Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

There are no measured data available to assess the reproductive toxicity potential of dimethoxymethylsilane, however, data are available for the closest structurally related substance trimethoxymethylsilane (CAS 1185-55-3) (MW ratio: target/source = 0.78). The following data are used as an interim approach for hazard and risk assessment until reliable data has been generated on the registered substance itself.

OECD TG 422, oral, rat:

NOAEL reproduction: 1000 mg/kg bw/day
MW corrected NOAEL reproduction: 780 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Reproductive performance:
no effects observed
"Mortality and day of death:         None.
"Number pregnant per dose level:  10
"Number aborting:  0 "Number of resorptions, early/late if available:  None detected.
"Number of implantations: Group Mean (standard deviation):  Control:  15 (2.2);    50 mg/kg: 16 (2.0);    250 mg/kg: 16 (1.4);  1000 mg/kg: 16 (1.9) 
"Number of corpora lutea: Group Mean (standard deviation): Control: 19(4.7); 50 mg/kg: 19(3.1); 250 mg/kg:18(2.0); 1000 mg/kg:  17(3.9)
"Duration of Pregnancy:  Group Mean (standard deviation):        Control: 21  (0.5); 50 mg/kg: 21(0.5); 250 mg/kg: 22(0.5);   1000 mg/kg: 22(0.5)
"Body weight:  No statistically significant differences in treatment group maternal body weight relative to control group animals.
"Food/water consumption:  No statistically significant differences in treatment group maternal food consumption relative to control group animals.
"Description, severity, time of onset and duration of clinical signs:  Thirty percent of the animals in the 50 mg/kg/day dose group and 100 % of the animals in the 250 and 1000 mg/kg/day dose groups exhibited a transient period of salivation and/or abnormal inactivity at least once over the course of treatment  immediately after dosing.
"Gross pathology incidence and severity:  Gross pathology of the  reproductive/developmental group animals was not an endpoint for this study.
"Organ weight changes, particularly effects on total uterine weight:   Organ weight was not assessed in the reproductive/developmental group animals.
"Histopathology incidence and severity:  Histopathology was not assessed in the reproductive/developmental group animals. No treatment-related effects were observed in any of the reproductive parameters evaluated. All females bred successfully and delivered live litters. 

There were no treatment-related effects apparent for any of the reproductive endpoints. All females bred successfully and delivered live litters. Litter sizes were comparable for all groups. Differences in group mean values for the treated groups relative to the control group were small and none were found to be statistically significant.
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects on reproduction up to the highest dose tested
Critical effects observed:
no
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined
No gross abnormalities were found for any of the pups, with the exception of a single runt in the 50 mg/kg/day group.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed up to highest tested dose
Reproductive effects observed:
not specified
Conclusions:
An OECD 422 (combined Repeated Dose Toxicity Study with the Reproductive/ Developmental Screening Test) is available by the oral route for the structural analogue substance trimethoxy(methyl)silane (CAS: 1185-55-3). Exposure to methyltrimethoxysilane was not associated with reproductive toxicity. As described in the Analogue Justification similar results can be expected with the target substance and thus the NOAEL for the target substance is considered to be 1000 mg/kg bw/day.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
780 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study was conducted in accordance with an appropriate OECD test guideline, and in compliance with GLP.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

No adequate repeated-dose toxicity data are available for dimethoxymethylsilane, therefore good quality oral and inhalation data on the closest structurally related substance trimethoxymethylsilane (CAS 1185 -55 -3) have been used as interim measure to conduct hazard and risk assessment for the registered substance. Both substances share a common hydrolysis product, methylsilanetriol, with the other hydrolysis product being methanol. Since methanol would not contribute to general systemic toxicity effects in rodents at the dose levels tested, it is considered that the observed toxicological effects are due to the action of the methylsilantriol moiety, although the specific toxicological mechanism cannot be determined from the available information. Both substance have log Kow in the range that is favourable for absorption across the respiratory tract (dimethoxy log Kow=0.8 and trimethoxy log Kow=0.73).

Acute oral and dermal LD50 values for both substances in rats are >2000 mg/kg. Furthermore, reliable acute inhalation toxicity studies in the rat are available for both the registration substance and the analogue substance. In both cases, the LC50 value is in excess of 4.6 mg/l following a single dose for 4 to 6 hours. It is therefore considered valid to read-across the results for the trimethoxy analogue to fill data gap for the registered substance. The molecular weight difference between target and source chemical is 106/136=0.78.

 

A key OECD 422 combined repeated dose/reproductive and developmental screening study is available by the oral route for the structural analogue substance trimethoxymethylsilane (CAS 1185-55-3). There were no treatment-related effects apparent for any of the reproductive endpoints. All females bred successfully and delivered live litters. Litter sizes were comparable for all groups. Differences in group mean values for the treated groups relative to the control group were small and none were found to be statistically significant. Therefore, exposure to trimethoxymethylsilane was not associated with reproductive toxicity and a NOAEL of 1000 mg/kg bw/day was identified (Dow Corning Corporation, 2005). This NOAEL corresponds to a NOAEL of 780 mg/kg bw/day for the target chemical diiethoxymethylsilane.


Effects on developmental toxicity

Description of key information

There are no experimental data available to assess the reproductive toxicity potential of dimethoxymethylsilane. Therefore, an OECD 414 study is in progress in order to evaluate developmental toxicity after repeated oral exposure. In the meanwhile, toxicity data from the closest structurally related substance trimethoxymethylsilane (CAS 1185-55-3) (MW ratio: target/source = 0.78) has been used as interim measure to conduct hazard and risk assessment for the registered substance.


OECD TG 422, oral, rat:
NOAEL developmental: 1000 mg/kg bw/day
NOAEL maternal: 50 mg/kg bw/day
MW corrected NOAEL developmental: 780 mg/kg bw/day
MW corrected NOAEL maternal: 39 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Remarks:
screening study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Remarks:
Doses / Concentrations:
0 (corn oil), 50, 250, and 1000 mg/kg/day
Basis:
actual ingested
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Clinical signs: Clinical signs included transient inactivity or salivation following dosing in both the reproductive and toxicity group females
Organ weights: not estimated for the reproductive group females
Gross pathology/histopathology: not estimated for reproductive group females.
In toxicity group females exposure to MTMS was associated with organ weight and/or histomorphological changes (liver, thyroid, duodenum, jejunum, and adrenal gland) at dose levels at or above 250 mg/kg bw/day.
Haematology: Not estimated for reproductive group females. In toxicity group females exposure was also associated with increased blood platelet concentration.

Body weight: No statistically significant differences in treatment group maternal body weight relative to control group animals.
Food/water consumption: No statistically significant differences in treatment group maternal food consumption relative to control group animals.

The NOAEL for maternal systemic toxicity was 50 mg/kg bw/day.
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No gross abnormalities were found for any of the pups, with the exception of a single runt in the 50 mg/kg/day group.
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no developmental effects observed up to the highest dose tested
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
An OECD 422 (combined Repeated Dose Toxicity Study with the Reproductive/ Developmental Screening Test) is available by the oral route for the structural analogue substance trimethoxy(methyl)silane (CAS: 1185-55-3). Exposure to methyltrimethoxysilane was not associated with developmental toxicity. The findings support a NOAEL of 1000 mg/kg/day. As described in the Analogue Justification similar results can be expected with the target substance and thus the NOAEL for the target substance is considered to be 1000 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
780 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study was conducted in accordance with the OECD test guideline 422, and in compliance with GLP.
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

A developmental toxicity study according to OECD 414 (rat, oral) is in progress with the registered substance. In the meanwhile, toxicity data from the closest structurally related substance trimethoxymethylsilane (CAS 1185 -55 -3) has been used as an interim measure to conduct hazard and risk assessment for the registered substance.

An OECD 422 combined repeated dose/reproductive and developmental screening study is available by the oral route for the structural analogue substance trimethoxymethylsilane (CAS 1185-55-3).There were no treatment-related effects apparent for any of the developmental endpoints and litter sizes were comparable for all groups. No gross abnormalities were found for any of the pups, with the exception of a single runt in the 50 mg/kg bw/day group. Therefore, exposure to trimethoxymethylsilane was not associated with developmental toxicity and a NOAEL of 1000 mg/kg bw/day was identified. However, there were signs of maternal toxicity based on clinical signs. Clinical signs included transient inactivity or salivation following dosing in both the reproductive and toxicity group females. In toxicity group females exposure to MTMS was associated with organ weight and/or histomorphological changes (liver, thyroid, duodenum, jejunum, and adrenal gland) at dose levels at or above 250 mg/kg bw/day. Therefore the NOAEL for maternal toxicity was determined to be 50 mg/kg bw/day (Dow Corning Corporation, 2005). This NOAEL corresponds to a NOAEL of 39 mg/kg bw/day for the target chemical dimethoxymethylsilane.

Justification for classification or non-classification

The available data on reproduction and developmental toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification of the registered substance.

No information is available on effects via lactation.