Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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 a good quality, guideline study, there was no evidence of embryo or fetal toxicity in rats at any dose (Tyl et al., 1988). Minimal fetal toxicity, evident as dilated lateral cerebral ventricles and reduced ossification in the forelimbs was present at 2.5 ml/kg dose level (equivalent to 2675 mg/kg bw). There was no evidence of embryotoxicity or teratogenicity at any of the doses used under the conditions of this study.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 675 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

Pregnant Fischer 344 rats were dosed with β-(3,4 -epoxycyclohexyl)ethyltrimethoxysilane in corn oil by gavage on gestational days 6 through to 15 at doses of 0, 0.25, 1.0 and 2.5 ml/kg. At termination on gestational day 21 live fetuses were examined for external, visceral and skeletal alterations. Maternal toxicity was observed at 1.0 and 2.5 ml/kg, as evidenced by reduced body weight gain and food consumption during treatment, clinical signs of toxicity, reduced body weight on gestation day 21 (corrected for gravid uterine weight), and increased relative liver weight. There were no significant differences among groups on pre- or postimplantation loss, fetal/litter body weight, or on the incidence of malformations. Minimal fetal toxicity, dilated lateral cerebral ventricles and reduced ossification in the forelimbs was observed at 2.5 ml/kg (equivalent to 2675 mg/kg bw). No embryotoxicity or teratogenicity was observed at any dose.

Pregnant New Zealand white rabbits were dosed with β-(3,4 -epoxycyclohexyl)ethyltrimethoxysilane in corn oil by gavage on gestational days 6 through to 18 at doses of 0, 0.05, 0.25 and 0.75 ml/kg (Tyl et al., 1988). At termination on gestational day 29 live foetuses were examined for external, visceral and skeletal alterations. Maternal mortality (2/20) dams and slightly (but statistically significant) elevated maternal relative kidney weight were observed at 0.75 ml/kg. Clinical signs of toxicity were observed at 0.25 and 0.75 ml/kg. Pre- and postimplantation loss, fetal/litter body weight and incidence of malformations were all unaffected by treatment. Minimal fetal toxicity, extra (13th) ribs and reduced ossification in lumbar arch 4, was observed at 0.75 ml/kg. Therefore administration of β-(3,4 -epoxycyclohexyl)ethyltrimethoxysilane during organogenesis in rabbits produced maternal toxicity at 0.25 and 0.75 ml/kg, and minimal fetal toxicity at 0.75 ml/kg (equivalent to 859 mg/kg bw). No embryotoxicity or teratogenicity was observed at any dose. The study in rabbits is in line with the result derived in the study with rats.

The overall conclusion from both studies is that no developmental toxicity is evident at any of the dose levels tested. The difference in the end dose descriptors (NOAELs) for the two studies is based on the difference in initial dose selection. Therefore, in the absence of embryotoxicity and teratogenicity, the higher NOAEL of 2675 mg/kg bw/day has been selected as the key value for the toxicity to reproduction endpoint to refelct the highest known concentration at which no effects occur. Furthermore, rat is conisdered the most relevant test species for the reproductive endpoint.


Justification for classification or non-classification

Based on the available information, no classification is required for developmental toxicity in accordance with Regulation (EC) No 1272/2008.

Additional information