Registration Dossier

Diss Factsheets

Administrative data

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 tetramethyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate (CAS No. 78 -10 -4) and the sodium salt of hydrolysis product, silicic acid, sodium salt (CAS 1344-09-8).

In the absence of measured data for tetramethyl orthosilicate, it is considered appropriate to use this result in support of the reproductive toxicity endpoint. Further information on read-across is given in Section 7.5.

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 Silic, 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.

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.

Methanol

Information about the effects of methanol on fertility is limited. Slight increases in sperm abnormalities were noted in a study in mice (1000 mg/kg/day) although the effect on fertility was not investigated. In a rat 2-generation study there were no effects on fertility. In a cynomolgus monkey study no effects on were noted. Where effects are noted they occur only at high doses.

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.

Conclusion

The non-silanol hydrolysis products of these substances, methanol and ethanol, would not contribute to any reproductive toxicity (fertility) effects at the dose levels tested.


Short description of key information:
There are no fertility data on tetramethyl 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 tetraethylorthosilicate in Sprague-Dawley rats. The NOAELs for parental systemic general toxicity were 10 and 50 mg/kg bw/day for males and females, respectively (CIT 2002).

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 tetramethyl 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 tetraethylorthosilicate 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 tetramethyl orthosilicate, therefore good quality data have been read-across from tetraethyl orthosilicate and silicic acide, sodium salt.

In the absence of measured data for tetramethyl orthosilicate, it is considered appropriate to use this result in support of the developmental toxicity endpoint. Further information on read-across is given in Section 7.5.

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 Silic, 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 products are discussed separately below.

Methanol

In rats, foetal NOAELs have been defined up to 5000 ppm after inhaled exposure. A corresponding figure of 1000 ppm has been defined for mice, which are considered to be more sensitive. At higher concentrations litter resorptions and increased incidences of foetal variations, and in some cases, malformations e. g. exencephaly and encephalocoele have been noted at 20000 ppm in rats and 5000 ppm in mice.

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.

Conclusion

The non-silanol hydrolysis products of these substances, methanol, ethanol and silicic acid would not contribute to any developmental toxicity effects at the dose levels tested.


Justification for selection of Effect on developmental toxicity: via oral route:
The selected study is the only developmental 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

The available read-across data suggest that tetramethyl orthosilicate does not require classification as a reproductive or developmental toxicant according to Regulation (EC) No 1272/2008.

Additional information