Kassotis Christopher D, LeFauve Matthew K, Chiang Yu-Ting Tiffany, Knuth Megan M, Schkoda Stacy, Kullman Seth W
Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC 27514, USA.
Toxics. 2022 Feb 20;10(2):99. doi: 10.3390/toxics10020099.
Alkylphenol polyethoxylates (APEOs), such as nonylphenol ethoxylates (NPEOs), are high-production-volume surfactants used in laundry detergents, hard-surface cleaners, pesticide formulations, textile production, oils, paints, and other products. NPEOs comprise -80% of the total production of APEOs and are widely reported across diverse environmental matrices. Despite a growing push for replacement products, APEOs continue to be released into the environment through wastewater at significant levels. Research into related nonionic surfactants from varying sources has reported metabolic health impacts, and we have previously demonstrated that diverse APEOs and alcohol polyethoxylates promote adipogenesis in the murine 3T3-L1 pre-adipocyte model. These effects appeared to be independent of the base alkylphenol and related to the ethoxylate chain length, though limited research has evaluated NPEO exposures in animal models. The goals of this study were to assess the potential of NPEOs to promote adiposity (Nile red fluorescence quantification) and alter growth and/or development (toxicity, length, weight, and energy expenditure) of developmentally exposed zebrafish (). We also sought to expand our understanding of the ability to promote adiposity through evaluation in human mesenchymal stem cells. Herein, we demonstrated consistent adipogenic effects in two separate human bone-marrow-derived mesenchymal stem cell models, and that nonylphenol and its ethoxylates promoted weight gain and increased adipose deposition in developmentally exposed zebrafish. Notably, across both cell and zebrafish models we report increasing adipogenic/obesogenic activity with increasing ethoxylate chain lengths up to maximums around NPEO-6 and then decreasing activity with the longest ethoxylate chain lengths. This research suggests metabolic health concerns for these common obesogens, suggesting further need to assess molecular mechanisms and better characterize environmental concentrations for human health risk assessments.
烷基酚聚乙氧基化物（APEOs），如壬基酚乙氧基化物（NPEOs），是产量高的表面活性剂，用于洗衣粉、硬表面清洁剂、农药制剂、纺织品生产、油类、油漆及其他产品。NPEOs占APEOs总产量的约80%，在各种环境基质中均有广泛报道。尽管对替代产品的需求日益增加，但APEOs仍通过废水大量排放到环境中。对来自不同来源的相关非离子表面活性剂的研究报告了其对代谢健康的影响，我们之前也证明了多种APEOs和醇聚乙氧基化物在小鼠3T3-L1前脂肪细胞模型中促进脂肪生成。这些作用似乎与基础烷基酚无关，而与乙氧基链长度有关，不过在动物模型中评估NPEO暴露的研究有限。本研究的目的是评估NPEOs促进肥胖（尼罗红荧光定量）以及改变发育中暴露的斑马鱼的生长和/或发育（毒性、体长、体重和能量消耗）的潜力。我们还试图通过在人间充质干细胞中的评估来扩展对促进肥胖能力的理解。在此，我们在两种不同的人骨髓来源间充质干细胞模型中证明了一致的脂肪生成作用，并且壬基酚及其乙氧基化物在发育中暴露的斑马鱼中促进体重增加并增加脂肪沉积。值得注意的是，在细胞和斑马鱼模型中，我们都报告了随着乙氧基链长度增加，脂肪生成/致肥胖活性增加，直至在NPEO-6左右达到最大值，然后随着乙氧基链长度最长而活性降低。这项研究表明这些常见致肥胖物存在代谢健康问题，这表明进一步需要评估分子机制并更好地表征环境浓度以进行人类健康风险评估。
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