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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.79 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
177.73 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 100 mg/kg bw /day was determined for the substance 2-ethylhexanoic acid in a developmental toxicity study in rats (Penannen 1992). This value was converted into the corrected inhalatory LOAEC taking into account the standard respiratory factor of 1/0.38 m³/kg/day, the absorption rates (oral 72 %, inhalation 100 %; the lower end of the oral absorption range as determined in the toxicokinetic study by Eastman Kodak 1982 was chosen here as a worst-case assumption for the route-to-route extrapolation), the standard respiratory volume in humans/ worker respiratory volume (6.7 m³ (8 h) / 10 m³ (8 h)) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

LOAEC corrected = 100 mg/kg bw/day * 1/0.38 m³/kg/day * 72/100 * (6.7 m³/10 m³) * 1.4 = 177.73 mg/m³

AF for dose response relationship:
3
Justification:
No NOAEL could be identified in the key study
AF for differences in duration of exposure:
6
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for inhalation endpoint as already included in the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute hazard was identified for the registered substance (LD50 > 2000 mg/kg bw/d for the oral and dermal route). Thus, the substance is also considered to be not acutely toxic by the inhalation route.

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:
0.16 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
144 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 100 mg/kg bw /day was determined for the substance 2-ethylhexanoic acid in a developmental toxicity study in rats (Penannen 1992). This value was converted into the corrected LOAEL taking into account the absorption rates (oral 72 %, dermal 70 %; the lower end of the oral absorption range as determined in the toxicokinetic study by Eastman Kodak 1982 was chosen here as a worst-case assumption for the route-to-route extrapolation) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

LOAEL corrected = 100 mg/kg bw/day * 72/70 * 1.4 = 144 mg/kg bw/d

AF for dose response relationship:
3
Justification:
No NOAEL could be identified in the key study
AF for differences in duration of exposure:
6
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute hazard was identified for the registered substance (LD50 > 2000 mg/kg bw/d for the oral and dermal route).

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:
0.14 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
62.61 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 100 mg/kg bw /day was determined for the substance 2-ethylhexanoic acid in a developmental toxicity study in rats (Penannen 1992). This value was converted into the corrected inhalatory LOAEC taking into account the standard respiratory factor of 1/1.15 m³/kg/day and the absorption rates (oral 72 %, inhalation 100 %; the lower end of the oral absorption range as determined in the toxicokinetic study by Eastman Kodak 1982 was chosen here as a worst-case assumption for the route-to-route extrapolation).

LOAEC corrected = 100 mg/kg bw/day * 1/1.15 m³/kg/day * 72/100 = 62.61 mg/m³

AF for dose response relationship:
3
Justification:
No NOAEL could be identified in the key study
AF for differences in duration of exposure:
6
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for inhalation endpoint as already included in the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
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:
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:
57.14 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
102.86 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 100 mg/kg bw /day was determined for the substance 2-ethylhexanoic acid in a developmental toxicity study in rats (Penannen 1992). This value was converted into the corrected dermal LOAEC taking into account the the absorption rates (oral 72 %, dermal 70 %; the lower end of the oral absorption range as determined in the toxicokinetic study by Eastman Kodak 1982 was chosen here as a worst-case assumption for the route-to-route extrapolation).

LOAEC corrected = 100 mg/kg bw/day * 72/70 = 102.86 mg/kg bw/d

AF for dose response relationship:
3
Justification:
No NOAEL could be identified in the key study
AF for differences in duration of exposure:
6
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute hazard was identified for the registered substance (LD50 > 2000 mg/kg bw/d for the oral and dermal route).

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:
55.56 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 100 mg/kg bw /day was determined for the substance 2-ethylhexanoic acid in a developmental toxicity study in rats (Penannen 1992). This value has not to be corrected as the absorption rates of humans and rats are expected to be similar.

AF for dose response relationship:
3
Justification:
No NOAEL could be identified in the key study
AF for differences in duration of exposure:
6
Justification:
default for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute hazard was identified for the registered substance (LD50 > 2000 mg/kg bw/d for the oral and dermal route).

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population