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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.23 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:
LOAEL
Value:
19 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
16.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral rat LOAEL was converted into the inhalative human LAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). For differences between oral absorption in rats and inhalative absorption in humans an additional assessment factor of 2 was used. The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 16.75 mg/m³.

AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
2
Justification:
The default AF of 2 for time extrapolation between sub-chronic (90d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
The AF has already been handled within the correction of the modification of the dose descriptor.
Therefore, no additional factor has to be applied.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is set in line with the REACH guidance R.8.
AF for intraspecies differences:
5
Justification:
The default factor of 5 for workers is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.13 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:
LOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For highly lipophilic substances (log P greater than 6) that come into contact with the skin, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Dermal uptake for such substances is expected to be low (ECHA GD 7c, 2008). Thus, for differences between oral and dermal absorption an additional assessment factor of 0.5 was used. The resulting corrected starting point for dermal DNEL derivation for workers is equal to 40 mg/kg bw/d.

AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is set in line with the REACH guidance R.8.
AF for intraspecies differences:
5
Justification:
The default factor of 5 for workers is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.06 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:
LOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
8.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral rat LOAEL was converted into the inhalative human LOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/d). For differences between oral absorption in rats and inhalative absorption in humans an additional assessment factor of 2 was used. The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 8.7 mg/m³.

AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure, according to Reach TGD
AF for interspecies differences (allometric scaling):
1
Justification:
The AF has already been handled within the correction of the modification of the dose descriptor.
Therefore, no additional factor has to be applied.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is set in line with the REACH guidance R.8.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.07 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:
LOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For highly lipophilic substances (log P greater than 6) that come into contact with the skin, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Dermal uptake for such substances is expected to be low (ECHA GD 7c, 2008). Thus, for differences between oral and dermal absorption an additional assessment factor of 0.5 was used. The resulting corrected starting point for dermal DNEL derivation for workers is equal to 40 mg/kg bw/d.

AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is set in line with the REACH guidance R.8.
AF for intraspecies differences:
10
Justification:
The default factor for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.03 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:
LOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For DNEL derivation the LOAEL of 20 mg/kg bw/d was considered the most appropriate point of departure covering systemic effects.

AF for dose response relationship:
3
Justification:
A LOAEL was chosen as starting point for DNEL derivation.
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is set in line with the REACH guidance R.8.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

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