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Description of key information

As titanium tetrabutanolate hydrolyses rapidly when in contact with water or moisture the bioaccumulation potential is related to the main degradation products, not the substance itself.
The key information of the hazardous degradation product (n-butanol):
Rapid absorption, metabolism and excretion of n-butanol were observed after oral and inhalation routes of administration. n-Butanol was excreted mainly as carbon dioxide in exhaled air. Minority of n-butanol is excreted as oxidized metabolites predominantly in urine.
Dermal absorption of n-butanol through rat skin is poor. Metabolism and excretion show no differences compared to the oral route.
The key information of the non-hazardous degradation product:
As titanium dioxide is not soluble and is eliminated mainly unabsorbed this substance is not expected to have bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No studies on titanium tetrabutanolate relating to toxicokinetics have been conducted. The assessment of the toxicokinetic behaviour is based on available information on the physical and chemical properties of the substance and the data obtained from the degradation products.

The substance is hydrolytically unstable. When it comes in contact with water or moisture, a complete hydrolysis will take place with no significant reaction products other than n-butanol (CAS 71-36-3) and hydrated titanium dioxide. These degradation products from hydrolysis study were determined by using OECD 111 method under Good Laboratory Practice (GLP) (Brekelmans, M. J. C., 2013). The hydrolysis reaction of titanium tetrabutanolate is rapid; the half-life is less than 5 minutes under physiological conditions. Thus, the toxicokinetic behaviour of n-butanol and titanium dioxide (TiO2) instead of the target substance is focused in CSA. As the substance is hydrolyzed, and the hazardous degradation product n-butanol is metabolized and excreted rapidly, the substance is not expected to have bioaccumulation potential.

Toxicokinetics of the hazardous degradation product

In an inhalation study, beagle dogs exposed to 50 ppm (0.15 mg/l) n-butanol over a 6-hour period absorbed approximately 55% of the inhaled vapor (DiVincenzo and Hamilton, 1979a). The concentration of n-butanol in the blood was below the detection limit both during and after the exposure.

Majority of n-butanol is rapidly metabolized by alcohol dehydrogenases and aldehyde dehydrogenases to carbon dioxide. In an oral study, CD rats excreted 83.3% of the n-butanol dose (450 mg/kg body mass) as carbon dioxide and 4.4% as glucuronide and sulfate conjugates in the urine. 1% was eliminated in feces and 12 % remained in carcass (DiVincenzo and Hamilton, 1979b). Rats dosed at 4.5 or 45 mg/kg exhibited a similar pattern of excretion. In the same publication it was reported that after dermal application of 14C-labeled n-butanol the absorption rate through the skin of dogs was 8.8 µg/min/cm2.In other dermal study, n-butanol was evaluated to absorb poorly following an in vitro dermal exposure (Boman and Maibach, 2000). The absorption during ventilation (i.e., allowing for n-butanol evaporation from the skin) resulted in ≤1% absorption.

Deisinger and English (2001) cited in UNEP (2004) administered intravenous (i.v.) doses of 21 mg/kg of n-butyl acetate, n-butanol, or 2.1 mg/kg n-butyric acid to groups of adult male Sprague-Dawley rats. In addition, they administered an i.v. infusion of approximately 21 mg/kg n-butyric acid over 3 minutes. Blood samples were collected and analyzed for each of the butyl series compounds. n-Butanol exhibited biphasic elimination and approached background levels by 18 minutes.

Overall, n-butanol is rapidly absorbed, metabolized, and excreted in rats. Accumulation of n-butanol or its metabolites is unlikely to occur.

Toxicokinetics of the non-hazardous degradation product

Titanium dioxide is insoluble in water and most ingested titanium is eliminated unabsorbed. In rats, about 95% ingested dose of titanium dioxide is recovered from feces indicating that the most ingested titanium is not absorbed from gastrointestinal tract by blood (Patty, F. 1965). However, in humans detectable amounts of titanium can be found in the blood, brain and parenchymatous organs (Friberg, L. et al.1986). Based on average titanium concentrations found in human urine of about 10 µg/liter, it can be calculated that the absorption is about 3% (WHO, 1982).

After chronic inhalation exposure to titanium dioxide, accumulation of the substance was shown in the lungs. Titanium was also present in the lymph nodes adjacent to the lung (HSDB, 2012). However, quantitative information on absorption through inhalation is lacking. Titanium dioxide released from titanium tetrabutanolate exists as hydrated form and thus human exposure via inhalation is not relevant.