Registration Dossier

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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.2 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
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 the NOAEC of 560 mg/m3 determined in the 90-day study with trimethoxy(methyl)silane.  NOAEC = 560 mg/m3 The following correction was made to NOAEC(inhalation): Correction for exposure duration: 6 h/8 h (default for workers).  Correction for respiratory rate and volume (rat to human worker): (6.7 m3/d/10 m3/d) (default) Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 560 mg/m3* (6h/8h)*(6.7 m3/d /10 m3)= 280 mg/m3

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (subchronic 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:
1.6 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
Modified dose descriptor starting point:
NOAEL
Value:
160 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 90-day inhalation study with trimethoxy(methyl)silane. In this study a NOAEC of 560 mg/m3 was derived based on kidney and urinary bladder effects in adult animals (males and females). No correction for molecular weight is made for read-across. The default assessment factor for inhalation to dermal extrapolation is 1. The following corrections were made: Correction for exposure duration: 6 h/8 h (default for workers). Correction for respiratory volume: 0.38 m3/kg (default, rat, 8 hour). The corrected NOAEL(dermal) is therefore: (560*(6 h/8 h)*0.38 m3/kg) = 160 mg/kg/day.  

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (inhalation rat to dermal human)
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The composition of the registration substance has been updated (September 2020) from multiconstituent to UVCB. The change in composition means that changes to the chemical safety assessment are required. These changes are in progress but not included in the current dossier update.

Short-term high exposures are considered unlikely given the high levels of control in place at sites producing and using the substance. DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated.

The 90-day repeated inhalation study for the major constituent, trimethoxy(methyl)silane was selected as the starting point for DNEL calculation since this is the study of longest duration that is available and represents the worst-case in respect of adverse effects observed in studies that are available.

General Population - Hazard via inhalation 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
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:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
A clear NOAEL was established.
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There is no potential for exposure of consumers via the dermal or inhalation routes to amino functional alkoxysilanes, therefore DNELs for the dermal and inhalation routes for consumers are not calculated. A DNEL for the oral route is calculated for the purposes of assessment of humans exposed via the environment.