Lithium hexafluorophosphate(1-)

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Remarks:

other: review including information on repeat-dose (subacute) inhalation toxicity

Type of information:

other: Information on major hydrolysis product of the registered substance (released rapidly on contact with water/moisture).

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Authoritative expert review of HF exposure and toxicity.

Justification for type of information:

Part of weight-of-evidence approach adapting the information requirements of Annex VIII 8.6.1 and Annex IX 8.6.2 under REACH in accordance with Annex XI Section 1.2. Lithium hexafluorophosphate is reactive and unstable in water and air. Reaction in contact with water proceeds rapidly, with release of hydrogen fluoride (forming hydrofluoric acid). Such local generation of hydrogen fluoride/hydrofluoric acid at the site of contact with skin or other membranes, with consequent potential for serious local tissue damage, is a major cause of the observed corrosivity of the substance, and secondary tissue necrosis due to localised free fluoride ion concentrations is also a likely contributor to this: delayed onset of deep tissue damage and pain is known after skin contact with HF solutions below 20% in concentration. Ethical and practical reasons therefore make it inappropriate to conduct repeat-dose toxicity testing of lithium hexafluorophosphate in animals; since information is available on systemic toxicity of the ultimate hydrolysis products hydrogen fluoride, lithium/Li+, fluoride/F- and phosphoric acid/phosphate, such testing is also scientifically unnecessary. In accordance with Annex XI, 1.2 of the REACH Regulation testing is not scientifically necessary based on weight-of evidence approach, and on humane grounds, as indicated in Article 15, 2 of Directive 2010/63/EU, such testing (expected to involve severe pain, suffering or distress likely to be long-lasting) should not be performed.

Data source

Reference

Reference Type:

secondary source

Title:

EU Risk assessment Report, Hydrogen Fluoride CAS-No. 7664-39-3 EINECS-No. 231-634-8

Author:

The Netherlands VROM, with SZW and VWS

Year:

2001

Bibliographic source:

European Commission JRC 1st Priority List Volume:8

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

Restricted list of tissues examined

Principles of method if other than guideline:

Report of a Russian inhalation toxicity study

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen fluoride

EC Number:

231-634-8

EC Name:

Hydrogen fluoride

Cas Number:

7664-39-3

IUPAC Name:

fluoride

Test material form:

other: inhaled test atmosphere

Test animals

Species:

rat

Sex:

female

Details on test animals or test system and environmental conditions:

Groups of differently-aged rats were exposed to HF.

Administration / exposure

Route of administration:

inhalation

Details on inhalation exposure:

6h/day for 1 month

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1 month

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mg/cu.m
Basis:
no data

Control animals:

yes

Examinations

Sacrifice and pathology:

Expected fluoride target sites only examined:
- dental enamel
- bones
- respiratory system.

Results and discussion

Results of examinations

Details on results:

Damage to dental enamel recorded: especially notable in young animals, which also showed atrophy of respiratory organs/tissues with local oedema of bronchial mucosa.
Older animals showed peribronchial hyperplasia.
Animals around 1 year in age showed cavity formation in their bones.

Effect levels

Dose descriptor:

NOAEL

Remarks:

Single test concentration

Effect level:

1 mg/m³ air

Based on:

test mat.

Remarks:

HF

Sex:

female

Basis for effect level:

other: see 'Remark'

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Exposure to HF by inhalation at 1 mg/cu.m over a 1-month period caused evident toxicity at the expected target sites.