Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.1 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):
36
Modified dose descriptor starting point:
NOAEC
Value:
183.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
there is no evidence that route-to-route extrapolation cannot be applied. Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.
AF for dose response relationship:
1
Justification:
NOAEL in reliable subacute oral toxicity study in rat
AF for differences in duration of exposure:
3
Justification:
Assuming chronic exposure of the worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation
AF for other interspecies differences:
1
Justification:
According to ECETOC guidance
AF for intraspecies differences:
3
Justification:
According to ECETOC guidance
AF for the quality of the whole database:
2
Justification:
Based on data from read-across substance
AF for remaining uncertainties:
2
Justification:
No data on reproduction/developmental toxicity
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:
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:
0.72 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):
144
Modified dose descriptor starting point:
NOAEL
Value:
104 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
there is no evidence that route-to-route extrapolation cannot be applied. Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.
AF for dose response relationship:
1
Justification:
NOAEL in subchronic oral toxicity study in rat
AF for differences in duration of exposure:
3
Justification:
Assuming chronic exposure of the worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand rat to human
AF for other interspecies differences:
1
Justification:
According to ECETOC guidance
AF for intraspecies differences:
3
Justification:
According to ECETOC guidance
AF for the quality of the whole database:
2
Justification:
Based on data from read-across substance
AF for remaining uncertainties:
2
Justification:
No data on reproduction/developmental toxicity
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:
1.51 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):
60
Modified dose descriptor starting point:
NOAEC
Value:
90.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
there is no evidence that route-to-route extrapolation cannot be applied. Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.
AF for dose response relationship:
1
Justification:
NOAEL in reliable subchronic oral toxicity study in rat
AF for differences in duration of exposure:
3
Justification:
Assuming chronic exposure of the worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation
AF for other interspecies differences:
1
Justification:
According to ECETOC guidance
AF for intraspecies differences:
5
Justification:
According to ECETOC guidance
AF for the quality of the whole database:
2
Justification:
Based on data from read-across substance
AF for remaining uncertainties:
2
Justification:
No data on reproduction/developmental toxicity
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:
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:
0.43 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):
240
Modified dose descriptor starting point:
NOAEL
Value:
104 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
there is no evidence that route-to-route extrapolation cannot be applied. Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.
AF for dose response relationship:
1
Justification:
NOAEL in subchronic oral toxicity study in rat
AF for differences in duration of exposure:
3
Justification:
Assuming chronic exposure of the worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand rat to human
AF for other interspecies differences:
1
Justification:
According to ECETOC guidance
AF for intraspecies differences:
5
Justification:
According to ECETOC guidance
AF for the quality of the whole database:
2
Justification:
Based on data from read-across substance
AF for remaining uncertainties:
2
Justification:
No data on reproduction/developmental toxicity
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:
0.43 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):
240
Modified dose descriptor starting point:
NOAEL
Value:
104 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
Justification:
NOAEL in subchronic oral toxicity study in rat
AF for differences in duration of exposure:
3
Justification:
Assuming chronic exposure of the worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand rat to human
AF for other interspecies differences:
1
Justification:
According to ECETOC guidance
AF for intraspecies differences:
5
Justification:
According to ECETOC guidance
AF for the quality of the whole database:
2
Justification:
Based on data from read-across substance
AF for remaining uncertainties:
2
Justification:
No data on reproduction/developmental toxicity
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