Pharmaceuticals have garnered considerable attention due to their extensive presence in the environment. However, studies regarding their impact on the marine ecosystem remain limited, and toxicity data for many pharmaceuticals toward marine species are still severely lacking. This study systematically investigated the toxicity and ecological risks of ten pharmaceuticals on nine marine species spanning three trophic levels, including four species of marine microalgae, four invertebrates, and one fish species. The effect/lethal concentrations 50% (EC50/LC50) revealed that microalgae exhibited the highest sensitivity, whereas vertebrate marine medaka (Oryzias melastigma) embryos showed the greatest tolerance. Species sensitivity distribution (SSD) models were constructed based on acute toxicity endpoints, and predicted no-effect concentrations (PNECs) for the target pharmaceuticals were derived, ranging from 0.003 to 59 mg/L. Amitriptyline (AMT) demonstrated the lowest PNEC, indicating the highest potential ecotoxicity among the ten pharmaceuticals. The microalga Isochrysis galbana, which showed the highest sensitivity to AMT, was selected for exposure experiments at environmentally relevant concentration gradients to investigate the underlying mechanisms of toxicity. The result demonstrated that AMT inhibits ribosomal biogenesis and translation-related signaling pathways, while also triggering oxidative stress, leading to cellular damage and ultimately suppressing microalgal growth. This study provides critical benchmarks for environmental risk assessment of pharmaceuticals in marine environments.Pharmaceuticals have garnered considerable attention due to their extensive presence in the environment. However, studies regarding their impact on the marine ecosystem remain limited, and toxicity data for many pharmaceuticals toward marine species are still severely lacking. This study systematically investigated the toxicity and ecological risks of ten pharmaceuticals on nine marine species spanning three trophic levels, including four species of marine microalgae, four invertebrates, and one fish species. The effect/lethal concentrations 50% (EC50/LC50) revealed that microalgae exhibited the highest sensitivity, whereas vertebrate marine medaka (Oryzias melastigma) embryos showed the greatest tolerance. Species sensitivity distribution (SSD) models were constructed based on acute toxicity endpoints, and predicted no-effect concentrations (PNECs) for the target pharmaceuticals were derived, ranging from 0.003 to 59 mg/L. Amitriptyline (AMT) demonstrated the lowest PNEC, indicating the highest potential ecotoxicity among the ten pharmaceuticals. The microalga Isochrysis galbana, which showed the highest sensitivity to AMT, was selected for exposure experiments at environmentally relevant concentration gradients to investigate the underlying mechanisms of toxicity. The result demonstrated that AMT inhibits ribosomal biogenesis and translation-related signaling pathways, while also triggering oxidative stress, leading to cellular damage and ultimately suppressing microalgal growth. This study provides critical benchmarks for environmental risk assessment of pharmaceuticals in marine environments.Pharmaceuticals have garnered considerable attention due to their extensive presence in the environment. However, studies regarding their impact on the marine ecosystem remain limited, and toxicity data for many pharmaceuticals toward marine species are still severely lacking. This study systematically investigated the toxicity and ecological risks of ten pharmaceuticals on nine marine species spanning three trophic levels, including four species of marine microalgae, four invertebrates, and one fish species. The effect/lethal concentrations 50% (EC50/LC50) revealed that microalgae exhibited the highest sensitivity, whereas vertebrate marine medaka (Oryzias melastigma) embryos showed the greatest tolerance. Species sensitivity distribution (SSD) models were constructed based on acute toxicity endpoints, and predicted no-effect concentrations (PNECs) for the target pharmaceuticals were derived, ranging from 0.003 to 59 mg/L. Amitriptyline (AMT) demonstrated the lowest PNEC, indicating the highest potential ecotoxicity among the ten pharmaceuticals. The microalga Isochrysis galbana, which showed the highest sensitivity to AMT, was selected for exposure experiments at environmentally relevant concentration gradients to investigate the underlying mechanisms of toxicity. The result demonstrated that AMT inhibits ribosomal biogenesis and translation-related signaling pathways, while also triggering oxidative stress, leading to cellular damage and ultimately suppressing microalgal growth. This study provides critical benchmarks for environmental risk assessment of pharmaceuticals in marine environments.

Marine environmental benchmarks; Antibiotics; Artificial sweetener; Acute toxicity test; Transcriptomic analysis