000 mg/kg bw/day.
Females on last day after administration: Leucocytes were found in 1000 mg/kg bw/day.
Males and females after recovery period: No changes were observed. - Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- Salivation was observed in males and females of 1000 mg/kg bw/day after administration. Ease of removal from cage was decreased in 250 mg/kg bw/day but this was observed before administration. Salivation was observed in 1000 mg/kg bw/day. No changes were noted in both sexes regarding sensory response and grip strength. Increased spontaneous motor activity was noted in males 250 mg/kg bw/day but this was not regarded as a specific toxic effect due to lack of dose response. No change of spontaneous motor activity was reported in females.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- reduced thymus weight (females, all dose groups)
Body weight of males in 1000 mg/kg bw/day after administration period was increased. Decrease in absolute weight of thymus, increase in absolute weight of kidney, increase in relative weight of spleen, kidney and adrenals were observed in males of 1000 mg/kg bw/day after administration period. In same group, decrease in absolute weight of pituitary was also observed but this was not caused by the test item, since no change was detected in its relative weight. Absolute weight of brain was also increased. However, this change was not regarded as compound-related effect but caused by the difference of body weight.
No changes in body weight were detected in females after administration groups. Relative weight of thymus was decreased in females of 62.5 and 250 mg/kg. Decreased absolute weight of thymus, decreased relative weight of thymus and increased relative weight of liver were observed in females after administration period.
No changes of body weight was detected in males after recovery period. Decreased absolute weight of pituitary and increased relative weight of heart was observed in males in 62.5 mg/kg bw/day. However, these changes were not considered as a toxic effect of the test item, since there was no dose-response. Absolute weight of kidney was increased in males of 250 mg/kg bw/day but this was not caused by the test item due to lack of dose dependency. Relative weight of kidney was increased in males. Absolute weight of pituitary was also decreased. This was not caused by the test item because no change was detected in relative weight.
No changes of body weight were found in females after recovery period. Increased absolute and relative weight of uterus were observed in 250 and 1000 mg/kg bw/day after recovery period. However, these changes were not caused by the test item since no changes were observed after administration period. Furthermore, these data was similar to the background data of the test facility (absolute weight: 672 mg, relative weight: 229 mg (%)). - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: kidney enlargement
Two dead male animals in 1000 mg/kg bw/day showed atrophy of thymus and spleen. One dead male animal in 1000 mg/kg bw/day showed enlargement of kidneys and dark read glandular mucosa were noted in males of the 1000 mg/kg bw/day group. Enlargement of kidney was observed in four males in 1000 mg/kg bw/day after administration period. Atrophy of spleen was observed in one male of control group after recovery period.
One dead female showed atrophy of thymus and spleen in 1000 mg/kg bw/day. One female in 1000 mg/kg bw/day showed the enlargement of kidney. This was related to hydronephrotic kidney which was observed by histopathological examination and accidentally occurred. No abnormalities were found in females after recovery period. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 250 mg/kg bw/day: hyperplasia (urinary bladder)
In dead males in 1000 mg/kg bw/day, two animals showed postmortal change in whole organs and tissues. One dead male showed vacuolization of lamina propria in jejunum, one male showed hyperplasia of transitional epithelium in kidney, two males showed slight hyperplasia of transitional epithelium in urinary bladder, two males showed hyperplasia of transitional epithelium in urethra, one animal showed atrophy of seminiferous tubule in testis and one animal showed cell debris in lumen in epididymis.
One death occurred in females in 1000 mg/kg bw/day. The dead animal showed moderate postmortal change in whole organs and tissues, slight cellular infiltration of heart, slight hyperplasia of transitional epithelium in kidney and slight hyperplasia of transitional epithelium in urinary bladder. However, these observed changes in dead males and female were not marked. Death was caused by deteriorating general conditions by the test substance.
Histopathological findings after administration and recovery phase are listed in Tables.
On histopathological examination, hyperplasia of transitional epithelium in the urinary bladder was noted in males at all doses. The effect seemed to be substance-related and followed a dose-response relationship. The incidence of hyperplasia in the 250 and 1000 mg/kg bw/day groups was statistically significantly increased up to the end of the recovery period, although a slight decrease (mild to slight) in severity was observed from end of administration period to the end of the recovery period. Hyperplasia that was observed in 2/6 male rats of the 62.5 mg/kg bw/day group after the administration period seemed to be treatment-related, as there were no incidences in the control group; hyperplasia was not observed in the urinary bladder of females in the 62.5 mg/kg bw/day group. In general, hyperplasia in the urinary tract/bladder is not a typical spontaneous lesion, but simple hyperplasia may also occur in untreated animals. Often it is a secondary effect provoked by inflammation or physical damage. The effects observed in males at 62.5 mg/kg bw/day were not evaluated as adverse, as the incidence was not increased statistically significantly and the severity of the effect was stated as "slight". In addition the effects were fully reversible within the recovery period. - Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 62.5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- System:
- urinary
- Organ:
- bladder
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Any other information on results incl. tables
Table 1: Body weights of male and female rats of the administration and recovery period.
Group |
Control |
Test substance |
||
mg/kg |
0 |
62.5 |
250 |
1000 |
Number of males |
12 |
12 |
12 |
12 |
Days of administration |
|
|
|
|
1 |
399±13 |
399±15 |
400±15 |
400±15 |
11 |
430±16 |
417±14 |
420±23 |
392±27** |
22 |
456±18 |
446±20 |
447±27 |
417±21** |
32 |
491±21 |
481±21 |
479±26 |
440±22** |
42 |
516±26 |
498±27 |
496±28 |
447±13** |
|
|
|
|
|
Number of males |
6 |
6 |
6 |
6 |
Days of recovery |
|
|
|
|
1 |
518±29 |
511±34 |
508±25 |
449±16** |
4 |
524±30 |
516±36 |
518±23 |
472±24* |
8 |
531±30 |
527±38 |
528±22 |
489±26 |
14 |
542±32 |
536±38 |
541±26 |
511±35 |
|
|
|
|
|
|
|
|
|
|
Number of females |
6 |
|
6 |
6 |
Days of administration |
|
|
|
|
1 |
266±10 |
|
264±8 |
266±10 |
42 |
331±25 |
|
313±9 |
317±27 |
Number of females |
6 |
|
6 |
6 |
Days of recovery |
|
|
|
|
1 |
328±26 |
|
314±13 |
316±26 |
14 |
340±25 |
|
329±16 |
334±19 |
|
|
|
|
|
|
|
|
|
|
Significantly different from control group (*: p<0.05; **: p<0.01)
Table 2: Haematology results of male and female rats after the administration period.
Group |
Control |
Test substance |
||
mg/kg |
0 |
62.5 |
250 |
1000 |
Number of males |
6 |
6 |
6 |
5 |
At termination of administration period |
|
|
|
|
RBC (104/µl) |
836±43 |
829±34 |
813±32 |
755±59* |
HGB (g/dl) |
15.4±0.9 |
15.3±0.6 |
14.9±0.5 |
13.3±1.1** |
HCT (%) |
45.5±2.4 |
45.4±1.8 |
44.2±2.0 |
39.5±3.6** |
MCV (fl) |
54.5±1.5 |
54.7±1.1 |
54.4±0.8 |
52.3±1.6* |
MCH (pg) |
18.4±0.6 |
18.5±0.4 |
18.4±0.2 |
17.7±0.4* |
MCHC (g/dl) |
33.9±0.4 |
33.7±0.4 |
33.8±0.5 |
33.7±0.4 |
PLT (104/µl) |
94.1±9.3 |
92.6±2.3 |
96.1±14.1 |
95.1±9.2 |
RET (‰) |
26±5 |
23±4 |
27±4 |
23±5 |
PT (sec.) |
16.1±1.9 |
18.0±2.3 |
16.6±2.4 |
16.1±1.9 |
APTT (sec.) |
22±1.4 |
23.5±2.0 |
21.1±2.1 |
21.8±2.0 |
Fbg (mg/dl) |
210.6±10.5 |
223.2±13.3 |
210.8±17.8 |
263.4±8.4** |
WBC (10²/µl) |
72±18 |
55±5 |
68±18 |
102±35 |
|
|
|
|
|
Number of females |
6 |
6 |
6 |
6 |
At termination of administration period |
|
|
|
|
RBC (104/µl) |
714±25 |
725±11 |
687±36 |
697±33 |
HGB (g/dl) |
14.3±0.5 |
14.3±0.5 |
13.8±0.4 |
13.5±0.6* |
HCT (%) |
42.1±1.1 |
41.6±1.4 |
39.9±1.6* |
39.5±1.5* |
MCV (fl) |
59±2.4 |
57.4±2.1 |
58.1±1.4 |
56.7±1.0 |
MCH (pg) |
20.1±0.8 |
19.7±0.8 |
20±0.7 |
19.3±0.4 |
MCHC (g/dl) |
34.1±0.4 |
34.3±0.2 |
34.5±0.5 |
34±0.6 |
PLT (104/µl) |
103.3±6.0 |
101±7.5 |
105.8±8.5 |
95.2±15 |
RET (‰) |
56±12 |
53±12 |
60±12 |
62±24 |
PT (sec.) |
13.8±0.4 |
13.8±0.3 |
14.1±0.4 |
13.6±0.6 |
APTT (sec.) |
17.3±0.8 |
18±0.6 |
18.4±1.1 |
18.8±0.7** |
Fbg (mg/dl) |
210.4±18.6 |
214.6±16.2 |
237.5±57.6 |
189.2±7.3 |
WBC (10²/µl) |
52±15 |
52±6 |
53±18 |
48±9 |
Significantly different from control group (*: p<0.05; **: p<0.01)
Table 3: Organ weights of male and female rats after the administration period.
Group |
Control |
Test substance |
||
mg/kg |
0 |
62.5 |
250 |
1000 |
Number of males |
6 |
6 |
6 |
5 |
At termination of administration period |
|
|
|
|
Body weight (g) |
496±24 |
474±13 |
469±33 |
422±18** |
Brain (g) |
2.08±0.08 |
2.11±0.09 |
2.08±0.07 |
2.07±0.05 |
(g%) |
0.42±0.03 |
0.44±0.03 |
0.45±0.03 |
0.49±0.02** |
Pituitary (mg) |
13.9±0.7 |
14.3±1.4 |
13±0.7 |
11.8±1.2** |
(mg%) |
2.8±0.2 |
3±0.3 |
2.8±0.2 |
2.8±0.3 |
Thymus (mg) |
287±43 |
241±43 |
323±41 |
189±38** |
(mg%) |
58±8 |
51±10 |
69±9 |
45±10 |
Spleen (mg) |
777±99 |
752±115 |
723±136 |
832±136 |
(mg%) |
156±16 |
159±25 |
154±23 |
196±25* |
Kidney (g) |
3.14±0.25 |
3.14±0.36 |
3.1±0.18 |
4.27±0.99* |
(g%) |
0.63±0.03 |
0.66±0.06 |
0.66±0.05 |
1.01±0.25** |
Adrenals (mg) |
55.4±7.7 |
60.3±7.4 |
60.6±4.4 |
61.1±4.9 |
(mg%) |
11.2±1.6 |
12.7±1.5 |
13±1.3 |
14.5±1.7** |
|
|
|
|
|
Number of females |
12 |
11 |
11 |
10 |
Body weight (g) |
302±17 |
312±18 |
311±19 |
286±19 |
Thymus (mg) |
307±56 |
256±66 |
247±60 |
170±52** |
(mg%) |
103±22 |
82±19* |
80±21* |
59±16** |
Liver (g) |
9.48±0.78 |
10.01±0.65 |
10.11±0.99 |
9.86±0.87 |
(g%) |
3.14±0.17 |
3.21±0.16 |
3.25±0.19 |
3.44±0.19** |
Significantly different from control group (*: p<0.05; **: p<0.01)
Table 4: Organ weights of male and female rats after the recovery period.
Group |
Control |
Test substance |
||
mg/kg |
0 |
62.5 |
250 |
1000 |
Number of males |
6 |
6 |
6 |
5 |
At termination of recovery period |
|
|
|
|
Body weight (g) |
519±29 |
513±36 |
514±23 |
483±33 |
Pituitary (mg) |
17.3±1.1 |
15±1.3* |
16.1±2.3 |
14.9±1* |
(mg%) |
3.3±0.2 |
2.9±0.4 |
3.1±0.5 |
3.1±0.2 |
Heart (g) |
1.46±0.14 |
1.61±0.14 |
1.49±0.08 |
1.48±0.07 |
(g%) |
0.28±0.02 |
0.31±0.02* |
0.29±0.02 |
0.31±0.02 |
Kidney (g) |
3.08±0.13 |
3.33±0.18 |
3.36±0.25* |
3.28±0.13 |
(g%) |
0.6±0.04 |
0.65±0.05 |
0.65±0.03 |
0.68±0.04** |
|
|
|
|
|
Number of females |
6 |
0 |
6 |
6 |
Body weight (g) |
319±22 |
|
309±13 |
311±18 |
Uterus (mg) |
543±32 |
|
753±186* |
734±97* |
(mg%) |
171±17 |
|
243±54** |
236±30* |
Significantly different from control group (*: p<0.05; **: p<0.01)
Table 5: Histopathological findings of male and female rats after the administration and recovery period.
Group |
Control |
Test substance |
||
mg/kg |
0 |
62.5 |
250 |
1000 |
Number of males |
6 |
6 |
6 |
5 |
After administration period/recovery period |
|
|
|
|
Duodenum, vacuolization, lamina propria |
0/0 |
0/0 |
1 (slight)/ 1 (slight) |
3 (slight)*/2 (slight-mild) |
Ileum, vacuolization, lamina propria |
0/0 |
0/0 |
1 (slight)/0 |
5 (mild)**/ 5 (mild)** |
Mesenteric lymph node, vacuolization simus |
0/0 |
0/0 |
0/0 |
2 (slight)/4 (slight)** |
Kidney, hyperplasia, transitional epithelium |
0/0 |
0/0 |
0 |
5 (mild)** |
Pyelonephritis |
0/0 |
0/0 |
0 |
5 (mild-moderate)** |
Regeneration, urinary tubule |
0/0 |
1 (slight)/0 |
0/0 |
0/5 (slight-mild)** |
Urinary bladder, hyperplasia, transitional epithelium |
0/0 |
2 (slight)/0 |
6 (slight-mild)**/ 5 (slight)** |
5 (mild)**/ 5 (slight)** |
Urethra, hyperplasia, transitional epithelium |
0/0 |
0/0 |
0/0 |
4 (slight-mild)**/0 |
|
|
|
|
|
Number of females |
6 |
6 |
6 |
6 |
Duodenum, vacuolization, lamina propria |
0/0 |
0/- |
1 (slight)/0 |
2 (slight-mild)/5 (slight)** |
Jejunum, vacuolization, lamina propria |
0/0 |
0/- |
0/0 |
6 (mild)**/ 6 (mild)** |
Mesenteric lymph node, vacuolization simus |
0/0 |
0/- |
0/0 |
3 (slight-mild)*/ 3 (slight)* |
Kidney, hyperplasia, transitional epithelium |
0/0 |
0/- |
0/0 |
3 (slight-mild)*/ 3 (slight)* |
Regeneration, urinary tubule |
0/0 |
0/- |
0/0 |
3 (slight)*/ 4 (slight)* |
Urinary bladder, hyperplasia, transitional epithelium |
0/0 |
0/- |
6 (slight-mild)**/ 6 (slight-mild)** |
6 (mild)**/6 (slight-mild)** |
Urethra, hyperplasia, transitional epithelium |
|
|
|
|
Significantly different from control group (*: p<0.05; **: p<0.01)
Applicant's summary and conclusion
- Conclusions:
- In the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test, conducted according to OECD Test Guideline 422 and in compliance with GLP, administration of trimethoxy(vinyl)silane at a dose of 62.5 mg/kg bw/day did not lead to organ damage including irreversible morphological effects permanently impairing the function of the organ/tissue (reversibility after recovery period). Also, no other effects such as necrosis or other cell death were reported, which could contribute to the degeneration of the metabolically-functional tissue. The No Observed Adverse Effect Level (NOAEL) was therefore determined to be 62.5 mg/kg bw/day. The Lowest Observed Adverse Effect Level (LOAEL) was set to 250 mg/kg bw/day, based on the histopathological changes in the urinary bladder observed in all animals (males and females) at this dose level.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)