title: Investigation of the teratogenic potential of ochratoxin A and B using the FETAX system.
abstract: BACKGROUND
  Ochratoxin A (OTA) is a mycotoxin produced by certain Aspergillus and Penicillium species. It has been observed to be teratogenic in a number of animal models including rat, mouse, hamster, and chick, with reduced birth weight and craniofacial abnormalities being the most commonly observed malformations. Neither the potential of OTA to cause malformations in humans nor its teratogenic mode of action is known. The FETAX system is an embryotoxicity assay system, with a high correlation to animal models and epidemiological data. Analysis of OTA-mediated teratogenesis using this system could provide a useful tool for the generation of high numbers of samples for mechanistic studies.
  
  
  METHODS
  Using the standard ASTM 96-hr exposure protocol, the effect of OTA and its structural analogue OTB on the development of Xenopus laevis embryos in vitro was assessed. The accumulation of both substances in Xenopus embryos was also examined using tritiated OTA and OTB.
  
  
  RESULTS
  Both OTA and OTB caused craniofacial malformations, while OTA also caused reduced embryo growth. As expected, OTA was far more potent in inducing these effects than OTB. This could at least in part be due to greater levels of OTA being accumulated within the embryos.
  
  
  CONCLUSIONS
  The ability of FETAX to differentiate between close structural analogues indicates the assay has great potential for the elucidation of the embryotoxic and teratogenic mechanisms of action. Hence, the model could provide a suitable system for the investigation of other known teratogens or for the pre-screening of new agents for teratogenic potential.
authors.affiliation: Environmental Toxicology, University of Konstanz, Konstanz, Germany. Evelyn.OBrien@Uni-Konstanz.de
authors.forename: E
authors.initials: E
authors.lastname: O'Brien
authors.forename: A
authors.initials: A
authors.lastname: Prietz
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Dietrich
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000209:etiology*; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects*; D005260:Female; D008297:Male; D009183:Mycotoxins / Q000633:toxicity; D009793:Ochratoxins / Q000378:metabolism / Q000633:toxicity*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D002273:Carcinogens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A; C045354:ochratoxin B