Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.9 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):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 242.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
no inhalatory study available - Oral readacross study used for route to route extrapolation
AF for dose response relationship:
1
Justification:
corrected NOEC
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic default
AF for interspecies differences (allometric scaling):
1
Justification:
route-route concentration no AS applied
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
Worker – default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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:
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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 409.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal study available - Oral read across study used for route to route extrapolation
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default
AF for interspecies differences (allometric scaling):
4
Justification:
default - rat
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Worker – default
AF for the quality of the whole database:
2
Justification:
due to read across starting point
AF for remaining uncertainties:
1
Justification:
none known
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

Long term systemic inhalatory NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 24.9 mg/m3.

Long term systemic dermal NOEL calculated as described in guidance R.8 example B.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 7.0 mg/m3.

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

No local effects were observed, therefore no Local DNEL was derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.1 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):
100
Modified dose descriptor starting point:
NOAEC
DNEL value:
612.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
no inhalatory study available - Oral read across study used for route to route extrapolation
AF for dose response relationship:
1
Justification:
NOEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
route-route concentration AF not required
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
General Population - default
AF for the quality of the whole database:
2
Justification:
due to read across starting point
AF for remaining uncertainties:
1
Justification:
none known
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:
3.5 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):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 409.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal study available - Oral read across study used for route to route extrapolation
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default
AF for interspecies differences (allometric scaling):
4
Justification:
AS rat default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
General Population - default
AF for the quality of the whole database:
2
Justification:
due to read across starting point
AF for remaining uncertainties:
1
Justification:
none known
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:
3.5 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):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 409.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not required - oral 90d study
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic default
AF for interspecies differences (allometric scaling):
4
Justification:
default AS rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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

Long term systemic inhalatory NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 6.1 mg/m3.

Long term systemic dermal NOEL calculated as described in guidance R.8 example B.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 3.5 mg/m3.

Long term systemic oral NOEL provided by 90d read across study. The above factors were used to calculate a DNEL of 3.5 mg/m3.

No local effects were observed, therefore no Local DNEL was derived.

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.