Laboratory-Simulated UV-Triggered Transformation of Ambroxol in Aquatic Environments: Photoproduct Characterization and Ecological Risk to Model Aquatic Species

Ambroxol (AMB), a common expectorant, enters aquatic environments via wastewater, yet its ecological risks remain unclear. Under UV exposure (15 mJ·cm^-2, λ = 185-400 nm), AMB undergoes photolysis, among the photoproducts, 4-((2-amino-3-bromobenzyl)amino) cyclohexanol (P1) and 2-amino-3,5-dibromobenzaldehyde (DBA) are major species, comprising over 50% of the total photoproduct peak area at the photolytic plateau. Acute toxicity tests with AMB, P1, and DBA in four aquatic species at different trophic levels revealed: the highest sensitivity in Danio rerio (LC₅₀ = 0.56-51 ng/L), intermediate sensitivity in D. rerio embryos (LC₅₀ = 4.8-240 ng/L), and relative tolerance in Artemia salina (LC₅₀ = 8.4-265.7 ng/L) and Chlorella (LC₅₀ = 138.4-450.6 μg/L), illustrating clear trophic-level differences. UV-irradiation significantly potentiated the AMB toxicity in zebrafish by promoting reactive oxygen species (ROS) generation and inducing oxidative stress, leading to multiple developmental malformations. Integrated biomarker response and metabolomic analyses confirmed that UV-irradiation aggravated AMB-induced oxidative damage and disrupted key metabolic pathways, including purine metabolism, CoA-biosynthesis, and cytochrome-P450 metabolism. Western blot analysis revealed that UV-irradiated AMB activated apoptotic pathways via oxidative stress. These results underscore the necessity of including photochemically induced aquatic toxicity risk assessments for AMB and similar bromine-containing pharmaceuticals.