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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
Rats were obtained from Charles River Deutschland GmbH
Animals were a minimum of 8 weeks of age at delivery. Males were 309-377 grams and females were 204-248 grams. Animals were acclimated for 7 days prior to treatment, under test conditions with an evaluation of the health status. Animals rooms were air conditioned with 10-15 air changes per hour; the environment was monitored continously with recordings of temperature and relative humidity, 12 hours artificial fluorescent light/12 hours dark with background music played at a centrally defined low volume for at least 8 hours during the light period. Animals were housed in Makrolon (R) cages with wire mesh tops and standard granulated softwood bedding. Pelleted standard rat/mouse maintenance diet was available ad libitum. Tap water from Fullinsdorf in bottles was available ad libitum.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
(3-Chloropropyl)trimethoxysilane was administered for 6 hours daily by  whole-body vapour inhalation to male rats for 28 days and to female rats  throughout the 14-day pre-pairing, pairing and gestation period until the  individual day 19 post coitum. 
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
The nominal atmosphere concentration was determined once daily by weighing the test item container before and after each exposure.
The weight of the test item used was divided by the total air flow volume to give the nominal concentration. The test atmosphere
concentration in each chamber was determined daily, 5 times per hour per chamber during each hour of exposure.
Details on mating procedure:
During the pairing period, rats were housed overnight with one male and one female in Makrolon pairing cages. The femlae was placed with the same male until mating occurred or two weeks elapsed.

Duration of treatment / exposure:
Exposure period: 28 days
Premating exposure period (males): 14 days
Premating exposure period (females): 14 days
Duration of test: until the individual day 19 post coitum

(3-Chloropropyl)trimethoxysilane was administered for 6 hours daily by whole-body vapour inhalation to male rats for 28 days and to female rats throughout the 14-day pre-pairing, pairing and gestation period until the individual day 19 post coitum.
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 5, 25 and 100 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes, concurrent no treatment
Details on study design:
The animals were exposed to the following mean test item concentrations:
Group 1: 0 ppm (air control)
Group 2: 5 ppm
Group 3: 25 ppm
Group 4: 100 ppm
Control animals were exposed to air only under the same conditions as animals exposed to the test item.
P generation males were sacrificed after they had been treated for 28 days, P generation females and pups were sacrificed on day 4 post partum.

Examinations

Maternal examinations:
Animals were observed twice daily for mortalities and clinical signs. Detailed clinical observations were performed once per week. A Functional Observational battery (modified Irwin screen test) was performed once during the test (on day 3 post-partum). Body weights and food consumption was recorded.
Ovaries and uterine content:
For pregnant females, the number of corpora lutea and the number of impantation sites were recorded, mated females that did not deliver were sacrificed on gestation day 24-27. Histological exam of ovaries and uterus was carried out on any females that did not give birth.
Fetal examinations:
Pups were sacrificed on day 4 post partum.The litters were examined for litter size, live birth, stillbirth and any gross anomalies.
Statistics:
Statistical Methods: Mean and standard deviation of data were calculated. Univariate one-way analysis of variance was used to assess the
significance of intergroup differences. If the variables were assumed to follow a normal distribution, the Dunnett t-test, based on a pooled variance estimate, was used for intergroup comparisons. The Steel test (rank test) was applied when the data could not be assumed to follow a normal distribution. Fisher's Exact test for 2x2 tables was applied if the variables could be dichotomized without loss of information.
Indices:
Reproductive indices
Fertlity and mating performance
Duration of gestation
Implantation rate and Post-implantation loss
Litter size at first litter check
Postnatal loss day 0 - 4 post partum


Offspring viability indices
Abnormal findings at first litter check and during lacatation to weaning
Sex ratios
Pup weights to day 4 post partum

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
The fertility rate was high resulting in at least 9 litters per group for evaluation of reproduction data. At all concentrations, there were
no treatment-related effects on precoital time, fertility indices, mean duration of gestation, number of implantations, post-implantation
loss through to scheduled sacrifice on day 4 post partum. The mean number of corpora lutea per dam (determined at necropsy) was
similar in all groups and gave no indication of a test item-related effect. There were no findings, which distinguished test item-treated
animals from controls. In particular, no treatment-related histopathological findings were observed in the reproductive organs of either
sex from the parental generation.

Effect levels (maternal animals)

Dose descriptor:
NOAEC
Effect level:
>= 100 ppm (nominal)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No abnormal findings were noted for pups at first litter check or during  the first 4 days post partum. Sex ratios at first litter check and on day  4 post partum were unaffected by treatment with the test item.  Mean pup weights on day 0 and day 1 post partum were unaffected by  treatment with the test item. Mean pup weight development during the  first 4 days post partum lactation was unaffected by treatment with the  test item. 
No test item-related findings were noted at macroscopical examination of  pups.

Effect levels (fetuses)

Dose descriptor:
NOAEC
Effect level:
>= 100 ppm (nominal)
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Exposure to (3-Chloropropyl)trimethoxysilane up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item.
Based on these results the NOEC (no observed effect concentration) was established as >=100 ppm.