Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits

Andrew G Hendrickx, P. E. Peterson, R. W. Tyl, L. C. Fisher, L. J. Fosnight, M. F. Kubena, M. A. Vrbanic, G. V. Katz

Research output: Contribution to journalArticle

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Abstract

Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits. Hendrickx, A. G., Peterson, P. E., Tyl, R. W., Fisher, L. C., Fosnight, L. J., Kubena, M. F., Vrbanic, M, A., and Katz, G, V, (1993). Fundam. Appl. Toxicol. 20, 199-209. This study was carried out to assess the developmental toxicity of orally administered 2-ethylhexanoic acid (2-EHA) throughout organogenesis in the rat and the rabbit. Treatment of Fischer 344 inbred rats with doses of 100 to 1000 mg 2-EHA/ kg/day on (Gestation Days) (GD) 6-15 in a range-finding and a definitive study resulted in a high level of maternal death at 1000 mg/kg/day. Clinical signs of maternal toxicity, including increased liver weight, as well as increased resorptions, dead fetuses, and growth retardation, but no malformations, were observed at 500 mg/kg/day. Slight developmental toxicity, manifested as a reduction in skeletal ossification, occurred in fetuses exposed to 250 mg/kg/day. No adverse effects of treatment were associated with the lower 2-EHA doses (100 and 125 mg/kg/ day). Maternal toxicity was also observed in range-finding and definitive studies in New Zealand white rabbits exposed to 25 to 1000 mg 2-EHA/kg/day on GD 6-18 with excessive mortality observed at the highest doses (500 and 1000 mg/kg/day). A low incidence of maternal death as well as abortion occurred following treatment with 125 and 250 mg 2-EHA/kg/day. Less severe clinical signs (reduced weight and food consumption and hypoactivity) were also observed in the 250 mg/kg/day group. There were no adverse effects on fetal viability, growth, or morphology at any dose level. Thus, exposure to 2-EHA during the entire period of organogenesis caused developmental toxicity only at maternally toxic doses in the rat or adverse maternal effects in the absence of developmental toxicity in the rabbit. No evidence of teratogenicity was associated with 2-EHA in this classical safety assessment regimen in either species. The no observed adverse effect levels (NOAELs) for maternal and developmental toxicities in rats are 250 and 100 mg/kg/day, respectively; the corresponding NOAELs for rabbits are 25 mg/kg/day (maternal) and ≥250 mg/kg/day (developmental).

Original languageEnglish (US)
Pages (from-to)199-209
Number of pages11
JournalFundamental and Applied Toxicology
Volume20
Issue number2
DOIs
StatePublished - Feb 1993

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Toxicity
Rats
Rabbits
Mothers
No-Observed-Adverse-Effect Level
Maternal Death
Organogenesis
Fetus
Fetal Viability
Weights and Measures
Pregnancy
2-ethylhexanoic acid
Poisons
Inbred F344 Rats
Fetal Development
Osteogenesis
Liver
Safety
Food
Mortality

ASJC Scopus subject areas

  • Toxicology

Cite this

Hendrickx, A. G., Peterson, P. E., Tyl, R. W., Fisher, L. C., Fosnight, L. J., Kubena, M. F., ... Katz, G. V. (1993). Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits. Fundamental and Applied Toxicology, 20(2), 199-209. https://doi.org/10.1006/faat.1993.1027

Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits. / Hendrickx, Andrew G; Peterson, P. E.; Tyl, R. W.; Fisher, L. C.; Fosnight, L. J.; Kubena, M. F.; Vrbanic, M. A.; Katz, G. V.

In: Fundamental and Applied Toxicology, Vol. 20, No. 2, 02.1993, p. 199-209.

Research output: Contribution to journalArticle

Hendrickx, AG, Peterson, PE, Tyl, RW, Fisher, LC, Fosnight, LJ, Kubena, MF, Vrbanic, MA & Katz, GV 1993, 'Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits', Fundamental and Applied Toxicology, vol. 20, no. 2, pp. 199-209. https://doi.org/10.1006/faat.1993.1027
Hendrickx AG, Peterson PE, Tyl RW, Fisher LC, Fosnight LJ, Kubena MF et al. Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits. Fundamental and Applied Toxicology. 1993 Feb;20(2):199-209. https://doi.org/10.1006/faat.1993.1027
Hendrickx, Andrew G ; Peterson, P. E. ; Tyl, R. W. ; Fisher, L. C. ; Fosnight, L. J. ; Kubena, M. F. ; Vrbanic, M. A. ; Katz, G. V. / Assessment of the Developmental Toxicity of 2-Ethylhexanoic Acid in Rats and Rabbits. In: Fundamental and Applied Toxicology. 1993 ; Vol. 20, No. 2. pp. 199-209.
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