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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.7 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 175 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the derivation of all DNELs a NOAEL of 1000 mg/kg bw/day obtained in an oral combined repeated dose (28 days) reproductive toxicity screening study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.

For workers:

Corrected inhalatory NOAEC = oralNOAEL x 1/sRVanimal x ABS oral-rat / ABS inh-human x sRVhuman/wRV

The standard respiratory volume (sRV) for the 8 h exposure is 0.38 m³/kg bw for rats and 6.7 m³ (per person) in humans. The default 8-h respiratory volume of a worker (wRV) is 10 m³ taking increased activity into account. The inhalatory absorption in humans is regarded to be slightly higher than the oral absorption in rats. In analogy to the "Evaluation of new scientific evidence concerning DINP and DIDP" by the ECHA (2013), 75% isused for inhalatory absorption in humans, whereas 50% is used for oral absorption in rats.

This results in the following equation:

Corrected inhalatory NOAEC = 1000 mg/kg bw/d x 1/0.38 m³/kg bw x 50 / 75 x 6.7 m³ / 10 m³ = 1175 mg/m³

AF for dose response relationship:
1
Justification:
The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Dose descriptor starting point is the NOAEL of a subacute study.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
5
Justification:
Default AF for the worker.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
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:
41.7 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):
300
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
12 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the derivation of all DNELs a NOAEL of 1000 mg/kg bw/day obtained in an oral combined repeated dose (28 days) reproductive toxicity screening study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.

For workers:

Corrected dermal NOAEL = oralNOAEL x ABS oral-rat / ABS dermal-rat x ABS dermal-rat / ABS dermal-human

The dermal absorption in humans is regarded to be very low. In analogy to the "Evaluation of new scientific evidence concerning DINP and DIDP" by the ECHA (2013), 4% is used for dermal absorption in humans, whereas 50% is used for oral absorption in rats.

This results in the following equation:

Corrected dermal NOAEL = 1000 mg/kg x 50 / 4 = 12500 mg/kg

AF for dose response relationship:
1
Justification:
The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
The DNEL is derived from a subacute (28 days) repeated dose toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for differences between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
5
Justification:
Default AF for the worker.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
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:
3.87 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
580 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the derivation of all DNELs a NOAEL of 1000 mg/kg bw/day obtained in an oral combined repeated dose (28 days) reproductive toxicity screening study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.

General population (in case of 24h exposure/day):

Corrected inhalatory NOAEC = oralNOAEL x 1/sRVanimal x ABS oral-rat / ABS inhalation-human

The standard respiratory volume (sRV) for the 24h exposure is 1.15 m³/kg bw for rats. The inhalatory absorption in humans is regarded to be slightly higher than the oral absorption in rats. In analogy to the "Evaluation of new scientifc evidence concerning DINP and DIDP" by the ECHA (2013), 75% is used for inhalatory absorption in humans, whereas 50% is used for oral absorption in rats.

This results in the following equation:

Corrected inhalatory NOAEC = 1000 mg/kg bw/d x 1/1.15 m³/kg bw x 50 / 75 = 580 mg/m³

AF for dose response relationship:
1
Justification:
The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
The DNEL is derived from a subacute (28 days) repeated dose toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
10
Justification:
Default AF for the general population.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
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:
20.8 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
12 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the derivation of all DNELs a NOAEL of 1000 mg/kg bw/day obtained in an oral combined repeated dose (28 days) reproductive toxicity screening study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.

For general population:

Corrected dermal NOAEL = oralNOAEL x ABS oral-rat / ABS dermal-rat x ABS dermal-rat / ABS dermal-human

The dermal absorption in humans is regarded to be very low. In analogy to the "Evaluation of new scientific evidence concerning DINP and DIDP" by the ECHA (2013), 4% is used for dermal absorption in humans, whereas 50% is used for oral absorption in rats.

This results in the following equation:

Corrected dermal NOAEL = 1000 mg/kg x 50 / 4 = 12500 mg/kg

AF for dose response relationship:
1
Justification:
The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
The DNEL is derived from a subacute (28 days) repeated dose toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for differences between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
10
Justification:
Default AF for the general population.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
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:
0.83 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
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the derivation of all DNELs a NOAEL of 1000 mg/kg bw/day obtained in an oral combined repeated dose (28 days) reproductive toxicity screening study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.

For general population:

Corrected oral NOAEL = oralNOAEL x ABS oral-rat / ABS oral-human

The oral absorption in humans is regarded to be higher than that in the rat. In analogy to the "Evaluation of new scientific evidence concerning DINP and DIDP" by the ECHA (2013), 50% is used for oral absorption in the rat, whereas 100% is used for oral absorption in humans.

This results in the following equation:

Corrected oral NOAEL = 1000 mg/kg x 50 / 100 = 500 mg/kg

AF for dose response relationship:
1
Justification:
The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Dose descriptor starting point is the NOAEL of a subacute study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for differences between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
10
Justification:
Default AF for the general population.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
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