Hydrogen fluoride

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: Review / summary of available information

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Secondary source: review of published data

Objective of study:

toxicokinetics

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

Radiolabelling:

no

Species:

other: various species, including man

Strain:

not specified

Sex:

not specified

Route of administration:

other: oral, inhlation, dermal

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

Various

Remarks:

Doses / Concentrations:
Various

No. of animals per sex per dose / concentration:

Various

Control animals:

not specified

Preliminary studies:

No data

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 of fluoride is likely to be minimal except 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.

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.

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

Conclusions:

Interpretation of results: 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.

Description of key information

Short description of key information on bioaccumulation potential result: 
The available data are summarised in the EU RAR (2001).
Short description of key information on absorption rate: 
Only limited data are available and are summarised in the EU RAR and reported in the basic toxicokinetics section.

Additional information

The significant literature on the toxicokinetics of HF and fluoride has been reviewed in the EU RAR and is summarised below.

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 of fluoride is likely to be minimal except 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.

Distribution

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.

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.

Discussion on bioaccumulation potential result:

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 of fluoride is likely to be minimal except 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.

Distribution

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.

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.

Discussion on absorption rate:

Following dermal exposure to HF, absorption of fluoride is likely to be minimal expect in cases where the normal skin structure is compromised as a consequence of the corrosive effects of the substance. A number of human case studies have noted elevated plasma fluoride concentrations and/or systemic fluoride poisoning in burns cases, indicating the ability of HF to be absorbed through damaged skin.