Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.7 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
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
617.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the inhalation route available. Therefore, the worker-DNEL long-term for inhalation route - systemic is derived from the NOAEL of 250 mg/kg bw/day, obtained in the Subchronic Repeated Dose Toxicity Study in Wistar rats. The NOAECcorr. is calculated as follows:

- standard respiratory volume (rat) = 0.38 m³/kg (8h exposure)

- standard respiratory volume (human) = 6.7 m³/person (8h exposure)

- worker respiratory volume = 10 m³/person (8h exposure)

--> modified dose descriptor (corrected inhalatory NOAEC) = oral NOAEL/0.38 x (6.7/10) x (7 exposure days/week; rat/5 exposure days/week; worker) = 617.1 mg/m³

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance (starting point for the DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance (good/standard quality of the database)
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.9 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
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
488.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the dermal route available. Therefore, the worker-DNEL long-term for dermal route - systemic is derived from the NOAEL of 250 mg/kg bw/day, obtained in the Subchronic Repeated Dose Toxicity Study in Wistar rats. The NOAELcorr. is calculated as follows:

- absorption (oral, rat) = 100 % (default)

- absorption (dermal, rat) = 71.6 % (see also IUCLID chapter 7.1)

--> modified dose descriptor (corrected dermal NOAEL) = oral NOAEL/71.6 x 100 x (7 exposure days/week; rat/5 exposure days/week; worker) = 488.8 mg/kg bw

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance (starting point for the DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance (good/standard quality of the database)
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are adequate experimental data on the oral route available. Therefore, the general population-DNEL long-term for oral route - systemic is derived from the NOAEL of 250 mg/kg bw/day, obtained in the Subchronic Repeated Dose Toxicity Study in Wistar rats. The NOAELcorr. is calculated as follows:

- absorption (oral, rat) = 100 % (default)

--> modified dose descriptor (corrected oral NOAEL) = oral NOAEL/100 x 100 = 250 mg/kg bw

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance (starting point for the DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance (good/standard quality of the database)
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

In general, no exposure of the general population to the registered substance is expected.