Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
881.59 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL of 1000 mg/kg bw/day available from a repeat dose toxicity study via the oral route
AF for dose response relationship:
1
Justification:
NOAEL value available
AF for differences in duration of exposure:
6
Justification:
Default value for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Accounted for in correction of starting dose
AF for other interspecies differences:
2.5
Justification:
Default value for remaining differences
AF for intraspecies differences:
5
Justification:
Default value for a worker
AF for the quality of the whole database:
1
Justification:
Available study assigned a Klimisch 1
AF for remaining uncertainties:
1
Justification:
None
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:
3.33 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL of 1000 mg/kg bw/day available from a repeat dose toxicity study via the oral route
AF for dose response relationship:
1
Justification:
NOAEL value available
AF for differences in duration of exposure:
6
Justification:
Default value for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat
AF for other interspecies differences:
2.5
Justification:
Default value for remaining differences
AF for intraspecies differences:
5
Justification:
Default value for a worker
AF for the quality of the whole database:
1
Justification:
Available study assigned a Klimisch 1
AF for remaining uncertainties:
1
Justification:
None
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

The substance is not classified for human health. The DNELs that have been derived are for long-term systemic effects for dermal and inhalation routes and can be used to assess the risk to workers following exposure.

The results used to derive the DNELs was the NOAEL result of 1000 mg/kg bw/day for systemic toxicity, obtained from the OECD 422 combined repeated dose toxicity study with the reproductive/ developmental toxicity screening in the rat via the oral route. The corrected dose descriptors were calculated in accordance with REACH guidance on information requirements and chemical safety assessment, Chapter R.8: characterisation of dose [concentration]-response for human health. Modification of the oral result into an inhalation and dermal starting point was performed.

For inhalation exposure, the worst case assumption for absorption was used, i.e. the absorption percentage for the oral route is half that for the inhalation route. Therefore, 50 % absorption was assumed for oral absorption and 100 % absorption assumed for inhalation. This leads to the most conservation corrected dose descriptor.

For dermal exposure, it was assumed that dermal absorption would not be greater than oral absorption. Therefore, 50 % absorption was assumed for oral absorption and 50 % absorption assumed for dermal.

Default values were used for the remaining parameters.

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
Modified dose descriptor starting point:
NOAEC
DNEL value:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL of 1000 mg/kg bw/day available from a repeat dose toxicity study via the oral route
AF for dose response relationship:
1
Justification:
NOAEL value available
AF for differences in duration of exposure:
6
Justification:
Default value for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Accounted for in correction of starting dose
AF for other interspecies differences:
2.5
Justification:
Default value for remaining differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Available study assigned a Klimisch 1
AF for remaining uncertainties:
1
Justification:
None
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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL of 1000 mg/kg bw/day available from a repeat dose toxicity study via the oral route
AF for dose response relationship:
1
Justification:
NOAEL value available
AF for differences in duration of exposure:
6
Justification:
Default value for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat
AF for other interspecies differences:
2.5
Justification:
Default value for remaining differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Available study assigned a Klimisch 1
AF for remaining uncertainties:
1
Justification:
None
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:
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
Modified dose descriptor starting point:
NOAEL
DNEL 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:
NOAEL value available
AF for differences in duration of exposure:
6
Justification:
Default value for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat
AF for other interspecies differences:
2.5
Justification:
Default value for remaining differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Available study assigned a Klimisch 1
AF for remaining uncertainties:
1
Justification:
None
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

The substance is not classified for human health. The DNELs that have been derived are for long-term systemic effects for inhalation, dermal and oral routes and can be used to assess the risk to the general population following exposure.

The results used to derive the DNELs was the NOAEL result of 1000 mg/kg bw/day for systemic toxicity, obtained from the OECD 422 combined repeated dose toxicity study with the reproductive/ developmental toxicity screening in the rat via the oral route. Where necessary, the corrected dose descriptors were calculated in accordance with REACH guidance on information requirements and chemical safety assessment, Chapter R.8: characterisation of dose [concentration]-response for human health. Modification of the oral result into an inhalation and dermal starting point was performed.

For inhalation exposure, the worst case assumption for absorption was used, i.e. the absorption percentage for the oral route is half that for the inhalation route. Therefore, 50 % absorption was assumed for oral absorption and 100 % absorption assumed for inhalation. This leads to the most conservation corrected dose descriptor.

For dermal exposure, it was assumed that dermal absorption would not be greater than oral absorption. Therefore, 50 % absorption was assumed for oral absorption and 50 % absorption assumed for dermal.

Default values were used for the remaining parameters.