Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.82 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:
NOAEL
Value:
333 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
587 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the 28-day oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.

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:
6
Justification:
Dosing in the selected study was for 28-days
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.1 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:
NOAEL
Value:
333 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
3 330 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the 28-day oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.

AF for dose response relationship:
1
Justification:
The substance does not have a steep dose response-curve.
AF for differences in duration of exposure:
6
Justification:
Dosing in the selected study was for 28-days
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 PK.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

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:
1.93 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:
NOAEL
Value:
333 mg/kg bw/day
Value:
290 mg/m³
Explanation for the modification of the dose descriptor starting point:

Standard correction factors or oral to inhalation

AF for dose response relationship:
1
Justification:
The substance does not have a steep dose-response curve.
AF for differences in duration of exposure:
6
Justification:
Dosing in the selected study was for 28-days
AF for interspecies differences (allometric scaling):
1
Justification:
Not required 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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.55 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:
NOAEL
Value:
333 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
3 330 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Adjustment due to assumed 10% absorption from 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:
6
Justification:
Dosing in the selected study was for 28-days
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 PK.
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 findings.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.555 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:
NOAEL
Value:
333 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
333 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:
6
Justification:
Dosing in the selected study was for 28-days
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 PK.
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