Triadimefon causes branchial arch malformations in Xenopus laevis embryos

• Published in: Environmental science and pollution research international 2006-07, Vol.13 (4), p.251-255
• Main Authors: Papis, Elena, Bernardini, Giovanni, Gornati, Rosalba, Prati, Mariangela
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced; Amphibians; Animals; Antifungal agents; Anura; Branchial Region - abnormalities; Branchial Region - drug effects; Cartilage; Cell migration; Cell walls; Craniofacial Abnormalities - chemically induced; Developmental stages; Domestic animals; Dose-Response Relationship, Drug; Embryos; Ergosterol; Fetal Development - drug effects; Frogs; Fungicides; Fungicides, Industrial - toxicity; Gastrulation; Hyperpigmentation; Lanosterol; Larvae; Lethal Dose 50; Mesenchyme; Models, Animal; Mortality; Neural crest; Pesticides; Population decline; Reptiles & amphibians; Teratogenicity; Teratogens - toxicity; Triadimefon; Triazoles; Triazoles - toxicity; Urban agriculture; Urban areas; Xenopus laevis; Xenopus laevis - abnormalities; Xenopus laevis - embryology
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1065/espr2006.01.014

Triazole-derivatives are potent antifungal agents used as systemic agricultural fungicides and against fungal diseases in humans and domestic animals. They act by inhibiting the cytochrome P-450 conversion of lanosterol to ergosterol, thus resulting in faulty fungal cell wall synthesis. Some data have been published about the teratogenic activity of triazoles on rodent embryos: Hypoplasias, abnormal shape, agenesis of the branchial arches, for example, were reported as typical induced malformations. Unfortunately, no data are available on the embryotoxicity of these compounds in amphibians, despite the increasing concern among the scientific community about the phenomenon of global amphibian population declines. The aim of the present work is to evaluate the embryo-lethal and teratogenic potentials of Triadimefon (FON), a triazole-derivative widely used as an antimycotic in agriculture, by the test FETAX (Frog Embryos Teratogenic Assay, Xenopus) with particular attention being paid to the analysis of branchial arch malformations. Xenopus laevis embryos were exposed continuously from stage 9 to increasing concentrations of FON and analyzed at stage 47 for mortality and teratogenicity (group I) to determine the median lethal (LC50) and teratogenic (TC50) concentrations. Another two pools of larvae were exposed to FON for a 2 hour period at early gastrula (Group II) or neurula (Group III) stages to verify which period of development is the most sensitive to FON. The malformations observed were further investigated by histological section and cartilage staining with Alcian blue. The assay has estimated LC50 and TC50 values of 63.8 microM and 2.73 microM, respectively; the resulting TI (Teratogenic Index = LC50/TC50) value of 23.4 has underlined the very high teratogenic risk associated with this compound. Neurulation was more sensitive to FON exposure than gastrulation, since the TC50 estimated values for group III (neurula exposed) specimens was 7.6 times lower than those of group II (gastrula exposed). Interestingly, for each group analyzed, 100% of malformed embryos showed alterations at branchial arch derived cartilages: Anterior cartilages were reduced, missing, fused or incorrectly positioned while gill cartilages were altered only in the most severely affected specimens. In some cases these malformations were associated with hyperpigmentation. Our results support the hypothesis that FON can interfere with Neural Crest Cell (NCC) migration, since craniof