Lead bis(tetrafluoroborate)

Endpoint summary

Additional information

No toxicokinetic studies performed with lead bis(tetrafluoroborate) are available. However, the substance as registered is produced, marked and used in an aqueous solution which contains lead(2+) and tetrafluoroborate(-) in solution. Therefore, an assessment of the toxicokinetic behaviour is given in the following for lead compounds and tetrafluoroborate salts.

 

Lead:

 

Animal studies serve to validate mechanistic inferences derived from observational human studies. The majority of information pertaining to lead toxicokinetics has been accurately defined in humans of different ages and degrees of susceptibility to lead toxicity. A number of toxicokinetic models have been developed to predict the effects of external lead exposure upon internal or systemic levels of lead. The Integrated Exposure Uptake Biokinetic (IEUBK) is now widely applied to assess relationships between environmental lead exposure and blood lead in children. Due to limitations in the ability of the IEUBK model to assess the deposition and subsequent remobilisation of lead from bone, use of the IEUBK model is generally restrict to predict exposures in children six years of age or younger.

Physiologically-based pharmacokineitc models (e.g. the O'Flaherty Model) have been developed to predict lead uptake in humans of all ages but is most commonly applied in the assessment of adult exposures. Both the O'Flaherty and IEUBK models are available as computer simulation models and are discusses in greater detail in section 7.10.5.

Lead is most easily taken up into the body through inhalation or ingestion – dermal uptake makes a negligible contribution to systemic lead levels. Once taken up into the body, lead is not metabolized. However, lead will distribute to a variety of tissue compartments such as blood, bone and soft tissues. The half-life of lead in the body varies as a function of body compartment. Lead in blood has a half life of 30 – 45 days – measurement of lead in blood thus provides an integrated assessment of average lead exposure (via all routes) over the preceding month. Lead is retained far longer in bones. Depending upon bone type, the retention time of lead can vary between 8 and 30 years. Such lead can both serve as a source of endogenous lead exposure and as a cumulative index of exposure over a time frame of years. Lead excretion is primary via urinary and biliary excretion routes.

Tetrafluoroborate:

Sodium tetrafluoroborate(source: www. bgchemie. de)

Following daily oral intake of 6.4 mg sodium tetrafluoroborate by a volunteer for a period of 14 days, a daily average of 100% was excreted in urine and 1.6% in the faeces. The fluoride content of the volunteer’s food was not determined. Sodium fluoroborate is therefore well absorbed, but the fluoride which enters the body is not stored. The authors attributed this to slow hydrolysis of the tetrafluoroborate ion. In another study with 3 volunteers and a study duration of 7 to 38 weeks, there were indications that fluoride which was absorbed in the form of sodium tetrafluoroborate was stored in the body. The amount was less than 10% of that absorbed into the bloodstream.

Potassium tetrafluoroborate(sorce: www. bgchemie. de)

Rats (approx. 200 g; 4 animals/group) were given a single intraperitoneal injection of 5 μg¹⁸F-labelled potassium tetrafluoroborate (it was not specified whether per kilogram body weight or per rat). After 40, 60, 100 and 120 minutes, various organs were assessed for relative specific tetrafluoroborate activity (tissue/blood specific activity ratio). The results are shown in Table below.

 

Table 2: Relative specific activity of K¹⁸F-tetrafluoroborate (tissue/blood activity ratio) in organs of rats following single intraperitoneal injections (mean value of 4 rats)

Time after injection (min)	40	60	100	120
Muscle	1.93	1.65	1.90	1.42
Liver	1.27	1.34	0.99	1.24
Spleen	1.35	1.01	0.85	1.03
Brain	0.67	0.23	0.49	0.86
Thyroid gland	12.3	15.7	21.0	0.86

 

The highest activity was found in the thyroid gland, where it was 26- to 42-fold higher than in the other organs after 2 hours. Increases in dose to 50, 500 and 1000 μg potassium tetrafluoroborate did not increase the specific activity in the thyroid gland, but reduced it relative to the values found after administration of 5 μg, e.g. by about a factor of 20, 210 minutes after 1000 μg. In a further study by the same investigators on the distribution of potassium tetrafluoroborate in various tissues, male albino rats (weighing 110 to 150 g; aged 11 to 13 weeks) were each intravenously injected with 1 μmol 18F-labelled potassium tetrafluoroborate (no details of the specific radioactivity). At 120 minutes after injection, the following relative specific activities (activity per gram of tissue/activity in serum) were determined: liver 0.29, spleen 0.37, kidney 0.60, lung 0.60, muscle 0.14, brain 0.03, femoral diaphysis 0.26, femoral epiphysis 0.29, incisors 0.27, cranial bone 0.27, cartilage 0.30. Further relative specific activities at 30, 120 and 240 minutes after injection were reported for serum/total injected dose as 1.75, 0.28 and 0.07, respectively, for muscle/serum as 0.14, 0.15 and 0.35, respectively, as well as for femoral epiphysis/serum as 0.35, 0.85 and 1.35, respectively, and for femoral epiphysis/femoral diaphysis as 1.0, 2.3 and 2.4, respectively.