Residual behaviors and metabolic pathway of ethylparaben in Drosophila melanogaster.

ABSTRACT

OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.