Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.88 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:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL(oral) converted to NOAEC(inhal) (1000 mg/kg x [1/0.38 x 50% oral absorption rat/100% inhalation absorption human x 6.7/10]) = 882 mg/m3
AF for dose response relationship:
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
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 other interspecies differences:
2.5
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 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:
2
Justification:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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:
8.33 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:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL(oral) converted to NOAEL(dermal) (1000 mg/kg x [50% oral absorption rat/10% dermal absorption humans] = 5000 mg/kg bw/day
AF for dose response relationship:
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
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 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:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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:
2
Justification:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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 does not show any local or acute effects and so DNELs for local and/or acute effects have not been calculated. The available repeat dose (oral) toxicity study is considered as the most relevant study for the dose descriptor starting point and the NOAEL of 1000 mg/kg bw/day from this study has been used as the starting point for the calculation of the systemic DNELs.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.45 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL(oral) converted to NOAEC(inhal) (1000 mg/kg x [1/1.15 x 50% oral absorption rat/100% inhalation absorption human]) = 867 mg/m3
AF for dose response relationship:
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
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 other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
2
Justification:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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:
4.17 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL(oral) converted to NOAEL(dermal) (1000 mg/kg x [50% oral absorption rat/10% dermal absorption humans]) = 5000 mg/kg bw/day
AF for dose response relationship:
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
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 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:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
2
Justification:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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:
0.83 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Same oral abosprtion in rat and humans
AF for dose response relationship:
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
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 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:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
2
Justification:
Limited data on the substance itself with regards to repeat dose toxicity and developmental and reprotoxicity
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 does not show any local or acute effects and so DNELs for local and/or acute effects have not been calculated. The available repeat dose (oral) toxicity study is considered as the most relevant study for the dose descriptor starting point and the NOAEL of 1000 mg/kg bw/day from this study has been used as the starting point for the calculation of the systemic DNELs.