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Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
813 mg/m³
Study duration:
subacute
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no reproductive toxicity data on (3-chloropropyl)dimethoxymethylsilane or its hydrolysis product, (3-chloropropyl)methylsilanediol, so good quality data for the related substance 3-chloropropyltrimethoxysilane (CAS 2530-87-2) have been used to assess the reproductive toxicity of (3-chloropropyl)dimethoxymethylsilane.

Further details on read-across are given in Section 7.5.

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. The non-silanol hydrolysis product methanol would not contribute to any reproductive toxicity (fertility) effects at dose levels tested.


Short description of key information:
There are no reproductive toxicity data on (3-chloropropyl)dimethoxymethylsilane or its hydrolysis product, (3-chloropropyl)methylsilanediol, so good quality data for the related substance 3-chloropropyltrimethoxysilane (CAS 2530-87-2) have been used to assess the reproductive toxicity of (3-chloropropyl)dimethoxymethylsilane.

3-Chloropropyltrimethoxysilane was tested in an inhalation OECD 422 study (Marburger, 2005), whole-body in rats, up to and including the highest concentration of 100 ppm. In this study there were no signs of adverse effects on reproduction. Therefore based on these results the NOAEC was established to be at least 100 ppm (813 mg/m3).

Justification for selection of Effect on fertility via inhalation route:
The selected study is the only study of reproductive toxicity that is available for a suitable 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 (3-chloropropyl)dimethoxymethylsilane or its hydrolysis product, (3-chloropropyl)methylsilanediol, so good quality data for the related substance 3-chloropropyltrimethoxysilane (CAS 2530-87-2) have been used to assess the developmental toxicity of (3-chloropropyl)dimethoxymethylsilane.
3-Chloropropyltrimethoxysilane was tested in an inhalation OECD 422 study (Marburger, 2005), whole-body in rats, up to and including the highest concentration of 100 ppm. In this study there were no signs of adverse effects on development. Therefore based on these results the NOAEC was established to be at least 100 ppm (813 mg/m3).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
813 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no developmental toxicity data on (3-chloropropyl)dimethoxymethylsilane or its hydrolysis product, (3-chloropropyl)methylsilanediol, so good quality data for the related substance 3-chloropropyltrimethoxysilane (CAS 2530-87-2) have been used to assess the developmental toxicity of (3-chloropropyl)dimethoxymethylsilane.

In addition, a test proposal is included for a pre-natal developmental toxicity study using another surrogate substance, (3-chloropropyl)triethoxysilane (CAS 5089-70-3). This surrogate material is another member of the same chloroalkyl alkoxysilane analogue group and is proposed in order to avoid testing with a corrosive material. The proposal forms part of a wider test plan for alkoxysilane substances.

Following oral exposure, which is the preferred route for developmental toxicity testing, (3-chloropropyl)triethoxysilane will hydrolyse very rapidly to (3-chloropropyl)silanetriol; the same hydrolysis product is generated from (3-chloropropyl)trimethoxysilane. The measured half-life at pH 7 and 25°C is 35 hours, and at pH4 <24 minutes.

For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalyzed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

kobs= k0+ kH3O+[H3O+] + kOH-[OH-] + ka[acid] + kb[base]

At extremes of pH and under standard hydrolysis test conditions, it is reasonable to suggest that the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism. This is supported by studies for various organosilicon compounds in which calculation of kH3O+and kOH-from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7 (REFERENCES NEEDED).

Therefore, at low pH:

kobs≈kH3O+[H3O+]

At pH 4 [H3O+]=10-4mol dm-3and at pH2 [H3O+]=10-2mol dm-3; therefore, kobsat pH 2 should be approximately 100 times greater than kobsat pH 4.

The half-life of a substance at pH 2 is calculated based on:

t1/2(pH 2) = t1/2(pH 4) / 100

The calculated half-life of (3-chloropropyl)triethoxysilane at pH 2 is therefore:

<0.24 minutes (< ca. 14 seconds).

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50(XºC) = DT50(T) x e(0.08. (T-X))

Where T = temperature for which data are available and X = target temperature.

Therefore, at 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is approximately 5 seconds. Systemic uptake from the gut will thus relate only to hydrolysis products. These will be rapidly excreted via urine. There is no evidence of developmental effects in a screening study with (3-chloropropyl) trimethoxysilane.

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.

Thus, no developmental effects due to ethanol, generated by hydrolysisin vivo, are expected at a typical limit dose of 1000 mg/kg/day in the proposed study.

For 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. The non-silanol hydrolysis product methanol would not contribute to any developmental toxicity effects at dose levels tested.


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

Justification for classification or non-classification

Based on the available read across data (3-chloropropyl)dimethoxymethylsilane is not classified for reproductive or developmental toxicity according to Regulation (EC) No 1272/2008.