On the Capacity of Nitroheterocyclic Compounds to Elicit an Unusual Axial Asymmetry in Cultured Rat Embryos

Details

• Personal Author:
  Fantel AG ; Greenaway JC ; Juchau MR ; Fantel AG ; Greenaway JC ; Juchau MR
• Description:
  A series of nitroheterocyclic compounds with antimicrobial and radiosensitizing properties was tested for embryotoxicity in cultured Sprague-Dawley rat embryos, and their effects were compared with various other five-membered heterocycles. Nifuroxime, furazolidone, nitrofurazone, niridazole, 2-nitroimidazole, and ronidazole each elicited a striking malformation characterized by asymmetrical, right-sided hypoplasia when coincubated with embryos for 26 hr. Minimum concentrations required to elicit this unusual defect ranged from 0.01 mm with nifuroxime and furazolidone to 0.5 mm with ronidazole and were roughly correlated with single electron redox potentials; i.e., agents with relatively high redox potentials were generally more effective than those with low potentials. Nitrofurantoin failed to elicit this unusual malformation but exhibited an extremely steep dose-response curve for embryolethality. Metronidazole and 4-nitroimidazole, nitroheterocyclic agents with relatively low redox potentials, did not produce the asymmetric abnormality nor were they highly embryotoxic, even at concentrations up to 2 mm. 2-Amino-5-nitrothiazole and 4'-methylniridazole also failed to evoke the asymmetric malformation but produced significant embryotoxicity as manifested by decreased growth parameters and elicitation of other kinds of malformations. Heterocyclic compounds not bearing a nitro group (furosemide, 2-aminothiazole, and 2-aminoimidazole) failed to elicit axial asymmetry at concentrations up to 1.0 mm but produced other signs of embryotoxicity at the highest concentrations tested. The results suggest that the presence of a reducible nitro group is critical for generation of the unusual malformation and that the single-electron redox potential of the nitro group plays a dominant but not exclusive role in the capacity of these chemicals to evoke axial asymmetry in cultured rat embryos. [Description provided by NIOSH]
• Subjects:
  Animals Biochemistry Occupational Health Safety Teratogenesis
• Keywords:
  Animal Studies Antimicrobials Embryopathology Embryotoxicity In Utero Exposure Pharmacology Teratogens
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  307-315
• Volume:
  82
• Issue:
  2
• NIOSHTIC Number:
  nn:20060326
• Citation:
  Toxicol Appl Pharmacol 1986 Feb; 82(2):307-315
• Contact Point Address:
  Mont R. Juchau, Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195
• Federal Fiscal Year:
  1986
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bdb3cdf6a419059680c03254f6a0cccaaf4c8bbae38c9ff9ae285236100599cda071b4ac4b399e269c292976bb7aa915c754aab865d190f5c53806e90a1ff5d3
• Download URL:
  https://stacks.cdc.gov/view/cdc/224268/cdc_224268_DS1.pdf
• File Type:
  [PDF - 482.42 KB ]