Premium
Evaluation of the developmental toxicity of five compounds with the frog embryo teratogenesis assay: Xenopus (FETAX) and a metabolic activation system
Author(s) -
Fort Douglas J.,
James Brenda L.,
Bantle John A.
Publication year - 1989
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550090603
Subject(s) - developmental toxicity , teratology , xenopus , toxicity , embryo , biology , toxicology , metabolism , microsome , metabolic pathway , pharmacology , biochemistry , chemistry , andrology , enzyme , genetics , fetus , medicine , pregnancy , organic chemistry , gene
The potential teratogenic hazard of five compounds was evaluated using the Frog Embryo Teratogenesis Assay— Xenopus (FETAX) and a metabolic activation system. Embryos of the South African clawed frog, Xenopus laevis , were exposed to (i) three compounds suspected to be proteratogenic in mammalian test systems—[2‐acetylaminofluorene (2‐AAF), rifampicin (RA) and benzo[ a ]pyrene (BP)] for 96 h; (ii) one compound unaffected by mixed‐functional oxidase (MFO) metabolism—ZnSO 4 ; (iii) one compound thought to be inactivated by cytochrome P‐450—cytochalasin D (CD). Two separate static renewal tests were conducted with and without the presence of an exogenous metabolic activation system (MAS). The metabolic activation system consisted of Aroclor 1254‐induced rat liver microsomes. The teratogenic potential of each compound and the effects of metabolic activation were based on teratogenic indices [ TI =96 h LC 50 /96 h EC 50 (malformation)], types and severity of malformation, and effects on embryo growth. Metabolic activation increased the potential teratogenic hazard of 2‐AAF, RA and BP by TI factors of 1.3, 2.8 and 6.8, respectively. The teratogenic potential of ZnSO 4 was virtually unaffected by the MAS. The MAS significantly reduced the teratogenic potential of CD by a TI factor of 2.7. These results demonstrate the utility and importance of a MAS for in vitro developmental toxicity screens such as FETAX. Consistent use of a MAS with FETAX should reduce the number of potential false‐positive and false‐negative test results.