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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.35 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
176.32 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point was chosen to be 200 mg/kg bw/day from a 28 days repeated dose oral toxicity study.

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 0.4 m³/kg bw. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest was considered to be 6.7 m³/10 m³. Therefore the modified dose descriptor starting point is 176.32 mg/m³ (= 200 / 2 / 0.4 x (7/10)).

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.33 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Currently no repeated dose dermal toxicity study is available to assess the hazards via inhalation route. Hence, the dose descriptor starting point was chosen to be 200 mg/kg bw/day from a 28 days repeated dose oral toxicity study.

Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal route.

The starting point is converted to dermal NOAEL for humans by correcting for differences in absorption between routes as well as for differences in dermal absorption between rats and humans. Based on exposure model from ATG Textilien des Bundesinstituts fur Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2%. Therefore a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore the modified dose descriptor starting point is 10000 mg/kg bw/day.

Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rabbit / ABSORPTION dermal human

= 200 * 25 = 10000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL6
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.49 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
74.07 mg/m³
Explanation for the modification of the dose descriptor starting point:

The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) iused to modify the dose descriptor starting point to 74.07 mg/m³.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Currently no repeated dose dermal toxicity study is available to assess the hazards via inhalation route. Hence, the dose descriptor starting point was chosen to be 200 mg/kg bw/day from a 28 days repeated dose oral toxicity study.

Since only a sub-acute oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal route.

The starting point is converted to dermal NOAEL for humans by correcting for differences in absorption between routes as well as for differences in dermal absorption between rats and humans. Based on exposure model from ATG Textilien des Bundesinstituts fur Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2%. Therefore a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore the modified dose descriptor starting point is 10000 mg/kg bw/day.

Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rabbit / ABSORPTION dermal human

= 200 * 25 = 10000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point was chosen to be 200 mg/kg bw/day from a 28 days repeated dose oral toxicity study.

AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL.
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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:
medium hazard (no threshold derived)

Additional information - General Population

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