Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert dermal NOAEL to oral NOAEL: 1000 mg/kg/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day. Convert oral NOAEL to inhalation NOAEC: 200 mg/kg/day x [1/0.38 x 50/100 x 6.7/10] = 176 mg/m3
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
DMEL (Derived Minimum Effect Level)
Value:
1.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
900
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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

The substance is not acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance is not irritating to the skin or the eye and did not show any sensitising potential. DNELs for local effects on skin and respiratory system are not required.

Based on the available studies used to support the registration, the substance is considered to not be genotoxic.

In a 28-day dermal toxicity study only local effects but no adverse effects were observed for systemic toxicity and the NOAEL for systemic effects was set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the starting point for systemic DNELs calculation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert dermal NOAEL to oral NOAEL: 1000 mg/kg/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day. Convert oral NOAEL to inhalation NOAEC: 200 mg/kg/day x [1/1.15 x 50/100] = 87 mg/m3
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 800
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
0.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 800
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL Covert dermal NOAEL to oral NOAEL: 1000 mg/kg bw/day x (10% dermal absorption/50% oral absorption) = 200 mg/kg/day
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
3
Justification:
Limited information on chronic, reproductive and developmental toxicity – only a dermal repeat-dose study available.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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

The substance is not acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance is not irritating to the skin or the eye and did not show any sensitising potential. DNELs for local effects on skin and respiratory system are not required.

Based on the available studies used to support the registration, the substance is considered to not be genotoxic.

In a 28-day dermal toxicity study only local effects but no adverse effects were observed for systemic toxicity and the NOAEL for systemic effects was set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the starting point for systemic DNELs calculation.