Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 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
DNEL value:
625.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation not necessary.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEC was established in the study.
AF for differences in duration of exposure:
2
Justification:
As per REACH guidance 8.4.3.1, a factor of 2 may be used for duration extrapolation (i.e., sub-chronic to chronic).
AF for interspecies differences (allometric scaling):
2.5
Justification:
As per REACH guidance 8.4.3.1
AF for other interspecies differences:
1
Justification:
As per REACH guidance 8.4.3.1
AF for intraspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
75 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL

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:
0.208 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):
72
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of study data for the dermal route, route to route extrapolation needed to be considered in the present case. Dose descriptor starting value for the dermal DNEL is equal to the one determined in the oral study as (in the absence of toxicokinetics information) it can be assumed that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
1
Justification:
No AF for additional differences was identified.
AF for intraspecies differences:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3 may be supported by data from similar compounds. Toxicological evaluation of other structurally similar oxime silanes demonstrated similar toxicities whose severity did not increase with longer duration exposure and showed recoverability once compound exposure was stopped.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is used as starting point is a reliable one, suitable for route-to route extrapolation.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.624 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

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:
low hazard (no threshold derived)

Additional information - workers

DNEL (worker, inhalation, long-term, systemic/local effects)

 

RELEVANT DOSE DESCRIPTOR

1244.5

mg/m3

301 ppm (corresponding to 1244.5 mg/m³ at 25 °C and 1013 mbar), was considered a No-Observed-Adverse-Effect Concentration (NOAEC) for local and systemic toxicity

AF - DURATION (starting point modification)

0.75

H

Due to difference in duration of exposure for workers. Workers will be exposed for 8 h compared to 6 h exposure in current experimental condition

AF - VOLUME (starting point modification)

0.67

m3

Due to difference in volume of exposure for workers. Workers will be exposed to 10 m3compared to 6 h exposure in current experimental condition

MODIFIED DOSE-DESCRIPTOR

625.4

mg/m3

 

AF - INTERSPECIES (ALLOMETRIC)

2.5

 

A default assessment factor is applied according to REACH R.8

AF - INTRASPECIES

5

 

The default factor for workers is applied according to the REACH guidance R.8 because no substance-specific information is available for an adjustment.

AF - EXPOSURE DURATION

2

 

Adjustment for chronic exposure from sub-chronic exposure

AF - DOSE RESPONSE

1

 

NO AF as NOAEL was successfully generated from the study

AF - QUALITY OF DATA

1

 

 

DNEL

25

mg/m3

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.22 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
311.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation not necessary.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.
AF for differences in duration of exposure:
2
Justification:
As per REACH guidance 8.4.3.1, a factor of 2 may be used for duration extrapolation (i.e., sub-chronic to chronic).
AF for interspecies differences (allometric scaling):
2.5
Justification:
As per REACH guidance 8.4.3.1
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
As per REACH guidance 8.4.3.1
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.66 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL

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:
DNEL (Derived No Effect Level)
Value:
0.125 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):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of study data for the dermal route, route to route extrapolation needed to be considered in the present case. Dose descriptor starting value for the dermal DNEL is equal to the one determined in the oral study as (in the absence of toxicokinetics information) it can be assumed that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1, a factor of 5 may be supported by data from similar compounds. Toxicological evaluation of other structurally similar oxime silanes demonstrated similar toxicities whose severity did not increase with longer duration exposure and showed recoverability once compound exposure was stopped.
AF for intraspecies differences:
1
Justification:
No AF for additional differences was identified.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust and the effects observed were similar to those observed in studies conducted with other structurally similar oxime silanes following acute or repeated exposure by oral and inhalation routes of exposure.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.375 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

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:
0.125 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):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation not necessary.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
1
Justification:
No AF for additional differences was identified.
AF for intraspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1, a factor of 5 may be supported by data from similar compounds. Toxicological evaluation of other structurally similar oxime silanes demonstrated similar toxicities whose severity did not increase with longer duration exposure and showed recoverability once compound exposure was stopped.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust and the effects observed were similar to those observed in studies conducted with other structurally similar oxime silanes following acute or repeated exposure by oral and inhalation routes of exposure.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.375 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

DNEL (consumer, inhalation, long-term, systemic/local effects)

 

RELEVANT DOSE DESCRIPTOR

1244.5

mg/m3

301 ppm (corresponding to 1244.5 mg/m³ at 25°C and 1013 mbar), was considered a No-Observed-Adverse-Effect Concentration (NOAEC) for local and systemic toxicity

AF-DURATION (starting point modification)

0.25

h

Due to difference in duration of exposure for workers. Workers will be exposed for 24 h compared to 6 h exposure in current experimental condition

MODIFIED DOSE-DESCRIPTOR

311.1

mg/m3

 

AF-INTERSPECIES (ALLOMETRIC)

2.5

 

A default assessment factor is applied according to REACH R.8

AF-INTRASPECIES

10

 

The default factor for workers is applied according to the REACH guidance R.8 because no substance-specific information is available for an adjustment.

AF-EXPOSURE DURATION

2

 

Adjustment for chronic exposure from sub-chronic exposure

AF-DOSE RESPONSE

1

 

NO AF as NOAEL was successfully generated from the study

AF-QUALITY OF DATA

1

 

 

DNEL

6.22

mg/m3

 (311.1 mg/m3/(2.5*10*2*1*1)