Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
132 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:
LOAEC
Value:
1 587 mg/m³
Explanation for the modification of the dose descriptor starting point:
according to guidelines; there is no evidence that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
LOAEL based minor effects on liver, which have been demonstrated to be reversible. Comparable effects were observed both after 4 and 24 weeks of exposure.
AF for differences in duration of exposure:
2
Justification:
Assuming chronic exposure of the worker; comparable effects were observed both after 4 and 24 weeks of exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation.
AF for other interspecies differences:
1
Justification:
according to guideline
AF for intraspecies differences:
3
Justification:
according to guideline
AF for the quality of the whole database:
1
Justification:
whole dataset provides reliable information
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18 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):
84
Modified dose descriptor starting point:
other:
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
according to guidelines; there is no evidence that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
LOAEL based minor effects on liver, which have been demonstrated to be reversible. Comparable effects were observed both after 4 and 24 weeks of exposure.
AF for differences in duration of exposure:
2
Justification:
assuming chronic exposure of the worker; comparable effects were observed both after 4 and 24 weeks of exposure
AF for interspecies differences (allometric scaling):
7
Justification:
mice to humans
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
3
Justification:
according to guideline (difference in sensitivity among workers)
AF for the quality of the whole database:
1
Justification:
whole dataset provides reliable information
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

According to ECHA Guidance R8 (2012), for exposure to dust, the general dust limits of 10 mg/m3for the inhalable airborne fraction and 3 mg/m3for the respirable airborne fraction used in setting Occupational Exposure Limits in many countries should be considered in combination with nature of the dust. For non-soluble inert dusts (such as cholesterol) if the derived DNEL for inhalation is above the dust limits, the general dust limits should apply for exposure scenarios with exposure to dust. For cholesterol the DNELs based on the dataset are above the general dust limit. Consequently, the general dust limit needs to be considered for cholesterol.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
39 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance/ ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
LOAEC
Value:
783 mg/m³
Explanation for the modification of the dose descriptor starting point:
according to guidelines; there is no evidence that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
LOAEL based minor effects on liver, which have been demonstrated to be reversible. Comparable effects were observed both after 4 and 24 weeks of exposure.
AF for differences in duration of exposure:
2
Justification:
Assuming chronic exposure of the worker; comparable effects were observed both after 4 and 24 weeks of exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation.
AF for other interspecies differences:
1
Justification:
according to guidelines
AF for intraspecies differences:
5
Justification:
according to guidelines
AF for the quality of the whole database:
1
Justification:
whole dataset provides reliable information
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.7 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):
140
Modified dose descriptor starting point:
other:
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
according to guidelines; there is no evidence that route-to-route extrapolation cannot be applied.
AF for dose response relationship:
2
Justification:
LOAEL based minor effects on liver, which have been demonstrated to be reversible. Comparable effects were observed both after 4 and 24 weeks of exposure.
AF for differences in duration of exposure:
2
Justification:
Assuming chronic exposure of the worker; comparable effects were observed both after 4 and 24 weeks of exposure.
AF for interspecies differences (allometric scaling):
7
Justification:
mice to humans
AF for other interspecies differences:
1
Justification:
according to guideline
AF for intraspecies differences:
5
Justification:
according to guideline (difference in sensitivity among the general population)
AF for the quality of the whole database:
1
Justification:
whole dataset provides reliable information
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:
10.7 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):
140
Modified dose descriptor starting point:
other: NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable, as starting point is oral toxicity study.
AF for dose response relationship:
2
Justification:
LOAEL based minor effects on liver, which have been demonstrated to be reversible. Comparable effects were observed both after 4 and 24 weeks of exposure.
AF for differences in duration of exposure:
2
Justification:
Assuming chronic exposure of the worker; comparable effects were observed both after 4 and 24 weeks of exposure.
AF for interspecies differences (allometric scaling):
7
Justification:
mice to humans
AF for other interspecies differences:
1
Justification:
according to guideline
AF for intraspecies differences:
5
Justification:
according to guideline
AF for the quality of the whole database:
1
Justification:
whole dataset provides reliable information
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