N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There is no need to conduct an extended one-generation reproductive toxicity study with the registered substance, N-(dimethyl-vinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691-02-3), since no adverse effects were observed in the available 90-day oral repeated dose toxicity study and prenatal developmental toxicity study in the reproductive organs, reproductive function or foetal development.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

In the key prenatal developmental toxicity study, conducted according to OECD Test Guideline 414 and in compliance with GLP, the concluded NOAEL for maternal and developmental toxicity was greater than 100 mg/kg bw/day based on no adverse effects observed at the highest dose tested (Eurofins Munich / BSL Munich Study, 2020).

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 November 2018 to 20 December 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Version / remarks:

adopted 25 June 2018

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han) (Full Barrier)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 11-12 weeks old
- Weight at study initiation: males: 353 – 418 g (mean: 383.8 g, ± 20 % = 307.0 – 460.5 g); females: 196 – 247 g (mean: 217.4 g, ± 20 % = 173.9 – 260.9 g)
- Fasting period before study: no
- Housing: The animals were kept individually in IVC cages for most of the study period. During the pre-mating period, females were kept in groups of two animals and during mating period, two females were paired with one male.
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test item was weighed into a tared plastic vial on a suitable precision balance and the vehicle was added to give the appropriate final concentration of the test item. The formulation was vortexed and/or stirred until visual homogeneity was achieved.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil was selected as the vehicle in consultation with the study sponsor and based on the test item's characteristics.
- Concentration in vehicle: 0, 6.25, 12.5, 25 mg/ml
- Amount of vehicle (if gavage): 4 ml/kg bw
- Lot/batch no. (if required): MKCH1635
- Purity: not specified

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Before the beginning of the treatment period, formulation samples were prepared and analysed in order to obtain knowledge about stability and homogeneity of the test item. Study pre-start stability analysis was performed on the samples from high dose and low dose group and the investigation was made for 0 h, 6 h (RT), 10 day (RT), 10 day (2-8 °C) and 10 day -15 to -35 °C.
Prestart homogeneity investigation was performed on the samples collected from various levels (top, middle and bottom) of high dose and low dose groups.
As the test item was shown to be homogenous (after 30 min without stirring), samples were not collected during the study for the investigation of homogeneity and only samples were taken for substance concentration in the first and last week of the study for all doses (8 samples in total).
Each sample taken during the study was retained in duplicate (sample A, sample B, each of at least 3 mL). The A-samples were analysed and then stored under appropriate conditions based on available stability data. The B-samples are retained at below -15 °C and discarded after completion of the final study report.

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:2 (male to female)
- Length of cohabitation: not specified
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Any other deviations from standard protocol: no

Duration of treatment / exposure:

From gestation day 5 to 19

Frequency of treatment:

daily

Duration of test:

20 days

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Remarks:

control group (C)

Dose / conc.:

25 mg/kg bw/day (actual dose received)

Remarks:

low dose (LD)

Dose / conc.:

50 mg/kg bw/day (actual dose received)

Remarks:

middle dose (MD)

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Remarks:

high dose (HD)

No. of animals per sex per dose:

142 animals (50 males and 92 females) were included in the study. 20 animals per group.

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dose levels used in the study were chosen in consultation with the study sponsor and based on two dose range-finding studies. In the first dose range-finding study pthe test substance caused severe signs of toxicity at 125 mg/kg bw/day.In the second dose range-finding study, pregnant Wistar rats were treated with the test item at doses of 25, 75 and 100 mg/kg bw. No mortality or toxicologically relevant adverse effects were observed in the dose range finding study up to 100 mg/kg bw (the highest dose tested due to the corrosive nature of the test substance). The highest dose level was chosen with the aim of inducing toxic effects, but not death or severe suffering. Thereafter, a descending sequence of dose levels was selected with a view to demonstrate any dose-related response and a NOAEL.
- Rationale for animal assignment (if not random): random

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: The health condition of the animals was recorded. Twice daily all animals were observed for morbidity and mortality except on weekends and public holidays when observations were made once daily.
- Cage side observations checked included: general health condition; morbidity and mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: General clinical observations were made at least once a day, preferably at the same time each day. The observations included spontaneous activity, lethargy, recumbent position, convulsions, tremors, apnoea, asphyxia, vocalisation, diarrhoea, changes in the skin and fur, eyes and mucous membranes (salivation, discharge), piloerection and pupil size. Changes in gait, posture, response to handling as well as the presence of clonic or tonic movements, stereotypes or difficult or bizarre behaviour were recorded.

BODY WEIGHT: Yes
- Time schedule for examinations: The sperm positive females were weighed during GD 0, 5, 8, 11, 14, 17 and 20. Males were not weighed in this study except once before initiation of pairing.

FOOD CONSUMPTION: Yes
- Food consumption of sperm positive females was measured on GD 5, 8, 11, 14, 17 and 20.

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: thyroid/parathyroid glands

OTHER: Thyroid hormone levels from all dams were assessed at the end of the treatment period. Blood samples were collected and serum levels assessed for thyroid hormones (T3, T4, TSH0).

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: [one half of each litter ]
- Soft tissue examinations: Yes: [one half of each litter ]
- Skeletal examinations: Yes: [the foetuses used for the soft tissue examination of 20 litters per group]
- Head examinations: Yes: [the heads of the foetuses used for the soft tissue examination of the first 20 litters per group]
- Anogenital distance: The anogenital distance of each fetus was measured.
- External foetal sex was compared with the internal gonadal sex for all foetuses.
- Any indication for incomplete testicular descent/cryptorchidism were noted for all male foetuses.

Statistics:

A statistical assessment of the results of the body weight and food consumption was performed by comparing values of dosed animals with control animals using a one-way ANOVA and a post-hoc Dunnett Test. Results of absolute and relative organ weights, thyroid hormones and foetal evaluation parameters like external, visceral, craniofacial and skeletal parameters were statistically analysed by comparing values of dosed with control animals using either a parametric one-way ANOVA and a post-hoc Dunnett Test or a non-parametric Kruskal-Wallis Test and a post-hoc Dunn’s Test, based on the results of homogeneity and normality tests. The statistics were performed with GraphPad Prism V.6.01 software or Ascentos 1.3.4 software (p<0.05 is considered as statistically significant).

Historical control data:

Historical control data are included in the attachments.

Clinical signs:

no effects observed

Description (incidence and severity):

There were no treatment related clinical signs of toxicological relevance observed in the females of any treatment group. None of the females showed signs of abortion or premature delivery prior to the scheduled sacrifice.

Mortality:

no mortality observed

Description (incidence):

No mortality was observed during the treatment period and all animals survived until the end of the study.

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

The mean body weight remained unaffected by treatment with the test item and increased with the progress of the study in the control, LD, MD and HD groups throughout the study period. No statistical significance was achieved in any treatment groups on any day or interval of body weight measurement and all values in the treatment groups were comparable to the controls. However, mean body weight gain was slightly decreased and without statistical significance on GDs 5-8 in LD group (13.74% below control) and in HD group (87.61% below control); later on GDs11-14 (24.78% below control), GDs 11-14 (23.57% below control) and GDs 17-20 (10.95% below control) in HD group when compared to the control. As this effect on group mean body weight gain was seen in the LD and MD groups without dose dependency, hence it was not considered related to treatment with test item.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

Food consumption in the LD, MD and HD groups was comparable to the control. Slightly lowered food consumption was observed on GDs 0-5 in LD (11% below control) and HD (15% below control) groups. Statistically significant lower food consumption was observed on GDs 8-11 (14% below control) and GDs 11-14 (17% below control) in HD group. Food consumption in the HD group was slightly lowered during GDs 5-20 (11% below control).

Food efficiency:

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Statistical analysis of post fixed thyroid/parathyroid weights from all dams revealed no statistically significant differences in the absolute and relative (to body weight) thyroid/parathyroid weights of the dose groups when compared to the control group.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No gross pathological changes were observed during the macroscopic examination of the any females of the control, LD, MD and HD groups, except ureters fluid filled in one control animal (no. 10), enlarged spleen in one control animal (no. 7) and abnormal, spotted thymus in animal no. 140 of HD group. These are considered to be an incidental finding and not toxicologically relevant.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

There were no treatment related findings at histopathological evaluation of the thyroid gland in any of the treated groups.

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Description (incidence and severity):

In all terminally sacrificed females, no statistically significant or toxicologically relevant effect was observed on group mean T3, T4 and TSH hormone levels and values were comparable with the controls; except slight but statistically significant increase in T3 levels were observed in HD group. This finding is considered not to be toxicologically significant, since there was no corresponding increase or decrease in T4 or TSH levels and there were no histopathological findings in the thyroid evaluation.

Number of abortions:

no effects observed

Description (incidence and severity):

None of the females showed signs of abortion.

Pre- and post-implantation loss:

no effects observed

Description (incidence and severity):

Pre- and post-implantation loss remained unaffected in the dose groups when compared to the control group.

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Description (incidence and severity):

Early/late resorptions were unaffected in the dose groups when compared to the control group.

Dead fetuses:

no effects observed

Description (incidence and severity):

No dead foetuses were observed in all dose groups.

Changes in pregnancy duration:

no effects observed

Description (incidence and severity):

None of the females showed signs of abortion or premature delivery prior to the scheduled sacrifice.

Changes in number of pregnant:

no effects observed

Description (incidence and severity):

None of the females showed signs of abortion or premature delivery prior to the scheduled sacrifice.

Details on maternal toxic effects:

There were no biologically relevant or statistically significant effects on prenatal data. Prenatal parameters like number of corpora lutea, implantation sites, and early/late resorptions, pre- and post-implantation loss remained unaffected in the dose groups when compared to the control group. Slight differences between dose groups and the controls followed no dose-dependency and thus were not considered toxicologically relevant. No dead foetuses were observed in any of the test item-treated groups or the control group.
Successful mating resulted in 22/23 pregnancies in the LD group, 18/23 in the MD group and 19/22 in the HD group compared to 19/23 pregnancies in the control group.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: No adverse effects observed.

Abnormalities:

no effects observed

Fetal body weight changes:

no effects observed

Description (incidence and severity):

There were no test item-related effects of toxicological relevance observed for the mean foetus weight, male and female foetus weight on litter basis (group mean of individual litter mean) in any of the treatment groups when compared with the controls. However, marginal but statistically significantly lower mean male foetus weight was observed on an individual basis (sum of weight of all foetuses in group divided by total number of foetuses in respective group) in the MD group (2.5% below control, p < 0.05)) and in the HD group (4.3% below control, p < 0.001) and mean female foetus weight of HD (4.6% below control, p < 0.001) when compared with the control. As this difference was marginal and in the light of no significant effect on male and female foetus weight observed based on the litter means, it was considered not to be biologically relevant.

Reduction in number of live offspring:

no effects observed

Description (incidence and severity):

Live foetuses remained unaffected in the dose groups when compared to the control group.

Changes in sex ratio:

no effects observed

Description (incidence and severity):

Sex ratio remained unaffected in the dose groups when compared to the control group.

Changes in litter size and weights:

no effects observed

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Description (incidence and severity):

There were no external abnormalities considered to be of toxicological relevance in any of the dose groups. One foetus from control group (Dam No. 4, foetus no. 10, male) showed generalized oedema and one foetus from HD group (Dam No. 79, foetus no.3, female) showed umbilical hernia, these findings were not considered test item-related and incidental in nature.

Skeletal malformations:

effects observed, non-treatment-related

Description (incidence and severity):

Skeletal examination of the Alizarin red stained foetuses revealed a range of findings which occurred at an incidence generally comparable to or slightly lower or higher in the dose groups when compared to the control group.
The observed incomplete ossification without achieving statistical significance of a few bones and a few other skeletal findings in the HD group were either marginally lower or higher or within historical control data range. Generally delayed ossification is not regarded to persist postnatally and not associated with long-term consequences on survival, general growth and development and therefore is not considered to be adverse.
There was no statistical significance and no indication of a test item-related trend in the type and/or incidences of other skeletal findings and they were therefore considered to be spontaneous in nature.

Visceral malformations:

effects observed, non-treatment-related

Description (incidence and severity):

Internal observation of the foetal viscera by free hand microdissection technique revealed a range of visceral findings in all groups including the control group. Visceral findings observed in the dose groups were at frequencies generally comparable to or in some cases slightly higher or lower in frequency compared to controls. As the observed findings were either minor variations and/or due to a lack of dose dependency and consistency, no toxicological significance can be attributed to these findings and they were considered to be spontaneous in nature.
Higher litter incidences of long thymus in the HD groups were observed (26.3%) when compared to control (11%). There were lower or higher litter incidences umbilical artery malpositioned (46%, 67% and 32% in LD, MD and HD respectively compared to 37 % in control) observed. There were lower or higher litter incidences of liver, lobe supernumerary (27%, 56% and 21% in LD, MD and HD respectively compared to 32 % in control) observed. There were lower or higher litter incidences of azygos vein (bilateral) (64%, 83% (statistically significance) and 32% in LD, MD and HD respectively compared to 47 % in control) observed. There were lower or higher litter incidences of azygos vein (bilateral) (64%, 83% and 32% in LD, MD and HD respectively compared to 47 % in control) observed. There were higher litter incidences of testis, malpositioned (14%, 33% and 11% in LD, MD and HD respectively compared to 5 % in control) observed. There were lower litter incidences of abdomen, internal haemorrhage (68%, 67% and 53% in LD, MD and HD respectively compared to 84 % in control) observed. Lower litter incidence of small, kidney was observed in HD group (5%).
Craniofacial examination by razor blade serial sectioning technique revealed a higher incidences of head, subcutaneous hematoma at all treated (68%, 56% and 47% in LD, MD and HD group respectively) and control groups (68%). Slightly higher incidences of head, subcutaneous oedema and perimeningeal space (large) were observed in HD group (11%) and slightly higher incidences of mid brain, haematoma, subdural was observed in MD and HD group (6% and 11% respectively). These findings were considered to be spontaneous in nature and not related to the treatment with the test item. Statistical analysis of the data revealed no statistical significance for any of these findings.

Other effects:

no effects observed

Description (incidence and severity):

In males, the absolute and relative anogenital distance (AGD) in treatment groups remained unaffected and no statistical significance was observed in any of the treatment group except but statistically significantly higher relative anogenital distance in MD group was observed when compared to the control. The respective means were within the range of historical control data (absolute anogenital distance: between 1.77 mm and 3.71 mm; relative anogenital distance: between 1.15 and 2.40), hence this is not considered to be treatment related effects. In females, the absolute and relative anogenital distance (AGD) was comparable to the control group.
All male foetuses were checked for indication of incomplete testicular descent/cryptorchidism and evaluation revealed completion of testicular descent in all male foetuses from all groups.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed.

Abnormalities:

no effects observed

Developmental effects observed:

no

Conclusions:

In the prenatal developmental toxicity study, conducted according to OECD Test Guideline 414 and in compliance with GLP, the concluded NOAEL for maternal and developmental toxicity is greater than 100 mg/kg bw/day based on no adverse effects observed at the highest dose tested.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In a 14-day dose range finding study, rats were exposed to the registered substance N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine at concentrations of 25, 75 and 100 mg/kg bw/day in corn oil. The highest dose of the study was chosen based on the effects seen at 250 and 125 mg/kg bw/day in a 14-day dose range-finding (BSL Bioservice, 2019b) study in which rats were administered the test substance at 0 (control, corn oil), 250, 50 and 125/75 mg/kg bw/day. The highest dose of 100 mg/kg bw/day for this study was chosen with the aim of inducing toxic effects, but not death or severe suffering. Thereafter, a descending sequence of dose levels was selected (25 and 75 mg/kg bw/day) with a view to demonstrate any dose-related response and a NOAEL. Maternal toxicological effects were observed in regards to the body weight gain, food consumption, and uterine weight. Additionally, pre-implantation loss was higher in all dose groups and post-implantation loss was higher following administration of 75 mg/kg bw/day compared to the control group. Consequently, litter size was slightly smaller at the 75 mg/kg bw/day compared to controls. However, these findings are considered to be incidental and therefore not of toxicological relevance. Moreover, a statistically significant reduction in mean foetal weight was observed in both male and female foetuses at 100 mg/kg bw/day, although it is not considered to be of toxicological relevance. With this background, it was considered suitable to select the doses of 25, 50 and 100 mg/kg bw/day for the main developmental toxicological study.

In the main prenatal developmental toxicity study, conducted according to OECD Test Guideline 414 and in compliance with GLP (Eurofins Munich / BSL Munich Study, 2020), 0, 25, 50 or 100 mg/kg bw/day of N-(dimethyl-vinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691-02-3) in corn oil, were administered orally by gavage to pregnant female rats during gestation days (GD) 5 to 19. The 4 groups comprised 23 female Wistar rats. Animals of the control group were handled identically as the dose groups, but received dried and de-acidified corn oil, the vehicle used in this study.

No treatment related mortality was observed during the treatment period and all animals survived until the end of the study.There was no treatment related or adverse clinical signs of toxicological relevance observed in the females of any treatment group. None of the females showed signs of abortion or premature delivery prior to the scheduled sacrifice. The mean body weight remained unaffected by treatment with the test item and increased with the progress of the study in the control, LD, MD and HD groups. Food consumption in the LD, MD and HD groups was comparable to the control. No test item-related effects of toxicological relevance were noted for any prenatal parameters including terminal body weight, adjusted maternal weight (carcass weight), uterus weight, net weight change from GD 0, number of corpora lutea, implantation sites, early and late resorptions, number of live foetuses, anogenital distance, number of male and female foetuses, sex ratios and percent pre- and post-implantation loss in treatment groups when compared to the controls. No dead foetuses were noted in any of the groups. Successful mating resulted in 22/23 pregnancies in the LD group, 18/23 in the MD group and 19/23 in the HD group compared to 19/23 pregnancies in the control group. No gross pathological changes were observed during the macroscopic examination in any of the females. In all terminally sacrificed females, no toxicologically relevant effect was observed on group mean T3, T4 and TSH hormone levels and values were comparable with the controls. Statistical analysis of post fixed thyroid/parathyroid weights from all dams revealed no statistically significant differences in the absolute and relative (to body weight) thyroid/parathyroid weights of the dose groups when compared to the control group.There were no treatment related findings at histopathological evaluation of the thyroid gland in any of the treated groups.

In male and female foetuses weight and cube root of foetuses weight were comparable to control and no treatment related findings were observed.

In males, the absolute and relative anogenital distance (AGD) in treatment groups remained unaffected and no statistical significance was observed in any of the treatment groups except for statistically significantly higher relative anogenital distance in MD group. The respective means were within the range of historical control data, hence this is not considered to be treatment related effects. In females, the absolute and relative anogenital distance (AGD) was comparable to the control group.  All male foetuses were checked for indication of incomplete testicular descent/cryptorchidism and evaluation revealed completion of testicular descent in all male foetuses from all groups. There were no test item-related effects of toxicological relevance observed for the mean foetus weight, male and female foetus weight on a per litter basis (group mean of individual litter mean) in any of the treatment groups when compared with the controls. There were no external abnormalities considered to be of toxicological relevance in any of the dose groups.

Internal observation of the foetal viscera revealed a range of visceral findings in all dose groups including control. Visceral findings observed in the dose groups were at frequencies generally comparable to or in some cases slightly higher or lower in frequency when compared to controls. As the observed findings were either minor variations and/or due to a lack of dose dependency and consistency, no toxicological significance was attributed to these findings and they were considered to be spontaneous in nature. All litter incidences from dose groups were within the historical control data range and statistically insignificant when compared with the control. Craniofacial examination revealed a higher incidences of head, subcutaneous hematoma at all treated and control groups. Slightly higher incidences of head, subcutaneous oedema and perimeningeal space (large) were observed in the HD group and slightly higher incidences of mid brain, haematoma, subdural were observed in the MD and HD groups. These findings were considered to be spontaneous in nature and not related to the treatment with the test item. Statistical analysis of the data revealed no statistical significance for any of these findings. Skeletal examination of the foetuses revealed a range of findings which occurred at an incidence generally comparable to or slightly lower or higher in the dose groups when compared to the control group. The observed incomplete ossification without achieving statistical significance of a few bones and a few other skeletal findings in the HD group were either marginally lower or higher or within historical control data range. Generally delayed ossification is not regarded to persist postnatally and not associated with long-term consequences on survival, general growth and development and therefore is not considered to be adverse. There was no statistical significance and no indication of a test item-related trend in the type and/or incidences of other skeletal findings and they were therefore considered to be spontaneous in nature.

The concluded NOAEL for maternal and developmental toxicity was greater than 100 mg/kg bw/day based on no adverse effects observed in any of the test groups at the highest dose tested.

Justification for classification or non-classification

Based on the available data, N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine does not require classification for reproductive or developmental toxicity according to Regulation (EC) No 1272/2008.