Hexadecyltrimethoxysilane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In order to fulfil the standard information requirements, a GLP-compliant extended one-generation reproductive toxicity study in rats via the oral route following OECD TG 443 is proposed according to Annex X, Column 1, Section 8.7.3.

Effect on fertility: via oral route

Endpoint conclusion:

no study available (further information necessary)

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

Prenatal developmental toxicity study (OECD TG 414), rat: NOAEL maternal and fetal toxicity: 300 mg/kg bw/day

In order to fulfil the standard information requirements, a GLP-compliant prenatal developmental toxicity study in rabbits via the oral route following OECD TG 414 is proposed according to Annex X, Column 1, Section 8.7.2.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, of Regulation (EC) No. 1907/2006.

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 prenatal developmental toxicity study according to OECD TG 414 and in compliance with GLP, nulliparous and non-pregnant female Wistar rats were mated with males (2:1 ratio) and divided into four groups of each 23 animals (BSL, 2021). The pregnant females were administered the test substance hexadecyl(trimethoxy)silane via gavage from gestation day (GD) 5 to 19 at dose levels of 75, 300 and 1000 mg/kg bw/day, respectively. The animals of the control group received the vehicle dried and de-acidified corn oil.

No test item-related mortality was observed during the study. Test item-related clinical signs like piloerection, spontaneous reduced activity, hunched posture, nasal discharge, dehydration, wasp waist, moving the bedding and increased salivation at post dose were observed mainly between GD 12 and GD 20. These are considered to be treatment related effects in the high-dose group.
No test item-related effects of toxicological relevance were noted for any prenatal parameter including number of corpora lutea, implantation sites, late resorptions, number of live foetuses, anogenital distance (AGD), number of male and female foetuses as well as sex ratios in treatment groups when compared to the control group. No dead foetuses were noted in any of the groups.

Terminal body weight, adjusted maternal weight (carcass weight) and net weight change from GD 0 did not show a treatment related effect in the low-dose group. In the mid-dose group, a slight but non-significant reduction net weight change from GD 0 was seen. A statistically significant reduction in adjusted maternal weight (carcass weight) was observed in the high-dose group (17.1% below control). A statistically significant reduction in net weight change from GD 0 was observed in the high-dose group (122.6% below control).

No statistically significant or test item-related effects were observed for group mean T3, T4 and TSH hormone levels and values were comparable between all animal groups, except for the mid- and high-dose groups in which T4 was found to be statistically significantly reduced. Due to the absence of weight effects and histopathological effects in the thyroid/parathyroid in any of the treated groups, the statistically significant reduction in group mean T4 levels is not considered to represent test item-related effects. In addition, there were no corresponding changes in either in T3 or TSH hormone levels.
Test item-related effects were observed for the mean foetal weight, male and female foetal weight on a per litter basis (group mean of individual litter mean) in the high-dose group when compared to the control. These effects are considered to be secondary to maternal toxicity i.e. lowered body weight and food consumption.
No test item-related or toxicologically relevant external, visceral or craniofacial findings were observed in the treatment groups. However, there were skeletal findings observed in the high-dose group, but the incidence of these did not achieve statistical significance. As an effect that is generally classified as variation, the incidences of altered ossification were clearly increased in the high-dose group but were considered to be a secondary effect of lower foetal weight in the foetus as a results of maternal toxicity.
Therefore, a NOAEL for maternal and foetal toxicity could be established at 300 mg/kg bw/day.

Justification for classification or non-classification

The currently available data on toxicity of reproduction of the test substance including the fertility parameters examined in the subchronic repeated dose toxicity study do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.