Registration Dossier

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source: review of published data on from a read across substance.

Data source

Reference
Reference Type:
review article or handbook
Title:
European Union Risk Assessment Report, hydrogen fluoride.
Author:
European Chemicals Bureau
Year:
2001
Bibliographic source:
European Union Risk Assessment Report, Volume 8, Institute for Health and Consumer Protection, European Chemicals Bureau.

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
The EU RAR summarises the findings of various published studies reporting the toxicokinetics of HF.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The EU RAR summarises the findings of various published studies reporting the toxicokinetics of HF.
Radiolabelling:
no

Test animals

Species:
other: various species, including man
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: oral, inhalation, dermal
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
Various
Doses / concentrations
Remarks:
Doses / Concentrations:
Various
No. of animals per sex per dose:
Various
Control animals:
not specified

Results and discussion

Preliminary studies:
No data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Hydrogen fluoride is absorbed into the body and will ionise (>99.99%) to form the hydrogen (hydronium) and fluoride ions under physiological conditions. The absorption of inorganic fluoride across mucous membranes is passive and is independent of the fluoride source.
Following inhalation exposure to HF, experiments in various species including man have demonstrated that the large majority of inhaled HF does not reach the lungs but is absorbed via the upper respiratory tract mucosa. Plasma fluoride levels are directly related to HF inhalation and peak at between 60-120 hours after the start of exposure.
Following dermal exposure to HF, absorption is of fluoride likely to be minimal expect in cases where the normal skin structure is compromised as a consequence of the corrosive effects of the substance.
The absorption of fluoride following oral administration of HF has not been investigated, but is likely to be rapidly absorbed.
Details on distribution in tissues:
Absorbed fluoride is distributed primarily in the blood, 75% in the plasma and 25% associated with erythrocytes. Half of the plasma fluoride may be bound to organic molecules. Fluoride is rapidly distributed and is sequestered in the bones and teeth, where exchange with hydroxyl groups results in incorporation into the bone and tooth structure. Levels of fluoride in bones and teeth are directly correlated with exposure levels.
Details on excretion:
Fluoride is excreted rapidly as a consequence of glomerular filtration, with a plasma half-life of 2-9 hours. The half-life for skeletal fluoride in humans is reported to be 8-20 years.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Not relevant. HF is ionised under physiological conditions (99.99%) to form hydronium and fluoride ions and is not metabolised as such.

Any other information on results incl. tables

HF is rapidly absorbed following inhalation exposure, rapidly distributed and excreted. However sequestration/accumulation of fluoride occurs in bones and teeth.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): high bioaccumulation potential based on study results
HF is rapidly absorbed following inhalation exposure, rapidly distributed and excreted. However sequestration/accumulation of fluoride occurs in bones and teeth.
Executive summary:

HF is rapidly absorbed following inhalation exposure, rapidly distributed and excreted. However sequestration/accumulation of fluoride occurs in bones and teeth.