3-(trichlorosilyl)propiononitrile

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

not known

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP, using a related test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: USEPA OPPTS 870.3650

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: OECD 422

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(triethoxysilyl)propiononitrile

EC Number:

213-050-5

EC Name:

3-(triethoxysilyl)propiononitrile

Cas Number:

919-31-3

IUPAC Name:

3-(triethoxysilyl)propanenitrile

Details on test material:

3-(triethoxysilyl)propanenitrile (CAS # 919-31-3); purity was >97.8 %
Lot 4A-4363-BS
Colorless to clear liquid
expiration 18-APR-2005

Test animals

Species:

rat

Strain:

other: HanBrl:WIST (SPF)

Details on test animals or test system and environmental conditions:

Rats were obtained from RCC Ltd Laboratory Animal Services, Fullinsdorf, Switzerland.
Animals were a minimum of 8 weeks of age at delivery. Males were 227-271 grams and females were 165-216 grams. Animals were acclimated for 7 days prior to pairing, 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:

oral: gavage

Vehicle:

corn oil

Details on exposure:

The test item was administered once daily, by gavage. All animals received a dose volume of 2 ml/kg body weight with a daily adjustment of the individual volume to the actual body weight. Control animals were dosed with the vehicle alone.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples for determination of actual test item concentrations, stability (7 day) and homogeneity in the prepared mixtures were taken on the first day of preparation. Samples for determination of actual test item concentrations and homogeneity were also taken on one occasion during the gestation period. Analysis were performed using a Gas Chromatographic method.

Details on mating procedure:

After a pre-paring period of 14 days, males and females in the Reproductive groups were paired overnight, in the ratio of 1 male to 1 female. The female was placed with the same male until mating occured or two weeks had elapsed. The day on which spermatozoa was observed was designated day 0 post coitum. After mating was asecertained, the animals were separated and housed individually. The feamles were allowed to litter and rear their progeny to day 4 of lactation.

Duration of treatment / exposure:

Pre-mating (14 days), mating, gestation, and postpartum days 1-3 for a maximum total of 44 days depending on duration of mating phase.

Frequency of treatment:

daily

Duration of test:

Exposure period: Premating (14 days), mating, gestation, and postpartum days 1-3 for a maximum total of 44 days depending on
duration of mating phase.
Premating exposure period (males): 14 days
Premating exposure period (females): 14 days
Duration of test: up to a maximum of 44 days

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 500, and 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:

10/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

Sex: male/female
Duration of test: up a maximum total of 44 days
Animals of both sexes received test article for 14 days prior to pairing and during pairing period. Daily dosing of the females was 
continued throughout pregnancy and up to day 3 of  lactation. Males were dosed for a minimum of 28 days.

Examinations

Maternal examinations:

The dams and pups were  observed daily for survival and behavioral abnormalities in nursing. No tissues were  collected from the dams 
or pups for microscopic examination.

Ovaries and uterine content:

Organs examined at necropsy (macroscopic and microscopic): The number of implantation sites and corpora lutea were determined
at necropsy.

Fetal examinations:

Pup litter size,  any gross abnormalities and weight, sex ratios, pup viability, litter  weight gain, and macroscopic observations. The dams and 
pups were observed daily for survival and behavioral abnormalities in nursing.   Macroscopic examination was performed at necropsy for the 
pups.  No tissues were collected from the dams or pups for microscopic examination.

Statistics:

Statistical methods: Mean and standard deviations of data of various parameters were calculated. Univariate one-way analysis of variance was 
used to assess the significance of intergroup differences. 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. For pup data, the litter is the appropriate unit 
for statistical comparison. Statistically significant probabilities are reported at either the p<0.05 or p<0.01 levels.

Indices:

Gonadal function, mating behavior, conception, development of the conceptus and parturition

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Result: No treatment-related effects were observed in any of the developmental  parameters evaluated. No abnormal findings were noted in 
any treated groups during 4 days  post-partum. No treatment-related effects were observed in any of the  developmental parameters evaluated.  
"        Fetal data, provide at a minimum qualitative descriptions of responses  where dose related effects were seen: 
¢        Litter size and weights:  Not affected by treatment.
¢        Number viable (number alive and number dead):  Not affected by treatment.
¢        Sex ratio:  Not affected by treatment.
¢        Grossly visible abnormalities, external, soft tissue and skeletal  abnormalities:  None.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

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:

Based on the results of this screening study, the NOAEL for maternal and developmental toxicity of 3-(triethoxysilyl)propanenitrile in the rat
via oral dosing was determined to be 1000 mg/kg bw/day.