Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.735 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance in combination with company/substance specific justifications
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
13.22 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC = NOAEL of 15 mg/kg bw/day * 1/0,38 * 6,7/10 * 1/2 (= default factor of 2 for oral to inhalation extrapolation as no route specific information is available.
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):
1
Justification:
No interspecies differences are to be taken into account for an inhalation DNEL
AF for other interspecies differences:
1
Justification:
No interspecies differences are to be taken into account for an inhalation DNEL
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 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:
2.205 mg/m³
Most sensitive endpoint:
acute 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
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:
other: ECHA REACH guidance in combination with company/substance specific justifications
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
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 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:
0.624 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:
medium hazard (no threshold derived)

Additional information - workers

According to the REACH "Guidance on information requirements and chemical safety assessment", a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

As there is only a repeated dose study available for the oral route of exposure all DNELs have been derived using the NOAEL of that study as starting point.

Oral short term:

Short-term – oral, systemic effects. The REACH guidance states that the most relevant DNELacutefor workers and the general population is by inhalation. However, inhalation data for OS-1600 (or MPKO, the major hydrolysis product of OS-1600) is not available. Due to the limited data set (acute oral LD50) and the high level of uncertainty introduced by route-to-route extrapolation, the oral DNELacutewas based on the highest oral DNELlong term. An assessment factor of 3 was used, based on the GHS classification for acute toxicity (Category 4) for this material.

 

DNELacute= (DNELlong term) x 3 = 0.21 mg/kg bw/day x 3 = 0.63 mg/kg bw

 

Oral long term:

Long-term – oral, systemic effects. The DNELlong term was derived from the 28 -day repeat dose toxicity study of MPKO, the major hydrolysis product of OS-1600, in rats that was conducted with multiple dose levels and included evaluation of several endpoints.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL:
15 mg/kg bw/day

MPKO affected the red blood cells, spleen weight and macroscopic appearance at dose levels of 50 mg/kg bw/day and above and hemosiderosis was seen at dose levels of 15 mg/kg bw/day and above with indicators of congestion and extramedullary hemopoisis at higher doses. The effects observed at 15 mg/kg bw/day were not considered adverse.

Step 2) Modification of starting point

-

None needed

Step 3) Assessment factors

Interspecies

4

According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.

Intraspecies

3

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.

Exposure duration

6

As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).

Dose response

1

As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.

Quality of database

1

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.

DNELLong Term

Value

15 / (72) = 0.21 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.217 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance in combination with company/substance specific justifications
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Value:
6.52 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC = NOAEL of 15 mg/kg bw/day * 1/1,15 * 1/2 (= default factor of 2 for oral to inhalation extrapolation as no route specific information is available.
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):
1
Justification:
No interspecies differences are to be taken into account for an inhalation DNEL
AF for other interspecies differences:
1
Justification:
No interspecies differences are to be taken into account for an inhalation DNEL
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:
0.651 mg/m³
Most sensitive endpoint:
acute 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
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:
other: ECHA REACH guidance in combination with company/substance specific justifications
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
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
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No justification required as there is no route to route extrapolation required (starting value is oral study).
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:
medium hazard (no threshold derived)

Additional information - General Population

As there is only a repeated dose study available for the oral route of exposure, all DNELs have been derived using the NOAEL of that study as starting point.

Oral short term:

Short-term – oral, systemic effects. The REACH guidance states that the most relevant DNELacutefor workers and the general population is by inhalation. However, inhalation data for OS-1600 (or MPKO, the major hydrolysis product of OS-1600) is not available. Due to the limited data set (acute oral LD50) and the high level of uncertainty introduced by route-to-route extrapolation, the oral DNELacutewas based on the highest oral DNELlong term. An assessment factor of 3 was used, based on the GHS classification for acute toxicity (Category 4) for this material.

 

DNELacute= (DNELlong term) x 3 = 0.125 mg/kg bw/day x 3 = 0.375 mg/kg bw


 

Oral long term:

Long-term – oral, systemic effects. The DNELLong Term was derived from the 28-day repeat dose toxicity study of MPKO, the major hydrolysis product of OS-1600, in rats that was conducted with multiple dose levels and included evaluation of several endpoints.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL:
15 mg/kg bw/day

MPKO affected the red blood cells, spleen weight and macroscopic appearance at dose levels of 50 mg/kg bw/day and above and hemosiderosis was seen at dose levels of 15 mg/kg bw/day and above with indicators of congestion and extramedullary hemopoisis at higher doses. The effects observed at 15 mg/kg bw/day were not considered adverse.

Step 2) Modification of starting point

-

None needed

Step 3) Assessment factors

Interspecies

4

According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.

Intraspecies

5

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.

Exposure duration

6

As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).

Dose response

1

As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEL was established in the study.

Quality of database

1

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.

DNELLong Term

Value

15 / (120) = 0.125 mg/kg bw/day