Registration Dossier

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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:
17.63 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
440.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAELdermal to NOAELoral: 250 mg/kg bw/day = 1000 mg/kg/day x 25% rat dermal absorption/100% rat oral absorption. NOAELoral to NOAECinhal: 440.8 mg/m3 = 250 mg/kg/day x [(1/0.38) x (rat oral absorption (100%) / human inhalation absorption (100%)) x (6.7/10)]

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:
2
Justification:
Extrapolation from subchronic 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):
1
Justification:
Already taken into account during the correction of starting point
AF for other interspecies differences:
2.5
Justification:
Default value for remaining toxicodynamic differences 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:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
10 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 000 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:
2
Justification:
Extrapolation from subchronic 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 extrapolating toxicokinetics from Rat to Human 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 for remaining toxicodynamic differences 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 for workers 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:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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 was not considered mutagenic in studies that were adequately conducted. In reliable OECD 411 repeat dose (dermal) toxicity studies in the rat the NOAEL was established at the limit dose (1000 mg/kg bw) with no adverse effects. Developmental toxicity (NOAEL 710 mg/kg) seen with a read across substance is not considered relevant because the likely mechanism for the developmental toxicity (related to the physical chemical properties/narcotic properties of the read-across substance, which the substance to be registered does not possess) can not operate with the substance for registration. Otherwise, pharmcodynamically, the read-across substance gives reassurance that there is unlikely to be cause for concern with respect to reproductive toxicity for the registered substance. In addition there is a MoS of 71 fold between the proposed long term dermal DNEL for workers and the NOAEL for developmental toxicity for the read-across substance. No adverse effects were observed at the limit dose in the acute oral or dermal toxicity studies. No local tolerance issues were identified from skin irritation, skin sensitisation, or eye irritation studies.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
217.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAELdermal to NOAELoral: 250 mg/kg bw/day = 1000 mg/kg/day x (25% rat dermal absorption x 100% rat oral absorption). NOAELoral to NOAECinhal: 217.4 mg/m3 = 250 mg/kg/day x [(1/1.15) x (rat oral absorption (100%) / human inhalation absorption (100%)) ]

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:
2
Justification:
Extrapolation from subchronic 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):
1
Justification:
Already taken into account during the correction of starting point
AF for other interspecies differences:
2.5
Justification:
Default value for remaining toxicodynamic differences 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:
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:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
5 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 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:
2
Justification:
Extrapolation from subchronic 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 for remaining toxicodynamic differences 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:
10
Justification:
Default value for the general population 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:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
1.25 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAELdermal to NOAELoral: 250 mg/kg bw/day = 1000 mg/kg/day x (25% rat dermal absorption x 100% rat oral absorption).

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:
2
Justification:
Extrapolation from subchronic 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 for remaining toxicodynamic differences 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:
10
Justification:
Default value for the general population 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:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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 was not considered mutagenic in studies that were adequately conducted. In reliable OECD 411 repeat dose (dermal) toxicity studies in the rat the NOAEL was established at the limit dose (1000 mg/kg bw) with no adverse effects. Developmental toxicity (NOAEL 710 mg/kg) seen with a read across substance is not considered relevant because the likely mechanism for the developmental toxicity (related to the physical chemical properties/narcotic properties of the read-across substance, which the substance to be registered does not possess) can not operate with the substance for registration. Otherwise, pharmcodynamically, the read-across substance gives reassurance that there is unlikely to be cause for concern with respect to reproductive toxicity for the substance to be registered. In addition there is a MoS of 142 fold between the proposed long term dermal DNEL for the general population and the NOAEL for developmental toxicity for the read-across substance. No adverse effects were observed at the limit dose in the acute oral or dermal toxicity studies. No local tolerance issues were identified from skin irritation, skin sensitisation, or eye irritation studies.