Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
353 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):
12.5
Dose descriptor starting point:
NOAEL
DNEL value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
4 408 mg/m³
Explanation for the modification of the dose descriptor starting point:

Converted dose to account for rat inhalative volume for 8 hours/day and increased worker respiratory volume, and 100% absorption in rat and human.

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep.
AF for differences in duration of exposure:
1
Justification:
Dosing in the selected study was for multiple generations, and the ultimate endpoint selected was based on fetotoxicity.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when converting animal oral exposure to human inhalation exposure.
AF for other interspecies differences:
2.5
Justification:
No data available to justify alterations to standard factor.
AF for intraspecies differences:
5
Justification:
Standard factor to be applied for workers.
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns.
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:
50 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Modified dose descriptor not needed.  Assumed that absorption was 100% for all dose routes.

AF for dose response relationship:
1
Justification:
The substance does not have a steep dose response-curve.
AF for differences in duration of exposure:
1
Justification:
Dosing in the selected study was for multiple generations, and the ultimate endpoint selected was based on fetotoxicity.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor to extrapolate from rat to human
AF for other interspecies differences:
2.5
Justification:
Standard factor to account for potential differences in pharmacokinetics.
AF for intraspecies differences:
5
Justification:
Standard factor to account for worker variability.
AF for the quality of the whole database:
1
Justification:
The database is robust given the number and type of studies available, and consistency of findings
AF for remaining uncertainties:
1
Justification:
No additional assessment factors needed.
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
87 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
DNEL value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
2 174 mg/m³
Explanation for the modification of the dose descriptor starting point:

Adjusted for rat respiratory volume and assumed 100% absorption for all dose routes in both species.

AF for dose response relationship:
1
Justification:
The substance does not have a steep dose-response curve.
AF for differences in duration of exposure:
1
Justification:
Dosing in the selected study was for multiple generations, and the ultimate endpoint selected was based on fetotoxicity.
AF for interspecies differences (allometric scaling):
1
Justification:
Not requred when extrapolating from oral studies in rats to inhalation exposure in humans.
AF for other interspecies differences:
2.5
Justification:
Standard adjustment factor.
AF for intraspecies differences:
10
Justification:
Standard assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The database is robust given the number and type of studies available, and consistency of findings
AF for remaining uncertainties:
1
Justification:
No additional assessment factor needed.
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:
25 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
DNEL value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Adjustment not required due to assumed 100% absorption from both oral and dermal dose routes.

AF for dose response relationship:
1
Justification:
Substance does not have a steep dose-response curve.
AF for differences in duration of exposure:
1
Justification:
Dosing in the selected study was for multiple generations, and the ultimate endpoint selected was based on fetotoxicity.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard scaling factor for extrapolating from rats to humans
AF for other interspecies differences:
2.5
Justification:
Standard factor to account for potential differences in pharmacokinetics.
AF for intraspecies differences:
10
Justification:
Standard factor for general population.
AF for the quality of the whole database:
1
Justification:
The database is robust given the number and type of studies available, and consistency of findingsngs.
AF for remaining uncertainties:
1
Justification:
No assessment factor needed
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:
25 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
DNEL value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification needed due to same dose route and assumed 100% absorption in both species.

AF for dose response relationship:
1
Justification:
The substance has low oral toxicity and does not have a steep dose-response curve.
AF for differences in duration of exposure:
1
Justification:
Dosing in the selected study was for multiple generations, and the ultimate endpoint selected was based on fetotoxicity.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard assessment factor to extrapolate from rat to human.
AF for other interspecies differences:
2.5
Justification:
Standard assessment factor to account for differences in pharmacokinetics.
AF for intraspecies differences:
10
Justification:
Standard assessment factor for the general population.
AF for the quality of the whole database:
1
Justification:
The database is robust given the number and type of studies available, and consistency of findings
AF for remaining uncertainties:
1
Justification:
No additional assessment factor needed.
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