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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
53.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
1 335 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC: Modification for experimental exposure duration (6 h in study to 8 h in workers): 0.75. Modification for respiratory volume (rat to human): 6.7/10. Therefore the corrected NOAEC for repeat dose effects via the inhalation route is: 2657*0.75*(6.7/10) = 1335 mg/ m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
repeat dose NOAEC from 2-generation reproductive toxicity study, animals dosed for at least 90-days (therefore sub-chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (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:
333 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
100 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on a reliable in vitro dermal absorption study, 0.023% of the dose was absorbed through the skin. for the purposes of the DNEL calculation, a conservative figure of 1% absorption is used. The following correction was made to the NOAEL: human absorption = 1%, therefore modified NOAEL = 1000*(100/1) = 100000 mg/kg/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (dermal rat to dermal human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
664 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEC: Modification for experimental exposure duration (6 h in study to 24 h in General Population): 6/24 = 0.25. Therefore the corrected NOAEC for repeat dose effects via the inhalation route is: 2657*0.25 = 664 mg/.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
repeat dose NOAEC from 2-generation reproductive toxicity study, animals dosed for at least 90-days (therefore sub-chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation rat to inhalation human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (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:
167 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
100 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on a reliable in vitro dermal absorption study, 0.023% of the dose was absorbed through the skin. for the purposes of the DNEL calculation, a conservative figure of 1% absorption is used. The following correction was made to the NOAEL: human absorption = 1%, therefore modified NOAEL = 1000*(100/1) = 100000 mg/kg/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (dermal rat to dermal human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (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:
0.27 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No corrections were made to the NOAEL
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to oral human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (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

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