Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 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
DNEL value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
149.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Since no long-term inhalation toxicity data are available the oral NOAEL must be converted to an inhalation value to use as the starting point. Using the formula for workers in Figure R.8-3 of Chapter R.8 (p.27) and the oral NOAEL of 85 mg/kg, the resulting inhalation NOAEC would be 149.9 mg/m3. Because this conversion includes interspecies exposure duration differences, no allometric scaling assessment factor is required.

AF for dose response relationship:
1
Justification:
no other uncertainties
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for other interspecies differences:
2.5
Justification:
toxicokinetic/toxicodynamic differences
AF for intraspecies differences:
5
Justification:
DNEL derived for workers
AF for the quality of the whole database:
1
Justification:
the database is complete
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
repeated dose toxicity
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:
85 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
DNEL value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
8 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on data from a dermal absorption study of a C12LAS homologue in isolated human epidermis (Howes 1975) that indicated < 0.065% of the applied dose penetrated the skin in 48 hours, 1% dermal absorption is conservatively assumed. The dermal NOAEL is therefore 8500 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
no other uncertainties
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to humans
AF for other interspecies differences:
2.5
Justification:
toxicokinetic/toxicodynamic differences
AF for intraspecies differences:
5
Justification:
DNEL for workers
AF for the quality of the whole database:
1
Justification:
the data base is sufficient
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
1.5 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
DNEL value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
73.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point corrected for route to route extrapolation factor (oral-to-inhalation extrapolation)

AF for dose response relationship:
1
Justification:
no other uncertainties
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for other interspecies differences:
2.5
Justification:
toxicokinetic/toxicodynamic differences
AF for intraspecies differences:
10
Justification:
DNEL for the general population
AF for the quality of the whole database:
1
Justification:
the data base is sufficient
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
repeated dose toxicity
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:
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
DNEL value:
85 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
8 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on data from a dermal absorption study of a C12LAS homologue in isolated human epidermis (Howes 1975) that indicated < 0.065% of the applied dose penetrated the skin in 48 hours, 1% dermal absorption is conservatively assumed. The dermal NOAEL is therefore 8500 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
no other uncertainties
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to humans
AF for other interspecies differences:
2.5
Justification:
toxicokinetic/toxicodynamic differences
AF for intraspecies differences:
10
Justification:
DNEL for general population
AF for the quality of the whole database:
1
Justification:
the data base is sufficient
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

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
DNEL value:
85 mg/kg bw/day
AF for dose response relationship:
1
Justification:
no other uncertainties
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to humans
AF for other interspecies differences:
2.5
Justification:
toxicokinetic/toxicodynamic differences
AF for intraspecies differences:
10
Justification:
DNEL for general population
AF for the quality of the whole database:
1
Justification:
the data base is sufficient
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 for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population