Potassium titanium oxide (K1.88-2.13Ti8O16.94-17.07)

Endpoint summary

Description of key information

Terracess TF is a stable insoluble inorganic substance and its physicochemical properties indicate that it will not be absorbed or accumulate in living organisms. This is supported by the lack of any adverse findings in toxicological studies, other than local effects due to the physical presence of the substance.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetics assessment of Terracess TF

The substance is an inorganic oxide and as such has a macromolecular structure and very little solubility over the whole polarity range of solvents. It is a dense white powder and at room temperature with approximately 49% of the particles less than 10 µm in size (Terracess TF-S) and 10% of particles less than 8 µm (Terracess TF-L). Due to the intrinsic insolubility of the substance determination of the n-octanol-water partition coefficient is neither feasible nor relevant. The lack of solubility in water of Terracess-TF means that degradation in water is unlikely and biodegradation is not applicable as the substance is inorganic. Its high molecular weight, lack of solubility, and partitioning behaviour suggest that it will not be biologically available.

Absorption:

The acute oral and dermal toxicity studies and the acute and 90-day inhalation studies did not reveal any evidence of absorption of the test substance via the oral, dermal or inhalation routes. The water solubility is low (<1mg/L) and is considered a rate-limiting factor for the absorption of the compound from the gastro-intestinal tract. This is supported by the low acute oral toxicity of Terracess TF (LD50 > 2000 mg/kg body weight) with no toxic effects observed (no treatment related clinical signs, no weight loss and no gross lesions observed during necropsy).

The partitioning behaviour of Terracess TF suggests that the substance will not penetrate the skin. No treatment related effect were observed in rats in the acute dermal toxicity study (LD50>5000 mg/kg body weight). Uptake via inhalation of the substance cannot be excluded because of the relatively small particle size of the compound. However the acute and repeat dose inhalation toxicity was found to be low (4h-LC50 > 5.2 g/m3 and 90-day NOAEL=10 mg/ m3). In the 90-day inhalation study, no systemic effects were observed. The increase of lung-to-body weight ratios, the histologic evaluation and the microscopic findings were consistent with exposure to a non-pathogenic dust. There was evidence that in the lung macrophages were involved with the ingestion of the test substance and subsequent clearance. This was considered to be a normal physiological response typical of a "nuisance dust".

Distribution:

The acute oral and dermal toxicity studies and the 90-day inhalation study did not reveal any evidence of distribution to the systemic circulation nor to the peripheral or central nervous systems. It was not absorbed via the gastrointestinal tract or the skin but it was found to be inhaled. In the 90-day inhalation study, the organ weight, macroscopic findings and microscopic findings indicated that the test substance was localised in the lung.

Metabolism:

The acute oral and dermal toxicity studies and the acute and 90-day inhalation studies did not reveal any evidence of metabolism. Terracess TF is insoluble, inorganic therefore it is not reactive and not metabolised. Excretion: The acute oral and dermal toxicity studies and the 90-day inhalation study did not reveal any evidence of systemic excretion. There was evidence that in the lung macrophages were involved with the ingestion of the test substance and subsequent clearance. This was considered to be a normal physiological response typical of a "nuisance dust". Particles are swallowed after being expelled from the respiratory tract by mucocilliary clearance.

Discussion:

Based on the physico-chemical properties and the results of the toxicology studies, it is therefore expected that the bulk of the substance is not readily absorbed by either the oral, dermal or inhalation routes. However in case some of the elements/cations (Potassium and Titanium) which form Terracess TF dissociate due to physical or chemical effects (friction, low pH in the stomach), uptake and systemic exposure may occur. Therefore, the anticipated toxicokinetic behaviour of the cations is discussed. Potassium will be readily absorbed and used by the body as if it was coming from the diet. In contrast, titanium is poorly absorbed from the gut, and no essential metabolic role has yet been ascribed to this element. Titanium compounds appear to be biologically inert (Kazantzis, 1981). The minute absorption of titanium from the gastrointestinal tract was demonstrated in a study in which mice were given 44Ti intragastrically (without marker). The whole body count after 24 h did not exceed the background level (Thomas & Archuleta, 1980). A comparison of organ contents of 44Ti after oral and intravenous administration of the isotope (3 µCi), indicated a gastrointestinal absorption of less than 5% in lambs (Miller et al., 1976). Environmental Health Criteria for titanium, an evaluation of the effects of titanium on human health and the quality of the environment, states that "titanium compounds are poorly absorbed from the gastrointestinal tract, which is the main route of exposure for the general population"(WHO 1982). Few studies have been reported on the absorption of titanium from the gastrointestinal tract in man. Perry & Perry (1959) reported a mean concentration of 10 µg/litre in pooled urine indicating absorption; however, the extent of the absorption is not known. Accepting this amount in the urine, and assuming a daily intake of 300 µg of titanium, Schroeder et al. (1963) calculated that about 3% of the dietary dose would be absorbed. Wide variations in titanium levels in different organs in man have been found, the lungs frequently containing the highest amount. Hamilton et al. (1972/1973) found titanium in the lung and in the brain, demonstrating that titanium passes the blood-brain barrier. In a male worker not occupationally exposed to metals, the highest concentration was found in the hilar lymph nodes followed by the lung (Teraoka, 1980). Most of ingested titanium is eliminated unabsorbed with the faeces. Under normal circumstances, titanium is excreted with the urine probably at a rate of about 10 µg/litre (Perry & Perry, 1959; Schroeder et al., 1963).

REFERENCES

Acute toxicity: oral, SNIF#001-4.1.11-01

Acute toxicity: inhalation, SNIF#001-4.1.20-01

Acute toxicity: dermal, SNIF#001-4.1.30-01

90-day repeated dose toxicity: inhalation, DuPont-16363

HAMILTON, E.I. & MINSKI, M.J. (1972/1973) Abundance of the chemical elements in man's diet and possible relations with environmental factors. Sci. Total Environ., 1: 375-394.

G. Kazantzis. Role of cobalt, iron, lead, manganese, mercury, platinum, selenium and titanium in carcinogenesis. Environ. Health Perspect. 40 (1981) pp 143-161.

J.K. Miller, F.C. Madsen, S.L. Absorption, Excretion, and Tissue Deposition of Titanium in Sheep. Hansard Journal of Dairy Science Volume 59, Issue 11, November 1976, Pages 2008–2010

PERRY. H.M. & PERRY, E.F. (1959) Normal concentrations of some trace metals in human urine: changes produced by ethylenediamine tetraacetate. J. clin. Invest., 38: 1452-1463.

TERAOKA, H. (1980) Distribution of 24 elements in the internal organs of normal males and the metallic worker in Japan. Arch. environ. Health, 36(4): 155-164.

THOMAS, R.G. & ARCHULETA, R.F. (1980) Titanium retention in mice. Toxicol. Lett., 6: 115-118. WHO (1976) Environmental Health Criteria 24: Titanium, Geneva, World Health Organization, p69.