53 Studies in Detoxication

The octyl alcohol, DL-2-ethyl-fl-hexanol, is used industrially as a solvent and, in the form of the ester, di-2-ethylhexyl phthalate, as a plasticizer. According to Shaffer, Carpenter & Smyth (1945) this ester is saponified in rats and rabbits, phthalic acid being excreted and there being also an increase in the short-chain fatty acids in the urine. After feeding the DL-alcohol to rabbits, Akiya & Yamakawa (1950) isolated o-ethylhexanoic acid (aethylcaproic) from the urine, showing a slight positive rotation. They also found a dibasic acid with a slight positive rotation. No reports of the formation ofglucuronide from the alcohol have been made. The toxicity of 2-ethylhexanol is comparable with that of isooctyl alcohol, the anaesthetic dose of both alcohols being near the lethal dose in rats (Nelson, 1951). It has thus been proved that 2-ethylhexanol is oxidized in vivo to the corresponding fatty acid and it would be expected that 2-ethylbutanol would be similarly oxidized to diethylacetic acid (a-ethylbutyric acid). Blum & Koppel (1911) injected diethylacetic acid into a dog and reported methyl n-propyl ketone in the urine. Dziewiatkowski, Venkataraman & Lewis (1949) also fed and injected this acid into rats and rabbits, but were unable to detect any ketone in the urine. They did, however, observe that both diethylacetic and 2-ethylhexanoic acids gave rise to copper-reducing urines and extra glucuronic acid. This suggested that these acids were being excreted partly as ester glucuronides. In the rabbit extra glucuronic acid corresponding to 25-52 % of the dose of diethylacetic acid and to 83-87 % of the m-ethylhexanoic acid was excreted. The ester glucuronides, however, were not isolated. In the present work it has been found that 2ethylbutanol and 2-ethylhexanol give rise in the rabbit to the excretion of the esterglucuronides ofdiethylacetic and oc-ethylhexanoic acids respectively. These glucuronides have been isolated and appear to be the first ester glucuronides of fatty acids to be described. EXPERIMENTAL In the preceding paper (Kamil, Smith & Williams, 1953) it was shown that extra glucuronic acid was excreted by rabbits after dosing with 2-ethylbutanol and 2-ethylhexanol. The glucuronic acid excretion corresponded to 40% of the dose of 2-ethylbutanol and 87 % of 2-ethylhexanol (dose 25 m-moles/ 3 kg. rabbit).