Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.3 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):
12
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no indication that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
Value is NOAEL; study has been performed with analogue
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure worker
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling rat human included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
Not relevant
AF for intraspecies differences:
3
Justification:
Differences in sensitivity amongst workers
AF for the quality of the whole database:
1
Justification:
Not relevant, reliable studies and all endpoints required are covered adequately
AF for remaining uncertainties:
1
Justification:
Not relevant (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 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):
48
Modified dose descriptor starting point:
NOAEL
Value:
100 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 exposure in the absence of evidence of the opposite
AF for dose response relationship:
2
Justification:
Value is NOAEL; study has been performed with analogue
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic 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:
Not relevant
AF for intraspecies differences:
3
Justification:
Differences in sensitivity amongst workers
AF for the quality of the whole database:
1
Justification:
Not relevant, reliable studies and all endpoints required are covered adequately
AF for remaining uncertainties:
1
Justification:
Not relevant (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

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:
2.2 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):
20
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no indication that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
Value is NOAEL; study has been performed with analogue
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling rat human included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
Not relevant
AF for intraspecies differences:
5
Justification:
Differences in sensitivity amongst general population
AF for the quality of the whole database:
1
Justification:
Not relevant, reliable studies and all endpoints required are covered adequately
AF for remaining uncertainties:
1
Justification:
Not relevant (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no indication that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
Value is NOAEL; study has been performed with analogue
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Differences in sensitivity amongst general population
AF for the quality of the whole database:
1
Justification:
Not relevant, reliable studies and all endpoints required are covered adequately
AF for remaining uncertainties:
1
Justification:
Not relevant (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not relevant.
AF for dose response relationship:
2
Justification:
Value is NOAEL; study has been performed with analogue
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
1
Justification:
Not relevant
AF for intraspecies differences:
5
Justification:
Differences in sensitivity amongst general population
AF for the quality of the whole database:
1
Justification:
Not relevant, reliable study and all endpoints required are covered adequately
AF for remaining uncertainties:
1
Justification:
Not relevant (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:
no hazard identified

Additional information - General Population