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Su, Y., Li, F., Xiao, X., Li, H., Wang, D., & You, J. (2023). Ecological risk of galaxolide and its transformation product galaxolidone: evidence from the literature and a case study in Guangzhou waterways. Environmental Science: Processes & Impacts, 25(8), 1337-1346.

Abstract. Galaxolidone (HHCB-lac) is a major transformation product of the commonly used synthetic musk galaxolide (HHCB) and is ubiquitous in the environment along with the parent compound. Although many studies have shown the harmful effects of HHCB, little attention has been paid to the potential ecological risk of HHCB-lac. Herein, we reviewed the concentrations and ratios of HHCB and HHCB-lac (HHCB-lac : HHCB) in different media reported in the literature, derived the predicted no-effect concentrations (PNECs) for the two compounds using ECOSAR predictions and species sensitivity distribution (SSD) estimates, and assessed their ecological risks in the aquatic environment. The literature data indicated that HHCB-lac and HHCB were generally present in the environment at ratios of 0.01–10. Using the derived PNECs (2.14 and 18.4 μg L−1 for HHCB and HHCB-lac, respectively), HHCB in the aquatic environment was assessed to have medium to high risks, while HHCB-lac was assessed to have low risks. Furthermore, we carried out a case study on the occurrence and ecological risks of HHCB and HHCB-lac in Guangzhou waterways. The concentrations of the two compounds in Guangzhou waterways ranged from 20 to 2620 ng L−1 and 3 to 740 ng L−1, respectively, and the ratios were in the range of 0.15 to 0.64. The field study data also showed medium to high risks of HHCB and low risks of HHCB-lac. Additionally, the endocrine effects of HHCB and HHCB-lac were confirmed by Endocrine Disruptome, which calls for greater scrutiny of the potential effects of HHCB and HHCB-lac on human health.

Simmons, D. B., Marlatt, V. L., Trudeau, V. L., Sherry, J. P., & Metcalfe, C. D. (2010). Interaction of Galaxolide® with the human and trout estrogen receptor-α. Science of the Total Environment, 408(24), 6158-6164.

Abstract. Synthetic musks have been detected in sewage effluents, surface waters, and fish tissues where the polycyclic musk compound, HHCB (Galaxolide®) is the dominant compound in those matrices. In the present study, the Galaxolide® formulation was tested in the yeast estrogenicity screening (YES) assay, and also tested in in vitro and in vivo teleost systems to determine whether it interacts with the estrogen receptor as either an agonist or antagonist. In those tests, Galaxolide® did not act as an estrogen agonist, however there was strong evidence of antagonistic activity as Galaxolide® inhibited the estrogenic activity of 17β-estradiol (E2). In the YES assay based on a recombinant strain of yeast containing the human estrogen receptor (i.e. hERα), Galaxolide® inhibited the effects of E2 in a dose-dependent manner (IC50 = 1.63 × 10−5 M). In a luciferase reporter gene assay based on the rainbow trout estrogen receptor (i.e. rtER) transfected into a rainbow trout gonadal (RTG-2) cell line, the IC50 for the antagonistic effect of Galaxolide® was 2.79 × 10−9 M. In an in vivo assay based on modulation of vitellogenin in rainbow trout, Galaxolide® i.p. injected into trout at a dose of 3.64 mg/kg caused inhibition of E2-induced vitellogenin production. That dose is within the range of concentrations of Galaxolide® that have been detected in tissues of fish from contaminated locations.

Parolini, M., Magni, S., Traversi, I., Villa, S., Finizio, A., & Binelli, A. (2015). Environmentally relevant concentrations of galaxolide (HHCB) and tonalide (AHTN) induced oxidative and genetic damage in Dreissena polymorpha. Journal of Hazardous Materials, 285, 1-10.

Abstract. Synthetic musk compounds (SMCs) are extensively used as fragrances in several personal care products and have been recognized as emerging aquatic pollutants. Among SMCs, galaxolide (HHCB) and tonalide (AHTN) are extensively used and have been measured in aquatic ecosystems worldwide. However, their potential risk to organisms remains largely unknown. The aim of this study was to investigate whether 21-day exposures to HHCB and AHTN concentrations frequently measured in aquatic ecosystems can induce oxidative and genetic damage in Dreissena polymorpha. The lipid peroxidation (LPO) and protein carbonyl content (PCC) were measured as oxidative stress indexes, while the DNA precipitation assay and the micronucleus test (MN test) were applied to investigate genetic injuries. HHCB induced significant increases in LPO and PCC levels, while AHTN enhanced only protein carbonylation. Moreover, significant increases in DNA strand breaks were caused by exposure to the highest concentrations of HHCB and AHTN tested in the present study, but no fixed genetic damage was observed.

Li Y, Liu J, Feng X, Xue Z, Liu R, Gao M, Guo J. Reveal resistance mechanisms of Mirabilis jalapa L. when exposed to galaxolide and polystyrene microplastics stress, from individual, cellular and molecular level. Plant Physiol Biochem. 2025 Jun;223:109803. doi: 10.1016/j.plaphy.2025.109803. Epub 2025 Mar 18. PMID: 40199163.

Obaid WA, Madany MMY, Waznah MS, Sonbol H, Aloufi AS, Korany SM, Reyad AM, Ahmed ES, Selim S, AbdElgawad H. Modulation of plant carbon and nitrogen metabolism by novel actinobacteria Rhodospirillum sp. to combat galaxolide toxicity in barley and maize plants. Plant Physiol Biochem. 2025 Mar;220:109403. doi: 10.1016/j.plaphy.2024.109403. Epub 2024 Dec 12. PMID: 39884151.