[3-(trimethoxysilyl)propyl]urea

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction (fertility): no data available

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

Additional information

Toxicity to reproduction (fertility)

According to Regulation (EC) No 1907/2006, Annex VIII 8.7.1. Column 2, a screening study for reproductive/developmental toxicity for assessment of reproductive toxicity is not required if a pre-natal developmental toxicity study (Annex IX, 8.7.2) or an Extended One-Generation Reproductive Toxicity Study (Annex IX, Section 8.7.3) is available. A GLP compliant pre-natal developmental toxicity study (rat, oral route) with the source substance (structural analogue or surrogate) ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters (CAS 116912-64-2) is available and has been used as read-across. The read-across is conducted based on an analogue approach, in accordance with the Regulation (EC) 1907/2006 to avoid tests in terms of animal welfare. Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

Effects on developmental toxicity

Description of key information

Prenatal developmental toxicity study (OECD TG 414, GLP): NOAEL=1000 mg/kg/bw/day (highest dose tested) (RA from CAS 116912-64-2)

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no adverse clinical signs, no treatment-related effect on body weight, food consumption, prenatal data parameters and gross pathology

Key result

Abnormalities:

no effects observed

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related and toxicologically relevant effect on litter weight data, external, skeletal, visceral or craniofacial foetal findings

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The study was conducted according to an appropriate OECD test guideline and in compliance with GLP.

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

No data on repeated dose toxicity on 1-[3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) are available. Therefore, the risk assessment was performed based on the available data from the source substance ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters (CAS 116912-64-2). The source substance is the reaction mass of 1-[3-(trimethoxysilyl)propyl]urea, 1-[3-(dimethoxyethoxysilyl)propyl]urea, 1-[3-(methoxydiethoxysilyl)propyl]urea and 1-[3-(triethoxysilyl)propyl]urea and therefore contains the target substance as one of its components. In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from the analogue substance has been applied to support the human health hazard assessment of 1-[3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3).

Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

In an OECD 414 study conducted in accordance to GLP, nulliparous and non-pregnant females were mated with males (2:1 ratio) and divided into four groups based on their body weights on the day of sperm positive vaginal smears (GD 0) (BSL, 2021). The test item ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters (CAS 116912-64-2) was administered via gavage during gestation days 5 to 19 at dose levels of 100, 300 and 1000 mg/kg bw/day. The control group received sterile water. The 4 groups comprised 25 female Wistar rats each.

 

In dams, no mortality occurred during the treatment period of this study and all animals survived until terminal sacrifice. Additionally, there were no clinical signs of toxicological relevance observed in any of the treatment groups. The mean body weight remained unaffected and increased during the progress of the study in the control and treatment groups. There was no effect on body weight gain (gestation day 0-20) observed in any of the treatment groups when compared to the controls. In correlation to the body weight and body weight gain, food consumption in the treatment groups was comparable to the controls. There was no statistically significant effect observed on food consumption in treatment groups throughout the study period when compared with the controls.
No test item-related effects of toxicological relevance or statistical significance were noted for any of prenatal data parameters like terminal body weight, gravid uterus weight, adjusted maternal weights, number of corpora lutea, implantation sites, live foetuses, early and late resorptions, number of male and female foetuses, sex ratio, number of foetuses in each uterine horn and percent pre- and post-implantation loss. No dead foetuses were noted in any of the groups. Successful mating resulted in 24/25 pregnancies in the mid- and high-dose groups compared to 25/25 pregnancies in the control and low-dose group. No gross pathological changes of toxicological relevance were observed during the macroscopic examination of the treated females.

There were no test item-related effects of toxicological relevance or statistical significance observed for any litter data parameters like mean foetus weight (individual and litter basis), male and female foetus weight (individual basis), the total, male and female litter weight (litter basis) in any of the treatment groups when compared with the controls. All group mean values and individual values for various litter data parameters from treatment groups were comparable with the controls.

There were no external, visceral, or craniofacialabnormalities considered to be of toxicological relevance in any of the dose groups. Statistical analysis of data revealed no significant differences compared to the control group.

Skeletal examination of the Alcian blue and 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. Most of the skeletal findings observed in HD group were within the historical control data range.

At the high dose when compared to the concurrent control group, slightly higher litter incidences, but without achieving statistical significance were noted for: incomplete ossification of frontal (B) (25% compared to 15% in controls), interparietal (85% compared to 65% in controls), parietal (B) (55% compared to 30% in controls), squamosal (B and R) (15-25% compared to 0-5% in controls), zygomatic arch (B) (15% compared to 5% in controls), femur (B) (15% compared to 5% in controls), basioccipital with small hole (15% compared to 5% in controls), scapula bent (B) (5% compared to 0% in control), scapula bent (R) (20% compared to 0% in control), branched xiphoid cartilage (65% compared to 55% in control), left 14th rudimentary rib (65% compared to 50% in control), wavy ribs (65% compared to 55% in controls), rudimentary 7th cervical rib (5-15% compared to 0% in control) misshapen humerus (20% compared to 5% in controls), unossified forelimb metacarpals (55% compared to 30% in controls) and pelvic girdle (B) caudal shift (20% compared to 10% in control). The observed reduced ossification without achieving statistical significance of few bones at 1000 mg/kg bw/day that normally exhibit rapid ossification during the last days of gestation indicates a slight generalised skeletal delay at 1000 mg/kg bw/day. Generally slightly 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. Rudimentary/short ribs are considered as transient abnormalities. In contrast, full/long ribs are considered permanent and may cause health effects in humans; however, postnatal consequences in rats are unknown but are assumed to be minimal. This finding was not considered to be treatment-related but spontaneous in nature. Wavy ribs and bent scapulae are common findings in rodent studies and are considered to be postnatally reversible. Thus, wavy ribs are classified as variations and were not considered as an adverse effect of the treatment with the test item.

 

No effects of ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters on females and foetuses were found at dose levels up to 1000 mg/kg bw/day. The NOAEL for maternal toxicity and embryo-foetal toxicity of the test substance in this study is considered to be =1000 mg/kg bw/day.

Justification for classification or non-classification

The available data on developmental toxicity of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008. However, as no study is available to address fertility, the overall conclusion for classification of reproductive toxicity is data lacking.