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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Weight of evidence: Based on experimental results obtained in repeated dose toxicity studies with supporting substances acetic acid and sodium acetate, read-across approach was applied and the NOAEL (28 days in rats) for diacetoxydi-tert-butoxysilane was calculated to be greater than 6416.41 mg/kg bw/day (based on no effects observed at the highest dose).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Diacetoxydi-tert-butoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance diacetoxydi-tert-butoxysilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on results:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 3600 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 6416.41 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 6 416.41 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (Read-across approach from sodium acetate effect level based on test material and based on no effects observed at the only dose tested)
Key result
Critical effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 3600 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 6416.41 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 3600 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 6416.41 mg/kg bw/day.

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
No data on GLP and no guideline was followed. Furthermore, only males were exposed to the substance, the administered doses were really low doses, a small number of animals was used and no separate untreated controls are available for comparison.
Principles of method if other than guideline:
Male rats were chronically treated via drinking water with 50 or 500 ppm (0.005 or 0.05 mg/kg bw/day) sodium acetate from weaning. Behavioral testing on a fixed-ration (FR) schedule of reinforcement began at 55 days of age.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Long-Evans
Sex:
male
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
8 months
Frequency of treatment:
Daily
Dose / conc.:
0.005 mg/kg bw/day (nominal)
Remarks:
Equivalent to 50 ppm
Basis: in water
Dose / conc.:
0.05 mg/kg bw/day (nominal)
Remarks:
Equivalent to 500 ppm
Basis: in water
No. of animals per sex per dose:
Six male rats per dose
Control animals:
no
Observations and examinations performed and frequency:
Body weights were monitored weekly until behavioral testing began, at which point weights were obtained daily.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
>= 0.05 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on no effects observed at the highest dose tested.
Key result
Critical effects observed:
no

No effects were mentioned on survival, reinforcement behaviour or body weight gain.

Conclusions:
No effects were mentioned on survival, reinforcement behaviour or body weight gain.
Executive summary:

Male rats were chronically treated via drinking water with 50 or 500 ppm (0.005 or 0.05 mg/kg bw/day) sodium acetate from weaning. Behavioral testing on a fixed-ration (FR) schedule of reinforcement began at 55 days of age. No effects were mentioned on survival, reinforcement behaviour or body weight gain.

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
No specific test guideline was reported; however, a scientifically defensible approach was used to conduct the study.
Principles of method if other than guideline:
Male rats of the Wistar strain were used. They came from mothers who were transferred from a stock ration to a vitamin B12-deficient ration at parturition and continued on the deficient ration during lactation. After being weaned at 25 days of age, they were divided at about 28 days of age into experimental groups. Since variation in growth response on the vitamin B12- deficient ration occurred between litters due to such factors as the amount of stored vitamin derived from the mother, one member of each litter was assigned randomly to each group and then started on the experimental rations. Weight gain averages are based on groups of littermates in which both members of the litter survived the experimental period. They were fed ad libitum a 25% protein, vitamin B12-deficient ration either as such or modified by the addition of fatty acids (sodium acetate) for four weeks. The body weights were determined.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Four weeks
Frequency of treatment:
Daily
Dose / conc.:
3.58 other: % (nominal in diet)
Remarks:
(approximately 3600 mg/kg bw/day)
No. of animals per sex per dose:
13 male rats per dose
Control animals:
no
Observations and examinations performed and frequency:
Body weights
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 600 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on no effects observed at the only dose tested
Key result
Critical effects observed:
no

No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested).

Conclusions:
No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested, during 28 days).
Executive summary:

Male rats of the Wistar strain were used. They came from mothers who were transferred from a stock ration to a vitamin B12-deficient ration at parturition and continued on the deficient ration during lactation. After being weaned at 25 days of age, they were divided at about 28 days of age into experimental groups. Since variation in growth response on the vitamin B12- deficient ration occurred between litters due to such factors as the amount of stored vitamin derived from the mother, one member of each litter was assigned randomly to each group and then started on the experimental rations. Weight gain averages are based on groups of littermates in which both members of the litter survived the experimental period. They were fed ad libitum a 25% protein, vitamin B12-deficient ration either as such or modified by the addition of fatty acids (sodium acetate) for four weeks. The body weights were determined. No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested).

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: No GLP and no guideline was followed. Furthermore, only males were exposed to the substance, a small number of animals was used and only the body weights and several indices of thyroid function were studied.
Principles of method if other than guideline:
Male Long-Evans rats were randomly divided into two groups which received 0 or 21 mg/kg bw/day sodium acetate in the diet. The investigation was terminated 3 months later and several indices of thyroid function examined.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Long-Evans
Sex:
male
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
3 months
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
in diet
Dose / conc.:
21 mg/kg bw/day (nominal)
Remarks:
in diet
No. of animals per sex per dose:
Control: 10 males
Treatment group: 10 males
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
Body weights and several indices of thyroid function
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
>= 21 other: mg/kg bw/day (estimated from the food intake)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on no evidence of clearly adverse effects at the only dose tested
Key result
Critical effects observed:
no

Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals was used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance.

Conclusions:
Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals was used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance.
Executive summary:

Male Long-Evans rats were randomly divided into two groups which received 0 or 21 mg/kg bw/day sodium acetate in the diet. The investigation was terminated 3 months later and several indices of thyroid function examined.

Dietary ingestion of sodium acetate for 3 months caused a significant reduction in body weights of male Long-Evans rats. While thyroid gland weights of sodium acetate treated rats were increased significantly above the glands of control rats, thyroid weight related to body weight was almost double that observed in control rats. Moreover, thyroidal 131I uptake was also markedly increased in treated rats but the circulating T4 levels were not significantly different from the serum T4 levels observed in the control group. The enhancement in thyrotropic activity evidenced by the elevated serum TSH levels in rats ingesting sodium acetate was responsible for the increases in thyroid weight and thyroid uptake of radioiodine. Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals was used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited used in evaluating the toxicity of the substance.

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: No data on GLP and no guideline was followed. Furthermore, only males were exposed to the substance, the administered doses were really low doses, a small number of animals was used and no separate untreated controls are available for comparison.
Principles of method if other than guideline:
Complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning (day 21 postpartum). Training for the latent learning task began on day 143 for the young adults.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
112 days
Frequency of treatment:
Daily
Dose / conc.:
100 ppm
Remarks:
Approximately 0.01 mg/kg bw/day.
Basis: nominal in water
No. of animals per sex per dose:
8 male rats per dose
Control animals:
no
Observations and examinations performed and frequency:
Cognitive function
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
>= 0.01 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on no effects observed at the only dose tested
Key result
Critical effects observed:
no

No evidence of impairment of simple task performance was observed.

Conclusions:
No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance.
Executive summary:

Complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning (day 21 postpartum). Training for the latent learning task began on day 143 for the young adults. No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance.

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Diacetoxydi-tert-butoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance diacetoxydi-tert-butoxysilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on results:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.01 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 0.02 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 0.02 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (Read-across approach from sodium acetate effect level based on test material and based on no effects observed at the only dose tested)
Key result
Critical effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.01 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 0.02 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.01 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 0.02 mg/kg bw/day.

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
A scientific study.
Principles of method if other than guideline:
8 month test with 3 times/week 60 mg/kg bw of Acetic acid. Nine outbred white male rats weighing approximately 100 g were used in the acetic acid alone study. Rats were given either N-nitrosarcosin ethyl ester (NSEE; a known carcinogen) alone, NSEE with the acetic acid solution, or the acetic acid solution alone. All doses were given by intubation into the esophagus. Animals were killed by ether inhalation after 8 months of experiments and autopsied.
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approx. 100 g
Route of administration:
oral: drinking water
Duration of treatment / exposure:
8 months
Frequency of treatment:
3 times per week
Dose / conc.:
60 mg/kg bw/day (nominal)
Remarks:
(in water)
No. of animals per sex per dose:
9
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
60 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: overall effects
Critical effects observed:
not specified
Conclusions:
NOAEL=60 mg/kg bw.
Executive summary:

Acetic acid NOAEL=60 mg/kg bw.

Endpoint:
chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Diacetoxydi-tert-butoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on results:
Based on the experimental results obtained with the supporting substance acetic acid for male rats (NOAEL = 60 mg/kg diet), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 146.08 mg/kg diet.
Key result
Dose descriptor:
NOAEL
Effect level:
146.08 mg/kg diet
Basis for effect level:
other: (Read-across approach from acetic acid effect level based on test material and basis for effect: overall effectsl)
Critical effects observed:
not specified
Conclusions:
Based on the experimental results obtained with the supporting substance acetic acid for male rats (NOAEL = 60 mg/kg diet), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 146.08 mg/kg diet.
Executive summary:

Based on the experimental results obtained with the supporting substance acetic acid for male rats (NOAEL = 60 mg/kg diet), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 146.08 mg/kg diet.

Endpoint:
chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Diacetoxydi-tert-butoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance diacetoxydi-tert-butoxysilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on results:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.05 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be >= 0.09 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 0.09 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (Read-across approach from sodium acetate effect level based on test material and based on no effects observed at the highest dose tested)
Key result
Critical effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.05 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be >= 0.09 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 0.05 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be >= 0.09 mg/kg bw/day.

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Diacetoxydi-tert-butoxysilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance diacetoxydi-tert-butoxysilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on results:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 21 mg/kg bw/day), the read-aross approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 37.42 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 37.42 other: mg/kg bw/day (estimated from the food intake)
Sex:
male
Basis for effect level:
other: (Read-across approach from sodium acetate effect level based on test material and based on no evidence of clearly adverse effects at the only dose tested)
Key result
Critical effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 21 mg/kg bw/day), the read-aross approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 37.42 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with the supporting substance sodium acetate for male rats (NOAEL >= 21 mg/kg bw/day), the read-across approach is applied and the NOAEL for diacetoxydi-tert-butoxysilane is calculated to be 37.42 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
6 416.41 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Several studies available with Klimisch scores = 2 and 3 in a weight of evidence approach. The overall quality of the database was determined as appropriate for assessment.

Additional information

Weight of evidence:

 

Read-across from experimental results with acetic acid:

 

In the first study, Alexandrov et. al., 1989 (reliability 2), an 8 month test with 60 mg/kg bw acetic acid (3 times per week, by intubation into the esophagus) in male rats was performed. The NOAEL (chronic) in male rats for acetic acid was 60 mg/kg bw. (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and NOAEL for diacetoxydi-tert-butoxysilane was calculated to be 146.08 mg/kg bw.

 

Read-across from experimental results with sodium acetate:

 

In the study by Cory Slechta, 1986 (reliability 3), male rats were chronically treated via drinking water with sodium acetate from weaning. No effects were mentioned on survival, reinforcement behaviour or body weight gain. Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 0.05 mg/kg bw/day, based on no effects observed at the highest dose tested.), the read-across approach was applied and NOAEL for diacetoxydi-tert-butoxysilane was calculated to be >= 0.09 mg/kg bw/day.

 

In the study by Dryden et. al., 1965 (reliability 2), male rats were daily treated by feed with sodium acetate during four weeks. No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested). Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 3600 mg/kg bw/day), the read-across approach was applied and NOAEL for diacetoxydi-tert-butoxysilane was calculated to be >= 6416.41 mg/kg bw/day.

 

In the study by Goldman, 1981 (reliability 3), male rats received a daily dose of sodium acetate in the diet during 3 months. Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals were used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 21 mg/kg bw/day, based on no evidence of clearly adverse effects at the only dose tested), read across approach was performed and NOAEL for diacetoxydi-tert-butoxysilane was calculated to be >= 37.43 mg/kg bw/day.

 

In the study by Massaro et. al., 1987 (reliability 3) complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning. No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 0.01 mg/kg bw/day, based on no effects observed at the only dose tested), read-across approach was performed and NOAEL for diacetoxydi-tert-butoxysilane was calculated to be >= 0.02 mg/kg bw/day.

 

Key value for chemical safety assessment:

 

According to the experimental results with supporting substances acetic acid and sodium acetate and the read-across approaches, No Observed Adverse Effect Level NOAEL (subacute) for diacetoxydi-tert-butoxysilane taken into account for chemical safety assessment is >= 6416.41 mg/kg bw/day (based on no effects observed at the highest dose tested).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

According to the experimental results with supporting substances acetic acid and sodium acetate and the read-across approaches, No Observed Adverse Effect Level NOAEL (subacute) for diacetoxydi-tert-butoxysilane taken into account for chemical safety assessment is >= 6416.41 mg/kg bw/day (based on no effects observed at the highest dose tested).The subacute study was selected since the test method fits better the current guidelines.

Justification for classification or non-classification

Based on the available information the EC50 for diacetoxydi-tert-butoxysilane is greater than 100 mg/kg/bw and therefore, according to the CLP Regulation it is not classified.