Registration Dossier

Administrative data

Key value for chemical safety assessment

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
2 210 mg/m³
Study duration:
subacute
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no adequate reproductive toxicity data on chloro(dimethyl)vinylsilane or its hydrolysis product, dimethyl(vinyl)silanol, so good quality data for the related monosilanol, trimethylsilanol (1066-40-6) have been used to assess the potential for adverse effects on reproductive parameters following exposure to chloro(dimethyl)vinylsilane.

It is considered not to be either ethical or technically feasible to perform reproductive toxicity testing with chloro(dimethyl)vinylsilane by any route of exposure due to its known corrosive properties, which will dominate the toxicity profile of this substance. Following repeated oral dosing, the corrosive nature of the product could affect the lining of the stomach, giving rise to hyperplasia and a subsequent reduced food intake. This would confound the interpretation of any systemically driven effects. A guideline-compliant reproductive toxicity inhalation study should elicit systemic toxicity at the highest test concentration. Since the local corrosive effects of chloro(dimethyl)vinylsilane would be significant a valid inhalation study according to the relevant guidelines is technically not feasible. It is also unlikely that any systemic effects would be seen at dose levels made sufficiently low to prevent the known corrosive effects and/or distress in the test species. This has been confirmed in a 28-day inhalation study with another chlorosilane, dichloro(dimethyl)silane (WIL Research, 2014) in which there were no effects of treatment on clinical signs, body weight or food consumption that would indicate a systemic effect. Furthermore, the histopathology in the study indicated that the effects in the upper respiratory tract were similar to HCl. It is therefore concluded that HCl will determine the inhalation toxicity profile of chloro(dimethyl)vinylsilane.

With regard to the dermal route, due to the known corrosive effects of chloro(dimethyl)vinylsilane appropriate H-phrases and P-statements are included in the labelling, but repeated skin contact is unlikely to occur. Any accidental skin contact is expected to cause severe local effects but would be unlikely to cause any systemic effects.

INHALATION ROUTE

There are no adequate reproductive toxicity data on chloro(dimethyl)vinylsilane or its hydrolysis product, dimethyl(vinyl)silanol, so good quality inhalation data for the related monosilanol, trimethylsilanol (1066-40 -6) have been used to assess the potential for adverse effects on reproductive parameters following exposure to chloro(dimethyl)vinylsilane.

Three groups of Crl:CD(SD) rats, each group consisting of 10 males, 10 toxicity phase females and 10 reproductive phase females, were exposed via whole-body inhalation to vapour atmospheres of the test article, trimethylsilanol, 6 hours/day, 7 days/week. Target exposure concentrations were 60, 300 and 600 ppm. A concurrent control group was exposed to filtered air on a comparable regimen. F0 males and reproductive phase females were exposed daily for 14 days prior to mating, throughout the mating period and continuing through the day prior to euthanasia (males) or gestation day 20 (reproductive phase females). F0 reproductive phase females with no evidence of mating or that failed to deliver were exposed through post-mating or post-cohabitation day 24 (the day prior to euthanasia) for a total of 52 consecutive days. F0toxicity phase females were exposed for 28 consecutive days. Animals were examined according to OECD test guideline 422.

One F0 toxicity phase female in the 300 ppm group was found dead on study day 35, the day of scheduled necropsy.  While the cause of death for this female was not determined, there were no mortalities in the 600 ppm group.  Therefore, this mortality at 300 ppm was not attributed to test substance exposure. All other toxicity phase females and all F0 males and reproductive phase females survived to the scheduled necropsies.  There were no test substance-related macroscopic findings or effects on organ weights. There were no remarkable clinical observations noted at any exposure level. Mean body weights, body weight gains and food consumption for males and females at all exposure levels were similar to the control group for all phases. There were no test article-related effects on FOB parameters, including home cage, handling, open field, sensory, neuromuscular or physiological observations and no effects on locomotor activity patterns for males and toxicity phase females. No remarkable shifts in the pattern of habituation occurred during locomotor activity assessments in any of the test article-exposed groups when the F0 males and toxicity phase females were evaluated prior to the initiation of exposure or during the study week 4 evaluation. Decreased mean eosinophil and lymphocyte counts were noted for the 600 ppm group F0 males.  In addition, increased mean alanine aminotransferase values were noted for F0 males and toxicity phase females in the 600 ppm group when compared with the control group.  Although these changes were considered test article‑related, they were not considered adverse in the absence of correlating histopathology.

Mean mating, fertility and copulation/conception indices for all exposure concentrations were similar to the control group.  Mean gestation lengths, postnatal survival and F1 body weights were similar to the control group. There were no test substance-related macroscopic findings observed in pups. Test substance-related effects were limited to changes in haematology (lower eosinophil and lymphocyte counts for males) and serum chemistry (higher alanine aminotransferase for males and toxicity phase females) at 600 ppm. These changes occurred in the absence of correlating histologic changes and were not considered adverse. 

Therefore, under the conditions of this screening study, an exposure level of 600 ppm was considered to be the no-observed-adverse-effect concentration (NOAEC) for reproductive, systemic and neonatal toxicity of trimethylsilanol when administered via whole-body inhalation exposure to Crl:CD(SD) rats.

Limited data are available regarding the reproductive toxicity in animals following oral, dermal or inhalation exposure to hydrogen chloride. However, protons and chloride ions exist as normal constituents of body fluid in animals, hence low concentrations of hydrogen chloride appear not to cause adverse effects in animals. Therefore the hydrolysis product of chloro(dimethyl)vinylsilane, HCl, would not be expected to cause reproductive toxicity in experimental animals or humans following initial exposure to chloro(dimethyl)vinylsilane.

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. In the case of repeated dose toxicity and reproductive toxicity relevant properties are structural similarity as well as physical-chemical and basic toxicological parameters in the same range. In the following paragraphs the read-across approach for chloro(dimethyl)vinylsilane is evaluated point by point.

Read-across hypothesis

Chloro(dimethyl)vinylsilane is very unstable in the presence of water and will hydrolyse very rapidly to dimethyl(vinyl)silanol and hydrogen chloride in the presence of moisture (see Section 5.1.2 of the technical dossier). Most, if not all of this will have occurred before absorption into the body. Therefore the use of hydrolysis product data is considered appropriate in the assessment of the repeat dose systemic and reproductive toxicity profile of chloro(dimethyl)vinylsilane. As has been demonstrated by the 28-day repeated dose inhalation study with dichloro(dimethyl)silane (WIL, 2014) there would also be additional corrosive local effects from HCl if chloro(dimethyl)vinylsilane were to be administered.

Local corrosive effects of chloro(dimethyl)vinylsilane can be assessed qualitatively or quantitatively by considering the amount of HCl produced by hydrolysis.

Analogue approach justification

(a) Structural similarity

The fundamental basis for the read across approach is the similarity between the hydrolysis product of the registration substance, dimethyl(vinyl)silanol, and the surrogate substance trimethylsilanol. These substances differ by replacement of one methyl group with a vinyl group. The surrogate substance is the only monosilanol for which measured mammalian toxicological data are available.

The properties of monosilanols differ substantially from those of di- and trisilanols. All silanols can be self-reactive, but whereas for monosilanols the reaction is self-limiting dimerization, di- and trisilanols can proceed to form oligomers and polymers. In the case of trisilanols these oligomers and polymers can be highly crosslinked. It is therefore not valid to read-across data from such silanols (or di/tri-alkoxysilanes) to a monosilanol-producer.

(b) Similar physicochemical characteristics

Due to the very rapid hydrolysis of chloro(dimethyl)vinylsilane, it is not feasible to measure some key physicochemical properties; however, the hydrolysis product has similar physicochemical characteristics to the read-across substance, trimethylsilanol. A data matrix is attached in Section 13 of the IUCLID dossier, and the key physicochemical parameters are summarised below.

CAS Number

1719-58-0

1066-40-6

Chemical Name

Chloro(dimethyl)vinylsilane

Trimethylsilanol

Si hydrolysis product

Dimethyl(vinyl)silanol

Not applicable

Molecular weight

120.65

90.20

log Kow(parent)

Not measurable

1.2

log Kow(silanol hydrolysis product)

1.5

Not applicable

Water sol (parent)

Not measurable

995 mg/l

Water sol (silanol hydrolysis product)

3700 mg/l

Not applicable

Vapour pressure (parent)

9500 Pa at 20oC

1290 Pa at 20oC

Vapour pressure (silanol hydrolysis product)

250 Pa at 25oC

Not applicable

 

Hydrolysis t1/2at pH 7 and 25°C

<1 minute

Not applicable

  

Hydrolysis t1/2at pH 2 and 37°C

 <1 minute  Not applicable

Chloro(dimethyl)vinylsilane hydrolyses very rapidly in contact with moisture and therefore any systemic exposure to the substance would relate only to hydrolysis products.

(c) Similar toxicokinetics

The only potential route for oral exposure applicable to chloro(dimethyl)vinylsilane is for humans exposed via the environment. As explained above, exposure would be predominantly to monomeric silanol and it is not feasible to conduct a meaningful study for this endpoint. Nevertheless, the available repeated dose toxicity data for an analogous monosilanol (trimethylsilanol) are included for completeness.

For the inhalation route, dimethyl(vinyl)silanol and trimethylsilanol have similar molecular weight and log Kow values, indicating that systemic uptake in the respiratory tract is similar. The higher vapour pressure of trimethylsilanol means that the available inhalation study was conducted at a concentration higher than could be achieved with the hydrolysis product of the registration substance and thus represents a worst case in terms of exposure concentration.

The critical effect following dermal exposure to chloro(dimethyl)vinylsilane is corrosion and therefore significant systemic exposure is not expected since appropriate measures are in place to prevent local effects (see Section 9 of the CSR).

(d) Acute toxicity

Although an acute oral toxicity study is available for the registration substance (LPT, 2002), it is not appropriate to directly compare the results of this study with the available data for trimethylsilanol due to the potential for confounding effects due to the corrosive nature of the chlorosilane.

The available oral toxicity study for trimethylsilanol (Bayer, 1985), reports an LD50 for trimethylsilanol of 3.5 ml/kg bw (2835 mg/kg bw based on a density of 0.81 g/cm3) in rats. There was a general deterioration in the animals' health, including anaesthesia, lateral position, ruffled fur. All surviving animals appeared symptom-free after ten days.

In an acute inhalation study (WIL, 2007), the reported 4 hour LC50of trimethylsilanol was 3151 ppm (11.8 mg/l) in rats. Significant clinical observations for the surviving animals decreased respiration, shallow respiration, rales, hypoactivity, prostration, ataxia, lacrimation of the eyes, partial closure of the eyes, decreased defecation, decreased urination, opacity of the eyes.

In comparison, acute oral and inhalation have been included for a number of alkoxysilane substances which contain vinyl groups, as shown in the table below, which indicate that the presence of the vinyl group in place of methyl does not lead to any enhanced acute systemic toxicity and in fact trimethylsilanol may be regarded as a worst case.

CAS Number

1066-40-7

1825-61-2

16753-62-1

2768-02-7

78-08-0

Chemical name

Trimethylsilanol

Methoxytrimethylsilane

Dimethoxymethylvinylsilane

Trimethoxyvinylsilane

Triethoxy(vinyl)silane

Hydrolysis product

Not applicable

Trimethylsilanol

Methylvinylsilanediol

Vinylsilanetriol

Vinylsilanetriol

Acute oral LD50(rat)

3.5 ml/kg (2835 mg/kg)

3575 mg/kg

 No data

7.34 ml/kg males; 7.46 ml/kg females.

>5000 mg/kg

Acute inhalation LC50(rat)

11.8 mg/l

43.1 mg/l

>5 mg/l

2773 ppm (16.9 mg/l)

 

These indicate that the presence of the vinyl group in place of methyl does not lead to any enhanced acute systemic toxicity and in fact trimethylsilanol may be regarded as a worst case.

(e) Discussion of repeated systemic toxicity of the non-silanol hydrolysis product

In a 90-day repeated inhalation study with HCl, no serious adverse systemic effects were observed in rats and mice exposed up to 50 ppm (ca. 70 mg/m3) for 6 hours per day, 5 days per week. The only significant adverse finding relating to systemic toxicity was decreased body weight at the highest dose level. Local effects on the nasal turbinates of mice were observed at all dose levels tested (10, 20 and 50 ppm). Testing with HCl at higher test concentrations is neither ethically nor technically feasible since severe corrosive effects would lead to discomfort and distress in the test animals. The author of this CSR considers that the apparent systemic effects at 50 ppm in the study were most likely secondary to local corrosive effects at this dose level.

Following uptake of HCl, hydrogen and chloride ions will enter the body’s natural homeostatic processes and significant systemic effects are unlikely.

(f) Discussion of local inhalation toxicity of HCl and chlorosilanes

No long-term toxicity studies are available for the registration substance, chloro(dimethyl)vinylsilane. A non-standard acute inhalation study (Dow Corning, 1969) is available. In this study, all 5 animals exposed to saturated vapour died within 27 minutes. Significant ocular and respiratory irritation was observed after 3 minutes of exposure.

Comparison of the acute inhalation toxicity of chlorosilanes to that of hydrogen chloride showed a correlation between toxicity (LC50) and the amount of HCl generated by the chlorosilanes (Jean et al., 2006).

In a 4-week inhalation study (WIL, 2014) conducted specifically to assess respiratory tract changes and local toxicity, dichloro(dimethyl) silane was administered to rats at 5 or 25 ppm resulting in concentration-related effects in the nasal cavity indicative of a local irritant effect. The local effects noted at 25 ppm (resulting in 50ppm HCl on hydrolysis) were considered to be generally comparable to the group receiving hydrogen chloride at 50 ppm in the same study.

Given the comparability of existing results for chlorosilanes and HCl, and the rapid hydrolysis of chlorosilanes in the atmosphere, the effects of HCl dominate local toxicity on the respiratory tract and therefore data for HCl can be used to assess the local repeated-dose toxicity of chlorosilanes.


Short description of key information:
In an inhalation study conducted in accordance with OECD 422 with trimethylsilanol (Fleeman, 2008), which was conducted to GLP, there were no effects on reproduction parameters. Therefore, under the conditions of this screening study, an exposure level of 600 ppm was considered to be the no-observed-adverse-effect concentration (NOAEC) for reproductive toxicity.

Justification for selection of Effect on fertility via inhalation route:
The key study is the only available study for the reproductive toxicity endpoint. It was conducted in accordance with a relevant OECD test guideline and in compliance with GLP.

Effects on developmental toxicity

Description of key information
In an oral OECD 414 developmental toxicity study with the hydrolysis product, trimethylsilanol (Harlan, 2014), the maternal and fetal NOAELs were 150 mg/kg/day. In an inhalation study conducted in accordance with OECD 422 with trimethylsilanol (Fleeman, 2008), which was conducted to GLP, there were no effects on developmental parameters. Therefore, under the conditions of this screening study, an exposure level of 600 ppm was considered to be the no-observed-adverse-effect concentration (NOAEC) for developmental toxicity. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 210 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no adequate developmental toxicity data on chloro(dimethyl)vinylsilane or its hydrolysis product, dimethyl(vinyl)silanol, so good quality data for the related monosilanol, trimethylsilanol (1066-40-6) have been used to assess the potential for adverse effects on developmental parameters following exposure to chloro(dimethyl)vinylsilane.

It is considered not to be either ethical or technically feasible to perform developmental toxicity testing with chloro(dimethyl)vinylsilane by any route of exposure due to its known corrosive properties. Following repeated oral dosing, the corrosive nature of the product could affect the lining of the stomach, giving rise to hyperplasia and a subsequent reduced food intake. This would confound the interpretation of any systemically driven effects. A guideline-compliant reproductive toxicity inhalation study should elicit systemic toxicity at the highest test concentration. Since the local corrosive effects of chloro(dimethyl)vinylsilane would be significant a valid inhalation study according to the relevant guidelines is technically not feasible. It is also unlikely that any systemic effects would be seen at dose levels made sufficiently low to prevent the known corrosive effects and/or distress in the test species. This has been confirmed in a 28-day inhalation study with another chlorosilane, dichloro(dimethyl)silane (WIL Research, 2014) in which there were no effects of treatment on clinical signs, body weight or food consumption that would indicate a systemic effect. Furthermore, the histopathology in the study indicated that the effects in the upper respiratory tract were similar to HCl. It is therefore concluded that HCl will determine the inhalation toxicity profile of chloro(dimethyl)vinylsilane.

With regard to the dermal route, due to the known corrosive effects of chloro(dimethyl)vinylsilane appropriate H-phrases and P-statements are included in the labelling, but repeated skin contact is unlikely to occur. Any accidental skin contact is expected to cause severe local effects but would be unlikely to cause any systemic effects.

ORAL ROUTE

There are no adequate oral developmental toxicity data on chloro(dimethyl)vinylsilane or its hydrolysis product, dimethyl(vinyl)silanol, so good quality oral data for the related monosilanol, trimethylsilanol (1066-40-6) have been used to assess the potential for adverse effects on developmental parameters following exposure to chloro(dimethyl)vinylsilane.

In the key OECD 414 developmental toxicity study (Harlan, 2014) oral administration of the hydrolysis product, trimethylsilanol, to rats resulted in clinical signs (including uncoordinated movement and/or decreased activity) and reduced food consumption and body weight gain at the highest dose tested, 450 mg/kg/day. The reductions in food consumption and body weight again were considered to be adverse so the maternal No-Observed-Adverse-Effect-Level was considered to be 150 mg/kg/day. Reduced fetal weight, delayed ossification and increased incidence of some cartilaginous variations were noted in fetuses at 450 mg/kg/day and considered to be adverse, therefore the fetal NOAEL was considered to be 150 mg/kg/day.

INHALATION ROUTE

There are no adequate inhalation developmental toxicity data on chloro(dimethyl)vinylsilane or its hydrolysis product, dimethyl(vinyl)silanol, so good quality inhalation data for the related monosilanol, trimethylsilanol (1066-40-6) have been used to assess the potential for adverse effects on developmental parameters following exposure to chloro(dimethyl)vinylsilane.

In a supporting OECD 422 screening developmental toxicity study rats were exposed via whole-body inhalation to vapor atmospheres of the test article, trimethylsilanol, 6 hours/day, 7 days/week. Target exposure concentrations were 60, 300 and 600 parts per million (ppm). There were no test article-related macroscopic findings observed for pups therefore the developmental the no-observed-adverse-effect concentration (NOAEC) was considered to be 600 ppm.

Limited data are available regarding the reproductive toxicity in animals following oral, dermal or inhalation exposure to hydrogen chloride. However, protons and chloride ions exist as normal constituents of body fluid in animals, hence low concentrations of hydrogen chloride appear not to cause adverse effects in animals. Therefore the hydrolysis product of chloro(dimethyl)vinylsilane, HCl, would not be expected to cause reproductive toxicity in experimental animals or humans following initial exposure to chloro(dimethyl)vinylsilane.

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. In the case of repeated dose toxicity and reproductive toxicity relevant properties are structural similarity as well as physical-chemical and basic toxicological parameters in the same range. In the following paragraphs the read-across approach for chloro(dimethyl)vinylsilane is evaluated point by point.

Read-across hypothesis

Chloro(dimethyl)vinylsilane is very unstable in the presence of water and will hydrolyse very rapidly to dimethyl(vinyl)silanol and hydrogen chloride in the presence of moisture (see Section 5.1.2 of the technical dossier). Most, if not all of this will have occurred before absorption into the body. Therefore the use of hydrolysis product data is considered appropriate in the assessment of the repeat dose systemic and reproductive toxicity profile of chloro(dimethyl)vinylsilane. As has been demonstrated by the 28-day repeated dose inhalation study with dichloro(dimethyl)silane (WIL, 2014) there would also be additional corrosive local effects from HCl if chloro(dimethyl)vinylsilane were to be administered.

Local corrosive effects of chloro(dimethyl)vinylsilane can be assessed qualitatively or quantitatively by considering the amount of HCl produced by hydrolysis.

Analogue approach justification

(a) Structural similarity

The fundamental basis for the read across approach is the similarity between the hydrolysis product of the registration substance, dimethyl(vinyl)silanol, and the surrogate substance trimethylsilanol. These substances differ by replacement of one methyl group with a vinyl group. The surrogate substance is the only monosilanol for which measured mammalian toxicological data are available.

The properties of monosilanols differ substantially from those of di- and trisilanols. All silanols can be self-reactive, but whereas for monosilanols the reaction is self-limiting dimerization, di- and trisilanols can proceed to form oligomers and polymers. In the case of trisilanols these oligomers and polymers can be highly crosslinked. It is therefore not valid to read-across data from such silanols (or di/tri-alkoxysilanes) to a monosilanol-producer.

(b) Similar physicochemical characteristics

Due to the very rapid hydrolysis of chloro(dimethyl)vinylsilane, it is not feasible to measure some key physicochemical properties; however, the hydrolysis product has similar physicochemical characteristics to the read-across substance, trimethylsilanol. A data matrix is attached in Section 13 of the IUCLID dossier, and the key physicochemical parameters are summarised below.

CAS Number

1719-58-0

1066-40-6

Chemical Name

Chloro(dimethyl)vinylsilane

Trimethylsilanol

Si hydrolysis product

Dimethyl(vinyl)silanol

Not applicable

Molecular weight

120.65

90.20

log Kow(parent)

Not measurable

1.2

log Kow(silanol hydrolysis product)

1.5

Not applicable

Water sol (parent)

Not measurable

995 mg/l

Water sol (silanol hydrolysis product)

3700 mg/l

Not applicable

Vapour pressure (parent)

9500 Pa at 20oC

1290 Pa at 20oC

Vapour pressure (silanol hydrolysis product)

250 Pa at 25oC

Not applicable

 

Hydrolysis t1/2at pH 7 and 25°C

<1 minute

Not applicable

  

Hydrolysis t1/2at pH 2 and 37°C

 < 1 minute  Not applicable

Chloro(dimethyl)vinylsilane hydrolyses very rapidly in contact with moisture and therefore any systemic exposure to the substance would relate only to hydrolysis products.

(c) Similar toxicokinetics

The only potential route for oral exposure applicable to chloro(dimethyl)vinylsilane is for humans exposed via the environment. As explained above, exposure would be predominantly to monomeric silanol and it is not feasible to conduct a meaningful study for this endpoint. Nevertheless, the available repeated dose toxicity data for an analogous monosilanol (trimethylsilanol) are included for completeness.

For the inhalation route, dimethyl(vinyl)silanol and trimethylsilanol have similar molecular weight and log Kowvalues, indicating that systemic uptake in the respiratory tract is similar. The higher vapour pressure of trimethylsilanol means that the available inhalation study was conducted at a concentration higher than could be achieved with the hydrolysis product of the registration substance and thus represents a worst case in terms of exposure concentration.

The critical effect following dermal exposure to chloro(dimethyl)vinylsilane is corrosion and therefore significant systemic exposure is not expected since appropriate measures are in place to prevent local effects (see Section 9).

(d) Acute toxicity

Although an acute oral toxicity study is available for the registration substance (LPT, 2002), it is not appropriate to directly compare the results of this study with the available data for trimethylsilanol due to the potential for confounding effects due to the corrosive nature of the chlorosilane.

The available oral toxicity study for trimethylsilanol (Bayer, 1985), reports an LD50 for trimethylsilanol of 3.5 ml/kg bw (2835 mg/kg bw based on a density of 0.81 g/cm3) in rats. There was a general deterioration in the animals' health, including anaesthesia, lateral position, ruffled fur. All surviving animals appeared symptom-free after ten days.

In an acute inhalation study (WIL, 2007), the reported 4 hour LC50 of trimethylsilanol was 3151 ppm (11.8 mg/l) in rats. Significant clinical observations for the surviving animals decreased respiration, shallow respiration, rales, hypoactivity, prostration, ataxia, lacrimation of the eyes, partial closure of the eyes, decreased defecation, decreased urination, opacity of the eyes.

In comparison, acute oral and inhalation have been included for a number of alkoxysilane substances which contain vinyl groups, as shown in the table below, which indicate that the presence of the vinyl group in place of methyl does not lead to any enhanced acute systemic toxicity and in fact trimethylsilanol may be regarded as a worst case.

CAS Number

1066-40-7

1825-61-2

16753-62-1

2768-02-7

78-08-0

Chemical name

Trimethylsilanol

Methoxytrimethylsilane

Dimethoxymethylvinylsilane

Trimethoxyvinylsilane

Triethoxy(vinyl)silane

Hydrolysis product

Not applicable

Trimethylsilanol

Methylvinylsilanediol

Vinylsilanetriol

Vinylsilanetriol

Acute oral LD50(rat)

3.5 ml/kg (2835 mg/kg)

3575 mg/kg

 No data

7.34 ml/kg males; 7.46 ml/kg females.

>5000 mg/kg

Acute inhalation LC50(rat)

11.8 mg/l

43.1 mg/l

>5 mg/l

2773 ppm (16.9 mg/l)

 

These indicate that the presence of the vinyl group in place of methyl does not lead to any enhanced acute systemic toxicity and in fact trimethylsilanol may be regarded as a worst case.

(e) Discussion of repeated systemic toxicity of the non-silanol hydrolysis product

In a 90-day repeated inhalation study with HCl, no serious adverse systemic effects were observed in rats and mice exposed up to 50 ppm (ca. 70 mg/m3) for 6 hours per day, 5 days per week. The only significant adverse finding relating to systemic toxicity was decreased body weight at the highest dose level. Local effects on the nasal turbinates of mice were observed at all dose levels tested (10, 20 and 50 ppm). Testing with HCl at higher test concentrations is neither ethically nor technically feasible since severe corrosive effects would lead to discomfort and distress in the test animals. The author of this CSR considers that the apparent systemic effects at 50 ppm in the study were most likely secondary to local corrosive effects at this dose level.

Following uptake of HCl, hydrogen and chloride ions will enter the body’s natural homeostatic processes and significant systemic effects are unlikely.

(f) Discussion of local inhalation toxicity of HCl and chlorosilanes

No long-term toxicity studies are available for the registration substance, chloro(dimethyl)vinylsilane. A non-standard acute inhalation study (Dow Corning, 1969) is available. In this study, all 5 animals exposed to saturated vapour died within 27 minutes. Significant ocular and respiratory irritation was observed after 3 minutes of exposure.

Comparison of the acute inhalation toxicity of chlorosilanes to that of hydrogen chloride showed a correlation between toxicity (LC50) and the amount of HCl generated by the chlorosilanes (Jeanet al., 2006).

In a 4-week inhalation study (WIL, 2014) conducted specifically to assess respiratory tract changes and local toxicity, dichloro(dimethyl) silane was administered to rats at 5 or 25 ppm resulting in concentration-related effects in the nasal cavity indicative of a local irritant effect. The local effects noted at 25 ppm (resulting in 50ppm HCl on hydrolysis) were considered to be generally comparable to the group receiving hydrogen chloride at 50 ppm in the same study.

Given the comparability of existing results for chlorosilanes and HCl, and the rapid hydrolysis of chlorosilanes in the atmosphere, the effects of HCl dominate local toxicity on the respiratory tract and therefore data for HCl can be used to assess the local repeated-dose toxicity of chlorosilanes.


Justification for selection of Effect on developmental toxicity: via oral route:
Study was conducted in accordance with an appropriate guideline and in compliance with GLP.

Justification for selection of Effect on developmental toxicity: via inhalation route:
The key study is the only available study for the reproductive toxicity endpoint. It was conducted in accordance with a relevant OECD test guideline and in compliance with GLP.

Justification for classification or non-classification

Based on the available data from trimethylsilanol (an analogue of the silanol hydrolysis product),

chloro(dimethyl)vinylsilane does not require classification for reproductive or developmental toxicity according to Regulation (EC) 1272/2008.

Additional information