Nanoplastics (NPLs) became ubiquitous in the environment, from the air we breathe to the food we eat. One of the main concerns about the NPLs risks is their role as carrier of other environmental contaminants, potentially increasing their uptake, bioaccumulation and toxicity to the organisms. Therefore, the main aim of this study was to understand how the presence of polystyrene NPLs (∅ 44 nm) will influence the toxicity (synergism, additivity or antagonism) of the antihistamine diphenhydramine (DPH), towards zebrafish (Danio rerio) embryos, when in dual mixtures. After 96 hours (h) exposure, at the organismal level, NPLs (0.015 or 1.5 mg/L) + DPH (10 mg/L) induced embryo mortality (90%) and malformations (100%) and decreased hatching (80%) and heartbeat rates (60%). After 120 h exposure, NPLs (0.015 or 1.5 mg/L) + DPH (0.01 mg/L) decreased larvae swimming distance (30–40%). At the biochemical level, increased glutathione S-transferases (55–122%) and cholinesterase (182–343%) activities were found after 96 h exposure to NPLs (0.015 or 1.5 mg/L) + DPH (0.01 mg/L). However, catalase (CAT) activity remained similar to the control group in the mixtures, inhibiting the effects detected after the exposure to 1.5 mg/L NPLs alone (increased 230% of CAT activity). In general, the effects of dual combination – NPLs + DPH (even at concentrations as low as 10 μg/L of DPH) – were more harmful than the correspondent individual exposures, showing the synergistic interactions of the dual mixture and answering to the main question of this work. The obtained results, namely the altered toxicity patterns of NPLs + DPH compared with the individual exposures, show the importance of an environmental risk assessment considering NPLs as a co-contaminant due to the potential NPLs role as vector for other contaminants.

纳米塑料 (NPL) 在环境中无处不在，从我们呼吸的空气到我们吃的食物。NPLs 风险的主要担忧之一是它们作为其他环境污染物的载体，可能会增加它们的吸收、生物累积和对生物体的毒性。因此，本研究的主要目的是了解聚苯乙烯 NPLs (∅ 44 nm) 的存在将如何影响抗组胺药苯海拉明 (DPH) 对斑马鱼 (Danio rerio) 的毒性（协同作用、加和作用或拮抗作用）) 胚胎，当处于双重混合物中时。暴露 96 小时 (h) 后，在有机体水平上，NPLs（0.015 或 1.5 mg/L）+ DPH（10 mg/L）诱导胚胎死亡率 (90%) 和畸形 (100%) 以及孵化减少 (80%)和心跳率 (60%)。暴露 120 小时后，NPL（0.015 或 1.5 mg/L）+ DPH（0.01 mg/L）减少了幼虫的游泳距离（30-40%）。在生化水平上，在暴露于 NPL（0.015 或 1.5 mg/L）+ DPH（0.01 mg/L）96 小时后，发现谷胱甘肽 S-转移酶 (55–122%) 和胆碱酯酶 (182–343%) 活性增加。然而，过氧化氢酶 (CAT) 活性与混合物中的对照组相似，抑制了单独暴露于 1.5 mg/L NPL 后检测到的效果（CAT 活性增加 230%）。一般来说，双重组合的影响——NPLs + DPH（即使浓度低至 10 μg/L DPH）——比相应的单独暴露更有害，显示了双重混合物的协同相互作用并回答了这项工作的主要问题. 获得的结果，即与单独暴露相比，NPLs + DPH 的毒性模式发生了变化，显示了将 NPLs 视为共同污染物的环境风险评估的重要性，因为 NPLs 可能作为其他污染物的载体。