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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.658 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):
37.5
Dose descriptor starting point:
NOAEC
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
24.684 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point correction formula:

Corrected dose descriptor = oral NOAEL x 1/sRVan x Diff. exp. cond. x (ABSoral,an/ABSinh,hu) x sRVhu/wRV              

Given:

Experimental animal: rat    

Relevant human exposure route: inhalation

Oral NOAEL from original study (oral NOAEL) = 20 mg/kg bw/day (test result)

Standard respiratory volume, animal (sRVan) = 0.38 m3/kg bw/8 h (default)

Standard respiratory volume, human (sRVhu) = 6.7 m3 / person (default)

Differences in experimental/human exposure conditions (Diff exp. cond) = 1.4 (default)

Oral to inhalation extrapolation between animals and humans (ABSoral,an/ABSinh,hu) = 0.5 (default)

Worker respiratory volume (wRV) = 10 m3 / person (default)

Corrected dose descriptor:

corr inh NOAEC: 24.684 mg/m3

AF for dose response relationship:
1
Justification:
The dose descriptor is an NOAEL.
AF for differences in duration of exposure:
3
Justification:
Default for sub-acute to sub-chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Default for systemic effects by the inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default for systemic effects for other interspecies differences.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Default applied to good quality/standard databases.
AF for remaining uncertainties:
1
Justification:
Default applied to good quality/standard databases.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.658 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):
37.5
DNEL extrapolated from long term DNEL

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:
4.356 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):
150
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
653.33 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point correction formula:

Corrected dose descriptor = oral NOAEL x Diff. exp. cond. x (ABSoral,an/ABSderm,hu)     

Given:

Experimental animal: rat    

Relevant human exposure route: dermal

Oral NOAEL from original study (oral NOAEL) = 20 mg/kg bw/day (test result)

Differences in experimental/human exposure conditions (Diff exp. cond) = 1.4 (default)

Oral to dermal extrapolation between animals and humans (ABSoral,an/ABSderm,hu) = 23.33 (based on 70% absortion via the oral route and 3% absorption via the dermal route)

Corrected dose descriptor:              

corr dermal NOAEL:  653.33 mg/kg bw/d

AF for dose response relationship:
1
Justification:
The dose descriptor is an NOAEL.
AF for differences in duration of exposure:
3
Justification:
Default for sub-acute to sub-chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default for systemic effects by the dermal route.
AF for other interspecies differences:
2.5
Justification:
Default for systemic effects for other interspecies differences.
AF for intraspecies differences:
5
Justification:
Default value for workers.
AF for the quality of the whole database:
1
Justification:
Default applied to good quality/standard databases.
AF for remaining uncertainties:
1
Justification:
Default applied to good quality/standard databases.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.356 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):
150
DNEL extrapolated from long term DNEL

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:
0.296 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
Dose descriptor starting point:
NOAEC
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
22.222 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point correction formula:

Corrected dose descriptor = oral NOAEL x 1/sRVan x Diff. exp. cond. x (ABSoral,an/ABSinh,hu)    

Given:

Experimental animal: rat    

Relevant human exposure route: inhalation

Oral NOAEL from original study (oral NOAEL) = 20 mg/kg bw/day (test result)

Standard respiratory volume, animal (sRVan) = 0.45 m3/kg bw/8 h (default)

Standard respiratory volume, human (sRVhu) = 6.7 m3 / person (default)

Differences in experimental/human exposure conditions (Diff exp. cond) = 1 (default)

Oral to inhalation extrapolation between animals and humans (ABSoral,an/ABSinh,hu) = 0.5 (default)

Corrected dose descriptor:             

corr inh NOAEC: 22.222 mg/m3

AF for dose response relationship:
1
Justification:
The dose descriptor is an NOAEL.
AF for differences in duration of exposure:
3
Justification:
Default for sub-acute to sub-chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Default for systemic effects by the inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default for systemic effects for other interspecies differences.
AF for intraspecies differences:
10
Justification:
Default value for general population.
AF for the quality of the whole database:
1
Justification:
Default applied to good quality/standard databases.
AF for remaining uncertainties:
1
Justification:
Default applied to good quality/standard databases.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.296 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
DNEL extrapolated from long term DNEL

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:
1.556 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):
300
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
466.667 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point correction formula:

Corrected dose descriptor = oral NOAEL x Diff. exp. cond. x (ABSoral,an/ABSderm,hu)     

Given:

Experimental animal: rat    

Relevant human exposure route: dermal

Oral NOAEL from original study (oral NOAEL) = 20 mg/kg bw/day (test result)

Differences in experimental/human exposure conditions (Diff exp. cond) = 1 (default)

Oral to dermal extrapolation between animals and humans (ABSoral,an/ABSderm,hu) = 23.33 (based on 70% absortion via the oral route and 3% absorption via the dermal route)

Corrected dose descriptor:

corr dermal NOAEL: 466.667 mg/kg bw/d

AF for dose response relationship:
1
Justification:
The dose descriptor is an NOAEL.
AF for differences in duration of exposure:
3
Justification:
Default for sub-acute to sub-chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default for systemic effects by the dermal route.
AF for other interspecies differences:
2.5
Justification:
Default for systemic effects for other interspecies differences.
AF for intraspecies differences:
10
Justification:
Default value for the general population.
AF for the quality of the whole database:
1
Justification:
Default applied to good quality/standard databases.
AF for remaining uncertainties:
1
Justification:
Default applied to good quality/standard databases.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.556 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):
300
DNEL extrapolated from long term DNEL

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:
0.067 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):
300
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point correction formula:

Corrected dose descriptor = oral NOAEL x Diff. exp. cond. x (ABSoral,an/ABSoral,hu)       

Given:

Experimental animal: rat    

Relevant human exposure route: oral

Oral NOAEL from original study (oral NOAEL) = 20 mg/kg bw/day (test result)

Differences in experimental/human exposure conditions (Diff exp. cond) = 1 (default)

Oral to oral extrapolation between animals and humans (ABSoral,an/ABSoral) = 1 (default)

Corrected dose descriptor:

corr dermal NOAEL: 20 mg/kg bw/d

AF for dose response relationship:
1
Justification:
The dose descriptor is an NOAEL.
AF for differences in duration of exposure:
3
Justification:
Default for sub-acute to sub-chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default for systemic effects by the oral route.
AF for other interspecies differences:
2.5
Justification:
Default for systemic effects for other interspecies differences.
AF for intraspecies differences:
10
Justification:
Default value for the general population.
AF for the quality of the whole database:
1
Justification:
Default applied to good quality/standard databases.
AF for remaining uncertainties:
1
Justification:
Default applied to good quality/standard databases.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.067 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):
300
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population