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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
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

Only a 28 day study via oral route is available. In this study with the read across substance, the NOAEL was determined to be 200 mg/kg bw/day. Hence this was considered to be the dose descriptor starting point. The starting point is converted to inhalatory NOAEC for humans by using a default respiratory volume for the rat corresponding to the daily duration of human exposure, followed by a correction for differences in absorption between routes (if the case), and a correction for differences in inhalation absorption between rats and humans. For workers an additional correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity.

AF for dose response relationship:
1
Justification:
The starting dose descriptor is a NOAEL.
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):
1
Justification:
Allometric scaling has already been taken care in the conversion of oral NOAEL to modified inhalatory NOAEC.
AF for other interspecies differences:
2.5
Justification:
As recommended by the ECHA REACH guidance.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
High quality GLP study
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Workers - 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):
300
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point is 200 mg/kg bw/day from a repeated dose oral toxicity study with a read across substance. 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 (4 %) was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore the modified dose descriptor starting point is 4000 mg/kg bw/day.

Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rat / ABSORPTION dermal human = 200 * 100/4 = 5000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The dose descriptor starting point is from a subacute toxicity, hence an AF of 6 is required from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
As recommended by ECHA guidance R.8.
AF for other interspecies differences:
2.5
Justification:
As recommended by ECHA guidance R.8.
AF for intraspecies differences:
5
Justification:
For workers, as recommended by ECHA guidance R.8.
AF for the quality of the whole database:
1
Justification:
Study used was a GLP study
AF for remaining uncertainties:
1
Justification:
Not required
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 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 87 mg/m³ (= 200 / 2 / 1.15 ).

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL.
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):
1
Justification:
Not required as the allometric scaling is already accounted in dose descriptor conversion from oral to inhalation.
AF for other interspecies differences:
2.5
Justification:
As receommended by the ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population, As receommended by the ECHA guidance R.8.
AF for the quality of the whole database:
1
Justification:
GLP study
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 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
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point is 200 mg/kg bw/day from a repeated dose oral toxicity study with a read across substance. 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 (4 %) was taken into consideration as worst case for the oral to dermal route to route extrapolation. Therefore the modified dose descriptor starting point is 4000 mg/kg bw/day.

Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rat / ABSORPTION dermal human = 200 * 100/4 = 5000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
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 from rats to humans.
AF for other interspecies differences:
2.5
Justification:
As recommended by ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
For general population, as recommended by ECHA guidance R.8.
AF for the quality of the whole database:
1
Justification:
Study used was a GLP study.
AF for remaining uncertainties:
1
Justification:
Not required.
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
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
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 is chosen form the repeated dose toxicity study with a read across substance in rats and a NOAEL of 200 mg/kg bw was taken forward.

No route-to-route extrapolation is required as the dose descriptor is for oral route.

AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL.
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 other interspecies differences:
2.5
Justification:
As recommended by the ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers, by ECHA Guidance R.8.
AF for the quality of the whole database:
1
Justification:
Dose descriptor is taken from a GLP study.
AF for remaining uncertainties:
1
Justification:
Not required
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