Multiple dosing of 2-Ethylhexanoic acid alters maternal zinc (Zn) metabolism and is teratogenic in the rat

L. Bui, M. Taubeneck, W. Faber, Carl L Keen

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2-Ethylhexanoic acid (EHXA) is teratogenic in laboratory animals. We tested the hypothesis that EHXA produces developmental defects via the production of an acute phase reaction including synthesis of met allot hionein (MT), and subsequent Zn sequestration in maternal liver. In experiment 1 dams were fed gestation day (GD) 0-16 a 1. 25, or 100 μg Zn/g diet. Dams were given 3.5 mmol EHXA or 1.0 ml oil/kg/d from GD8-15, and killed on CD16 or 19. EHXA resulted in high maternal liver MT and low plasma Zn. Encephalocele and tail defects were noted in the GD16 fetuses of dams given EHXA. The incidence was higher in the low Zn group (44.7%, 32.0%) than in the high Zn group (2.0%, 4.8%). The incidence of these defects in the Oil groups was lower (15%, 28%- low Zn; 0.0%, 1.0% - high Zn). On GD19, tail defects were higher in tlio EHXA-groups than in controls. The highest incidence was in the low Zn diet EHXA group (33.0%). On GD19, encephalocele was only observed in the low Zn EHXA group. Fetal weight and length were most severely affected by both EHXA and low dietary Zn. In experiment 2, GD10 embryos from control dams were cultured 48h in serum from control or EHXA-treated animals fed a 4.5 or 25 μg Zn/g diet. Embryos in EHXA groups were developmentally delayed. To test if the teratogenicity of the EHXA serum was due to its low Zn concentration, embryos were cultured in Zn supplemented EHXA serum. Embryos grown in this medium developed normally, suggesting that Zn deficiency secondary to maternal EHXA tieatinent contributes to its developmental toxicity.

Original languageEnglish (US)
JournalFASEB Journal
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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