Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.823 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:
LOAEL
Value:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
61.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The LOAEL from the study according to OECD Guideline 408 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 (50 % inhalation, 100 % oral, please refer to Section 7.1 Toxicokinetics). Since the study is performed at 7 days/week, while the exposure of workers is 5 days/week, the LOAEL is also corrected by the factor of 1.4 (7/5). The resulting corrected LOAEC is the following:


corrected LOAEC = 12.5 mg/kg bw/day * (1/0.38) * (6.7/10) * (100 %/50 %) * 1.4 = 61.71 mg/m³

AF for dose response relationship:
3
Justification:
Default in case the starting point is a LOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default as allometric scaling is already included in corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.823 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
5.83 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):
300
Dose descriptor starting point:
LOAEL
Value:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The LOAEL from the study according to OECD Guideline 408 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 LOAEL is corrected by the factor of 1.4 (7/5). In addition, the oral and dermal absorption was accounted for (1 % dermal, 100 % oral, please refer to Section 7.1 Toxicokinetics). The resulting corrected LOAEL is the following:


corrected LOAEL = 12.5 mg/kg bw/day * (100 %/1 %) * 1.4 = 1750 mg/kg bw/day

AF for dose response relationship:
3
Justification:
Default in case the starting point is a LOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
0.145 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:
LOAEL
Value:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
21.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The LOAEL from the study according to OECD Guideline 408 has been modified accounting for the standard respiratory volume for rats (24 h) of 1.15 m³/kg bw. In addition, the oral and inhalative absorption was accounted for (50 % inhalation, 100 % oral, please refer to Section 7.1 Toxicokinetics). The resulting corrected LOAEC is the following:


corrected LOAEC = 12.5 mg/kg bw/day * (1/1.15) * (100 %/50 %) = 21.74 mg/m³

AF for dose response relationship:
3
Justification:
Default in case the starting point is a LOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default as allometric scaling is already included in corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default 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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.145 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
2.08 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:
LOAEL
Value:
12.5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The LOAEL from the study according to OECD Guideline 408 has been modified accounting for the oral and dermal absorption (1 % dermal, 100 % oral, please refer to Section 7.1 Toxicokinetics). The resulting corrected LOAEL is the following:


corrected LOAEL = 12.5 mg/kg bw/day * (100 %/1 %) = 1250 mg/kg bw/day

AF for dose response relationship:
3
Justification:
Default in case the starting point is a LOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default 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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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)

General Population - Hazard via oral route

Systemic effects

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

No correction of the LOAEL from the study according to OECD Guideline 408 was neccessary. The oral absorption of rats is considered to be equal to the oral absorption of humans.

AF for dose response relationship:
3
Justification:
Default in case the starting point is a LOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default for rats
AF for intraspecies differences:
10
Justification:
Default 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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20.8 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population