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Administrative data

Description of key information

A subchronic reproductive toxicity study on [3-(2,3-epoxypropoxy)¬propyl]trimethoxysilane resulted in parental and reproductive NOAELs of 500 and ≥ 1000 (the highest dose tested) mg/kg bw/d respectively, in rats. The parental NOAEL of 500 mg/kg/day from this study is selected as a worst case NOAEL for the oral repeat dose toxicity of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane.
This result is supported by a subchronic toxicity study with rats according to OECD Guideline 408 the NOAEL for beta-(3,4-epoxycyclohexyl)ethyltriethoxysilane was found to be 1000 mg/kg bw/day.
In the supporting oral study, following repeated oral exposure to [3-(2,3-epoxypropoxy)propyl]trimethoxysilane with gavage doses of 1000 mg/kg bw/day for 28 days, no adverse effects were observed in rats (DCC, 1981).
Following nine exposures to an aerosol of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (target concentrations 0, 75, 225 and 750 mg/m3) over a two week period there were no adverse effects found in rats. However, 5/10 males and 1/10 female rats died between day three and five of dosing when exposed to a concentration of 0.75 mg/l. The animals appeared to have died from exhaustion due to malnutrition. The NOAEC was 0.225 mg/l (Allied Corporation, 1982).
There is also a repeated inhalation study for the hydrolysate of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, which tested a single concentration of 0.119 mg/l for 28 days. A NOAEC could not be established as significant reductions in body weight (11% decrease in absolute body weight and 29% reduction in body weight gain) were observed at this concentration. The study was conducted to investigate the potential for induction of laryngeal granulomas and therefore did not include haematology, clinical chemistry or urinalysis investigations. There was no adverse pathology.
There are no reliable dermal studies available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
225 mg/m³

Additional information

There was only one oral study and one appropriate inhalation study for repeated dose toxicity of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane. These were of good quality and the inhalation study is assigned as key study for this route. A 90-day repeated dose oral toxicity study (OECD 408) is also available for the related substance beta-(3,4-epoxycyclohexyl)ethyltriethoxysilane, 10217-34-2.

Use of data for beta-(3,4-epoxycyclohexyl)ethyltriethoxysilane, 10217-34-2, to support the data set for [3-(2,3-epoxypropoxy)propyl]trimethoxysilane 2530-83-8, GLYMO, is justified based on the following arguments:

- The epoxy-ring is peripheral and connected to the silane in a similar way, yielding the same functionality;

- The similarity of chemical reactivity of the epoxy group in both molecules can be demonstrated in typical applications;

- The hydrolysis reaction of the alkoxysilane group results in formation of ethanol for beta-(3,4-Epoxycyclohexyl)ethyltriethoxysilane versus methanol for [3-(2,3-epoxypropoxy)­propyl]trimethoxysilane. Neither methanol nor ethanol has any significant toxicological effects in rats and rabbits used in standard laboratory tests.

Justification for classification or non-classification

There are no data to suggest that [3-(2,3-epoxypropoxy)propyl]trimethoxysilane should be classified for STOT-RE following oral or inhalation exposure.