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Description of key information

Short description of key information on bioaccumulation potential result: 
No evidence of absorption or accumulation

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Tin and soluble tin compounds:

Highly water-soluble inorganic tin substances such as tin bis(tetrafluoroborate) can safely be assumed to be fully dissociated in aqueous media. For this reason, the toxicokinetics of Sn(II) cations and tetrafluoroborate anions is described here further below:

 

Absorption, distribution, metabolism and elimination:

Absorption (oral):

Absorption of inorganic tin compounds from the gastrointestinal tract in humans and animals is reported to be low with as much as 98% being excreted directly in the faeces. The nature of the inorganic tin compound and its oxidation state appears to determine the extent of absorption (Calloway and McMullen, 1966; Hamiltonet al., 1972b; Tiptonet al., 1966 and 1969; Fritschet al., 1977a; WHO, 1980; ATSDR, 1992 and 2002).

Animals:

Gastrointestinal absorption of tin by the rat is extremely low. In one study, groups of 8 male Wistar rats (approximately 250 g) were fasted for 17 hours after which a dose of radiolabelled113SnCl2(50 mg/kg body weight; 0.5μCi/mg tin) was administered by gavage in either: (1) water; or with (2) aqueous sucrose at 5 g/kg body weight; (3) aqueous ascorbic acid at 0.5 g/kg body weight; (4) aqueous potassium nitrate 0.1 g/kg body weight; (5) an aqueous solution of all three compounds at the same dose; or in (6) 20% alcohol solution, equivalent to 2 g ethanol/kg body weight; or (7) a solution of albumin at 2.5 g/kg body weight; or (8) 1:1 (v/v) sunflower oil-1% Tween 20 emulsion at 10 mL/kg body weight. Rats were placed in metabolic cages, fasted for another 6 hours and then received a basal dietad libitum. Urine and faeces were collected from 0-24 and 24-48 hours.Animals were then sacrificed and excreta and selected organs and tissues analysed for radioactivity. Group mean values of the proportion of the administered dose excreted in the faeces within 48 hours or remaining in the gastrointestinal tract ranged from 98.7-99.8%. The mean percentage of the113Sn dose detected in the urine was less than 1.1% and in the organs and tissues examined was less than 0.005% (Fritschet al., 1977a; WHO, 1980; ATSDR, 1992 and 2002).

The effect of the anion and oxidation state on the gastrointestinal absorption of inorganic tin salts, labelled with113Sn, was studied in the rat. Following a 24-hour fast, groups of 10 female rats (Charles River, 200-225 g) were given a single 20 mg Sn/kg body weight oral dose of Sn2+citrate, fluoride or pyrophosphate or Sn4+ citrate or fluoride. Changing the anion from citrate to fluoride did not alter the absorption of either oxidation state, and approximately 2.8% and 0.6% of the Sn2+and Sn4+, respectively, were absorbed. In a 28-day study in which groups of 6 weanling female rats were fed with the Sn2+and Sn4+fluoride salts (20 mg Sn/kg body weight, on 6 days/week) the steady state urinary excretion wascirca0.35% and 0.12% of the total dose of tin from the Sn2+and Sn4+salts, respectively, confirming the greater absorption of the Sn2+ion (Hiles, 1974).

In a comparative study tracer dose of113SnCl2(2.6-4.4 mg Sn) were administered intravenously, intraperitoneally and by gavage to female RF mice, male Sprague-Dawley rats, male African white-tailed rats, male rhesus monkeys and male beagle dogs. In all species more than 95% of the oral gavage dose was excreted via the faeces within 3 days, whereas a greater percentage (15.9-62.8%) of the parenteral doses was excreted via the urine during the same time (Furchner and Drake, 1976).

 

Humans:

Absorption of inorganic tin compounds from the gastrointestinal tract in humans is very low with as much as 98% being excreted directly in the faeces at intakes around 10 mg/day or higher. Schryver (1909) reported the urinary excretion of tin in normal health adults weighing 65 kg, who ingested daily doses of sodium tin tartrate for 3 weeks.

After the first week, the tin excreted in 5-day periods in each week was related to the amount ingested, with 7.9 and 8.6% of the total excreted in the urine during the second and third weeks, respectively. There was no control period and no measures of dietary tin content were made (Schryver, 1909).

In a study by Calloway and McMullen (1966) faecal excretion of tin was high and approximated dietary intakes when the diet provided 9-190 mg tin per day. In adults given 50 mg tin per day the apparent absorption was around 3%, while it was about 50% when the intake was 0.1 mg/day (Johnson and Greger, 1985).

 

Absorption (inhalation):

Not relevant for the substancetin bis tetrafluoroborate, since it is (i) only marketed in aqueous solution (50%) and (ii) it is only stable in solution, so that inhalation exposure to dusts can be ruled out.

 

Absorption (dermal):

Substance-specific dermal absorption data for inorganictin(II) substances do not exist. For lack of such, a default dermal absorption factor of 1.0% should be assumed (HERAG, 2007).

 

Distribution:

Animals:

In rats (oral uptake), tissue distributions for Sn2+and Sn4+, respectively were skeleton, 1.02% and 0.24%, liver, 0.08% and 0.02%; and kidneys 0.09% and 0.02% (Hiles, 1974). When radioactive stannous chloride was administered by stomach tube to anaesthetised rats the bulk of the dose was excreted in faeces, and there was highly variable distribution of the absorbed fraction in the internal organs as measured for periods of up to 21 days (Kutzner and Brood, 1971).

Tin concentrations were measured in the liver, kidneys and femur of groups of 6 male weanling Wistar rats administered 0, 0.3, 1.0 and 3.0 mg Sn2+/kg body weight orally every 12 hours for a period of 90 days with a clear dose-related increase in femur concentration with statistical significance achieved at the 1.0 mg Sn2+/kg body weight dose. In the highest dose group the femur concentrations were 10-fold higher than the control values of 2.05 ± 0.41μg/g wet tissue and these were associated with significant reductions of the diaphysis and epiphysis concentrations of calcium. The concentrations of tin in the livers of control rats were 0.24 ± 0.01μg/g wet tissue and the levels were significantly increased by 58% at the highest dose. There were no significant increases in the kidney concentrations of 0.22 ± 0.41μg/g wet tissue (Yamaguchiet al., 1980).

Male Wistar rats were given SnCl2.2H2O in their drinking water for 1-18 weeks at concentrations of 100 mg/L (0.44mM), 250 mg/L (1.11 mM) or 500 mg/L (2.22 mM). Tin accumulated in the brain at the highest concentration (2.22 mM) throughout the experiment, but elevated tin concentrations in brain were found only after 15 and 18 weeks at 1.11 mM and tin did not increase in the brains of rats given 0.44 mM. Blood tin increased after one week at the highest dose (2.22 mM) without further accumulation, whereas blood tin levels did not differ from controls at the 2 lower doses. Tin exposure caused a dose-dependent increase in the cerebral and muscle acetylcholinesterase activity at the two highest doses (Savolainen and Valkonen, 1986).

Humans:

The mean concentration (± S.E.) of tin in 102 samples of human blood obtained through the UK National Blood Transfusion Service was 0.009 ± 0.002μg/g wet weight. The concentrations ± S.E. (n) in various organs obtained at autopsy were: whole brain, 0.06 ± 0.01 (10); whole kidney (0.2 ± 0.04 (8); liver, 0.4 ± 0.08 (11); lung, 0.8 ± 0.2 (11), lymph node, 1.5 ± 0.6 (6); muscle, 0.07 ± 0.01 (6); testis, 0.3 ± 0.1 (5); ovary, 0.32 ± 0.19 (6), allμg/g wet weight; bone (hard water area), 4.1 ± 0.6 (22); bone (soft water area), 3.7 ± 0.6 (22),μg/g ash (Hamiltonet al., 1972a).

 

Metabolism:

Methylation of inorganic tin compounds by a mechanism involving the oxidation of a stannous compound to the Sn (III) radical and the reaction of this with the cobalt-carbon bond of vitamin B12 to give a methylated tin derivative have been described. However, this type of reaction seems limited to anaerobic conditions (Ridleyet al., 1977 a and b; Woodet al., 1978; ATSDR, 1992 and 2002).

 

Elimination:

Animals:

The disappearance of radioactivity following intraperitoneal injection of a tracer of113SnCl2into 5 Swiss mice was followed by whole body counting. The biological half life of tin was estimated as 29 days (Brownet al., 1977). Intravenous injection of single bolus doses of 2 mg/kg body weight of either Sn2+or Sn4+(citrate and fluoride) resulted in the excretion of 30% of the dose in the urine, with 11% and 0% of Sn2+and Sn4+eliminated in the bile (Hiles, 1974).

Humans:

A baby fed on evaporated milk from an unlacquered tin can for the first 5 weeks of life was estimated to have ingested 11.23 mg Sn/24 hours. Excretion in the faeces was estimated as 10.64 mg Sn/24 hours and in the urine as 0.23 mg Sn/24 hours. The faecal excretion of tin decreased by 98% within 36 hours after changing to milk from a lacquered can (Hamiltonet al., 1972b). A 30-day balance study on a husband and wife aged 35 and 34 respectively, involved the collection of duplicate samples of their food and drink and total collection of faeces and urine. Mean daily faecal and urinary excretion of tin (measured by emission spectroscopy on dry-ashed samples) were, 2.13 and 0.11 mg, respectively for the wife, and 1.55 and 0.08 mg, respectively for the husband. The wife was in negative balance and the husband in positive balance (Tiptonet al., 1966). The same group studied two males, 23 and25 years old, using similar procedures for a period of 347 days. Both subjects were in positive balance and their mean daily faecal and urinary excretions of tin (mean ± S.E.) were 3.6 ± 0.7 and 0.085 ± 0.011 mg, respectively for the first subject, and 3.6 ± 0.5 and 0.058 ± 0.006 mg for the second subject. It was calculated that less than 10% of the amount of tin ingested was excreted within 24 days (Tiptonet al., 1969). A study of the tin content of army rations which had been stored at either 1 or 37º C for a period of 20 months indicated that these would provide mean tin intakes of 26.3 and 162.8 mg per day respectively as compared with a freshly prepared control diet (9.5 mg Sn per day). During ingestion of the control diet the faecal excretion of tin by 9 young adult male volunteers was slightly greater than the estimated intake and, during consumption of the high tin diet, faecal excretion was slightly lower than the intake; only trace amounts of tin were detected in the urine and these were unaffected by the diet (Calloway and McMullen, 1966). One study has reported results which were somewhat different from the other toxicokinetic studies. In adult males fed daily diets containing either 0.1 or 50 mg of tin in a 40-day study with a 20-day cross over period apparent absorption was 50 and 3% of the ingested tin, respectively (Johnson and Greger, 1982).

 

Tetrafluoroborate:

Absorption, distribution, metabolism and elimination:

Absorption (oral):

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(Institute for Statutory Accident Insurance and Prevention in the Chemical Industry (Berufsgenossenschaft der chemischen Industrie), Toxicological Evaluation No.136, Tetrafluoroboric Acid and its Salts, 2000).

 

Absorption (inhalation):

Not relevant for the substancetin bis tetrafluoroborate, since it is (i) only marketed in aqueous solution (50%) and (ii) it is only stable in solution, so that inhalation exposure to dusts can be ruled out.

 

Absorption (dermal):

Substance-specific dermal absorption data fortetrafluoroborate substances do not exist. For lack of such, a default dermal absorption factor of 1.0% should be assumed (HERAG, 2007).

 

Distribution:

Rats (approx. 200 g; 4 animals/group) were given a single intraperitoneal injection of 5μg18F-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.

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 1000μg potassium tetrafluoroborate did not increase the specific activity in the thyroid gland, but reduced it relative to the values found after administration of 5μg, e.g. by about a factor of 20, 210 minutes after 1000μg. 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 1μmol 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 (Institute for Statutory Accident Insurance and Prevention in the Chemical Industry (Berufsgenossenschaft der chemischen Industrie), Toxicological Evaluation No.136, Tetrafluoroboric Acid and its Salts, 2000).

 

Metabolism:

Metabolism of the tetrafluoroborate anion is not to be anticipated based on its chemical nature.

 

Elimination:

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 the urine and 1.6% in the faeces (Institute for Statutory Accident Insurance and Prevention in the Chemical Industry (Berufsgenossenschaft der chemischen Industrie), Toxicological Evaluation No.136, Tetrafluoroboric Acid and its Salts, 2000).