Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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):
25
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.58 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 1000 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67 = 881.58 mg/m³.

In the absence of route-specific information on the starting route, the oral absorption rate is by default considered to be half of that of the inhalation absorption (factor: 0.5/1).

ABSoral-rat = oral absorption rate in rats,

ABSinh-human = inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
A NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on an oral subchronic (90-day) toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
The AF for allometric scaling is already included in ECHA starting point derivation method; no further factor is required.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Database is of good quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertanties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = 1000 mg/kg bw/day*(1/1) = 1000 mg/kg bw/day.

ABSoral-rat = oral absorption rate in rats,

ABSdermal-human = dermal absorption rate in humans.

AF for dose response relationship:
1
Justification:
A NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on an oral subchronic (90-day) toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
The DNEL is based on a study in rat.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
The database is of good quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Since short-term exposure scenarios will not be assessed, only long-term DNELs for workers and the general population will be derived. The oral route is not relevant for workers. In addition it is assumed that only workers will come into contact with the neat substance. Due to the lack of an irritating or sensitising potential of the undiluted test substance the consideration of local DNELs is obsolete.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr=NOAELoral*(1/1.15 m³/kg/d)*(ABSoral-rat/ABSinh-human) = 1000 mg/kg/d*(1/1.15 m³/kg/d)*(0.5/1) = 434.78 mg/m³.

In the absence of route-specific information on the starting route, the oral absorption rate is by default considered to be half of that of the inhalation absorption (factor: 0.5/1).

ABSoral-rat = oral absorption rate in rats,

ABSinh-human = inhalation absorption rate in humans

AF for dose response relationship:
1
Justification:
A NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on an oral 90-day study.
AF for interspecies differences (allometric scaling):
1
Justification:
The AF for allometric scaling is already included in ECHA starting point derivation method; no further factor is required.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value for general population.
AF for the quality of the whole database:
1
Justification:
The database is of good quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=NOAELoral*( ABSoral-rat/ABSdermal-human) = 1000 mg/kg bw/day*(1/1) = 1000 mg/kg bw/day.

ABSoral-rat = oral absorption rate in rats,

ABSdermal-human = dermal absorption rate in humans.

AF for dose response relationship:
1
Justification:
A NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on an oral subchronic (90-day) toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
The DNEL is based on a study in rat.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value for general population.
AF for the quality of the whole database:
1
Justification:
The database is of good quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
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 needed.

AF for dose response relationship:
1
Justification:
A NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on an oral subchronic (90-day) toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
The DNEL is based on a study in rat.
AF for other interspecies differences:
2.5
Justification:
Default value.
AF for intraspecies differences:
10
Justification:
Default value for general population.
AF for the quality of the whole database:
1
Justification:
The database is of good quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Since short-term exposure scenarios will not be assessed, only long-term DNELs for workers and the general population will be derived. The oral route is not relevant for workers. In addition it is assumed that only workers will come into contact with the neat substance. Due to the lack of an irritating or sensitising potential of the undiluted test substance the consideration of local DNELs is obsolete.