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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.165 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
Modified dose descriptor starting point:
NOAEC
Value:
12.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, short-term) = 5 mg/kg bw/day
Correction factor for differences in respiratory volume (rat/workers): 1/0.38
Correction factor for light activity at work: 6.7/10
Correction factor for difference between human and experimental exposure conditions: 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).
Absorptions by inhalation and oral route were concluded to be equivalent (100%).
NOAEC = NOAEL x (1/0.38) x (6.7/10) x 7/5 = 5 x (1/0.38) x (6.7/10) x 7/5 = 12.34 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:
6
Justification:
Short-term to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
93.77 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Modified dose descriptor starting point:
LOAEC
Value:
3 516.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point: LOAEC (4h) = 2060 mg/m3


Time extrapolation:
Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with a coefficient of 3 for extrapolation from a longer to a shorter exposure duration: LOAEC (15 minutes) = 5191 mg/m3


Modification for respiratory volume:
Respiratory volume of human is 0.2 L/min/kg, for 15 minutes we have a respiratory volume of 3 L/kg, corresponding to 0.21 m3/person (70kg). Respiratory volume light activity for worker (8h) is 10 m3/person. For 15 minutes we have a respiratory volume of 0.31 m3/person. LOAEC = 5191 x 0.21/0.31 = 3516.5 mg/m3

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.233 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
Modified dose descriptor starting point:
NOAEL
Value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, short-term) = 5 mg/kg bw/day
Absorptions by the dermal route was concluded to represent 10% of the absorption following exposure via the oral route.
Correction factor for difference between human and experimental exposure conditions: 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).
NOAEL = NOAEL x 7/5 / 10% = 5 x 7/5 / 10% = 70 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:
6
Justification:
Short-term to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
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:
high 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:
0.029 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
Modified dose descriptor starting point:
NOAEC
Value:
4.35 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, short-term) = 5 mg/kg bw/day
Correction factor for differences in respiratory volume (rat/general population): 1/1.15
Absorptions by inhalation and oral route were concluded to be equivalent (100%).
NOAEC = NOAEL x (1/1.15) = 5 x (1/1.15) = 4.35 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:
6
Justification:
Short-term to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
69.2 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
LOAEC
Value:
5 191 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point: LOAEC (4h) = 2060 mg/m3


Time extrapolation:
Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with a coefficient of 3 for extrapolation from a longer to a shorter exposure duration: LOAEC (15 minutes) = 5191 mg/m3


No modification for respiratory volume is required for the general population.

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.083 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
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, short-term) = 5 mg/kg bw/day
Absorptions by the dermal route was concluded to represent 10% of the absorption following exposure via the oral route.
NOAEL = NOAEL / 10% = 5 / 10% = 50 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:
6
Justification:
Short-term to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
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:
high 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:
0.008 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
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:
6
Justification:
Short-term to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
AF for dose response relationship:
1
Justification:
This factor is applied because the dose-descriptor starting point is a NOAEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population