Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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):
6
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
17.6 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.

10 mg/kg bw/d x (1/0.38 m3/kg/d) x 100/100 (% oral/inh absorption) x (6.7 mg/m3/10 mg/m3) = 17.6 mg/m3

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic extrapolation
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 additional factor required
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies were used
AF for remaining uncertainties:
1
Justification:
not considered relevant
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:
0.4 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):
24
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 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: 10 x 100/100a = 10 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:
2
Justification:
Sub-chronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
No additional factor required
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable data-set
AF for remaining uncertainties:
1
Justification:
Not considered relevant
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

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:
1.76 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):
10
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
17.6 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. 10 mg/kg bw/d x (1/0.38 m3/kg/d) x 100/100 (% oral/inh absorption) x (6.7mg/m3/10mg/m3)= 17.6 mg/m3.

AF for dose response relationship:
1
Justification:
NOAEC used for calculation
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic extrapolation
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:
Not required
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within population
AF for the quality of the whole database:
1
Justification:
Reliable data-set
AF for remaining uncertainties:
1
Justification:
Not considered relevant
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:
0.25 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):
40
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 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 dermal and oral intake in the absence of evidence of the opposite. Correction dermal NOAEL: 10 x 100/100a= 10 mg/kg bw/day a: oral/dermal absorption.

AF for dose response relationship:
1
Justification:
Based on NOAEL.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation
AF for other interspecies differences:
1
Justification:
No additional factor required
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within population
AF for the quality of the whole database:
1
Justification:
Reliable data-set
AF for remaining uncertainties:
1
Justification:
Not considered relevant
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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):
40
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
No additional factor required
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable data-set used
AF for remaining uncertainties:
1
Justification:
Not considered relevant
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population