Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.528 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 763.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
Good quality oral study available. While no inhalation exposure anticipated, it is possible to derive systemic NOAEC for this route using default assumptions and the oral data to extrapolate, as per ECHA guidance ("Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.)
AF for dose response relationship:
1
Justification:
Adequate dosing and study information. No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation route
AF for other interspecies differences:
2.5
Justification:
According to Chapter R.8-Dose [Concentration]-Response Regarding Human Health, an additional assessment factor of 2.5 should be applied for remaining differences between test species and human. In cases where differences are not related to basal metabolic rate, the assessment factor should be modified. In terms of dynamics, one might assume that animals and humans will respond in the same way (p. 33). Based on the physicochemical properties, absorption is believed to be limited to such a degree that metabolic differences are not relevant for remaining differences. for more details see systemic dermal DNELs.
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study, good quality database
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As a conservative assumption the oral and dermal absorption is considered identical and therefore no modification to the dose descriptor is necessary.

AF for dose response relationship:
1
Justification:
Default value in accordance with ECHA guidance- Chapter R.8
AF for differences in duration of exposure:
2
Justification:
AF of 2 used for Subchronic to Chronic extrapolation (ECHA guidance- Chapter R.8)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor rat to human = 4 (ECHA guidance- Chapter R.8)
AF for other interspecies differences:
2.5
Justification:
Default value in accordance with ECHA guidance- Chapter R.8
AF for intraspecies differences:
5
Justification:
Intraspecies AF factor of 5 is used for workers (ECHA guidance- Chapter R.8)
AF for the quality of the whole database:
1
Justification:
Dataset of sufficient quality, therefore default value of 1.0 used accordance with ECHA guidance- Chapter R.8
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)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
5 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
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification required.

AF for dose response relationship:
1
Justification:
Default value in accordance with ECHA guidance- Chapter R.8
AF for differences in duration of exposure:
2
Justification:
AF of 2 used for Subchronic to Chronic extrapolation (ECHA guidance- Chapter R.8)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor rat to human = 4 (ECHA guidance- Chapter R.8)
AF for other interspecies differences:
2.5
Justification:
Default value in accordance with ECHA guidance- Chapter R.8
AF for intraspecies differences:
10
Justification:
Intraspecies AF factor of 10 is used for general population (ECHA guidance- Chapter R.8)
AF for the quality of the whole database:
1
Justification:
Dataset of sufficient quality, therefore default value of 1.0 used accordance with ECHA guidance- Chapter R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute hazards were identified for the registration substance.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population