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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Combined Repeated Dose and Reproductive / Developmental Toxicity Screening Test (Precursor Protocol of GL 422)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethoxyvinylsilane
EC Number:
220-449-8
EC Name:
Trimethoxyvinylsilane
Cas Number:
2768-02-7
Molecular formula:
C5H12O3Si
IUPAC Name:
trimethoxy(vinyl)silane
Test material form:
liquid

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: (P) 9 wks
- Weight at study initiation: (P) males: 317 - 423 g, females: 250 - 277 g
- Fasting period before study: no fasting period
- Housing: individual in stainless steel cages
- Diet: CRF-1, pelleted, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- 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 exposure:
PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared more than once a week. Concentration of stock solution was 200 mg/ml and sotred 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
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: max. 14 days
- Proof of pregnancy: vaginal plug and 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): Day 18 of gestation until day 4 of lactation: individual in plastic cage with wood chips
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:
Premating exposure period (males): 14 days prior to mating
Premating exposure period (females): 14 days prior to mating
Duration of test: males: 43 days; females: until day 6 of lactation
Frequency of treatment:
daily
Details on study schedule:
- Age at mating of the mated animals in the study: 12 weeks
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 reproduction toxicity study)
12 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 mg/kg bw/day 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

Additional details regarding this study are provided in section 7.5.1.

Examinations

Parental animals: Observations and examinations:
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, Hematocrit, MCV, MCH, MCHC, Platelets, Reticulocytes, PT, APTT, Fibrinogen, WBC, Differential leukocytes: Lymphocyte, Neutrophis, Eosinophis, 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
Oestrous cyclicity (parental animals):
Oestrous cycle length and normality were evaluated in females by vaginal smears prior to mating, and optionally during mating, until evidence of mating was found.
Sperm parameters (parental animals):
Parameters examined in P male parental generations:
testis weight, epididymis weight,
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

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 behavioural abnormalities

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead.
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals after administration period or recovery period
- Maternal animals: All surviving animals after day 6 of lactation

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
Postmortem examinations (offspring):
SACRIFICE
- All F1 offspring at 4 days of age.

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
Statistics:
Barlett test, Dunnett test, chi-square test, Cochran-Armitage test
Reproductive indices:
- Copulation index: (number of pairs with successful copulations/number of pairs)x100
- Fertility index: (number of pregnant females/number of pairs with successful copulation)x100
- Implantation index: (number of implantation scars/number of corpora lutea)x100
- Gestation index: (number of dams having live pups/number of pregnant dams)x100
- Delivery index: (number of pups born/number of implantation scars)x100
- Birth index: (number of live pups born/ number of implantation scars)x100
Offspring viability indices:
- Sex ratio at birth: (number of male pups/number of female pups
- Live birth index: (number of live pups born/number of pups born)x100
- Viability index: (number of live pups on Day 4 of lactation/number of live pups born)x100

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
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 bw/day groups.
Mortality:
mortality observed, treatment-related
Description (incidence):
Two males and 1 female from the 1000 mg/kg bw/day group died on Day 16 and 17 (males) and Day 8 (female).
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Low body weights were noted in males on Day 4 to 42 during administration period and Day 1 and 4 during recovery period.
Females of the 1000 mg/kg bw/day group showed also decrease in body weight.
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):
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 bw/day 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 bw/day 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):
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 bw/day 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 dat 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):
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
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
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 occured 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 goup. 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

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
effects observed, treatment-related
Description (incidence and severity):
The number of estrous cases before pairing in 1000 mg/kg bw/day was less than that of the control group.
Reproductive function: sperm measures:
no effects observed
Description (incidence and severity):
Moderate atrophy of seminiferous tubule, slight degeneration of semiferous tubule, slight vacuolization of Sertoli cell and slight retention of spermalid were observed in 1000 mg/kg bw/day. Slight decrease in sperm and slight or moderate cell debris in lumen in epididymis were observed in 1000 mg/kg bw/day.
Reproductive performance:
no effects observed
Description (incidence and severity):
No changes were observed in reproductive parameters.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No effects on reproductive performance.
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Low number of oestrous cases.
Dose descriptor:
NOAEL
Remarks:
systemic toxicity
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 (P0)

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

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
No changes were observed.
Mortality / viability:
no mortality observed
Description (incidence and severity):
No changes were observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Litter weight on Day 4 of lactation was decreased in 1000 mg/kg bw/day. However, this change occurred accidentally since no changes were found in mean pups weight on Day 0 and 4 of lactation, male and female weight on Day 0 and 4.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Anogenital distance (AGD):
not examined
Nipple retention in male pups:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
One dead pup showed atrophy of lung in 250 mg/kg bw/day administered group. This change was not related to the test item since no dose-responsibility was found. One survival pup showed dilatation of pelvis in 1000 mg/kg bw/day administration group. This change was not regarded as test compound related effect but accidentally happened.
Histopathological findings:
not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed.

Target system / organ toxicity (F1)

Critical effects observed:
no

Overall reproductive toxicity

Reproductive effects observed:
yes
Lowest effective dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Treatment related:
yes
Relation to other toxic effects:
reproductive effects occurring together with other toxic effects, but not as a secondary non-specific consequence of other toxic effects
Dose response relationship:
yes
Relevant for humans:
not specified

Any other information on results incl. tables

Table 1: Reproductive functions of male and female rats.

 

F0 (mg/kg/day)

Parameter

0

62.5

250

1000

Number of females

12

12

12

11

No. of estrous cases before pairing (14 days)

3.2±0.4

3.2±0.4

3.1±0.3

2.5±0.7*

Copulation index

100

91.7

91.7

90.9

No. of conceiving days

2.8±1.4

1.8±1.3

2.8±3.8

4.7±2.4

 

 

 

 

 

Female fertility index

100.0

100

100.0

100.0

 

Table 2: Observation of pups (F1).

 

F1 (mg/kg/day)

Parameter

0

62.5

250

1000

Length of gestation

22.2±0.4

22.5±0.7

22.5±0.5

22.6±0.5

Corpora lutea

16.7±1.8

16.3±3.5

15.8±1.5

15.6±1.3

Implantation scars

15±1.5

14.5±4.3

14.5±1.9

13.7±1.3

Implantation index (%)

90.1±6.4

87.2±17.7

91.3±7.6

88±6.8

Gestational index

100

100

100

100

Pups born

14.3±1.6

13.3±4.6

13.9±1.9

12.9±1.1

Stillbirths

0.4±0.7

0.1±0.3

0.3±0.5

0.2±0.6

Live pubs born

13.9±1.7

13.2±4.6

13.6±1.7

12.7±1.1

Sex ratio at birth

1.74±1.25

0.96±0.73

0.94±0.54

1.18±0.77

Delivery index (%)

92.9±7.7

88.7±13.5

94.7±6.3

93.1±7.3

Birth index (%)

92.8±7.7

88.6±13.5

94.6±6.3

93.0±7.3

Live birth index (%)

97.2±4.5

99.4±2.1

98.2±3.1

98.6±4.4

Live pups on day 4 of lactation

13.8±1.7

12.9±4.4

13.5±1.7

12.4±1.1

Sex ratio on day 4 of lactation

1.74±1.24

0.97±0.72

0.93±0.53

1.14±0.8

Viability index (%)

99.4±2.0

98.3±4.1

98.7±2.8

97.7±5.0

External abnormalities (%)

0

0

1.2±4.0

0

Acaudate

0

0

1.2±4.0

0

 

Table 3: General signs of pups.

 

F1 (mg/kg/day)

Parameter

0

62.5

250

1000

No. of pups

(normal/death)

 

 

 

 

day 0 of lactation

167/5

145/1

150/3

127/2

day 1 of lactation

166/1

145/0

149/1

125/2

day 2 of lactation

166/0

144/1

148/1

124/1

day 4 of lactation

166/0

143/1

148/0

124/0

day 4 of lactation

166/0

142/1

148/0

124/0

 

Table 4: Body weights of pups.

 

F1 (mg/kg/day)

Parameter

0

62.5

250

1000

Male weight

 

 

 

 

day 0 of lactation

6.7±0.6

6.6±0.8

7.0±0.7

6.8±0.7

day 4 of lactation

10.7±1.0

10.5±1.7

10.7±1.1

10.5±0.7

Female weight

 

 

 

 

day 0 of lactation

6.3±0.4

6.3±0.6

6.8±0.6

6.5±0.5

day 4 of lactation

10.1±0.9

9.8±1.2

10.6±1.0

10.3±0.6

Mean pups weight

 

 

 

 

day 0 of lactation

6.6±0.5

6.6±0.8

6.9±0.6

6.7±0.6

day 4 of lactation

10.4±0.9

10.3±1.7

10.7±1.0

10.4±0.7

Litter weight

 

 

 

 

day 0 of lactation

91.0±9.0

83.4±25.5

93.9±14.4

84.7±7.9

day 4 of lactation

143.4±11.7

126.8±35.1

142.8±18.0

128.6±10.5*

Significantly different from control group (*: p<0.05)

 

 

Applicant's summary and conclusion

Conclusions:
In a reliable study with trimethoxy(vinyl)silane, conducted according to OECD Test Guideline 422 and in compliance with GLP, NOAELs for reproductive performance of parental animals were estimated to be 1000 mg/kg bw/day for males and 250 mg/kg bw/day for females. The NOAEL for offspring was 1000 mg/kg bw/day. The NOAEL for systemic toxicity of the parents was 62.5 mg/kg bw/day.