Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.33 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
358.27 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL based on 90-day study (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.33 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.33 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL based on 90-day study (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
wokers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.33 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.06 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
406.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

No non-threshold effects for this substance were identified. The substance is considered that will be poorly taken up by the body because of its overall low solubility. The substance does not cause local effects. It also does not cause acute effects. The starting point for DNEL calculations is the NOAEL (oral route - rat) from a 90-day study = 406.4 mg/kg bw/day. Following the Practical Guide 14 and the ECHA Guidance R.8, the NOAEL oral is corrected to a NOAEC.

 

Correction of NOAELs for Workers

 

Oral NOAEL

Factor for standard respiratory volume rat

Factor for absorption rat oral/ human inhalation

Factor for standard respiratory volume man and 8-h exposure

Corrected NOAEC

406.4 mg/kg/day (rat chronic study)

1/0.38 m3/kg/d

0.5

6.7 m3(8h) / 10 m3(8h)

358.27 mg/ m3

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.534 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:
176.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL based on a 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling not used for inhalation
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.534 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.534 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.032 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:
406.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.032 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:
406.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
oral 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.032 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

No non-threshold effects for this substance were identified. The substance is considered that will be poorly taken up by the body because of its overall low solubility. The substance does not cause local effects. It also does not cause acute effects. The starting point for DNEL calculations is the NOAEL (oral route - rat) from a 90-day study = 406.4 mg/kg bw/day. Following the Practical Guide 14 and the ECHA Guidance R.8, the NOAEL oral is corrected to a NOAEC.

 

Correction of NOAELs for the general population

 

Oral NOAEL

Factor for standard respiratory volume rat

Factor for absorption rat oral/ human inhalation

Corrected NOAEC

406.4 mg/kg/day (rat chronic study)

1/1.15 m3/kg/d

0.5

176.7 mg/ m3

 

Assumption for NOAEC: 50% absorbed orally in rats, 100% absorbed after inhalation by man