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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.71 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):
25
Dose descriptor starting point:
NOAEL
Value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
168 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
119 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):
100
Dose descriptor starting point:
NOAEL
Value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
11 900 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the information requirements in accordance with ECHA guidance R7.5 -7.7 (2016) for assessing long-term systemic toxicity. Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. The starting point is the NOAEL from the 9 -months oral study in rats; 85 mg/kg bw/day.

Based on data from a dermal absorption study of a C12LAS homologue in isolated human epidermis (Howes, 1975), < 0.065% of the applied dose penetrated the skin in 48 hours. An oral absorption value of 80 -90% was experimentally derived. A route-to-route factor of 100, instead of 80/0.065=1230.8, was conservatively assumed. A correction for 5 day exposure is performed (7 days exposure per week in the study versus 5 days per week for workers); therefore the modified starting point = 85 x 100 x (7/5) = 11,900 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
The starting point for DNEL derivation is a sub-chronic study, hence the extrapolation to chronic exposure results in a factor of 2.
AF for interspecies differences (allometric scaling):
4
Justification:
Since the starting point is an oral study and extrapolation to dermal route of exposure will need allometric scaling. For rats, the default assessment factor, as a standard procedure, is 4.
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:
Default for good quality database is 1.
AF for remaining uncertainties:
1
Justification:
Since there are no further uncertainties, the default assessment factor is 1.
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:
low 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:
1.18 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):
50
Dose descriptor starting point:
NOAEL
Value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
59.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
42.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
8 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the information requirements in accordance with ECHA guidance R7.5 -7.7 (2016) for assessing long-term systemic toxicity. Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. The starting point is the NOAEL from the 9 -months oral study in rats; 85 mg/kg bw/day.

Based on data from a dermal absorption study of a C12LAS homologue in isolated human epidermis (Howes, 1975), < 0.065% of the applied dose penetrated the skin in 48 hours. An oral absorption value of 80 -90% was experimentally derived. A route-to-route factor of 100, instead of 80/0.065=1230.8, was conservatively assumed. Therefore the modified starting point = 85 x 100 = 8500 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
2
Justification:
The starting point for the DNEL calculation is a NOAEL from sub-chronic study. Therefore extrapolation to chronic exposure will result in the application of an assessment factor of 2.
AF for interspecies differences (allometric scaling):
4
Justification:
Since the starting point for DNEL derivation is from an oral study and the extrapolation into the dermal exposure route will result into application of allometric scaling factor. For rats, the default assessment factor, as a standard procedure, is 4.
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:
The database is of good quality.
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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.425 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):
200
Dose descriptor starting point:
NOAEL
Value:
85 mg/kg bw/day
Value:
85 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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