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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.118 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):
225
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg bw/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Braun et al., 2000), was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point LOAEC is 26.45 mg/m³ = 15 mg/kg bw/day x 1/0.38 m³/kg/day x 0.67. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under respective conditions (6.7 m³ for base level, 10 m³ for light activity). No additional correction factor for the route of exposure is needed since the bioavailability for both oral exposure and after inhalation is assumed to be 100%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
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:
0.033 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):
900
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Braun et al., 2000), was used to derive a DNEL long-term, systemic effects via dermal administration. After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is 15 mg/kg bw/day x 2 = 30 mg/kg bw/day. A correction factor of 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after dermal exposure is assumed to be 50%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
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:
DNEL (Derived No Effect Level)
Value:
30 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor:
other:
Value:
1 125 µg/m³
AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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):
450
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
13.04 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg bw/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Braun et al., 2000), was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point LOAEC is 13.04 mg/m³ = 15 mg/kg bw/day x 1/1.15 m³/kg/day. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 hours exposure of general public).

No additional correction factor for the route of exposure is needed since the bioavailability for both oral exposure and after inhalation is assumed to be 100%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
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:
0.017 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):
1 800
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Braun et al., 2000), was used to derive a DNEL long-term, systemic effects via dermal administration. After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is 15 mg/kg bw/day x 2 = 30 mg/kg bw/day. A correction factor of 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after dermal exposure is assumed to be 50%.

AF for dose response relationship:
3
Justification:
LOAEL is used as starting point
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
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:
0.008 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):
1 800
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
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