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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:
16.46 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 234.21 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the standard respiratory volume for rats (8 h) of 0.38 m3/kg bw, the standard respiratory volume for human under normal conditions (8 h) of 6.7 m3/person and under light activity of 10 m3/person (default weight of 70 kg). In addition, the oral and inhalative absorption was accounted for. As default value, since no route specific information is available, oral absorption is considered to be half of the inhalatory absorption (factor 1/2). Since the study is performed at 7 days/week, while the exposure of workers is 5 days/week, the NOAEL is also corrected by the factor of 1.4 (7/5). The resulting corrected NOAEC is the following:

1000 mg/kg bw/day*(1/0.38)*(6.7/10)*(1/2)*1.4 = 1234.21 mg/m3

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is already included in the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default, since no specific information is available
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The study was performed according to guideline and GLP. Therefore, the quality of the database is high.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
4.67 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the difference in exposure for workers and test animals. Since the study is performed at 7 days/week, while the exposure of workers is 5 days/week, the NOAEL is corrected by the factor of 1.4 (7/5). The dermal absorption is considered to be as high as the oral absorption (worst-case). The resulting corrected NOAEC is the following:

1000 mg/kg bw/day*1.4 = 1400 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default, since no specific information is available
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The quality of the database is high, since a study according to guideline and GLP is available
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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
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:

The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the standard respiratory volume for rats (24 h) of 1.15 m3/kg bw and the oral and inhalative absorption. As default value, since no route specific information is available, oral absorption is considered to be half of the inhalatory absorption (factor 1/2). The resulting corrected NOAEC is the following:

1000 mg/kg bw/day*(1/1.15)*(1/2) = 434.78 mg/m3

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is already included in the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default, since no specific information is available
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The study was performed in accordance with guideline and GLP. Therefore, the database is reliable.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
1.67 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
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:

The NOAEL from the study according to OECD Guideline 422 does not have to be modified. The dermal absorption is considered to be as high as the oral absorption (worst-case).

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default, since no specific information is available
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The quality of the database is high, since a study according to guideline and GLP is available
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 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
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 correction of the NOAEL from the study according to OECD Guideline 422 was neccessary. The oral absorption of rats is considered to be equal to the oral absorption of humans.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default, since no specific information is available
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The study was performed in accordance with guideline and GLP. Therefore, the quality of the database is high.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population