Lithium bis(oxalato)borate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

10

Additional information

General

The following sections provide an overview of the toxicological profile and toxicokinetic behaviour of lithium bis(oxalate)borate. This organometallic, white substance is a conductive agent used in high performance batteries like accumulators.

Toxicological profile of LiBOB

LiBOB was tested for acute oral toxicity (up-and down procedure) in rats resulting in a LD50 value of above 550 mg/kg bw. Following an administration of 2000 mg/kg bw 100% mortality occurred. The macroscopic examination revealed some minor alterations such as diffuse dark discoloration of the liver as well as dark, red, diffuse discoloration and mucosa in ileum, duodenum and jejunum. All treated animals showed the expected gains in body weight throughout the study period. Taken together, these findings are indicative for an acute systemic toxicity.

Acute dermal toxicity testing in rats with LiBOB revealed a LD50 above 2000 mg/kg bw (limit dose). No deaths occurred and no test substance-related clinical signs of toxicity were observed during testing. Therefore, the acute systemic toxicity of LiBOB following dermal exposure is expected to be very low.

In an acute dermal in vitro irritation study performed with a human skin model, LiBOB did not cause any signs of skin irritation and the substance was not considered being a skin irritant. A subsequent in vivo acute dermal irritation study with rabbits revealed very slight erythema after 24 and 48 hours after treatment. Reversibility occurred after 72 hours of treatment.

Based on the results of an acute eye irritation study in vitro (HET-CAM), the irritation potential of LiBOB was determined to be none to slight. A subsequent in vivo test with rabbits revealed corneal opacity, iritis and conjunctival irritation in all rabbits that persisted until day 21. The substance was determined to be a strong eye irritant that causes irreversible effects to the eyes.

LiBOB was analysed for skin sensitisation properties in a local lymph node assay (LLNA) in mice and was considered sensitising as immunological responses were determined. Furthermore, no signs of systemic toxicity were observed in this study and all treated animals showed the expected gains in body weight throughout the study period.

LiBOB was tested negative in a bacterial reverse mutation assay (Ames test) with and without metabolic activation (S9 mix) and was considered to be non-mutagenic in this test system. Also the results of an in vitro chromosome aberration test indicated that LiBOB did not induce chromosomal aberration in human peripheral lymphocytes with and without metabolic activation. Furthermore, the substance was tested negative in an in vitro HPRT test performed with CHO cells. Therefore, the substance was considered to be non-genotoxic under in vitro conditions.

LiBOB was tested for its repeated dose oral toxicity in a subacute 28-day study according to the current guideline, in male and female rats up to the highest dose. The substance was administered by oral gavage. For the subacute 28-day study, the substance was administered in dose levels of 0, 10, 40, and 160 mg/kg bw/day (the limit dose) using corn oil as vehicle. The 28-day study revealed a NOAEL of 40 mg/kg bw/day. Test item related signs of toxicity were noted in the body weight gain of males in the highest dosage group, because a significant decrease was detected. Furthermore, the test substance caused a decrease of haemoglobin in the high dose group of both male and female rats. The number of platelets was also decreased in the female rats of the high dose group. Also the red blood cells were significantly lower in males of the high dose group. Changes of the kidneys were seen in both sexes (higher organ weights and a decreased TP value in the high dose groups of both sexes; elevated BUN, CHE and decreased ALB values in the high dose males). Further, the pH of urine was decreased in both sexes. The gross pathology revealed no overt abnormalities in all animals. The histopathological findings included mid-grade degeneration and necrosis of the partial renal tubule with mid grade renal tubule crystal retention as well as light grade infiltration of inflammatory cells of interstitial tissue in both sexes of the high dose group. In a reproduction/developmental screening test LiBOB (10, 30, 100 mg/kg bw/day) caused no deaths of male and female rats. Male and female reproductive performance was not affected by the test item at any dose level. A slightly higher extra uterine mortality of the offspring was observed in the 100 mg/kg bw/day group, but was linked to maternal toxicity. In male and female parental rats renal lesions were observed in the highest dose group.

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.