Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point is 300 mg/kg bw/day from a repeated dose oral toxicity study with a read-across substance. 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. Corrected inhalation NOAEC humans = 264.4 mg/m³.

AF for dose response relationship:
1
Justification:
The 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):
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 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:
The study is 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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point is 300 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 (absorption 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 7500 mg/kg bw/day. Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rat / ABSORPTION dermal human = 300 * 100/4 = 7500 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:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Subacute to chronic
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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:
0.869 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.43 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 130.43 m³/kg bw (= 300 / 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 has been accounted for in the starting point dose descriptor conversion to inhalatory NOAEC.
AF for other interspecies differences:
2.5
Justification:
As recommeded by ECHA Guidance R.8
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
AF for the quality of the whole database:
1
Justification:
The study is a 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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point is 300 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 (absorption 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 7500 mg/kg bw/day. Corrected dermal NOAEL humans = oral NOAEL * ABSORPTION oral rat / ABSORPTION dermal human = 300 * 100/4 = 7500 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:
To cover other toxicodynamic differences, as recommended by the REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
For consumers, as recommended by the REACH Guidance R.8
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A repeated dose toxicity study by oral route in rats is available with a source substance, where a NOAEL of 300 mg/kg bw was determined. This NOAEL was carried forward as the dose descriptor starting point.

AF for dose response relationship:
1
Justification:
Staring 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, as recommended by ECHA Guidance R.8
AF for other interspecies differences:
2.5
Justification:
To cover other toxicodynamic differences, as recommended by ECHA Guidance R.8
AF for intraspecies differences:
10
Justification:
Assessment factor for consumers, as recommended by ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
The study is a 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population