Tetrapropyl orthosilicate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no fertility data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate (CAS No. 78-10-4) and the sodium salt of hydrolysis product of tetrapropyl orthosilicate, silicic acid, sodium salt (CAS 1344-09-8).In the absence of measured data for tetrapropyl orthosilicate, it is considered appropriate to use this result in support of the reproductive toxicity endpoint. Further information on read-across for these two substances is given in Section 5.6.3.

The hydrolysis product silicic acid is not a reproductive toxin. A data summary exists for synthetic amorphous silica (ECETOCJACC (Joint Assessment of Commodity Chemicals) Report 051- Synthetic Amorphous Silica, Brussels, September 2006;http: //www. ecetoc. org/jacc-reports)which supports this conclusion.

The registered substance, hydrolyses very rapidly following oral exposure to silicic acid. Test data are available for sodium silicate and since sodium ions are part of normal biological systems (and hence do not contribute any adverse reproductive effects), it is therefore directly relevant to read across the existing data in support of this endpoint for the silicate counterion. The non-silicon hydrolysis product, n-propanol, is discussed separately below.

n-Propanol

There is limited information on the effects of propanol on rat fertility and it comes from studies conducted by the inhaled route. No effects on fertility have been recorded at doses of up to 7000 ppm (17460 mg/m³) in female rats. In male rats at the same dose, a reduction in fertility was noted in that mating occurred but the females were found not to be pregnant. However, this effect was reversible after approximately 13 weeks. The male rat fertility No Adverse Effect Level has been established as 3500 ppm (8730 mg/m³). An inhaled dose of 7000 ppm (7 hours) converts approximately to an oral dose of 5800 mg/kg.

Ethanol

Ethanol is reported to have an effect on male fertility in some rat studies but not others and where noted generally involve sperm parameters. However, where effects are noted they occur only at high doses.

Based on the fact that adverse effect of propanol are only noted at very high administered doses in repeat dose and reproductive toxicity studies, these non-silanol hydrolysis products are not expected to contribute to any adverse effects for systemic or reproductive toxicity at the relevant dose levels.

The following information is taken into account for any hazard / risk assessment:

There are no fertility data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate (CIT, 2005) and the sodium salt of the hydrolysis product of tetrapropylorthosilicate (Smith, 1973).In an OECD 422 study there were no treatment-related adverse effects on reproduction evident up to 100 mg/kg bw/day tetraethyl orthosilicate in Sprague-Dawley rats. The NOAELs for parental systemic general toxicity were 10 and 50 mg/kg bw/day for males and females, respectively.

A limited 4-generation study assessed the effect of sodium silicate administered via drinking water to rats at doses corresponding to 79 and 159 mg sodium silicate/kg bw/d from weaning until mating. For 4 consecutive generations, the rats were mated and the total number of offspring analysed. The average litter sizes were 9.6, 6.8 and 8.4 animals/litter for the Control and treated groups respectively. Survival of offspring until weaning was poor, even in the controls (35, 24, and 11% at 0, 79, 159 mg/kg bw/d, respectively). The total number of offspring born was reduced to 67 % of the controls at 79 mg/kg bw/d and to 80 % at 159 mg/kg bw/d. Litters born to females receiving silicate were frequently stillborn or small and weak, with survival limited to only a few days. In addition, cannibalism was prevalent and necrosis of the tail and occasionally the feet was observed in offspring of silicate-treated animals. Severe limitations of the study and intercurrent deaths, including controls, make it difficult to draw any firm conclusions from this study.

Short description of key information:
There are no fertility data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate.

In an OECD 422 study there were no treatment-related adverse effects on reproduction evident up to 100 mg/kg bw/day tetraethyl orthosilicate in Sprague-Dawley rats. The NOAELs for parental systemic general toxicity were 10 and 50 mg/kg bw/day for males and females, respectively.

Justification for selection of Effect on fertility via oral route:
The selected study is the only reproductive toxicity study available for a relevant surrogate substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Effects on developmental toxicity

Description of key information

There are no developmental toxicity data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate. 
In an OECD 422 study there were no treatment-related adverse effects on development of offspring evident up to 100 mg/kg bw/day tetraethyl orthosilicate in Sprague-Dawley rats. The NOAELs for parental systemic general toxicity were 10 and 50 mg/kg bw/day for males and females, respectively. 

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

There are no developmental toxicity data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicateand the sodium salt of the hydrolysis product of tetrapropyl orthosilicate, silicic acid, sodium salt (CAS 1344-09-8).

In the absence of measured data for tetrapropyl orthosilicate, it is considered appropriate to use this result in support of the developmental toxicity endpoint. Further information on read-across for these two substances is given in Section 5.6.3.

Silicic acid is not a developmental toxin. A data summary exists for synthetic amorphous silica (ECETOCJACC (Joint Assessment of Commodity Chemicals) Report 051- Synthetic Amorphous Silica, Brussels, September 2006;http: //www.ecetoc.org/jacc-reports)which supports this conclusion. Furthermore, there was no evidence of an effect of treatment on developmental parameters in a developmental toxicity study in the mouse with silicic acid, sodium salt.

The registered substance, hydrolyses very rapidly following oral exposure to silicic acid. Test data are available for sodium silicate and since sodium ions are part of normal biological systems (and hence do not contribute any adverse developmental effects), it is therefore directly relevant to read across the existing data in support of this endpoint for the silicate counterion. The non-silicon hydrolysis product, n-propanol, is discussed separately below.

n-Propanol

There is limited information on the effects of propanol on developmental toxicity and it comes from studies conducted by the inhaled route. At high doses of 7000 (17460 mg/m³) or 10 000 ppm (24940 mgm³) increases in fetal malformations (skeletal and visceral) have been noted. No effects on fetal development have been recorded at doses of up to 3500 ppm (8730 mg/m³). No effects on post-natal development have been noted at doses up to 7000 ppm (17 460 mg/m³).

Ethanol

Rats and mice maintained on liquid diets containing 5 – 10% ethanol for 5 weeks or longer showed some adverse physical and functional effects on the testes. Some indications of toxicity to the foetus, including deaths, growth retardation and increased malformations have been noted in rats and mice given diets in which 15-35% of the calories were derived from ethanol. However in other studies, no effect on the foetuses were seen in mice and rabbits given drinking water containing up to 15% ethanol, or inhaling up to 20 000 ppm ethanol, during pregnancy. Based on the fact that adverse effect of propanol are only noted at very high administered doses in repeat dose and reproductive toxicity studies, these non-silanol hydrolysis products are not expected to contribute to any adverse effects for systemic or reproductive toxicity at the relevant dose levels.

The following information is taken into account for any hazard / risk assessment:

There are no developmental toxicity data on tetrapropyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate (CIT, 2005)and silicic acid, sodium salt (Sawaiet al. , 1980).

In an OECD 422 study there were no treatment-related adverse effects on development of offspring evident up to 100 mg/kg bw/day tetraethyl orthosilicate in Sprague-Dawley rats. The NOAELs for parental systemic general toxicity were 10 and 50 mg/kg bw/day for males and females, respectively.

In a study to investigate fetal and neo-natal development in mice there were no adverse effects noted up to the maximum dose tested of 200 mg/kg/day silicic acid.

Justification for selection of Effect on developmental toxicity: via oral route:
The selected study is the only reproductive toxicity study available for a relevant surrogate substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for classification or non-classification

There are no data to suggest that tetrapropyl orthosilicate should be classified for effects on reproduction, and development of offspring under Regulation 1272/2008 EC.