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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 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
Modified dose descriptor starting point:
NOAEC
Value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat dermal NOAEL was converted into human inhalatory NOAEC considering: the "8h exposure rat standard Respiratory Volume" (0.38 m3/kg); the "rat dermal absorption"/"human inhalatory absorption" ratio (50/100); the "8h human standard Respiratory Volume"/"8h worker  Respiratory volume" ratio (6.7 m3/10 m3).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute (28 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
no Allometric scaling factor is used when setting an inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 410 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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:
1.67 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
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat dermal NOAEL was converted into human dermal NOAEL considering the "rat dermal absorption"/"human dermal absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute (28 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 410 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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:
2.9 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
Modified dose descriptor starting point:
NOAEC
Value:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat dermal NOAEL was converted into human inhalatory NOAEC considering: the "24h exposure rat standard Respiratory Volume" (1.15 m3/kg); the "rat dermal absorption"/"human inhalatory absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute (28 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 410 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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:
0.83 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
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat dermal NOAEL was converted into human dermal NOAEL considering the "rat dermal absorption"/"human dermal absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute (28 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 410 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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:
0.83 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
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat dermal NOAEL was converted into human oral NOAEL considering the "rat dermal absorption"/"human oral absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute (28 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2, december 2010.
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The starting study has been performed according to OECD TG 410 and GLP (Klimisch code 1)
AF for remaining uncertainties:
1
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