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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.73 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):
20
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
14.67 mg/m³
Explanation for the modification of the dose descriptor starting point:

Body weight 70 kg

Table R.8 -2: worker 8h exercise : 10 m3/person

Table R.8-5 : subacute to chronic: AF=6

/4 (allometric) * 70kg / 10 m3/ person

AF for interspecies differences (allometric scaling):
4
Justification:
Table R.8-2: rat to human
AF for other interspecies differences:
1
Justification:
no metabolization expected
AF for intraspecies differences:
5
Justification:
Table R8-6 workers
AF for the quality of the whole database:
1
Justification:
GLP or NDA, validated by US-FDA data
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Dose descriptor starting point:
NOAEC
Justification:
Conservative choice: systemic exposure expected to be negligible due to rapid eliminination in exhaled air.
AF for the quality of the whole database:
1
Justification:
NDA data audited and validated by US-FDA
AF for remaining uncertainties:
1
Justification:
systemic exposure expected to be negligible.

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:
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):
10
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for differences in duration of exposure:
2
Justification:
NOAEL obtained in a 28 d study.
AF for interspecies differences (allometric scaling):
5
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.73 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):
240
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

inhalation rate, light exercise (RIVM ConsExpo Web, version 1.0.6, 13-02-2019) = 1.25 m3/h

Working day = 1h chosen as worst case: no exposure foreseen for general population

Total volume inhaled = 1.25 m3

Body weight = 70 kg

50 mg/kg/d corresponds to 3500 mg, to be inhaled through 20 m3

General population chronic inhalation NAEC = 175 mg/m3

AF for differences in duration of exposure:
6
Justification:
R8-6 subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
R.8-2 rat to human
AF for intraspecies differences:
10
Justification:
Table R.8-19
AF for the quality of the whole database:
1
Justification:
GLP and FDA validated data
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No toxicity was observed in acute toxicity studies.

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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No adverse effect observed in acute toxicity studies.

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:
250 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
AF for differences in duration of exposure:
1
Justification:
General population is not expected to be exposed to tetradecafluorohexane.
AF for interspecies differences (allometric scaling):
5
Justification:
As tetradecafluorohexane is eliminated rapidly due to high volatility, no significant systemic exposure is expected.
an AF 5 is set as a very conservative value
AF for intraspecies differences:
1
Justification:
As tetradecafluorohexane is eliminated rapidly due to high volatility, no significant systemic exposure is expected without influence of the differences of metabolism.
AF for the quality of the whole database:
1
Justification:
Data from NDA dossier audited and validated by US-FDA.
AF for remaining uncertainties:
1
Justification:
As the adverse effects were observed after administration of tetradecafluorohexane by IV route, associated with a galenic designed to dramatically enhance systemic exposure, their relevance for oral exposure is expected to be a very conservative hypothesis. therfore, remaining uncertainties are considered already taken into account.
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

No exposure expected for the general population.