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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
99 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2 468 mg/m³
Explanation for the modification of the dose descriptor starting point:

An overall NOAEL of 1000 mg/kg bw/d from an OECD 408/422 combined repeat dose /repro screening oral study with rats was used.


Originally this report concluded to a NOEAL of 300 mg/kg on the basis of possible decreased T4 at 1000 mg/kg, of which adversity could not be excluded. However, further studies that included serum hormone evaluations (THS, T4 and T3), have not confirmed effects on T4, nor shown effects on thyroid. Also in view of the absence of clear adverse effects in any of these studies, the overall NOAEL for repeated dose has been set at 1000 mg/kg bw.


 


The assumptions are as folows for route-to-route extrapolation:


Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/0.38 * 1 * 6.7/10


Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/sRVrat * ABSoral-rat/ABSinhhuman * 6.7/10


Rapid and complete absorption is expected for both oral and inhalation routes.


Correction is made for exposure condition between daily oral dosing and work week of 5 days/week: 5/7


Combined: 1000 * 1/0.38 * 1 * 6.7/10 * 5/7

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
14 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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

An overall NOAEL of 1000 mg/kg bw/d from an OECD 408/422 combined repeat dose /repro screening oral study with rats was used.


Originally this report concluded to a NOEAL of 300 mg/kg on the basis of possible decreased T4 at 1000 mg/kg, of which adversity could not be excluded. However, further studies that included serum hormone evaluations (THS, T4 and T3), have not confirmed effects on T4, nor shown effects on thyroid. Also in view of the absence of clear adverse effects in any of these studies, the overall NOAEL for repeated dose has been set at 1000 mg/kg bw.


Oral/dermal absorption was assumed to be 100%.


Correction is made for exposure condition between daily oral dosing and work week of 5 days/week: 5/7


Corrected NOAE: 1000 * 5/7 = 1400 mg/kg bw/d

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
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:
17.4 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

An overall NOAEL of 1000 mg/kg bw/d from an OECD 408/422 combined repeat dose /repro screening oral study with rats was used.


Originally this report concluded to a NOEAL of 300 mg/kg on the basis of possible decreased T4 at 1000 mg/kg, of which adversity could not be excluded. However, further studies that included serum hormone evaluations (THS, T4 and T3), have not confirmed effects on T4, nor shown effects on thyroid. Also in view of the absence of clear adverse effects in any of these studies, the overall NOAEL for repeated dose has been set at 1000 mg/kg bw.


The assumptions are as folows for route-to-route extrapolation:


Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/1.15 * 1 


Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/sRVrat * ABSoral-rat/ABSinhhuman


Rapid and complete absorption is expected for both oral and inhalation routes.


Combined: 1000 * 1/1.15 = 896.57

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

An overall NOAEL of 1000 mg/kg bw/d from an OECD 408/422 combined repeat dose /repro screening oral study with rats was used.


Originally this report concluded to a NOEAL of 300 mg/kg on the basis of possible decreased T4 at 1000 mg/kg, of which adversity could not be excluded. However, further studies that included serum hormone evaluations (THS, T4 and T3), have not confirmed effects on T4, nor shown effects on thyroid. Also in view of the absence of clear adverse effects in any of these studies, the overall NOAEL for repeated dose has been set at 1000 mg/kg bw.


Oral/dermal absorption was assumed to be 100%.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
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
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

An overall NOAEL of 1000 mg/kg bw/d from an OECD 408/422 combined repeat dose /repro screening oral study with rats was used.


Originally this report concluded to a NOEAL of 300 mg/kg on the basis of possible decreased T4 at 1000 mg/kg, of which adversity could not be excluded. However, further studies that included serum hormone evaluations (THS, T4 and T3), have not confirmed effects on T4, nor shown effects on thyroid. Also in view of the absence of clear adverse effects in any of these studies, the overall NOAEL for repeated dose has been set at 1000 mg/kg bw.


Oral absorption was assumed to be 100%.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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