# Developmental toxicity of fluconazole and 1,2,4-triazole in Xenopus laevis

## TL;DR

This study shows that fluconazole and its core structure, 1,2,4-triazole, can harm amphibian embryos by disrupting key developmental pathways and causing physical abnormalities.

## Contribution

The study reveals that the structural core of fluconazole alone can disrupt vertebrate developmental signaling, even at low concentrations.

## Key findings

- Both fluconazole and 1,2,4-triazole altered Wnt- and BMP-associated gene expression in amphibian embryos.
- Higher concentrations caused developmental abnormalities like reduced head size and digestive tract malformations.
- The findings suggest that azole compounds may pose risks to vertebrates through disruption of essential developmental pathways.

## Abstract

Fluconazole (FLU) is a widely used antifungal agent frequently detected in surface waters because of its extensive use in medicine, agriculture, and personal care products.

Despite concerns about its persistence and developmental toxicity in aquatic species, its effects on amphibians remain poorly understood. This study aimed to assess the developmental and molecular effects of FLU and its structural core, 1,2,4-triazole (TRI), in amphibian embryos. Xenopus laevis embryos were exposed to FLU or TRI and evaluated for mortality, hatching rate, heart rate, body length, malformation incidence, and changes in gene expression. Even at low micromolar concentrations, both azoles altered the expression of Wnt- and BMP-associated genes, indicating disruption of these signaling pathways. At higher micromolar concentrations, these molecular changes were accompanied by early signs of developmental abnormalities, which intensified at the highest doses. Observed phenotypes included reduced head size, altered skin pigmentation, prolonged body length, changes in heart rate, and mild digestive tract malformations. These findings demonstrate that even the core structural motif TRI can disrupt key developmental signaling pathways in vertebrate embryos, underscoring the need for closer monitoring of azole compounds in aquatic environments. Given the fundamental role of these pathways in vertebrate development, the results raise concerns about potential risks from long-term or prenatal exposure to azoles, in both environmental and clinical contexts.

The online version contains supplementary material available at 10.1038/s41598-025-30992-5.