Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.06 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
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:

The inhalation long-term systemic DNEL is based on the NOAEL of 15 mg/kg bw/day from the 90-day repeated dose oral toxicity study. The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, correction for respiratory volume (worker): 6.7 m³/10 m³. Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: oral 15*(1/0.38)*(6.7 m³/10 m³) = 26.45 mg/m³.

AF for dose response relationship:
1
Justification:
Default (a clear NOAEL was established)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral route rat to inhalation route human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (workers)
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:
15.6 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
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 560 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral absorption value for the analogue substance, D4, was concluded to be 52% following single oral administration to rats in corn oil. The dermal absorption value for D4 was concluded to be 0.5% based on a weight of evidence from several dermal absorption studies. Vi4D4 is expected to have similar oral and dermal absorption values based on its physicochemical properties and structural similarities with D4. Furthermore, Vi4D4 was administered orally in corn oil in the 90-day repeated dose toxicity study, in which the NOAEL was concluded to be 15 mg/kg bw/day.

The dermal long-term systemic DNEL is based on the oral NOAEL of 15 mg/kg bw/day. The following correction was applied to the oral NOAEL: Correction for oral to dermal absorption 52%/0.5%. Therefore, the corrected NOAEL for dermal exposure is 15 mg/kg bw/day*(52%/0.5%) = 1560 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default (a clear NOAEL was established)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral route rat to dermal route 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:
no hazard identified
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:
no hazard identified
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:
0.075 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
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral long-term systemic DNEL is based on the NOAEL of 15 mg/kg bw/day from the 90-day repeated dose oral toxicity study. No correction to the dose description starting point was applied.

AF for dose response relationship:
1
Justification:
Default (a clear NOAEL was established)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral route rat to oral route 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