Potassium tert-butanolate

Endpoint summary

Additional information

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

KOH is highly corrosive, but is not expected to become systemically available under normal handling conditions (at non-irritating concentrations). Potassium is an essential constituent of the body fluids important for neuronal and muscular cell functions regulated by K+/Na+ pumps. Severe toxic doses exceeding 310 mg/l lead to neuromuscular paralysis and, at 390 -470 mg/l death from cardiac arrest. Regulation of K+ concentration in blood is assured principally by renal excretion and reabsorption regulated by aldosterone liberation. 90% is excreted into the urine and 10% through the faeces (Saxena, 1989). The systemic toxicity of hydroxyl ions correlates with an elevated blood pH. Alkalosis causes hyperactivity of the central nervous system with, above pH 7.8, tetanus, extreme excitability, convulsions and respiratory stop. Neither the concentration of potassium in the blood nor the pH of the blood will be increased above normal limits (at non-irritating doses) and therefore absorbed KOH is not expected to cause systemically toxic levels in the blood. The renal excretion of K+ can be elevated and the OH- ion is neutralized by the bicarbonate buffer system in the blood and by respiratory compensation (OECD SIDS KOH 2004).

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 intravenous application, the distribution half-life was approximately 3 min. The elimination half-life was between 3.8 and 5 h in rats. The elimination 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, in a study published by Arco et al., 1994, 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, only 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 with the urine within 24 hours. Only 9 % of a 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 increase the formation of acetone after treatment with tert-butyl alcohol. Pretreatment with tert-butyl alcohol increased the rate of elimination of the substance after further exposure in mice, but not in rats. In addition, metabolites of tert-butyl alcohol were excreted with the feces, and were also exhaled (Arco 1994a; DECOS 1994; ECB, 1995; WHO 1987).