Metabolism of 2-ethylhexanol administered orally and dermally to the female Fischer 344 rat

Abstract

1. Excretion balance studies were conducted with 2-ethylhexanol (2-EH) in female Fischer 344 rats following single high (500 mg/kg) and low (50 mg/kg) oral doses of [14C]2-EH, following repeated oral dosing with unlabelled 2-EH at the low level, following dermal exposure for 6 h with a 1 g/kg applied dose of [14C]2-EH, and following a 1 mg/kg i.v. dose of [14C]2-EH. 2. The high, low and repeated low oral dose studies with 2-EH showed similar excretion balance profiles of [14C], with some evidence of metabolic saturation at the high dose. 3. No evidence of metabolic induction was seen following the repeated low oral dosing. 4. All of the oral doses were eliminated rapidly, predominantly in the urine during the first 24 h following dosing. 5. The dermal dosing resulted in only about 5% absorption of the 1 g/kg dose, with the major portion of the dose recovered unabsorbed from the dermal exposure cell at 6 h. 6. Urinary metabolites eliminated following the oral and dermal doses were predominantly glucuronides of oxidized metabolites of 2-EH, including glucuronides of 2-ethyladipic acid, 2-ethylhexanoic acid, 5-hydroxy-2-ethylhexanoic acid and 6-hydroxy-2-ethylhexanoic acid.

Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration

“…Disposition of 2-EH has been well described; both parent and metabolites are excreted in urine (Deisinger et al, 1994). Inhalation exposure studies found exposure to 120 ppm of 2-EH for 6 h per day for 90 days resulted in no adverse effects (Klimisch et al, 1998).…”

Flavouring Group Evaluation 04 −2-Ethylhexyl derivatives from chemical group 2 - Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC)

“…Minor urinary components were 2-heptanone and 4-heptanone. In addition, 2-ethyl-delta 5 -hexenoic acid and lactones of 5-hydroxy-2-EHA were also observed, but possibly these might be analytical artefacts, at least in part (Deisinger et al, 1994).…”

“…In addition, 1 mg/kg bw 1-14 C-2-EHol was also given as intravenous (i.v.) injection (Deisinger et al, 1994). Excretion products, including conjugates and exhaled radioactivity, were studied to draw up the excretion balance and, for the oral studies, to describe metabolic pattern.…”

Scientific Opinion on Flavouring Group Evaluation 10, Revision 2 (FGE.10Rev2): Aliphatic primary and secondary saturated and unsaturated alcohols, aldehydes, acetals, carboxylic acids and esters containing an additional oxygenated functional group and lactones from chemical groups 9, 13 and 30

“…If the methyl group is located at an odd-numbered carbon such as the 3-position, beta-oxidation is inhibited and omega-oxidation predominates, primarily leading to polar, acidic metabolites capable of being excreted in the urine as such or as conjugates (Williams, 1959a). Larger alkyl substituents (>C2) located at the alpha-or beta-position inhibit metabolism to CO 2 (Deisinger et al, 1994;Deuel, 1957;Albro, 1975) in which case there is either direct conjugation of the acid with glucuronic acid or omega-oxidation leading to diacid metabolites, which may be conjugated and excreted.…”