Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 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:
NOAEC
DNEL value:
208 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
104 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (van Triel, 2017). The starting concentration for DNEL calculation is a NOAEC of 208 mg/m3 (25.1 ppm).  The NAEC (8h) derived for workers is 104 mg/m3 (208 mg/m3 x 6h/8h x 6.7 m3/10 m3) after correction for difference in exposure conditions and between respiratory rates under standard conditions and under conditions of light activity.  

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
Not needed
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not 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
Most sensitive endpoint:
repeated dose toxicity
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:
3 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
DNEL value:
208 mg/m³
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (van Triel, 2017). The starting dose for DNEL calculation is a NOAEC of 208 mg/m3 (25.1 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure and a default inhalation absorption of 50%, the corresponding internal NOAEL is 30 mg/kg bw/d. TDM is expected to be poorly absorbed by the skin (10% of the dose), therefore the dermal NAEL derived for workers is 300 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default AF
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

A DNEL for short term duration (short term event, peak exposure) will not need to be derived in the case where an acute toxicity hazard (leading to C&L) has not been identified.    

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.665 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
not needed
AF for interspecies differences (allometric scaling):
1
Justification:
not needed
AF for other interspecies differences:
10
Justification:
default value
AF for intraspecies differences:
1
Justification:
not needed
AF for the quality of the whole database:
1
Justification:
not needed
AF for remaining uncertainties:
1
Justification:
not needed

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.74 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
DNEL value:
208 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
37.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (van Triel, 2017). The starting dose for DNEL calculation is a NOAEC of 208 mg/m3. The NAEC (24h) derived for the general population is 37.1 mg/m3 (208 mg/m3 x 6h/24h x 5d/7d) after correction for difference in exposure conditions.

AF for dose response relationship:
1
Justification:
Default AF
AF for differences in duration of exposure:
2
Justification:
Default AF
AF for interspecies differences (allometric scaling):
1
Justification:
Not needed
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not 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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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:
other: NOAEC = 208 mg/m3
Modified dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (Triel, 2017). The starting dose for DNEL calculation is a NOAEC of 208 mg/m3 (25.1 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure and a default inhalation absorption of 50%, the corresponding internal NOAEL is 30 mg/kg bw/d. TDM is expected to be well absorbed by the oral route (100% of the dose), therefore the oral NAEL derived for general population is 30 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default AF
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not 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:
low hazard (no threshold derived)

Additional information - General Population