Bérubé Roxanne, LeFauve Matthew K, Khalaf Aicha, Aminioroomi Darya, Kassotis Christopher D
Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202.
bioRxiv. 2024 Nov 5:2024.10.28.620642. doi: 10.1101/2024.10.28.620642.
Organic and inorganic chemicals co-occur in household dust, and these chemicals have been determined to have endocrine and metabolic disrupting effects. While there is increasing study of chemical mixtures, the effects of complex mixtures mimicking household dust and other environmental matrices have not been well studied and their potential metabolism disrupting effects are thus poorly understood. Previous research has demonstrated high potency adipogenic effects of residential household dust extracts using adipogenesis assays. More recent research simplified this to a mixture relevant to household dust and comprised of common co-occurring organic and inorganic contaminants, finding that these complex combinations often exhibited additive or even synergistic effects in cell models. This study aimed to translate our previous in vitro observation to an in vivo model, the developing zebrafish, to evaluate the metabolic effects of early exposure to organic and inorganic chemicals, individually and in mixtures. Zebrafish embryos were exposed from 1 day post fertilization (dpf) to 6 dpf, then metabolic energy expenditure, swimming behavior and gene expression were measured. Globally, we observed that most mixtures did not reflect the effects of individual chemicals; the BFR mixture produced a less potent effect when compared to the individual chemicals, while the PFAS and the inorganic mixtures seemed to have a more potent effect than the individual chemicals. Finally, the environmental mixture, mimicking household dust proportions, was less potent than the inorganic chemical mix alone. Additional work is necessary to better understand the mixture effect of inorganic and organic chemicals combined.
有机和无机化学物质共存于家庭灰尘中，并且已确定这些化学物质具有内分泌和代谢干扰作用。虽然对化学混合物的研究日益增多，但模拟家庭灰尘和其他环境基质的复杂混合物的影响尚未得到充分研究，因此对其潜在的代谢干扰作用了解甚少。先前的研究使用脂肪生成测定法证明了住宅家庭灰尘提取物具有高效的脂肪生成作用。最近的研究将其简化为一种与家庭灰尘相关的混合物，该混合物由常见的共存有机和无机污染物组成，发现这些复杂的组合在细胞模型中通常表现出相加甚至协同作用。本研究旨在将我们先前的体外观察结果转化为体内模型，即发育中的斑马鱼，以评估早期暴露于有机和无机化学物质单独及混合状态下的代谢影响。斑马鱼胚胎在受精后1天（dpf）至6 dpf期间接受暴露，然后测量其代谢能量消耗、游泳行为和基因表达。总体而言，我们观察到大多数混合物并未反映出单个化学物质的影响；与单个化学物质相比，溴化阻燃剂混合物产生的影响较小，而全氟辛烷磺酸混合物和无机混合物似乎比单个化学物质产生的影响更大。最后，模拟家庭灰尘比例的环境混合物的影响比单独的无机化学混合物要小。有必要开展更多工作以更好地了解无机和有机化学物质结合后的混合物效应。
