Ammonium tetrafluoroborate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and (iii) there is no or no significant human exposure

other:

Justification for type of information:

Since it is a salt it is not likely to pass biological membranes as ammonium tetrafluoroborate, but rather dissolve and be hydrolysed in water. Even the BF4 cation is being hydrolysed in water at room temperature. Research has proven that the toxicity of ionic liquids come from the length of the alkyl chains. Ammonium tetrafluoroborate is an ionic liquid, but it does not contain any alkyl chains on the cation or the anion.
Similar trends between the toxicity and length of alkyl chain on luminescence inhibition of Vibrio fischeri and promyelocytic leukemia rat cell line IPC-81 were reported by Ranke and co-workers. [84] Leukemia rat cell line IPC-81 was als,o used to observe the cytotoxic effect of commercially available anions. [85] No significant anion effect was found under the test system.
In employees working with tetrafluoroboric acid and its derivatives and undergoing regular Medical examinations, there have been no indications of enlargement or dysfunction of the thyroid gland over a period of more than 20 years. In Another chemical plant, 6 workers who had frequent Contact with tetrafluoroboric acid regularly underwent Medical examination. None of them had goitre or signs of hypothyroidism. The T3 and T4 levels were in the normal range.
Ammonia, which is being formed in water, has no structural alerts for DNA reactivity, and is not mutagenic. Ammonia has not been classified as a human carcinogen. Ammonia is not considered to be an animal carcinogen, ingestion by rats of ammonia as ammonium hydroxide for 2 years did not result in an increase in cancers.

Furthermore, potassium tetrafluoroborate can be used as a read-across for ammonium ion due to comparable size of potassium and ammonium cation and the anion being the exact same counterion. Hence, in a study on the distribution of potassium tetrafluoroborate in various tissues, male albino rats (weighing 110 to 150 g; aged 11-13 weeks) were each iv injected with 1 umol 18F-labelled potassium tetrafluoroborate. At 120 min 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 min 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.

Hydrogen fluoride is probably formed when ammonium tetrafluoroborate is being dissolved in aquatic environment. In aqueous form it is called hydrofluoric acid. Hydrogen fluoride is only a weak acid in dilute aqueous solution. This is in part a result of the strength of the hydrogen-fluorine bond, but also of other factors such as the tendency of HF, H2O, and F− anions to form clusters.
Hydrogen fluoride is not included in Reproductive and Developmental Toxicants, a 1991 report published by the U.S. General Accounting Office (GAO) that lists 30 chemicals of concern because of widely acknowledged reproductive and developmental consequences. Fluoride crosses the placenta, and at low doses is thought to be essential for normal fetal development in humans. It is rarely excreted in breast milk. There have been rare cases of mottling of deciduous teeth in infants born to mothers who had high daily intakes of fluoride during pregnancy; skeletal abnormalities are considered unlikely. No reproductive effects due to hydrogen fluoride are known.
It has also been concluded by Slooff (1998) that the limited data available indicate that accumulation through food chains (biomagnification) is of little significance in the aquatic environment.
In another two-generation study in rats NaF was administered via the drinking water at different concentrations. 22 days old males and females rats received fluoride for about 14 weeks. The differences that were observed in the end of the study were not treatment related and did not indicate toxicologically relevant effects. Testicular histological examination did not reveal any abnormalities. From another study it was concluded that no fertility effects occurred in rats exposed to NaF in the drinking water at concentrations up to 250 mg/l.

Regarding borate salts, surveys of Turkish and Chinese populations with elevated levels of borate salts in drinking water (9–25 mg boron/L) found no associations for chronic-duration exposure with reproductive effects. The essentiality of boron has been established for most plants and some animals, but not in humans.

For boron, oral exposure animal studies have clearly identified the reproductive system and developing fetus as the most sensitive targets of boron toxicity. Adverse developmental effects have been identified for acute-and intermediate-duration exposures. Decreases in the number of live fetuses and litters, decreases in body weight, and increases in the occurrence of external, visceral, and cardiovascular malformations were observed in the fetuses of rabbits administered 44 mg boron/kg/day on gestation days 6–19; no developmental effects were observed at 22 mg boron/kg/day. Following intermediate-duration exposure, decreases in body weight and increases in the occurrence of skeletal malformations have been observed in the fetuses of rats exposed to 13 mg boron/kg/day on gestation days 0–20; a no-observed-adverse-effect level (NOAEL) of 10 mg boron/kg/day was identified. Reproductive effects have been observed at higher doses. Histological alterations in the testes and sperm effects have been observed in rats administered 88 mg boron/kg/day for 2 weeks; the NOAEL was 44–53 mg boron/kg/day. Intermediate-duration exposure resulted in histological alterations in the testes and associated effects on spermatogenesis in rats exposed to doses of ≥26 mg boron/kg/day. No viable sperm were observed in male rats exposed to 101 mg boron/kg/day for 14 weeks. Impaired ovulation and failure to conceive was also observed in female rats (mated with unexposed males) exposed to 116 mg boron/kg/day for 14 weeks prior to mating. A NOAEL of 30 mg boron/kg/day was identified for reproductive effects (testicular atrophy) in males in a 3-generation rat study. Testicular atrophy has also been observed in rats exposed to 81 mg boron/kg/day and mice exposed to 201 mg boron/kg/day for 2 years; no testicular alterations were observed at 24 or 79 mg boron/kg/day, respectively. Testicular and spermatogenic effects were observed in rats receiving gavage doses of 88 mg boron/kg/day for 2 weeks (Fukuda et al. 2000; Kudo et al. 2000). No effects were observed at 44 or 53 mg boron/kg/day. Complete sterility was observed in rats exposed to 101 mg boron/kg/day as boric acid or borax for 14 weeks prior to mating (Weir and Fisher 1972); a lack of viable sperm was observed at this dose level. Additionally, female rats exposed to similar doses (116 mg boron/kg/day) for 14 weeks failed to become pregnant when mated with non-exposed males (Weir and Fisher 1972); the female sterility response at this dose level was associated with decreased ovulation. The Weir and Fisher (1972) 3-generation studies (males and females exposed to boric acid or borax) established a NOAEL of 30 mg boron/kg/day for reproductive toxicity in rats.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Studies:

• The results of microbial mutation test for forty-three industrial chemicals. Shimizu H, Suzuki Y, Takemura N, Goto S, Matsushita H. Sangyo Igaku. 1985 Nov;27(6):400-19.
• Toxicological evaluations, Tetrafluoroboric acid and its salts. No 136, BG Chemie