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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:
0.663 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
DNEL value:
99.4 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
49.95 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

The correction factors applied to starting point NOAEC value account for the difference of daily exposure time in rats (6hrs/day) compared to worker shift (8 hrs/day), and of respiratory volume.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Value:
362 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEC
DNEL value:
1 800 mg/m³
DNEL value:
4 525.6 mg/m³
AF for dose response relationship:
1
Justification:
Default
AF for interspecies differences (allometric scaling):
1
Justification:
inhalation study
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Justification:
Reliable study
AF for remaining uncertainties:
1
Justification:
Default

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.325 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
NOAEC
DNEL value:
99.4 mg/m³
AF for dose response relationship:
1
Justification:
Default value. A concentration-dependent response was observed.
AF for differences in duration of exposure:
6
Justification:
Default value. Local effects were observed in repeated-dose toxicity studies (14-day and 28-day)
AF for interspecies differences (allometric scaling):
1
Justification:
Default value. The exposure route is inhalation.
AF for other interspecies differences:
2.5
Justification:
Findings consisted in alterations in the nasal cavity. A greater sensitivity in rats is usually observed compared to humans because of the physiological differences in the rat nasal cavity (in particular due to the larger epithelium surface in contact with incoming airflow). Furthermore, a difference of sensitivity was observed between two rat strains. There were no findings in the nasal cavity of Wistar rats treated similarly.
However, in the absence of information related to the mechanism leading to the nasal effects in Sprague-Dawley rats and whether metabolism is involved, a default assessment factor for residual interspecies differences is applied conservatively.
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Default value. Effects on the nasal cavity were documented in a dose-range finding study (14-day) and a reliable 28-day study in Sprague-Dawley rats, not in Wistar rats treated for 28 days (males) and up to 47 days (females). Therefore the point of departure is considered conservative.
AF for remaining uncertainties:
1
Justification:
Default value.
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:
hazard unknown but no further hazard information necessary as no exposure expected
Value:
94.1 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEC
DNEL value:
99.4 mg/m³
DNEL value:
28.23 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default value (DNEL calculator) by route to route extrapolation, although negligible skin exposure is expected under industrial workplace conditions.

AF for dose response relationship:
1
Justification:
Default value (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default value (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default value (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default value (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default value (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Default value (DNEL calculator)
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:
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
118.3 µg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
DNEL value:
99.4 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
no hazard identified
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:
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:
39.8 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEC
Modified dose descriptor starting point:
NOAEL
DNEL value:
23.9 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Default (DNEL calculator)
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:
no hazard identified

Additional information - General Population