Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.931 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Explanation for the modification of the dose descriptor starting point:
Justification provided in "justification and comments" field below
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
133 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Explanation for the modification of the dose descriptor starting point:
Justification provided in "justification and comments" field below
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Calculation of DNELs for LiPF6 exposure

[1] Short-term DNELs

The reactive and corrosive properties of LiPF6 make calculation of short-term DNELs inappropriate. Skin contact or inhalation of particulate material is avoided by the use of appropriate containment procedures and PPE, as detailed in the relevant Guidance on Safe Use. 

 

[2] Long-term DNELs

The rapid hydrolysis of LiPF6 in contact with moisture, releasing HF, LiF and H3PO4 makes it appropriate to based long-term DNELs on the degradation products which could be absorbed and systemically distributed in the event of LiPF6 exposure. As discussed earlier, these degradants are HF, F-, Li+ and PO4-. Each is considered in turn.

 

In respect of HF: the IOELV of 1.5 mg/cu.m (as F-) would be appropriate as a long-term worker DNEL via inhalation, corresponding to 15 mg/day or 214 µg/kg/day.

In respect of F-: 100 µg/kg/day (7 mg/day) would be appropriate as a long-term worker DNEL via ingestion.

In respect of Li+: the human NOAEL of 14.3 µg/kg/day (1 mg/day) would be appropriate as a long-term worker DNEL via inhalation (and data from human therapeutic use demonstrate that a much higher oral dosage is well tolerated) .

In respect of PO4: the MTDI of 70 mg/kg/day (as P) or the lower ADI of 30 mg/kg/day would be appropriate as a long-term worker DNEL via ingestion.

 

Based on molecular weight, hydrolysis of 152 mg LiPF6 will release 7 mg Li+, 31 mg P, 100 mg HF and 114 mg F-. From this we can see that:

- for HF, 214 µg F-/kg/day corresponds to 325 µg LiPF6/kg/day (by inhalation)

- for F-, 100 µg/kg/day corresponds to 133 µg LiPF6/kg/day (by ingestion)

- for Li+, 14.3 µg/kg/day corresponds to 313 µg Li PF6/kg/day (by inhalation)

- for PO4, 70 mg P/kg/day corresponds to 343 mg LiPF6/kg/day; the lower ADI (unconditional) value of 30 mg P/kg/day corresponds to 147 mg LiPF6/kg/day (by ingestion).

It is therefore evident that the fluoride released as LiPF6 enters biological systems is the most toxic component, and provides the toxicity marker for long-term worker DNEL determination. Since this is readily absorbed both by skin contact and from the gastrointestinal tract, it is appropriate to apply an equal DNEL value for dermal and oral routes. In addition, since it is the toxicity of F- which causes much of the toxicity observed following HF exposure there is no reason to suppose that exposure by inhalation will elicit lesser toxicity than oral or dermal exposure, so to apply the precautionary principle the inhalation DNEL is reduced to equal that for ingestion or dermal contact. The following long-term worker DNEL values are therefore set for LiPF6:

- for inhalation exposure, 133 µg/kg/day (0.931 mg/m3)

- for dermal contact, 133 µg/kg/day

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:
no hazard identified
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

General population DNELs have not been derived as no consumer exposure to the substance is expected. Hazard assessment conclusion for the general population "no hazard identified" has been selected based on the fact that no exposure is expected to occur.