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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.52 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:
APPENDIX R. 8-2 Bioavailability, route-to-route extrapolation and allometric scaling of Chapter R.8: Characterisation of dose [concentration]-response for human health provides for modification of the dose descriptor in calculating DNEL for repeat dose inhalation toxicity.
AF for dose response relationship:
1
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
2
Justification:
Duration of exposure: subchronic to chronic
Justification:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step. NAECcorr_inh = oral NOAEL (from OECD 408 study (1000 mg/kg/bw) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 1763 mg/m3. Oral absorption in rats is assumed to be 100%. For the purposes of risk assessment, absorption in humans is also taken as 100%. Therefore, NAECcorr_inh = 1763 x 100/100 = 1763 mg/m3
AF for intraspecies differences:
5
Justification:
intraspecies – workers
AF for the quality of the whole database:
1
Justification:
quality of data base
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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:
100 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
APPENDIX R. 8-2 Bioavailability, route-to-route extrapolation and allometric scaling of Chapter R.8: Characterisation of dose [concentration]-response for human health provides for modification of the dose descriptor in calculating DNEL
AF for dose response relationship:
1
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
2
Justification:
duration of exposure: subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
5
Justification:
intraspecies – workers
AF for the quality of the whole database:
1
Justification:
quality of database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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

The test substance does not have any local irritating or sensitizing effects in animals. By extrapolation it is possible to calculate systemic and local DNELS for short term and some long term exposure; however calculation of long term local DNELS for local effects on the basis of the available data does not seem to be reasonable, as the substance is not classified for acute toxicological effects. The assessment factors applied for long term systemic effects are deemed to provide suitable exposure modelling for risk assessment.

The same toxicological endpoints chosen for setting the DNELs for workers have been used for setting DNELs for the general population. The increased assessment factor for interspecies sensitivity is considered sufficiently protective.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
APPENDIX R. 8-2 Bioavailability, route-to-route extrapolation and allometric scaling of Chapter R.8: Characterisation of dose [concentration]-response for human health provides for modification of the dose descriptor in calculating DNEL for repeat dose inhalation toxicity.
AF for dose response relationship:
1
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
2
Justification:
duration of exposure – subchronic to chronic
Justification:
Corrected dose descriptor: 869.6 mg/m3 (1000 mg/kg bw/day x 1/1.15 x 1 [rat oral abs 100%/human inhalation abs 100%])
AF for intraspecies differences:
10
Justification:
intraspecies – general population
AF for the quality of the whole database:
1
Justification:
Quality of the database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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:
50 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
APPENDIX R. 8-2 Bioavailability, route-to-route extrapolation and allometric scaling of Chapter R.8: Characterisation of dose [concentration]-response for human health provides for modification of the dose descriptor in calculating DNEL
AF for dose response relationship:
1
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
2
Justification:
duration of exposure – subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
10
Justification:
intraspecies – general population
AF for the quality of the whole database:
1
Justification:
quality of the database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
APPENDIX R. 8-2 Bioavailability, route-to-route extrapolation and allometric scaling of Chapter R.8: Characterisation of dose [concentration]-response for human health provides for modification of the dose descriptor in calculating DNEL
AF for dose response relationship:
1
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
2
Justification:
duration of exposure – subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
10
Justification:
intraspecies – general population
AF for the quality of the whole database:
1
Justification:
quality of database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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

The test substance does not have any local irritating or sensitizing effects in animals. By extrapolation it is possible to calculate systemic and local DNELS for short term and some long term exposure; however calculation of long term local DNELS for local effects on the basis of the available data does not seem to be reasonable, as the substance is not classified for acute toxicological effects. The assessment factors applied for long term systemic effects are deemed to provide suitable exposure modelling for risk assessment.

The same toxicological endpoints chosen for setting the DNELs for workers have been used for setting DNELs for the general population. The increased assessment factor for interspecies sensitivity is considered sufficiently protective.