Developmental toxicities of aflatoxins B₁ and G₁ : in vivo and in vitro assessments /

Bibliographic Details
Main Author: Maull, Elizabeth Anne
Other Authors: Heidelbaugh, Norman D. (degree committee member.), Rizzo, Peter J. (degree committee member.), Safe, Stephen H. (degree committee member.)
Format: Thesis Book
Language:English
Published: 1988.
Subjects:
Online Access:ProQuest, Abstract
Link to OAKTrust copy
Description
Abstract:Aflatoxins, secondary metabolites produced by Aspergillus flavus and parasiticus, are acutely toxic, mutagenic and carcinogenic agents. Aflatoxin B1 (AFB1) had been reported to be teratogenic in several laboratory species. Recently, basic concepts of teratology have been re-evaluated, making it necessary to re-examine the developmental hazard of previously tested chemicals. We examined the teratogenicity of AFB1 and aflatoxin G1 (AFG1), given orally throughout organogenesis (days 7-15) in the rat (Sprague-Dawley) while monitoring maternal toxicity; companion feed restriction studies provided insights into the influence of undernutrition on fetal development. Neither AFB1 and/or AFG1 produced dysmorphogenesis, although embryo-lethality and embryo-toxicity were observed in treatment groups. Feed restriction studies indicated that the term fetal body weights were somewhat influenced by the feed consumption of the dams. Two in vitro assays were examined to increase our knowledge of the influence of toxins on development and to construct a battery of assays to prioritize chemicals for further studies. Whole embryo culture (WEC) provided additional insight into the effects of AFB1 and AFG1 and their metabolites on the conceptus. AFB1 and AFG1 caused a reduction in yolk sac expansion and crown rump length, while AFB1 also reduced protein and DNA content. Viability remained high, while the malformation rate ranged from 18% (control) to a high of 48% (AFB1). The addition of a drug metabolizing enzyme system provided some protection from the toxin induced aberrations. WEC is insufficient for estimating the ratio between adult toxicity and embryo toxicity. To determine this ratio, a fresh water Coelenterate, Hydra attenuata, has been suggested. Dissociated cells centrifuged into pellets undergo progressive development similar to mammalian systems to form adult hydra. Toxins added to the medium of the adult and artificial embryos were capable of retarding development in the embryos or causing toxic reactions in both the adult and embryonic preparations. Aflatoxins B1 and G1 tested in the hydra assay produced results consistent with the in vivo study, ie. aflatoxins perturbed development only at concentrations producing maternal toxicity . The toxins also caused a retardation of development, similar to that which had been described for in vivo and in vitro responses.
Item Description:Typescript (photocopy).
Vita.
"Major subject: Food Science and Technology."
Physical Description:xii, 233 leaves : illustrations ; 29 cm
Bibliography:Includes bibliographical references (leaves 200-232).