Hypochlorination of Loratadine: Chemical identification and ecotoxicological effects of derivative byproducts

Loratadine (LORA) is a second-generation antihistamine widely used since its approval by the FDA in 1993. The significant excretion of LORA (approximately 40 % in urine and 42 % in feces) contributes to its frequent occurrence in wastewaters and subsequently in aquatic environments, where it is typically detected at ng/L levels. This study investigates the possible formation of LORA degradation byproducts (DBP) under neutral hypochlorination, a common water disinfection process. Eight DBPs were generated, and they were isolated via HPLC and fully characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Among them, 5 compounds have been reported here for the first time. Formation pathways were proposed for all identified DBPs. The acute and chronic toxicity of LORA and its DBPs was evaluated using ecotoxicological assays with freshwater species representing different trophic levels: the microalga Raphidocelis subcapitata (primary producer) and the rotifer Brachionus calyciflorus (primary consumer). Acute effects of the DBPs occurred at concentrations of hundreds of μg/L. Regarding chronic toxicity, algae showed low sensitivity to both LORA and its derivatives, while rotifers were more susceptible to the DBPs, with effective concentrations ranging from a few ng/L to hundreds of ng/L range. Conversely, LORA induced only a 38 % effect at 2000 ng/L, indicating higher chronic toxicity of DBPs compared to the parent compound. These results underscore the environmental relevance of LORA DBPs, which may pose a higher chronic risk to aquatic organisms than the parent compound, especially under typical water treatment conditions.