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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48.98 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite. Conversion of an oral NOAEL into a corrected NOAEC: For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV = 1000 * 1/0.38 m3/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m3 (8h)/10 m3 (8h) = 1000 * 1/0.38 m3/kg/8h * 0.5 * 6.7 m3 (8h)/10 m3 (8h) = 1000 /0.38 * 0.5* (6.7/10) = 881.6 mg/m3.

With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5, assuming no differences in inhalation absorption between rats and humans.

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:
6.9 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):
72
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite. Correction dermal NOAEL: 1000 x 50/100a = 500 mg/kg bw/day (a % oral/dermal absorption)

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:
re;liable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.3 mg/kg bw/day
Most sensitive endpoint:
acute 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):
12
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not relevant, route of original study = dermal exposure.

AF for dose response relationship:
1
Justification:
Value is NOAEL
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, dose-related response observed

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
21.6
Dose descriptor:
other: LOAEL (3.68 mg/cm2)
AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
1
Justification:
Local effects are not dependent on exposure duration.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Correction for caloric demand from rabbit 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:
DNEL (Derived No Effect Level)
Value:
0.17 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
12
Dose descriptor starting point:
other: LOAEL (3.68 mg/cm2)
AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for interspecies differences (allometric scaling):
2.4
Justification:
Correction for caloric demand from rabbit 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 study used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
4.35 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite. For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human = 300 * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human = 300 * 1/1.15 m3/kg * 0.5 = 130.5 mg/m3 With ABS: Absorption, sRV: Standard Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5, assuming no differences in inhalation absorption between rats and humans.

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
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:
5
Justification:
Difference in sensitivity among general public
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:
4.2 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction NOAEL: 1000 mg/ kg bw x 50/100a = 500 mg/kg bw/day (a % oral/dermal absorption)

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
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 among 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:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute 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):
20
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
Not relevant
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

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
36
Dose descriptor:
other: LOAEL (3.68 mg/cm2)
AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
1
Justification:
Local effects are not dependent on exposure duration
AF for interspecies differences (allometric scaling):
2.4
Justification:
Correction for caloric demand from rabbit 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:
DNEL (Derived No Effect Level)
Value:
0.1 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
20
Dose descriptor starting point:
other: LOAEL (3.68 mg/cm2)
AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for interspecies differences (allometric scaling):
2.4
Justification:
Correction for caloric demand from rabbit 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 differences

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.3 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:
1 000 mg/kg bw/day
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
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 among 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

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