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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Introduction

The physico-chemical properties,information on the chemistry ofF7Ta.2K(=K2TaF7) solutions,and the results ofin vivotoxicity studies have been used to determine a toxicokinetic profile.

The material is classified as a corrosive under CLP and “Irritant: Risk of severe damage to eyes” under the Dangerous Preparations Directive. The material was not irritating to skin in a skin irritation assay (Pößnecker, 1992).

 

Physicochemical propertiesand chemistry of solutions

The substance Dipotassium heptafluorotantalate is a white crystalline solid and has the molecular formulaF7Ta.2Kwith a molecular weight of392.13g/mol. It is moderately water soluble (819.5 mg/L at 30 °C).

 

The following information on the chemistry of K2TaF7solutions is taken from the review by Agulyansky (2003).

 

The substanceis sensitive to water, basic compounds and alcohols especially when heated. At physiological temperatures, saturated aqueous solutions contain ca. 5 mg/LK2TaF7and have a pH of 2.

 

At physiological temperatures, the solvation of K2TaF7producesK+ions and the complex ion TaF72-, which is a Lewis acid.

 

Equation 1: K2TaF7+ H2O D K+(aq) + TaF72-(aq)

 

Interaction with boiling water yields potassium oxyfluorotantalate, known as Marignac’s salt. X-ray crystal structure analysis and precision chemical analysis demonstrated that the actual composition is K2Ta2O3F. The hydrolysis interaction can be described as follows:

 

Equation 2: 2K2TaF7 + 3H2OK2Ta2O3F6+ 2KF + 6HF

 

Corrosive hydrofluoric acid is produced in this reaction, but as this requires boiling water, is unlikely to be produced at physiological temperature in, for example tears.  Therefore theTaF72-ion is likely to be solely responsible for the effects on eyes.

In gastric juice (up to 0.1 N HCl) additional processes may be in operation, which produce HF and KF in addition to the TaF72-acid ions initially produced on solvation. To understand the species produced in gastric juice it helps to understand the chemistry in the ‘wet’ production of K2TaF7.

Ultimately in the production process, K2TaF7is precipitated from a hydrofluoric acid solution with TaCl5and KF.  K2TaF7precipitates at HF concentrations less than ca. 42%. (Solutions having higher concentrations of HF give precipitation of potassium hexafluorotantalate - KTaF62-).  The equation is as follows:

 

Equation 3: 5HF + 2KF + TaCl5DK2TaF7+ 5HCl

In the stomach where HCl is already present, the equilibrium is driven towards the left hand side of the equation, producing HF, KF and TaCl2. TaCl5reacts with water to give Ta2O5and HCl – see equation 4 (thus driving the equilibrium in equation 3 further to the left).

Equation 4: 2TaCl5+ 5H2O " Ta2O5+ 10HCl

Ultimately theTaF72-ions will be consumed in Equations 3 and 4 and the sum of all the reactions taking place in the gastric juice might be expressed simply as in equation 5:

Equation 5: 2K2TaF7+ 5H2O " Ta2O5+4KF + 10HF

Therefore in the acidic conditions of the stomach (HCl), adding K2TaF7further acidifies the environment, initially through production of the Lewis acidTaF72-ion, but ultimately in production of corrosive fluoride ions (KF and HF).  It will be noted that considerable HF formation results.

 

Absorption

Oral absorption

There is no sense in trying to determine the extent of oral absorption for the substance itself, because the final products ofK2TaF7solvation in gastric juice are tantalum (V) oxide, Ta2O5, potassium fluoride, KF, and hydrofluoric acid, HF.

This is supported by results of the key acute oral toxicity study(Wolf, 2006), and by range-finding studies performed either by oral gavage or dietary administration.

In the acute oral toxicity study,K2TaF7was tested at 300 and 2000 mg/kg bw. All animals survived at 300 mg /kg bw, and there were no clinical signs or pathology. At 2000 mg/kg all animals died 2 to 4 hours of dosing. Prior to death clinical signs included increased lacrimation, unconsciousness, cyanosis and unspecific signs like sedation, piloerection, hunched posture, and closed eyes. At necropsy ulcers were seen in the mucosa of glandular stomach and small intestine, and blood was observed in the lumen of the stomach and small intestines.

In the range-finding study by gavage, 50% mortality occurred at the dose of 300 mg/kg bw/day, with necropsy findings in stomach, lung and kidney. At 30 mg/kg bw/day there were no mortality or body weight effects, but stomach and lung necropsy findings were noted in one of 5 rats.

Lethality and stomach findings (corrosion) in these studies would appear compatible with acute fluoride administration, considering that 2000 mg/kg bw K2TaF7is approximately equivalent to680 mg/kg bw fluoride, and 300 mg/kg bw/day to 100 mg/kg bw. WHO lists the LD50for fluoride at up to 100 mg/kg bw, withLD50values (for various fluorine salts) at 25-100 mg/kg bw. Typical acute fatal poisoning symptoms and findings were listed as “…corrosion of the stomach and sometimes other parts of the gastrointestinal tract. …”

Solutions of fluoride at 10 or 50 mM caused histological damage to stomach mucosa; 100 mM was associated with haemorrhage and loss of epithelial cells. Nephrotoxicity following a single oral dose to rats is reported at doses in the approximate range 14-22 mg/kg bw/day.

Fluoride ions released from readily soluble fluoride compounds, such ashydrofluoric acid, are almost completely absorbed.

In the dietary range-finding study, at 4000 ppm (500 mg/kg bw/day) marked retardation of weight gain and necropsy findings in the stomach were observed. At 1200 ppm, 400 ppm and 140 ppm necropsy findings in stomach were again observed. This study also supports that toxicity of the substance is due to the released fluoride, because it is know thatthe ingestion of fluoride with food retards its absorption and reduces its bioavailability (World Health Organisation; Environ Health Criteria 227: Fluorides, 2002).

Oral absorption of the otherfinal product ofK2TaF7solvation in gastric juice tantalum (V) oxide, Ta2O5is considered negligible, because of its physical form (ahighly resistant oxidised layersurrounding the inert tantalum metal),high molecular weight and insolubility in water; this is supported by the extremely high oral LD50values reported in literature.

Dermal absorption

Dipotassium heptafluorotantalate is a white crystalline solid with a molecular weight of392.13g/mol, and is moderately water soluble (819.5 mg/L at 30 °C).

The substancewas shown to be not irritating to the skin (Pößernecker, 1992), and no sensitising potential was detected in a fully compliant study in guinea pigs using the Maximization method (Sattler, 2006).

As a worst case estimate, low tomoderate absorption following dermal exposure can be expected.

Inhalation absorption

Aqueous solutions of K2TaF7at physiological temperatures yield the complex ion TaF72-, a Lewis acid which imparts a pH of 2 to the solution, which is capable of causing serious damage to eyes (when K2TaF7is introduced into rabbit eyes), and K+ions.

Similar effects were observed in an acute inhalation study(Weniger, 2006), where 4 hrs inhalation exposure lead to mortalities and local destruction in the lower airways and alveoli, with some reactive inflammation. The alteration persisted long enough in animals dying on day 3 after exposure to allow bacterial to grow within the necrotic material.

In the absence of quantitative data, absorption following inhalation is assumed to be complete.

 

Distribution

No information is available on distribution of Dipotassium heptafluorotantalate following dermal or inhalation absorption.

Following oral administration, in gastric juice (0.1 N HCl) the presence of hydrochloric acid promotes the degradation of K2TaF7to Ta2O5, KF and HF. 

Ta2O5, is biologically inert, and is expected not to be widely distributed within the body.

The fluoride ion will be dissociated in solution and not specifically physically associated with any particular cation inclusive of the H+of K+ions simultaneously evolved. Both H+and K+are highly prevalent physiological ions, particularly in gastric juice, and will be included and regulated within the normal body pools. The fluoride ions will be widely distributed.

 

 

Metabolism

The final products ofK2TaF7solvation in gastric juice are tantalum (V) oxide, Ta2O5, potassium fluoride, KF, and hydrofluoric acid, HF.

No metabolism is expected to occur following dermal application.

Production ofthe complex ion TaF72-and K+ions can be expected following inhalation.

 

Elimination

No information on elimination of the substance following inhalation is available however, given the large molecular weight,clearance by macrophages is likely to occur.

The major route for the removal of fluoride from the body is by the kidneys.

 

Conclusion

The physico-chemical properties,information on the chemistry ofF7Ta.2Ksolutions,and the results ofin vivoacute and short-term oral toxicity studies indicate that the substance will producetantalum (V) oxide, Ta2O5, potassium fluoride, KF, and hydrofluoric acid, HF, following oral administration. Of these, Ta2O5will be not widely distributed and likely excreted unchanged with the faeces; KF and HF will be responsible for portal-of-entry corrosive effects and the resulting high levels of fluoride, which will be completely absorbed, will be responsible for any repeat-dose toxicity.

Based on thephysico-chemical properties, low to moderate absorption following dermal exposure is expected to occur.

In the absence of quantitative data, absorption the complex ion TaF72-likely to be produced following inhalation of the substance is assumed to be complete.

Two additional papers (Venugopal & Luckey, 1978) and (Clayton & Clayton 1981) are provided as supporting information. However, as these references provided only very limited data and it was not possible to judge the bioaccumulation potential based on the study results they have not be included in the toxicokinetic assessment prepared for this substance.