Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
47 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
280 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³). No correction for molecular weight is applied for read-across. The following corrections were made: correction for experimental exposure duration (6 h/d to 8 h/d): 6/8 (ECHA default), correction for respiratory volume (worker): 6.7 m³/day/10 m³/day (ECHA default). Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 557*(6 h/ 8 h) *(6.7 m³/day/10 m³/day) =280 mg/m³.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
DNEL is based on inhalation study
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
3
Justification:
ECETOC default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
47 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
280 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³). No correction for molecular weight is applied for read-across. The following corrections were made: correction for experimental exposure duration (6 h/d to 8 h/d): 6/8 (ECHA default), correction for respiratory volume (worker): 6.7 m³/day/10 m³/day (ECHA default). Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 557*(6 h/ 8 h) *(6.7 m³/day/10 m³/day) =280 mg/m³.

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
158.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³) from the 90-day study in rats. No correction for molecular weight is applied for read-across. The following corrections were made: correction for exposure duration: 6 h/8 h (ECHA default for workers), correction for respiratory volume: 0.38 m³/kg (ECHA default, rat, 8 hour). The corrected NOAEL(dermal) is therefore: (557*(6 h/8 h) *0.38 m³/kg) = 158.7 mg/kg/day
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
3
Justification:
ECETOC default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
158.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³) from the 90-day study in rats. No correction for molecular weight is applied for read-across. The following corrections were made: correction for exposure duration: 6 h/8 h (ECHA default for workers), correction for respiratory volume: 0.38 m³/kg (ECHA default, rat, 8 hour). The corrected NOAEL(dermal) is therefore: (557*(6 h/8 h) *0.38 m³/kg) = 158.7 mg/kg/day

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Dermal route

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m3) from the 90-day study in rats.

No correction for molecular weight is applied for read-across. The following corrections were made:

Correction for experimental exposure duration: 6 h/8 h (ECHA default for workers)

Correction for respiratory volume: 0.38 m3/kg (ECHA default, rat, 8 hour)

 

The corrected NOAEL(dermal) is therefore: (557*(6 h/8 h)*0.38 m3/kg) = 158.7 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Assessment factor for route to route extrapolation (inhalation to dermal): 1 (ECHA default)

Assessment factor for allometric scaling (rat to human): 4 (ECHA default)

Assessment factor for extrapolation of exposure duration (sub-chronic to chronic): 2 (ECHA default)

Assessment factor for interspecies differences (systemic): 1 (ECETOC default)

Assessment factor for intraspecies differences (systemic): 3 (ECETOC default)

 

The overall DNEL (repeated-dose – systemic – dermal) is therefore 158.7/(1*4*2*1*3) =6.6 mg/kg bw/day

 

Inhalation route

The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m3).

No correction for molecular weight is applied for read-across. The following corrections were made:

Correction for experimental exposure duration (6 h/d to 8 h/d): 6/8 (ECHA default)

Correction for respiratory volume (worker): 6.7 m3/day/10 m3/day (ECHA default)

Therefore the corrected NOAEC for repeated-dose local effects via the inhalation route is:

557*(6 h/ 8 h)*(6.7 m3/day/10 m3/day) = 280 mg/m3.

The assessment factors used to determine the DNEL (inhalation) were selected on the following basis:

Assessment factor for extrapolation of exposure duration (sub-chronic to chronic): 2 (ECHA default)

Assessment factor for interspecies differences: 1 (ECECTOC default)

Assessment factor for intraspecies differences: 3 (ECETOC default)

The overall DNEL (repeated-dose – systemic – inhalation) is therefore: 280 mg/m3/(2*1*3)= 47 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
99.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³). No correction for molecular weight is applied for read-across. The following corrections were made: correction for experimental exposure duration (6 h/d to 24 h/d): 6/24 (ECHA default), correction for number of exposures per week: 5 d/7 d (study data). Therefore the corrected NOAEC for repeated-dose local effects via the inhalation route is: 557*(6 h/ 24 h) *(5 d/7 d) =99.5 mg/m³.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
DNEL is based on inhalation study
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
99.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl) silane (557 mg/m³). No correction for molecular weight is applied for read-across. The following corrections were made: correction for experimental exposure duration (6 h/d to 24 h/d): 6/24 (ECHA default), correction for number of exposures per week: 5 d/7 d (study data). Therefore the corrected NOAEC for repeated-dose local effects via the inhalation route is: 557*(6 h/ 24 h) *(5 d/7 d) =99.5 mg/m³.

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
114.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m³) from the 90-day study in rats. No correction for molecular weight is applied for read-across. The following corrections were made: correction for exposure duration: 6 h/24 h (ECHA default for consumers), correction for number of exposures per week: 5/7 (study data), correction for respiratory volume: 1.15 m³/kg (ECHA default, rat, 24 hour). The corrected NOAEL(dermal) is therefore: (560*(6 h/24 h)*(5/7)*1.15 m³/kg) = 114.4 mg/kg/day.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
114.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m³) from the 90-day study in rats. No correction for molecular weight is applied for read-across. The following corrections were made: correction for exposure duration: 6 h/24 h (ECHA default for consumers), correction for number of exposures per week: 5/7 (study data), correction for respiratory volume: 1.15 m³/kg (ECHA default, rat, 24 hour). The corrected NOAEL(dermal) is therefore: (560*(6 h/24 h)*(5/7)*1.15 m³/kg) = 114.4 mg/kg/day.

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
There are insufficient data to determine whether effects are in/dependent of exposure duration, therefore an assessment factor for extrapolation of exposure duration (sub-acute to chronic) has been applied.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects via the oral route is determined on the basis of the 28-day oral NOAEL for MTMS (50 mg/kg/day).

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Dermal route

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m3) from the 90-day study in rats.

No correction for molecular weight is applied for read-across. The following corrections were made:

Correction for exposure duration: 6 h/24 h (ECHA default for consumers)

Correction for number of exposures per week: 5/7 (study data)

Correction for respiratory volume: 1.15 m3/kg (ECHA default, rat, 24 hour)

 

The corrected NOAEL(dermal) is therefore: (557*(6 h/24 h)*(5/7)*1.15 m3/kg) = 114.4 mg/kg/day

 

The following assessment factors were applied to the corrected NOAEL:

Assessment factor for route to route extrapolation (inhalation to dermal): 1 (ECHA default)

Assessment factor for allometric scaling (rat to human): 4 (ECHA default)

Assessment factor for extrapolation of exposure duration (sub-chronic to chronic): 2 (ECHA default)

Assessment factor for interspecies differences (systemic): 1 (ECETOC default)

Assessment factor for intraspecies differences (systemic): 5 (ECETOC default)

 

The overall DNEL (repeated-dose – systemic – dermal - consumer) is therefore 114.4/(1*4*2*1*5) = 2.9 mg/kg/day

Oral route

The DNEL for systemic effects via the oral route is determined on the basis of the 28-day oral NOAEL for MTMS (50 mg/kg/day).

The assessment factors used to determine the DNEL (oral) were selected on the following basis:

There are insufficient data to determine whether effects are in/dependent of exposure duration, therefore an assessment factor for extrapolation of exposure duration (sub-acute to chronic) has been applied.

Assessment factor for extrapolation of exposure duration (sub-acute to chronic): 6 (ECHA default)

Assessment factor for allometric scaling (rat to human): 4 (ECHA default)

Assessment factor for interspecies differences: 1 (ECECTOC default)

Assessment factor for intraspecies differences: 5 (ECETOC default)

The overall DNEL (repeated-dose – systemic – oral) is therefore: 50 mg/kg/day/(6*4*1*5)= 0.42 mg/kg/day

Inhalation route

The DNEL for systemic effects via the inhalation route is determined on the basis of read-across of the 90-day inhalation NOAEC for trimethoxy(methyl)silane (557 mg/m3).

No correction for molecular weight is applied for read-across. The following corrections were made:

Correction for experimental exposure duration (6 h/d to 24 h/d): 6/24 (ECHA default)

Correction for number of exposures per week: 5 d/7 d (study data)

Therefore the corrected NOAEC for repeated-dose local effects via the inhalation route is:

557*(6 h/ 24 h)*(5 d/7 d) =99.5 mg/m3.

The assessment factors used to determine the DNEL (inhalation) were selected on the following basis:

Assessment factor for extrapolation of exposure duration (sub-chronic to chronic): 2 (ECHA default)

Assessment factor for interspecies differences: 1 (ECECTOC default)

Assessment factor for intraspecies differences: 5 (ECETOC default)

The overall DNEL (repeated-dose – systemic – inhalation) is therefore: 99.5 mg/m3/(2*1*5)= 10 mg/m3