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Administrative data

Workers - 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:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2.5
Dose descriptor:
NOAEC
AF for differences in duration of exposure:
1
Justification:
a factor of 1 is used because the local effect on the lung seems to be concentration rather than time dependent if the clearance mechanism of the lung is not impaired. This appears to be true for the effects caused by the pigment.
AF for interspecies differences (allometric scaling):
1
Justification:
the NOAEC is based on a local effect, therefore, the allometric scaling factor is set to 1, corrected NOAEC of 0.075 mg/m3 was multiplied by 6.7 m3/10 m3 to account for differences in the respiratory rate of humans at rest and workers (light activity) (POD = 0.075 mg/m3 x 0.67 = 0.050 mg/m3)
AF for other interspecies differences:
2.5
Justification:
a factor of 2.5 is used for remaining uncertainties (such as differences in lung clearance between rats and humans)
AF for intraspecies differences:
1
Justification:
a factor of 1 is used for the worker because healthy individuals are not expected to differ significantly in their susceptibility to local irritants/cytotoxicants
AF for the quality of the whole database:
1
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:
0.67 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
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 DNEL for long-term inhalation exposure - local effects was derived from the NOAEC of the 90 day repeated dose study (inhalation) where the substance caused cytotoxicity and respiratory tract irritation at concentrations of 0.1 mg/m3. The effect is thought to be due to particles that may accumulate at certain concentrations if the capacity of the clearance by aveolar macrophages is exceeded.

Point of Departure (POD)

a. exposure pattern: the 90 day NOAEC was modified to account for the difference in inhalation pattern between rats (6 h) and humans (8 h for the worker). 0.1 mg/m3 (NOAEC) x 6 h / 8 h = 0.075 mg/m3

b. correction for respiratory rate: the corrected NOAEC of 0.075 mg/m3 was multiplied by 6.7 m3/10 m3 to account for differences in the respiratory rate of humans at rest and workers (light activity) (POD = 0.075 mg/m3 x 0.67 = 0.050 mg/m3).

POD = 0.050 mg/m3

Assessment Factors

a. interspecies: the NOAEC is based on a local effect, therefore, the allometric scaling factor is set to 1, a factor of 2.5 is used for remaining uncertainties (such as differences in lung clearance between rats and humans).

b. intraspecies: a factor of 1 is used for the worker because healthy individuals are not expected to differ significantly in their susceptibility to local irritants/cytotoxicants.

c. subchronic to chronic extrapolation: a factor of 1 is used because the local effect on the lung seems to be concentration rather than time dependent if the clearance mechanism of the lung is not impaired. This appears to be true for the effects caused by the pigment.

Overall assessment factor is 1 x 2.5 x 1 x 1 = 2.5; the DNEL is 0.050 mg/m3 / 2.5 = 0.02 mg/m3.

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:
DNEL (Derived No Effect Level)
Value:
0.005 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
AF for differences in duration of exposure:
1
Justification:
a factor of 1 is used because the local effect on the lung seems to be concentration rather than time dependent if the clearance mechanism of the lung is not impaired. This appears to be true for the effects caused by the pigment
AF for interspecies differences (allometric scaling):
1
Justification:
the NOAEC is based on a local effect, therefore, the allometric scaling factor is set to 1
AF for other interspecies differences:
2.5
Justification:
the NOAEC is based on a local effect, therefore, the allometric scaling factor is set to 1
AF for intraspecies differences:
2
Justification:
a factor of 2 is used to account for differences in susceptibility to local irritants/cytotoxicants
AF for the quality of the whole database:
1
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:
0.33 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
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:
0.33 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
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 DNEL for long-term inhalation exposure - local effects was derived from the NOAEC of the 90 day repeated dose study (inhalation) where the substance caused cytotoxicity and respiratory tract irritation at concentrations of 0.1 mg/m3. The effect is thought to be due to particles that may accumulate at certain concentrations if the capacity of the clearance by aveolar macrophages is exceeded.

Point of Departure (POD)

exposure pattern: the 90 day NOAEC was modified to account for the difference in inhalation pattern between rats (6 h) and humans (24 h for the general population). 0.1 mg/m3 (NOAEC) x 6 h / 24 h = 0.025 mg/m3

POD = 0.025 mg/m3

Assessment Factors

a. interspecies: the NOAEC is based on a local effect, therefore, the allometric scaling factor is set to 1, a factor of 2.5 is used for remaining uncertainties (such as differences in lung clearance between rats and humans).

b. intraspecies: a factor of 2 is used to account for differences in susceptibility to local irritants/cytotoxicants.

c. subchronic to chronic extrapolation: a factor of 1 is used because the local effect on the lung seems to be concentration rather than time dependent if the clearance mechanism of the lung is not impaired. This appears to be true for the effects caused by the pigment.

Overall assessment factor is 1 x 2.5 x 2 x 1 = 5; the DNEL is 0.025 mg/m3 / 5 = 0.005 mg/m3.