Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
49.3 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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
Value:
1 230 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:
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 allometric scaling required
AF for other interspecies differences:
2.5
Justification:
Default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
5
Justification:
Assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Data available on target substance
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:
14 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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
Value:
1 400 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:
Corrected NOEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for study animal rats.
AF for other interspecies differences:
2.5
Justification:
Default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
5
Justification:
Worker default
AF for the quality of the whole database:
1
Justification:
Data available on target substance
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 based on the oral repeat dose NOAEL value as described in the guidance R.8 example B.3. The above factors were used to calculate a DNEL of 49.3 mg/m³.

Long-term systemic dermal NOEL calculated based on the oral repeat dose NOAEL value as described in Guidance R.8 . The above factors were used to calculate a DNEL of 14 mg/kg bw/day.

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.

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:
developmental toxicity / teratogenicity
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
Value:
435 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:
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 allometric scaling required
AF for other interspecies differences:
2.5
Justification:
Default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
General population default
AF for the quality of the whole database:
1
Justification:
Data available on target substance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

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.

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:
5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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
Value:
1 000 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:
Corrected NOEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for study animal rats.
AF for other interspecies differences:
2.5
Justification:
Default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Data available on target susbtance
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:
5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation necessary as is oral study.

AF for dose response relationship:
1
Justification:
Default for NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for study animal rats.
AF for other interspecies differences:
2.5
Justification:
Default for interspecies variability - remaining differences in case of no other specific susceptibility differences info available.
AF for intraspecies differences:
10
Justification:
General population default
AF for the quality of the whole database:
1
Justification:
Data available on target substance
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 based on the oral repeat dose NOAEL value as described in guidance R.8. The above factors were used to calculate a DNEL of 8.7 mg/m3.

Long-term systemic dermal NOEL calculated based on the oral repeat dose NOAEL value as described in guidance R.8. The above factors were used to calculate a DNEL of 5 mg/kg bw/day.

Long-term systemic oral NOEL provided by a developmental toxicity / teratogenicity study on the test substance was used to calculate the DNEL using the above assessment factors. The DNEL was 5 mg/kg bw/day.

No local effects were observed and therefore no DNEL derived.

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