Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.67 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:
875 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 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 875 mg/m3 (= 1000 / 2 / 0.4 x (7/10)).

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for interspecies differences (allometric scaling):
2.5
Justification:
Remaining difference
AF for intraspecies differences:
5
Justification:
Worker population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.3 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:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %.Subsequently, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation. The modified dose descriptor starting point is 25000 mg/kg bw/day.

AF for differences in duration of exposure:
6
Justification:
Difference in duration from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rats to humans
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Worker population
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
DNEL (Derived No Effect Level)
Value:
2.9 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:
434.8 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) is considered to be 1.15 m3/kg bw. Therefore the modified dose descriptor starting point is 434.8 m3/kg bw (= 1000 / 2 / 1.15 ).

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-acute toxicity study
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
DNEL (Derived No Effect Level)
Value:
41.67 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:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the exposure model from AG Textilien des Bundesinstituts für 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.

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required.

AF for differences in duration of exposure:
6
Justification:
Extrapolation to chronic exposure based on a sub-acute toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor.
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