Abstract
Although previous studies have confirmed the association between phthalate esters (PAEs) exposure and endocrine disorders in humans, few studies to date have systematically assessed the threats of new PAE alternatives to endocrine disruptions. Herein, zebrafish embryos were continuously exposed to two PAEs [di-n-butyl phthalate (DBP) and diisobutyl phthalate (DiBP)], two structurally related alternatives [diiononyl phthalate (DINP) and diisononyl hexahydrophthalate (DINCH)], and two non-PAE substitutes [dipropylene glycol dibenzoate (DGD) and glyceryl triacetate (GTA)], and the endocrine-disrupting effects were investigated during the early stages (8-48 hpf). For five endogenous hormones, including progesterone, testosterone, 17β-estradiol, triiodothyronine (T3), and cortisol, the tested chemicals disturbed the contents of at least one hormone at environmentally relevant concentrations (≤3.9 μM), except DINCH and GTA. Then, the concentration-dependent reduced zebrafish transcriptome analysis was performed. Thyroid hormone (TH)- and androgen/estrogen-regulated adverse outcome pathways (AOPs) were the two types of biological pathways most sensitive to PAE exposure. Notably, six compounds disrupted four TH-mediated AOPs, from the inhibition of deiodinases (molecular initiating event, MIE), a decrease in T3 levels (key event, KE), to mortality (adverse outcome, AO) with the quantitatively linear relationships between MIE-KE (|r| = 0.96, p = 0.002), KE-AO (|r| = 0.88, p = 0.02), and MIE-AO (|r| = 0.89, p = 0.02). Multiple structural analyses showed that benzoic acid is the critical toxicogenic fragment. Our data will facilitate the screening and development of green alternatives.
Original language | English |
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Pages (from-to) | 13744-13756 |
Number of pages | 13 |
Journal | Environmental Science & Technology |
Volume | 57 |
Issue number | 37 |
Early online date | 7 Sept 2023 |
DOIs | |
Publication status | Published - 19 Sept 2023 |
Bibliographical note
Funding Information:This work was supported by the National Key R&D Program of China (2022YFC3704500, 2022YFC3902104, and 2022YFC3202101), the National Natural Science Foundation of China (22276094 and 42207329), the Natural Science Foundation of Jiangsu Province for Young Scholars (BK20210190), the Jiangsu Province Key Research and Development Program (BE2022837), the Environmental Protection Research Project of Jiangsu Province (2021003), and the Fundamental Research Funds for the Central Universities (021114380204, 021114380213, and 14380196). The computational calculations were performed in the High Performance Computing Center (HPCC) of Nanjing University.
Publisher Copyright:
© 2023 American Chemical Society.
Keywords
- endocrine-disrupting activity
- phthalate ester and substitutes
- quantitative adverse outcome pathway
- reduced zebrafish transcriptome
- structural alert
- zebrafish
ASJC Scopus subject areas
- General Chemistry
- Environmental Chemistry