Lithium bis(oxalato)borate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Lithium bis(oxalato)borate

EC Number:

456-990-3

EC Name:

Lithium bis(oxalato)borate

Cas Number:

244761-29-3

Molecular formula:

C4BLiO8 (Hill Empirical Formula) C4BO8.Li (CAS Empirical Formula)

IUPAC Name:

boron(3+) lithium(1+) dioxalate

Applicant's summary and conclusion

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
Based on its physicochemical properties, particularly water solubility, octanol-water partition coefficient, vapour pressure and molecular weight and the results obtained from the comprehensive toxicological investigation, the substance lithium bis(oxalato)borate (LiBOB) will not, or only to minimal amounts become systemically available following dermal or inhalation exposure.
The oral route uptake is more relevant for the degradation products than for the undegraded substance since in particular the named hydrolysis products are assumed to be absorbed and becoming systemically available. Bioaccumulation of the hydrolysis products is not likely to occur based on the physico-chemical properties. Excretion of the different hydrolysis products occurs via the urine.

Executive summary:

Toxicokinetic analysis of LiBOB

Lithium bis(oxalate)borate (LiBOB) is a white solid at room temperature with a molecular weight of 193.79 g/mol. The substance is very soluble in water (507 – 1015 g/L). The logPow was determined as - 4.8 by a study. The vapour pressure of LiBOB was calculated to be 0.0042 Pa at 20°C. According to study results, LiBOB is degraded hydrolytically to boric acid, oxalic acid and dilithium oxalate with a half-life time of 38 to 48 min at 40°C. All three degradation products have higher calculated log Pow values than LiBOB (- 1.09, – 1.7 and -1.193 respectively) and a similar water solubility (above 10 g/L).

Absorption:

The likelihood of systemic absorption through the walls of the gastro-intestinal tract depends on several physico-chemical parameters. The favoured molecular weights for oral absorption are below 500 g/mol. Thus, due to its molecular weight of 193.79 g/mol LiBOB is expected be orally absorbed. However, based on the low log Pow value LiBOB can be regarded as hydrophilic substance and the systemic uptake from the gastro-intestinal tract is unlikely as the substance is not lipophilic enough to cross plasma membranes. Administered orally LiBOB showed toxic effects at concentrations of 550 mg/kg bw/day and 40 mg/kg bw/day in the acute and repeated dose toxicity studies, respectively. These effects may be explained by the hydrolysis of LiBOB. The three hydrolysis products boric acid, oxalic acid and dilithium oxalate have smaller molecular weights (boric acid: 61.83 g/mol; oxalic acid: 90.04 g/mol; dilithium oxalate: 101.90 g/mol) and higher log Pow values. Substances with log Pow values of -1 to 4 are favourable for absorption by passive diffusion and therefore can cross lipophilic membranes. They can even pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water because of their low molecular weight and their high water solubility.

Due to the very low vapour pressure of LiBOB and the resulting low volatility, an inhalation exposure of the compound’s vapour phase is rather unlikely. In addition, based on the substance particle size, even if inhaled in form of powder or dust almost exclusively the upper respiratory tract will be reached. A deposition in the deeper alveolar region is unlikely as only a negligible percentage of the particles have a diameter less than 10 µm. Based on substance characteristics and physicochemical properties, dermal absorption is unlikely. In general, substances with a molecular weight above 100 g/mol are considered to be slightly absorbed through the skin. Further the high water solubility of above 10 g/l (10000 mg/L) and the low logPow values of -4.8 to -1 of LiBOB and its degradation products prevent them to be uptaken into the lipid rich environment of the stratum corneum. Nevertheless, the low molecular weights of the hydrolysis products may lead to a slight dermal uptake. The assumption that no dermal absorption occurs is further strengthened by the results achieved from the dermal toxicity testing. In an acute dermal toxicity study, LiBOB did not cause any toxic effects. The LD50 was determined to be greater than the limit dose (2000 mg/kg bw). But the positive sensibility result obtained in the LLNA assay indicates systemic availability of the test substance.

Distribution:

Based on the physicochemical properties and the results achieved from the comprehensive toxicity testing, LiBOB or at least its hydrolysis products are systemically available. When reaching the body the substances may be distributed into the blood and the extracellular compartiments due to their high water solubility. This also indicates that a bioaccumulation is highly unlikely for LiBOB and its hydrolysis products.

Metabolism:

Because LiBOB and the hydrolysis products are very soluble in water, the substance will not come in contact with intracellular metabolising enzymes. Therefore, intracellular metabolism of the substance is highly unlikely.

Excretion:

As discussed above LiBOB hydrolyses and will thus not be excreted in its unhydrolysed form. The hydrolysis products have a molecular weight below 100 mol/L and a high water solubility. Thus, they will be excreted via the urine. This is proved in the 28-day repeated dose toxicity study. All animals of the high dosage groups showed a damage of the renal tubule including degeneration and necrosis of the partial renal tubule and crystal retention with infiltration of inflammatory cells of the interstitial tissue. This is further strengthened by the developmental toxicity screening study, where all animals of the high dosage group showed similar damages of the renal system than in the repeated dose study.

Summary

Based on its physicochemical properties, particularly water solubility, octanol-water partition coefficient, vapour pressure and molecular weight and the results obtained from the comprehensive toxicological investigation, the substance LiBOB will not, or only to minimal amounts become systemically available following dermal or inhalation exposure. The oral route uptake is more relevant for the degradation products than for the undegraded substance since in particular the named hydrolysis products are assumed to be absorbed and becoming systemically available. Bioaccumulation of the hydrolysis products is not likely to occur based on the physico-chemical properties. Excretion of the different hydrolysis products occurs via the urine. (SCC, 2013)