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Description of key information

As titanium tetra(octanolate), branched and linear 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:
Absorption: readily through gastrointestinal tract
Distribution: widely distributed to the tissues with no obvious accumulation in any tissues.
Metabolism: alcohols are initially oxidized to corresponding aldehydes and further to corresponding carboxylic acids finally to carbon dioxide.
Excretion: plasma half-lives are difficult to measure since many of the low molecular weight metabolites (e.g. aldehydes, carboxylic acids) are endogenous in humans.
In conclusion, as Exxal 8 is oxidized finally to CO2 and excreted, the substance is not expected to have bioaccumulation potential.
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 tetra(octanolate), branched and linear 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 organic degradation product (Exxal 8; alcohols, C7-9-iso, C8-rich) and hydrated titanium dioxide. These degradation products were determined by using OECD 111 method under Good Laboratory Practice (GLP) (Brekelmans M. J. C., 2013). The hydrolysis reaction of titanium tetra(octanolate), branched and linear is rapid; the half-life is less than 10 minutes under physiological conditions. Thus, the toxicokinetic behaviour of Exxal 8 and titanium dioxide instead of the target substance is focused in CSA. As Exxal 8 is metabolized and excreted as CO2, the substance is not expected to have bioaccumulation potential. Toxicokinetics of the hazardous degradation product Linear and branched chain alcohols exhibit similar patterns of absorption, metabolism, and excretion. Both types of alcohols are absorbed through the gastrointestinal tract and are rapidly eliminated from the blood (DeBruin, 1976; Lington and Bevan, 1994). These alcohols are initially oxidized to corresponding aldehydes and further to corresponding carboxylic acids by high capacity NAD+/NADH-dependent enzymes, which are then metabolized to carbon dioxide via the fatty acid pathways and the tricarboxylic acid cycle (Feron et al., 1991; Parkinson, 1996a). Plasma half-lives are difficult to measure since many of the low molecular weight metabolites (e. g. aldehydes, carboxylic acids) are endogenous in humans (Lington and Bevan, 1994). Alcohol dehydrogenase (ADH) enzymes are the cytosolic enzymes that are primarily responsible for the oxidation of alcohols to their corresponding aldehydes. Alcohols also can be oxidized to aldehydes by non-ADH enzymes present in the microsomes and peroxisomes, but these are generally quantitatively less important than ADH. Aldehyde dehydrogenases (ALDH) oxidize aldehydes to their corresponding carboxylic acids. Branched-chain aliphatic alcohols and aldehydes have been shown to be excellent substrates for ADH and ALDH (Albro, 1975; Blair & Bodley, 1969; Hedlund & Kiessling, 1969). As carbon chain length increases, the rates of ALD-mediated oxidation also increase (Nakayasu et al., 1978). The metabolism of branched-chain alcohols, aldehydes, and carboxylic acids containing one or more methyl substituents is determined primarily by the position of the methyl group on the branched-chain. Alcohols and aldehydes are rapidly oxidized to their corresponding carboxylic acids. The branched-chain acids are metabolized via beta-oxidation followed by cleavage to yield linear acid fragments which are then completely metabolized in the fatty acid pathway or the tricarboxylic acid cycle. Higher molecular weight homologues (>C10), may also undergo a combination of ω-, ω-1 and β-oxidation, and selective dehydrogenation and hydration to yield polar metabolites which are excreted as the glucuronic acid or sulfate conjugates in the urine and, to a lesser extent, in the feces (Diliberto et al., 1990). Thus, the principal metabolic pathways utilized for detoxification of these branched-chain substances are determined primarily by four structural characteristics: carbon chain length, and the position, number, and size of alkyl substituents. 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, detectable amounts of titanium can be found in the blood, brain and parenchymatous organs of individuals in the general population (Friberg, L. et al.1986). Based on average titanium concentrations found in human urine, 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 is released from titanium tetra(octanolate), branched and linear as hydrated form and thus human exposure via inhalation is not relevant.

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