Developmental toxicity evaluation of diacetoxyscirpenol /

Bibliographic Details
Main Author: Smith, Ernest Edison
Other Authors: Kubena, Leon F. (degree committee member.), Russell, Leon H. (degree committee member.), Safe, Stephen H. (degree committee member.)
Format: Thesis Book
Language:English
Published: 1989.
Subjects:
Online Access:Link to OAKTrust copy
Description
Abstract:Mycotoxins comprise a structurally diverse family of naturally occurring, fungal-elaborated poisons, many of which have been strongly implicated as chemical precursors of toxicity in man and animals. The trichothecene family of mycotoxins frequently occur as toxic contaminants of food and feed and have been linked to the etiology of mycotoxicoses (or mycotoxin-induced diseases) in man and animals. One of the trichothecenes, diacetoxyscirpenol (DAS), or 3-hydroxy-4,15-diacetoxy-12,13-epoxy-trichothec-9-ene, is produced by numerous species of fusarium molds and is reportedly toxic. However, its potential to elicit developmental toxicity has not been previously investigated. There is a critical need for rapid bioassays that can be used to accurately predict the development hazards of potent toxins such as DAS. This project was designed to evaluate the effects of DAS in cultures of Hydra attenuata and postimplantation rat embryos and to compare these findings with the results of an initial teratological study in mice.The in vitro and in vivo results of these studies support the following conclusions: (1) DAS is a coeffective teratogen in vivo resulting in a variety of malformations in the mouse. (2) The developmental hazard of DAS can be reliably predicted using cultures of Hydra attenuata and postimplantation rat embryos to detect, rank and confirm teratogenicity. (3) The hydra assay is unique to all other tests for teratogens in that it allows for the classification of a chemical as either intrinsic to the developing conceptus, co-effective (mother and conceptus), or maternally toxic (mother only). (4) DAS can be adequately categorized as a co-effective teratogen since it induces teratogenicity in the developing conceptus at concentrations that are also maternally toxic. With further evaluation and validation the hydra and postimplantation embryo assays may be useful in a two-tier testing protocol to prescreen a number of chemicals for teratogenicity. The primary purpose of such a system would be to reduce the cost and time required for teratogenic analysis. These systems may also prove to be sensitive biological models with which to elucidate the molecular mechanisms of teratogenicity and to characterize chemical structure-activity relationships.
Item Description:Typescript (photocopy).
Vita.
"Major subject: Food science and technology."
Physical Description:xi, 152 leaves : illustrations ; 29 cm
Bibliography:Includes bibliographical references.