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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.81 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
165 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
145.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

From 2 Generation study, a conservative NOAEL of 3300 ppm for F2 generation has been chosen for derivation of DNELs. Upon conversion of ppm to mg/kg a NOAEL of 165 mg/kg has been derived by applying factor of 20 (Ref: Table 2.2 conversion factors, Pocket Handbook of toxicology).

For modifying the dose descriptor, the factor of 0.38 was applied for conversion of mg/kg to mg/m³. A factor of 6.7 and 10 for respiratory volumes were applied. 50% bioavailibity has been selected for route to route extrapolation value.

Corrected NOAEC = 165 mg/kg bw/day * (1/0.38 m³/mg/kg bw/day) x 0.67 x 0.5 = 145.4 mg/m³.

AF for dose response relationship:
1
Justification:
default (no uncertainties in the dose descriptor = NOAEL/NOAEC)
AF for differences in duration of exposure:
2
Justification:
default for subchronic-to-chronic (second generation (until the weaning) NOAEL was selected for DNEL calculation)
AF for interspecies differences (allometric scaling):
1
Justification:
default for inhlation-to-inhalation (no additional assessment factor for allometric scaling is necessary, since the interspecies differences have already been taken into account (delineation of corrected NOAEC))
AF for other interspecies differences:
2.5
Justification:
default (a standard procedure to correct for differences in metabolic rate and differences in toxicokinetics and toxicodynamics)
AF for intraspecies differences:
5
Justification:
default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
default (no remaining uncertainties in the derived DNEL)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for.
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:
693 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
165 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
693 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From 2 Generation study, a conservative NOAEL of 3300 ppm for F2 generation has been chosen for derivation of DNELs. Upon conversion of ppm to mg/kg a NOAEL of 165 mg/kg has been derived by applying factor of 20 (Ref: Table 2.2 conversion factors , Pocket Handbook of toxicology). The same NOAEL has been chosen for DNEL dermal calculation.

For modifying the dose descriptor, the default dermal absorption factor of 100% is applied.

Furthermore the NOAEL is corrected for duration of exposure (24 h in the rats versus 8 h in workers - and - 7 days in the rat versus 5 days in workers)

Corr. NOAEL = 165 mg/kg bw/day * (24h/8h) * (7 d/ 5 d) = 693 mg/kg bw/day

AF for dose response relationship:
1
Justification:
default (no uncertainties in the dose descriptor = NOAEL/NOAEC)
AF for differences in duration of exposure:
2
Justification:
default for subchronic-to-chronic (second generation (until the weaning) NOAEL was selected for DNEL calculation)
AF for interspecies differences (allometric scaling):
4
Justification:
default - Allometric scalling factor for systemic effects oral to dermal for rats
AF for other interspecies differences:
2.5
Justification:
default (a standard procedure to correct for differences in metabolic rate and differences in toxicokinetics and toxicodynamics)
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default (no remaining uncertainties in the derived DNEL)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
1.434 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
165 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
71.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

From 2 Generation study, a conservative NOAEL of 3300 ppm for F2 generation has been chosen for derivation of DNELs. Upon conversion of ppm to mg/kg a NOAEL of 165 mg/kg has been derived by applying factor of 20 (Ref: Table 2.2 conversion factors, Pocket Handbook of toxicology).

For modifying the dose descriptor, the factor of 1.15 was applied for conversion of mg/kg to mg/m³. 50% bioavailibity has been selected for route to route extrapolation value.

Corrected NOAEC = 165 mg/kg bw/day * (1/1.15 m³/mg/kg bw/day) x 0.5 = 71.7 mg/m³.

AF for dose response relationship:
1
Justification:
default (no uncertainties in the dose descriptor = NOAEL/NOAEC)
AF for differences in duration of exposure:
2
Justification:
default for subchronic-to-chronic (second generation (until the weaning) NOAEL was selected for DNEL calculation)
AF for interspecies differences (allometric scaling):
1
Justification:
default for inhlation-to-oral (no additional assessment factor for allometric scaling is necessary, since the interspecies differences have already been taken into account (delineation of corrected NOAEC))
AF for other interspecies differences:
2.5
Justification:
default (a standard procedure to correct for differences in metabolic rate and differences in toxicokinetics and toxicodynamics)
AF for intraspecies differences:
10
Justification:
default assessment factor for consumer, intraspecies variability
AF for the quality of the whole database:
1
Justification:
default (no remaining uncertainties in the derived DNEL)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for.
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:
0.825 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
165 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
165 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From 2 Generation study, a conservative NOAEL of 3300 ppm for F2 generation has been chosen for derivation of DNELs. Upon conversion of ppm to mg/kg a NOAEL of 165 mg/kg has been derived by applying factor of 20 (Ref: Table 2.2 conversion factors, Pocket Handbook of toxicology).

For modifying the dose descriptor, the factor of 100 % bioavailibity has been selected. Default value for route to route extrapolation is 100%

Corrected NOAEC = 165 mg/kg bw/day * (100%/100%) = 165 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
default (no uncertainties in the dose descriptor = NOAEL/NOAEC)
AF for differences in duration of exposure:
2
Justification:
default for subchronic-to-chronic (second generation (until the weaning) NOAEL was selected for DNEL calculation)
AF for interspecies differences (allometric scaling):
4
Justification:
default - Allometric scalling factor for systemic effects oral to dermal for rats
AF for other interspecies differences:
2.5
Justification:
default (a standard procedure to correct for differences in metabolic rate and differences in toxicokinetics and toxicodynamics)
AF for intraspecies differences:
10
Justification:
default assessment factor for consumer, intraspecies variability
AF for the quality of the whole database:
1
Justification:
default (no remaining uncertainties in the derived DNEL)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for.
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:
0.825 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
165 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
165 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From 2 Generation study, a conservative NOAEL of 3300 ppm for F2 generation has been chosen for derivation of DNELs. Upon conversion of ppm to mg/kg a NOAEL of 165 mg/kg has been derived by applying factor of 20 (Ref: Table 2.2 conversion factors, Poclet Handbook of toxicology). The same NOAEL has been chosen for DNEL consumer oral calculation.

For modifying the dose descriptor, the factor of 100 % bioavailibity (oral to oral) has been selected. Default values for route to route extrapolation is 100%

Corrected NOAEC = 165 mg/kg bw/day * (100%/100%) = 165 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
default (no uncertainties in the dose descriptor = NOAEL/NOAEC)
AF for differences in duration of exposure:
2
Justification:
default for subchronic-to-chronic (second generation (until the weaning) NOAEL was selected for DNEL calculation)
AF for interspecies differences (allometric scaling):
4
Justification:
default - Allometric scalling factor for systemic effects oral to oral for rats
AF for other interspecies differences:
2.5
Justification:
default (a standard procedure to correct for differences in metabolic rate and differences in toxicokinetics and toxicodynamics)
AF for intraspecies differences:
10
Justification:
default assessment factor for consumer, intraspecies differences
AF for the quality of the whole database:
1
Justification:
default (no remaining uncertainties in the derived DNEL)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for.
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