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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.93 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
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
220 mg/m³
Explanation for the modification of the dose descriptor starting point:

250 x 1/0.38 x 6.7/10 x 0.5 [50% oral absorption rat / 100% inhalation absorption human].

AF for dose response relationship:
1
Justification:
NOAEL derived
AF for differences in duration of exposure:
6
Justification:
Subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
corrected starting point
AF for other interspecies differences:
2.5
Justification:
Systemic
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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
DNEL related information

Workers - 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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As stated in ECHA guidance R8, it is assumed that dermal absorption will not be higher than oral absorpion, therefore no default factor should be used when oral-to-dermal extrapolation.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat species
AF for other interspecies differences:
2.5
Justification:
systemic effects
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

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:
0.72 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:
NOAEC
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
109 mg/m³
Explanation for the modification of the dose descriptor starting point:

250 x 1/1.15 x 0.5 [50% oral absorption rat / 100% inhalation absorption human].

AF for dose response relationship:
1
Justification:
Dose response
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
modified starting point
AF for other interspecies differences:
2.5
Justification:
For effects on skin, eye and GI tract via local metabolism, for effects on respiratory tract.
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 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:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As stated in ECHA guidance R8, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
dose response
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat species
AF for other interspecies differences:
2.5
Justification:
systemic effects
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 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:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As this is an oral study, no modification of the starting point is needed.

AF for dose response relationship:
1
Justification:
dose response
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat species
AF for other interspecies differences:
2.5
Justification:
systemic effects
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
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:
medium hazard (no threshold derived)

Additional information - General Population