Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
DNEL value:
813 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
409 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the inhalation route is based on results from the inhalation OECD 413 study with 3-chloropropyl(trimethoxy)silane. In this study a NOAEC of at least 100 ppm as no adverse treatment-related effects were observed up to the highest concentration tested.  NOAEC ≥100 ppm (≥813 mg/m3 based on a molecular weight of 198.72). The following correction was made to the NOAEC:  Modification for experimental exposure duration (6 h in study to 8 h in workers): 0.75;  Modification for respiratory volume (rat to human): 6.7/10.  Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: [≥813 mg/m3*(6.7/10)*(0.75)] ≥ 409 mg/m3.

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
DNEL value:
813 mg/m³
Modified dose descriptor starting point:
NOAEL
DNEL value:
232 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 OECD 413 study with 3-chloropropyl(trimethoxy)silane. In this study a NOAEC of at least 100 ppm was derived, as no adverse treatment-related effects were observed up to the highest concentration tested.  NOAEC ≥100 ppm (≥813 mg/m3 based on a molecular weight of 198.72). The following correction was made to the NOAEC:  Modification for exposure duration: 6 h/8 h. Modification for respiratory volume: 0.38 m3/kg. The corrected NOAEL(dermal) is therefore: (≥ 813 mg/m3*(6/8)*0.38 m3/kg) ≥ 232 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Short-term high exposures are considered to be unlikely given the high levels of control in place at sites producing and using the substance (see exposure section). DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated. Although no adverse systemic effects were seen in repeated-dose studies with the read-across substance, mortalities and clinical findings were observed in the acute oral toxicity studies with both the registered substance and the read-across substance. While uptake by the inhalation route is likely to be lower than by the oral route, as a precautionary measure long-term DNELs are calculated from the repeated dose inhalation study for risk characterisation purposes.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
DNEL value:
813 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
145.18 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the inhalation route is based on results from the inhalation OECD 413 study with 3-chloropropyl(trimethoxy)silane. In this study a NOAEC of at least 100 ppm as no adverse treatment-related effects were observed up to the highest concentration tested.  NOAEC ≥100 ppm (≥813 mg/m3 based on a molecular weight of 198.72). The following correction was made to the NOAEC:  Modification for experimental exposure duration (6 h in study to 24 h for general population): 0.25 hours;  Correction for dosing frequency: 5 days/7 days: 5/7 days.  Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: [≥813 mg/m3*(0.25 hours)*5/7 days] ≥ 145.18 mg/m3.

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.84 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
168 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 OECD 413 study with 3-chloropropyl(trimethoxy)silane. In this study a NOAEC of at least 100 ppm was derived, as no adverse treatment-related effects were observed up to the highest concentration tested. NOAEC ≥100 ppm (≥813 mg/m3 based on a molecular weight of 198.72). The following correction was made to the NOAEC:  Modification for exposure duration: 6 h/24 h.  Modification for number of exposures per week (5 in study to 7 in human consumers): 5/7.  Correction for respiratory volume: 1.15 m3/kg.   The corrected NOAEL(oral) is therefore: (≥813 mg/m3*(6/24)*5/7*1.15 m3/kg) ≥168 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.84 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are no consumer uses of 3-chloropropyl(dimethoxy)methylsilane therefore DNELs for the dermal and inhalation routes are not required for consumers. An oral DNEL is presented for the purposes of assessment of man exposed via the environment.