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Teratogenic effects of nitroimidazopyridazine on the CNS in fetal Wistar (WU) rats

Archives of Toxicology volume 80, pages 458–464 (2006)Cite this article

Abstract

Teratogenic effects caused by a new nitroimidazopyridazine were examined in Wistar (WU) rats after repeated oral administration of 0, 2.5, 10, and 40 mg/kg, given on days 6–17 post coitum (p.c.) (Day of mating = Day 0) in a regular study on embryo-fetal development according to ICH S5A. At day 20 p.c., fetuses were removed and carefully examined under a dissecting microscope for external, visceral and skeletal malformations. The exposure to the high dose of the test compound during the organogenesis and early histogenesis periods of prenatal development induced prominent CNS malformations (exencephaly, neural tube defects (NTD)) associated with external malformations (hyperflexion of the forelimbs). To support the data from this study additional histological evaluation of the brains was performed with the following results: disorganization of the cerebral cortex associated with ectopic subcommissural organs. Additionally, an in vitro test (whole embryo culture, WEC) showed alterations of the developing neural tube after the incubation of rat embryos with the test compound on gestation days 9.5–11.5. Our data demonstrated that nitroimidazopyridazine caused NTDs and limb malformations during organogenesis. Based on these data the further development of the test compound was stopped.

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Acknowledgements

The technical assistance of Mrs. M.L. Veith, J. Dierich, and K. Meissner is gratefully acknowledged. For typing the manuscript we wish to thank Mrs. P. Knaack, Mrs. G. Enderlein, and Mr. R. Alberding for taking the photographs.

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  1. Institute for Pathology and Toxicology, ALTANA Pharma AG, Friedrich-Ebert-Damm 101, 22047, Hamburg, Germany

    Thomas Woehrmann, Jutta Volland, Klaus Tuch, Gerd Bode & Ulrich Hübel

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  1. Thomas Woehrmann
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  2. Jutta Volland
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  3. Klaus Tuch
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  4. Gerd Bode
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  5. Ulrich Hübel
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Correspondence to Thomas Woehrmann.

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Woehrmann, T., Volland, J., Tuch, K. et al. Teratogenic effects of nitroimidazopyridazine on the CNS in fetal Wistar (WU) rats. Arch Toxicol 80, 458–464 (2006). https://doi.org/10.1007/s00204-006-0057-5

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  • DOI: https://doi.org/10.1007/s00204-006-0057-5

Keywords

  • Nitroimidazopyridazine
  • Teratogenicity
  • CNS – malformations
  • Histopathology
  • Whole embryo culture (WEC)
  • Rat