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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
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
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 interspecies differences (allometric scaling):
1
Justification:
not required
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
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
Modified dose descriptor starting point:
NOAEL
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 the read across substance (C12 LAS 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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

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:
1.5 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
Modified dose descriptor starting point:
NOAEC
Value:
73.9 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 the general population 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 73.9 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:
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
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
Modified dose descriptor starting point:
NOAEL
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 the read across substance (C12 LAS 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:
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:
0.425 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
Explanation for the modification of the dose descriptor starting point:

The starting point oral value is taken from the 9-month repeated dose toxicity study, which resulted in a NOAEL of 85 mg/kg bw/d. No corrections for route-to-route extrapolation are necessary.

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:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population