**1. Introduction**

Increasing concentrations of chemical pollutants, including heavy metals and organic pollutants from anthropogenic activities, have significantly affected aquatic ecosystems by inhibiting cellular function and growth of aquatic organisms and even killing organisms [1–3]. Numerous ecological risk assessments have been conducted for various individual chemical pollutants [4,5]. However, the need to assess risks for combinations of chemicals has become apparent since organisms are exposed to mixtures of chemical pollutants in natural environments rather than individual compounds, especially in aquatic ecosystems [6–8].

Microalgae are major primary producers in aquatic ecosystems and biospheres. Microalgae can accumulate chemical pollutants in aquatic ecosystems and transfer them to higher trophic levels [9]. In addition, they are also sensitive to certain chemical pollutants, with many pollutants altering microalgal morphology, physiology, and genetics, thereby affecting their functions in aquatic ecosystems [9]. Consequently, microalgae are considered important models for assessing ecotoxicity, with numerous toxicity assessments previously published for microalgae [10–12].

Heavy metals and organic pollutants are two of the major toxic pollutants present. Nickel is a heavy metal used in diverse metallurgical, electronic, chemical, and food in-

**Citation:** Shi, X.; Guo, R.; Lu, D.; Wang, P.; Dai, X. Toxicity Effects of Combined Mixtures of BDE-47 and Nickel on the Microalgae *Phaeodactylum tricornutum* (Bacillariophyceae). *Toxics* **2022**, *10*, 211. https://doi.org/10.3390/ toxics10050211

Academic Editors: François Gagné, Stefano Magni and Valerio Matozzo

Received: 27 March 2022 Accepted: 16 April 2022 Published: 22 April 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

dustries. The prevalence of nickel-based products has led to the inevitable pollution of the environment, with concentrations reaching 74.56 mg/kg in coastal surface sediments [13]. Nickel is also a micronutrient essential for some microalgal enzymes, such as urease in the diatom *Phaeodactylum tricornutum* [14]. Nevertheless, excess nickel can inhibit photosynthesis and decrease protein, carbohydrate, and lipid concentrations in microalgae [10,15]. The toxic effects of nickel on *P. tricornutum* have recently been investigated, revealing that nickel can inhibit *P. tricornutum* photosynthesis and induce reactive oxygen species (ROS) production [16]. Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants and flame retardants that have been used in commercial products since the 1960s [17]. PBDE pollutants are globally distributed in aquatic ecosystems and have been extensively detected in biological samples [2,18–20]. Indeed, PBDEs in coastal waters have been detected at a concentration of 65.5 ng/L in the Bohai Sea of China [21]. However, their concentrations are generally higher in coastal sediments than in open waters, as high as 4212 (ng/g dw) [22]. In most areas, decabromodiphenyl ether (BDE-209) and 2,2',4,4' tetrabromodiphenyl ether (BDE-47) are the predominant types of identified PBDEs [21,22]. The toxicity of BDE-47 toward microalgae has been evaluated in the algae *Skeletonema costatum*, *Thalassiosira pseudonana*, *Phaeodactylum tricornutum*, *Platymonas subcordiformis*, *Alexandrium minutum*, and *Dunaliella salina* [23–25]. These studies have shown that BDE-47 can inhibit photosynthetic efficiency, arrest cell division, and induce H2O2 production in microalgal cells [25–28]. The toxic effects of nickel and BDE-47 have been identified in several microalgae species, although the toxicity mechanisms vary [10,26–29]. In *P. tricornutum*, BDE-47 can damage chloroplasts, reduce the oxygen evolution rate, alter the performance of photosystems, and stimulate ROS production [24]. Nevertheless, studies of the combined toxicity of nickel and BDE-47 in microalgae remain limited.

*P. tricornutum* is a cosmopolitan marine diatom species widely used to study ecotoxicity [30], and its complete genome sequence has been published [31]. Moreover, the toxicity mechanisms of nickel on *P. tricornutum* have been recently reported [16]. Furthermore, the toxic effects of BDE-47 have also been recently evaluated for *P. tricornutum* based on photosynthesis-related parameters [24]. This study investigated the combined toxicity effects of BDE-47 and nickel on P. tricornutum via physiological and transcriptomic responses. At the same time, the interaction patterns of BDE-47 and nickel in *P. tricornutum* were also measured. This study provides additional understanding of the toxic effects of BDE-47 and nickel mixtures on *P. tricornutum.*
