Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22 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
Modified dose descriptor starting point:
NOAEC
Value:
132 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
AF for dose response relationship:
1
Justification:
Value is NOAEL
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:
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 study 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:
no hazard identified
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:
2.7 mg/kg bw/day
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
90
Modified dose descriptor starting point:
LOAEL
Explanation for the modification of the dose descriptor starting point:
no extrapolation (test done via dermal exposure)
AF for dose response relationship:
3
Justification:
From LOAEL to NAEL
AF for differences in duration of exposure:
1
Justification:
Duration of exposure is not determining factor for induction (effect is more concentration dependent)
AF for interspecies differences (allometric scaling):
10
Justification:
Correction from mouse 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 correction for vehicle or matrix effect (LLNA matrix = dimethylformamide, can be regarded as worst case with regard to dermal adsorption)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

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:
6.52 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
Modified dose descriptor starting point:
NOAEC
Value:
65.2 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
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure general public
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 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:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.61 mg/kg bw/day
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
LOAEL
Explanation for the modification of the dose descriptor starting point:
no extrapolation, based on dermal application.
AF for dose response relationship:
3
Justification:
From LOAEL to NAEL
AF for differences in duration of exposure:
1
Justification:
Duration of exposure is not determining factor for induction (effect is more concentration dependent)
AF for interspecies differences (allometric scaling):
10
Justification:
Correction from mouse 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

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.9 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No extrapolation necessary as oral study was used.
AF for dose response relationship:
1
Justification:
Value is NOAEL
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:
Correction for difference is metabolic rate rat and 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 study 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:
no hazard identified

Additional information - General Population