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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 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
Modified dose descriptor starting point:
NOAEC
Value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:

8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
other: NO(A)EL = 500 mg/kg bw/day (repeated dose dermal study), 8 h exposure = 0.38 m^3/kg bw (respiratory volume for rat), NOAEC = 1315 mg/m^3/day
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic (required for inhalation as for systemic effects)
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

not required: NO(A)EL from repeated dose dermal study

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
LOAEL is 1000 mg/kg bw/day (LOAEC = 8 mg/cm^2) and NOEL is 500 mg/kg bw/day (NOAEC = 4 mg/cm^2); as rational, NOAEL could be = NOEL
AF for differences in duration of exposure:
1
Justification:
the toxic effect is driven by the exposure concentraiton
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling for local effects
AF for other interspecies differences:
1
Justification:
effects on skin via simple destruction of membranes
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The long-term inhalation DNEL for systemic effects is derived on the basis of the sub-acute oral toxicity study. The calculated DNEL is 3.5 mg/m^3, applying the assessment factor of 75.

The long-term inhalation DNEL for local effects is derived on the basis of the sub-acute dermal toxicity study (2-week study), since 1000 mg/kg bw/day dose was considered as LOAEL for local effects. For this DNEL derivation NOEL = 500 mg/kg bw/day was used. The calculated DNEL is 17.5 mg/m^3, applying the assessment factor of 75.

The acute/short term exposure inhalation DNEL for systemic and local effects was not assessed, since no acute inhalation study is available and Mexoryl SBO shows low acute toxicity when administered orally (LD50 > 2000 mg/kg bw).

The long-term dermal DNEL for systemic effects is derived on the basis of sub-acute dermal toxicity study (2-week study), where NOEL was 1000 mg/kg bw/day, the highest administered dose of Mexoryl SBO. The calculated DNEL is 3.3 mg/kg bw/day, applying the assessment factor of 300.

The long-term dermal DNEL for local effects is derived on the basis of the sub-acute dermal toxicity study (2-week study), where starting point is NOEL = 500 mg/kg bw/day (NOAEC = 4 mg/cm^2). The calculated DNEL is 0.8 mg/cm^2, applying the assessment factor of 5.

The acute/short term exposure dermal DNEL for systemic and local effects was not assessed, since no acute dermal study is available and Mexoryl SBO shows low acute toxicity when administered orally (LD50 > 2000 mg/kg bw).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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
Modified dose descriptor starting point:
NOAEC
Value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:

24 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not required for concentration
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor:
other: NO(A)EL = 500 mg/kg bw/day (repeated dose dermal study), 8 h exposure = 0.38 m^3/kg bw (respiratory volume for rat), NOAEC = 1315 mg/m^3/day
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic (required for inhalation as for systemic effects)
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
no required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

not required: NO(A)EL from repeated dose dermal study

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: LOAEL
AF for dose response relationship:
1
Justification:
LOAEL is 1000 mg/kg bw/day (LOAEC = 8 mg/cm^2) and NOEL is 500 mg/kg bw/day (NOAEC = 4 mg/cm^2); as rational, NOAEL = NOEL
AF for differences in duration of exposure:
1
Justification:
the toxic effect is driven by the exposure concentraiton
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling for local effects
AF for other interspecies differences:
1
Justification:
effects on skin via simple destruction of membranes
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
0.5 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route-to-route extrapolation performed

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
high hazard (no threshold derived)

Additional information - General Population

The long-term inhalation DNEL for systemic effects is derived on the basis of the sub-acute oral toxicity study. The calculated DNEL is 0.87 mg/m^3, applying the assessment factor of 150.

The long-term inhalation DNEL for local effects is derived on the basis of the sub-acute dermal toxicity study (2-week study), since 1000 mg/kg bw/day dose was considered as LOAEL for local effects. For this DNEL derivation NOEL = 500 mg/kg bw/day was used. The calculated DNEL is 8.8 mg/m^3, applying the assessment factor of 150.

The acute/short term exposure inhalation DNEL for systemic and local effects was not assessed, since no acute inhalation study is available and Mexoryl SBO shows low acute toxicity when administered orally (LD50 > 2000 mg/kg bw).

The long-term dermal DNEL for systemic effects is derived on the basis of sub-acute dermal toxicity study (2-week study), where NOEL was 1000 mg/kg bw/day, the highest administered dose of Mexoryl SBO. The calculated DNEL is 1.7 mg/kg bw/day, applying the assessment factor of 600.

The long-term dermal DNEL for local effects is derived on the basis of the sub-acute dermal toxicity study (2-week study), where starting point is NOEL = 500 mg/kg bw/day (NOAEC = 4 mg/cm^2). The calculated DNEL is 0.4 mg/cm^2, applying the assessment factor of 10.

The acute/short term exposure dermal DNEL for systemic and local effects was not assessed, since no acute dermal study is available and Mexoryl SBO shows low acute toxicity when administered orally (LD50 > 2000 mg/kg bw).

The long-term oral DNEL for systemic effects is derived on the basis of sub-acute oral toxicity study. The calculated DNEL is 0.5 mg/kg bw/day, applying the assessment factor of 600.

The acute/short term exposure oral DNEL for systemic effects was not assessed, since Mexoryl SBO shows low acute toxicity when administered orally (LD50 > 2000 mg/kg bw).

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