Perfluoroalkyl substances (PFAS) are a class of synthetic chemicals that are persistent in the environment. Due to adverse health outcomes associated with longer chain PFAS, shorter chain chemicals were used as replacements, but developmental toxicity assessments of the shorter chain chemicals are limited. Toxicity of three perfluoroalkyl acids (PFAAs) [perfluorooctanoic acid (PFOA), composed of 8 carbon (C8), perfluorohexanoic acid (PFHxA, C6), and perfluorobutanoic acid (PFBA, C4)] was compared in developing zebrafish (Danio rerio). LC₅₀s at 120 h post fertilization (hpf) assessed potency of each PFAA by exposing developing zebrafish (1–120 hpf) to range of concentrations. Zebrafish were then exposed to sublethal concentrations (0.4–4000 ppb, µg/L) throughout embryogenesis (1–72 hpf). Effects of the embryonic exposure on locomotor activities was completed with the visual motor response test at 120 hpf. At 72 hpf, morphological changes (total body length, head length, head width) and transcriptome profiles to compare altered molecular and disease pathways were determined. The LC₅₀ ranking followed trend as expected based on chain length. PFOA caused hyperactivity and PFBA hypoactivity, while PFHxA did not change behavior. PFOA, PFHxA, and PFBA caused morphological and transcriptomic alterations that were unique for each chemical and were concentration-dependent indicating different toxicity mechanisms. Cancer was a top disease for PFOA and FXR/RXR activation was a top canonical pathway for PFBA. Furthermore, comparison of altered biological and molecular pathways in zebrafish exposed to PFOA matched findings reported in prior epidemiological studies and other animal models, supporting the predictive value of the transcriptome approach and for predicting adverse health outcomes associated with PFHxA or PFBA exposure.

全氟烷基物质 (PFAS) 是一类在环境中持久存在的合成化学品。由于与长链 PFAS 相关的不良健康后果，短链化学品被用作替代品，但短链化学品的发育毒性评估有限。比较了三种全氟烷基酸 (PFAA) [全氟辛酸 (PFOA)，由 8 个碳 (C8)、全氟己酸 (PFHxA, C6) 和全氟丁酸 (PFBA, C4)] 对发育中的斑马鱼 ( Danio rerio) 的毒性。受精后 120 小时 (hpf) 的 LC ₅₀ s 通过将发育中的斑马鱼 (1-120 hpf) 暴露于一定浓度范围来评估每种 PFAA 的效力。然后，斑马鱼在整个胚胎发生过程中（1-72 hpf）暴露于亚致死浓度（0.4-4000 ppb，μg/L）。胚胎暴露对运动活动的影响通过 120 hpf 时的视觉运动反应测试完成。在 72 hpf 时，确定了形态变化（全身长度、头部长度、头部宽度）和转录组图谱，以比较改变的分子和疾病途径。 LC ₅₀排名遵循基于链长度的预期趋势。 PFOA 会导致多动，而 PFBA 会导致活动减退，而 PFHxA 不会改变行为。 PFOA、PFHxA 和 PFBA 会引起每种化学物质独特的形态和转录组学改变，并且具有浓度依赖性，表明不同的毒性机制。癌症是 PFOA 的首要疾病，FXR/RXR 激活是 PFBA 的首要典型途径。 此外，对暴露于 PFOA 的斑马鱼生物和分子途径改变的比较与之前的流行病学研究和其他动物模型中报告的结果相匹配，支持转录组方法的预测价值以及预测与 PFHxA 或 PFBA 暴露相关的不良健康结果。