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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
290.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral NOAELrat× (1/0.38 m3/kg bw) × (6.7 m3/10m3) × (50% /100%) = 330 mg/kg bw/day × 1/0.38 × 6.7/10 × 50/100

Inhalation NOAEChuman= 290.9 mg/m³

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required for inhalation
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
2
Justification:
Read across used.
AF for remaining uncertainties:
2.5
Justification:
any remaining difference
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor:
other: NOEL
Value:
96.98 mg/m³
AF for dose response relationship:
1
Justification:
A clear NOEL for local effects was obtained and was used to define the modified starting point for local effects (NOEC)
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
2
Justification:
read across used
AF for remaining uncertainties:
1
Justification:
Default value for local effects
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:
2.8 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
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 650 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral NOAELrat× (50%/10%) = 330 mg/kg/day x 5

Dermal NOAELhuman= 1650 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
5
Justification:
deafult value for workers
AF for the quality of the whole database:
2
Justification:
read across used
AF for remaining uncertainties:
2.5
Justification:
Default value for any remaining difference
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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:
0.48 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):
300
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
143.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral NOAELrat× (1/1.15 m3/kg bw) × (50%/100%) = 330 mg/kg bw/day × 1/1.15 × 50/100

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required for inhalation
AF for other interspecies differences:
1
Justification:
No other differences
AF for intraspecies differences:
10
Justification:
default value for general public
AF for the quality of the whole database:
2
Justification:
read across used
AF for remaining uncertainties:
2.5
Justification:
Default value for any remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor:
other: NOEL
Value:
47.83 mg/m³
AF for dose response relationship:
1
Justification:
A clear NOEL was obtained
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation or local effects
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
2
Justification:
Read across used
AF for remaining uncertainties:
1
Justification:
Default value for any remaining differences for local effects
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:
1.4 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):
1 200
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 650 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction of the starting point: Oral NOAELrat× (50%/10%) = 330 mg/kg/day x 5

Dermal NOAEChuman= 1650 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL was obtained
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rat
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
2
Justification:
read across used
AF for remaining uncertainties:
2.5
Justification:
Default value for any remaining difference
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.28 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):
1 200
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral NOAELrat= Oral NOAELhuman= 330 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL has been defined in a compliant GLP OECD 407 study
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
1
Justification:
No other differences expected
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
2
Justification:
read across used
AF for remaining uncertainties:
2.5
Justification:
Default for any remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

An oral repeat dose rat study identified a NOEL of 110 mg/kg/day, at 330 mg/kg (defined as the NOAEL). There were marked effects at the portal-of-entry (stomach) and all other findings were attributed to local effects of irritation in the stomach. It is therefore considered relevant to calculate a DNELoral-local for the general population:

Correction of the starting point: Oral NOELrat= Oral NOELhuman= 110 mg/kg bw/day

 AF:

dose reseponse = 1 (defined NOEL set)

allometric scaling (rat to human) = 1 (not applicable for local effects as the mode of action/mechanism is considered to be the same)

other interspecies differences = 1 (no other differences)

remaining differences = 1 (local effect in the stomach)

duration of exposure = 6 (subacute to chronic)

quality of dataset = 2 (read across)

intraspecies differences = 10 (default for general public)

total AF = 120

Therefore DNELoral= 110 mg/kg bw/day/120

DNELoral-local= 0.92 mg/kg bw/day

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