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Sodium tert-butanolate is the salt of tert-butyl alcohol ion and the sodium metal cation. In the presence of water it reacts under formation of tert-butyl alcohol and sodium hydroxide (NaOH).

NaOH is highly corrosive, but is not expected to become systemically available under normal handling conditions (at non-irritating concentrations).

Sodium is a normal constituent of the blood and an excess is excreted in the urine. Most of the sodium is taken up via the food because the normal uptake of sodium via food is 3.1-6.0 g per day according to Fodor et al. (1999). Exposure to NaOH could potentially increase the pH of the blood. However, the pH of the blood is regulated between narrow ranges to maintain homeostasis. Via exhalation of carbon dioxide and via urinary excretion of bicarbonate, the pH is maintained at the normal pH of 7.4-7.5 (EU RAR, 2007, section 4.1.2.1, page 63).

Mean daily sodium intakes of populations in Europe range from about 3-5 g (about 8 -11 g sodium hydroxide) and are well in excess of dietary needs (about 1.5 g sodium/day in adults) (EFSA, 2006). The main source of sodium in diet is from processed foods (about 70 -75% of the total intake), with about 10 -15% from naturally occuring sodium in unprocessed foods and about 10 -15% from discretionary sodium added during cooking and at the table. The major effect of increased sodium intake is elevated blood pressure which is linked to that of chloride. This is a continuous relationship which embraces the levels of sodium habitually consumed. For that reason, it is not possible to determine a threshold level of habitual sodium consumption below which there is unlikely to be any adverse effect on blood pressure. Evidence that high sodium intake might have a direct adverse effect on heart function, independent of any secondary effect due to changes in blood pressure, is not conclusive. The Panel (EFSA, 2006) concludes that the available data are not sufficient to establish an upper level (UL) for sodium from dietary sources.

Tert-butyl alcohol is the second reactant. For tert-butyl alcohol, a low dermal absorption and a low bioaccumulation could be shown. Less than 2 % was recovered in the urine, feces and tissues (Huntingdon Life Sciences Ltd, 1988). In a study published by Bernauer et al., 1998, 3 rats received a single oral dose of 13C-labelled tert-butyl alcohol. In the 24-hour pooled urine samples, the sulfate conjugate of tert-butyl alcohol was identified as the main metabolite. In addition, the substance itself, the glucuronide conjugate, 2-hydroxyisobutyric acid, 2-methyl-1 ,2-propanediol and small amounts of acetone could be found. (Bernauer et al. 1998). This was confirmed in studies performed with the structural analogue MTBA. Here, administration lead to a rapid and complete absorption (tmax 15 min) across the gastrointestinal tract. Several metabolites could be identified in the urine after 72 hours of inhalative application including tert-butyl alcohol, tert-butyl alcohol glucuronide, and tert-butyl alcohol sulfate, 2-hydroxyisobutyrate and 2-methyl-1,2 -propanediol (Miller et al., 1997). After intraveneous application, the distribution half-life was approximately 3 min. The elimination half-life was between 3.8 and 5 h in rats. The elmination decreased with increasing applied doses in male rats, indicating a saturation at high doses possibly leading to accumulation (Poet et al, 1997).

As documented in the MAK statement, the study published by Arco et al., 1994, showed that only 1 % of the administered substance was detected in feces. After inhalation or oral uptake, the levels in the blood increased linearly and were distributed quickly through the bloodstream in the organism. Two minutes following i.v. injection of 350 mg/kg body weight, 15 % of the administered radioactivity was detected in the blood of the rats. The absorbed tert-butyl alcohol is distributed mainly in aqueous compartments. In accordance with this, a distribution volume was determined after oral administration of tert-butyl alcohol to rats which corresponded more or less to the volume of water in the body. 25 % of the radioactivity after oral application was excreted via urine within one day. Only 9 % of an applied dose of 1500 mg/kg body weight was excreted. Over 97 % of renal excretion involved polar and relatively volatile metabolites (Arco 1994a). The metabolism of tert-butyl alcohol is not catalysed by alcohol dehydrogenase. As shown, sulfate and glucuronide conjugates, derivatives of tert-butyl alcohol hydroxylated on the methyl side-chains, acetone and formaldehyde were described as metabolites. In vitro studies performed with rat liver microsomes show that the small amounts of acetone and formaldehyde were formed during the transformation of tert-butyl alcohol by the mixed-function monooxygenase system by demethylation and with the involvement of reactive oxygen species. In rats, pretreatment with phenobarbital for the induction of cytochrome P450 enzymes did not raise the formation of acetone after treatment with tert-butyl alcohol. Pretreatment with tert-butyl alcohol increased the elimination rate of the substance after further exposure in mice, but not in rats. In addition, metabolites of tert-butyl alcohol were excreted with the faeces, and were also exhaled (Arco 1994a; DECOS 1994; ECB, 1995; WHO 1987).