Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
8.38 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.21 mg/m³
Explanation for the modification of the dose descriptor starting point:
Step 1) Relevant dose-descriptor: NOAEC (rat, 90d) = 8.38 mg/m3 for systemic effects. Step 2) Modification of starting point: * Correction of respiratory volume for relevant duration: For 8h of exposure, the respiratory volume of humans is 6.7 m3/ person, and the respiratory volume light activity for worker (8h exposure) is 10 m3/person. The correction factor is 6.7/10. * Correction or exposure duration in study (6h/d, 5d/wk) to default worker exposure (8h/d, 5d/wk): The correction factor is 6/8. * Correction for absorption difference between rat and human: No difference in inhalation absorption is expected between rats and humans. NOAEC corrected = 8.38 x 6/8 x 6.7/10 = 4.21 mg/m3
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEC.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
Value:
0.507 mg/m³
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEC.
AF for differences in duration of exposure:
1
Justification:
Not applicable for local effects.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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:
0.024 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
Value:
8.38 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
2.41 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Step 1) Relevant dose-descriptor: NOAEC, rat = 8.38 mg/m3 for systemic effects. Step 2) Modification of starting point: * Correction for absorption difference between rat and human, and between dermal and inhalation absorption:No difference in dermal and inhalation absorption is expected between rats and humans. A default inhalation and dermal absorption of 100% in rats and humans is used for DNEL derivation.  * Correction of respiratory volume for relevant duration: For a 6-h exposure, the respiratory volume of rats is 0.288 m3/kg bw. NOAEL (internal dose) = 8.38 x 0.288 = 2.41 mg/kg bw
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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:
0.03 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
8.38 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Step 1) Relevant dose-descriptor: NOAEC (rat, 90d) = 8.38 mg/m3 for systemic effects. Step 2) Modification of starting point: * Correction or exposure duration in study (6h/d, 5d/wk) to default general population exposure (24h/d, 7d/wk) :The correction factor is 6/24 x 5/7. * Correction for absorption difference between rat and human: No difference in inhalation absorption is expected between rats and humans. NOAEC corrected = 8.38 x 6/24 x 5/7 = 1.50 mg/m3
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEC.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.004 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
Value:
0.507 mg/m³
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEC.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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:
0.012 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEC
Value:
8.38 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
2.41 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Step 1) Relevant dose-descriptor:NOAEC (rat,90d) = 8.38 mg/m3 for systemic effects. Step 2) Modification of starting point: * Correction for absorption difference between rat and human, and between dermal and inhalation absorption: A default inhalation and dermal absorption of 100% in rats and humans is used for DNEL derivation.  Thereforethe correction factor is 1 (100/100 = 1). * Correction of respiratory volume for relevant duration: For 6h of exposure, the respiratory volume of rats is 0.288m3/kg bw. NOAEL (internal dose) = 8.38 x 0.288 = 2.41 mg/kg bw
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.012 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEC
Value:
8.38
Modified dose descriptor starting point:
NOAEL
Value:
2.41 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Step 1) Relevant dose-descriptor: NOAEC (rat, 90d) = 8.38 mg/m3 for systemic effects. Step 2) Modification of starting point: * Correction for absorption difference between rat and human, and between oral and inhalation absorption: A default inhalation and oral absorption of 100% in rats and humans is used for DNEL derivation.  * Correction of respiratory volume for relevant duration: For 6h of exposure, the respiratory volume of rats is 0.288m3/kg bw. NOAEL (internal dose)= 8.38 x 0.288 = 2.41 mg/kg bw/d
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a subchronic study (90-day).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population