Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.56 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
39 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance is stable in stomach acid. As it is poorly soluble, uptake after inhalation will be predominantly oral (after mucus transport and swallowing)

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route extrapolation
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.22 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
22 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance is expected to be poorly absorbed both after ingestion and skin contact. Absorption via the skin will be less since the substance is insoluble in water.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL

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

1. Identification of relevant dose descriptor

For the derivation of the DNELs, the 90-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 22 mg/kg/day.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic and no sensitizing potential. It is not teratogenic in rats. It is not irritating to skin and eyes.

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected)in accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

Workers: NOAEL (oral) = 22 mg/kg bw =>NOAEL(corrected)= 39 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.38 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):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
19 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance is stable in stomach acid. As it is poorly soluble, uptake after inhalation will be predominantly oral (after mucus transport and swallowing)

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic study available
AF for interspecies differences (allometric scaling):
1
Justification:
included in route-to-route extrapolation
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
22 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance is expected to be poorly absorbed both after ingestion and skin contact. Absorption via the skin will be less since the substance is insoluble in water.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
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:
0.11 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
22 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route-to-route extrapolation performed

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2.5
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

1. Identification of relevant dose descriptor

For the derivation of the DNELs, the 90-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 22 mg/kg/day.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

It is not irritating and not skin sensitizing.

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected)in accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

general population: NOAEL (oral) = 22 mg/kg bw =>NOAEL(corrected)= 19 mg/m3