Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
DNEL value:
1 300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
383 mg/m³
Explanation for the modification of the dose descriptor starting point:

Assumed rat dermal exposure was 10.9-fold greater than in vitro human exposure. Converted dose to account for rat inhalative volume for 8 hours/day and worker respiratory volume.  Assumed 100% inhalation exposure in humans.

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:
Extrapolated fomr a "sub acute - 28-day" study to chronic exposure. This is a standard ECHA factor.
AF for interspecies differences (allometric scaling):
1
Justification:
Already accounted for based on respiratory volume correction factors.
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:
47 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
DNEL value:
1 300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
14 190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Modified dose descriptor not needed.  Assumed that dermal absorption was 16.7% in rats and 1.53% in human.

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:
Extrapolated from a 28-day (sub-acute) study to chronic exposure.
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:
1.26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
DNEL value:
1 300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
189 mg/m³
Explanation for the modification of the dose descriptor starting point:

Assumed rat dermal exposure was 10.9-fold greater than in vitro human exposure value. Converted dose to account for rat and general population respiratory volumes.  Assumed 100% inhalation exposure in humans.

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:
Standard factor for extrapolating from 28-day sub-acute study to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Already accounted for when adjusting for rat and human respiratory volumes.
AF for other interspecies differences:
2.5
Justification:
Standard assessment factor for general population.
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 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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
DNEL value:
1 300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
14 190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assumed 16.7% dermal absorption in rats and 1.53% absorption in humans.

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:
Standard factor extrapolating from 28-day study to chronic study.
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 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:
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:
0.362 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
DNEL value:
1 300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
217 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assumed 16.7% dermal absorption in rat, and 100% oral absorption in both rat and human.

AF for dose response relationship:
1
Justification:
The substance did not exhibit toxicity following dermal dosing and does not have a steep dose-response curve.
AF for differences in duration of exposure:
6
Justification:
Standard factor for extrapolating from 28-day (sub-acute) study to chronic exposure.
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 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 effects.
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