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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
18
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
141 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human = 80 * 100/100 = 80 mg/kg bw.

Corrected inhalatory NOAEC = 80 * 1/0.38 * 6.7 m3/10 m3= 141 mg/m3

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
1.54 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
72
Dose descriptor starting point:
NOAEL
Value:
111 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal systemic DNEL was based on the NOAEL from a subacute dermal study in rats.

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.206 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
3
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
1
Justification:
Not considered relevant for local effects
AF for interspecies differences (allometric scaling):
1
Justification:
Not considered relevant for local effects
AF for other interspecies differences:
1
Justification:
Not considered relevant for local effects
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
2.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
69.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human =80 * 100/100 = 80 mg/kg bw.

Corrected inhalatory NOAEC = 80 * 1/1.15 = 69.6 mg/m3

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
0.925 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
111 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal DNEL systemic was based on the NOAEL from a subacute dermal study in rats.

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.123 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
1
Justification:
Not considered relevant for local effects
AF for interspecies differences (allometric scaling):
1
Justification:
Not considered relevant for local effects
AF for other interspecies differences:
1
Justification:
Not considered relevant for local effects
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining differences
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:
0.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral DNEL systemic was based on the NOAEL from a subacute oral study in rats.  

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure of the general population
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population