Comparative Toxicity and Molecular Recognition of Galaxolide and Its Phototransformation Product Galaxolide Lactone in Daphnia magna

Abstract

Galaxolide (HHCB) is a synthetic musk that has been widely detected in the environment. While the adverse effects of HHCB have raised significant concern, the potential ecological impacts of its transformation product, galaxolide lactone (HHCB-lac), remain largely overlooked. In this paper, we conducted a comparative study on the toxicity of HHCB and HHCB-lac using Daphnia magna as a model organism. Photodegradation experiments showed that while HHCB concentrations decreased rapidly due to phototransformation into HHCB-lac, the acute toxicity of the system did not decline correspondingly. The 48-h LC50 values for HHCB and HHCB-lac were 150.8–350.2 μg L-1 and 138.4–464.9 μg L-1, respectively, indiacting comparable acute toxcity between the two compounds. In chronic exposure tests, both HHCB and HHCB-lac (6–60 μg L-1 ) increased molting frequency, advanced the day of first brood, elevated total offspring production, and reduced body length in D. magna. Notably, the chronic effects of HHCB-lac were greater than those of HHCB. This finding was further supported by molecular docking simulations, which revealed a higher binding tendency of HHCB-lac than HHCB to the nuclear receptors Ecdysone Receptor (EcR) and Estrogen-related Receptor (ERR). The C=O group in HHCB-lac provided a key site for forming hydrogen bonds with amino acid residues of the nuclear receptors. Our work demonstrates that photodegradation products of HHCB can exhibit ecological toxicity comparable to or even greater than the parent compound, highlighting the necessity of incorporating transformation products into environmental risk assessments of synthetic musks.