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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:
16.29 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
1 221.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study available.
AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
6
Justification:
DNEL is based on 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for 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
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.31 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
693 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal study available.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
DNEL based on 28-day study
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
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

In the absence of any significant findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effects are considered to be repeated dose toxicity.

In the available key study (Dow Corning Corporation, 2002) the analogue substance N-(3 (trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) was tested for specific organ toxicity after subacute repeated exposure according to the OECD TG 422, and in compliance with GLP. 10 male and 10 female Sprague-Dawley rats per dose were daily administered the test material in corn oil via gavage for 28 and 29 consecutive days, respectively. The doses applied (25, 125, and 500 mg/kg bw/day) were based on a previous 7-day range-finding study, and concurrent control animals received the vehicle only. Except for nasal sounds and squeaky vocalisation, which was observed in every dose group, but not in control animals, no treatment related effects were observed in neither of the dosed animals. Hence, the NOAEL was set at ≥ 500 mg/kg bw for both male and female rats.  

Repeated-dose toxicity – systemic effects – dermal route – worker:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 500 mg/kg bw/day was derived for rats.

The following corrections were made:

No correction for dermal vs. oral absorption: 1 (default)

Correction for experimental vs. occupational exposure duration: 7 d/5 d

Molecular weight correction: 220.38/222.36=0.99

The corrected NOAEL is therefore 500 mg/kg bw/day×1×(7/5)×0.99=693 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (subacute to chronic): 6 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 4 (default)

Intraspecies differences (worker): 5 (default)

Total AF: 6×2.5×4×5=300

 

The overall DNEL (repeated-dose – systemic – dermal - worker) is therefore:

693 mg/kg bw/day/300=2.31 mg/kg bw/day.

 

Repeated-dose toxicity – systemic effects – inhalation route – worker:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 500 mg/kg bw/day was derived for rats.

The following correction was made to the NOAEL:

No correction for relative absorption oral vs. inhalation: 1

Correction for experimental vs. occupational exposure duration: 7 d/5 d

Correction for respiratory volume (rat/worker): 0.38 m³/kg bw (8 h)

Correction for respiratory volume (worker, light physical activity): 6.7 m³/10 m³

Molecular weight correction: 220.38/222.36=0.99

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

500 mg/kg bw/day×1×(7/5)/0.38 m³/kg bw×(6.7 m³/10 m³)×0.99=1221.9 mg/m³

 

The following assessment factors were applied to the corrected NOAEC:

Exposure duration (subacute to chronic): 6 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Intraspecies differences (worker): 5 (default)

Total AF: 6×2.5×5=75

 

The overall DNEL (repeated-dose – systemic – inhalation - worker) is therefore:

1221.9 mg/m3/75=16.29 mg/m³.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.87 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
430.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study available.
AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
6
Justification:
DNEL is based on 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for 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
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.825 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:
495 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal study available.
AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
6
Justification:
DNEL based on 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
default
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
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.825 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:
495 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
6
Justification:
DNEL based on 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
default
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
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

In the absence of any significant findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effects are considered to be repeated dose toxicity.

In the available key study (Dow Corning Corporation, 2002) the analogue substance N-(3 (trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) was tested for specific organ toxicity after subacute repeated exposure according to the OECD TG 422, and in compliance with GLP. 10 male and 10 female Sprague-Dawley rats per dose were daily administered the test material in corn oil via gavage for 28 and 29 consecutive days, respectively. The doses applied (25, 125, and 500 mg/kg bw/day) were based on a previous 7-day range-finding study, and concurrent control animals received the vehicle only. Except for nasal sounds and squeaky vocalisation, which was observed in every dose group, but not in control animals, no treatment related effects were observed in neither of the dosed animals. Hence, the NOAEL was set at ≥ 500 mg/kg bw for both male and female rats.  

Repeated-dose toxicity – systemic effects – dermal route – general population:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 500 mg/kg bw/day was derived for rats.

The following corrections were made:

No correction for dermal vs. oral absorption: 1 (default)

Molecular weight correction: 220.38/222.36=0.99

The corrected NOAEL is therefore 500 mg/kg bw/day×1×0.99=495 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (subacute to chronic): 6 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 4 (default)

Intraspecies differences (gen. pop.): 10 (default)

Total AF: 6×2.5×4×10=600

 

The overall DNEL (repeated-dose – systemic – dermal – gen. pop.) is therefore:

495 mg/kg bw/day/600=0.825 mg/kg bw/day.

 

Repeated-dose toxicity – systemic effects – inhalation route – general population:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral OECD 422 study. In this study a NOAEL of 500 mg/kg bw/day was derived for rats.

The following correction was made to the NOAEL:

No correction for relative absorption oral vs. inhalation: 1

Correction for respiratory volume (rat/gen. pop.): 1.15 m³/kg bw (24 h)

Molecular weight correction: 220.38/222.36=0.99

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

500 mg/kg bw/day×1/1.15 m³/kg bw×0.99=430.4 mg/m³

 

The following assessment factors were applied to the corrected NOAEC:

Exposure duration (subacute to chronic): 6

Interspecies differences (toxicodynamics): 2.5 (default)

Intraspecies differences (gen. pop.): 10 (default)

Total AF: 6×2.5×10=150

 

The overall DNEL (repeated-dose – systemic – inhalation – gen. pop.) is therefore:

430.4 mg/m3/150=2.87 mg/m³.

 

Repeated-dose toxicity – systemic effects – oral route – general population:

The DNEL for systemic effects via the oral route is determined on the basis of the oral OECD 422 study. In this study a NOAEL of 500 mg/kg bw/day was derived for rats.

The following corrections were made:

Molecular weight correction: 220.38/222.36=0.99

The corrected NOAEL is therefore 500 mg/kg bw/day×0.99=495 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (subacute to chronic): 6 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 4 (default)

Intraspecies differences (gen. pop.): 10 (default)

Total AF: 6×2.5×4×10=600

 

The overall DNEL (repeated-dose – systemic – oral – gen. pop.) is therefore:

495 mg/kg bw/day/600=0.825 mg/kg bw/day.