Pharmaceutical compounds (PhACs), continuously released into the environment, represent a growing ecotoxicological threat to aquatic ecosystems. While the toxicity of individual pharmaceuticals has been extensively investigated, the effects of complex mixtures, the so-called "cocktail effect", remain poorly understood, particularly for primary producers such as cyanobacteria. This study evaluates the individual and combined effects of four commonly detected pharmaceuticals in aquatic environments: acetaminophen (APAP), atenolol (ATN), carbamazepine (CBZ), and diazepam (DZP), using the model cyanobacterium Microcystis aeruginosa over a 25-day exposure period at environmentally relevant concentrations (0.01-545 µg/L). The results demonstrate a clear dose-dependent toxicity of the individual compounds (biomass reduced by 85-91%; chlorophyll reduced by 54-70%). Exposure to lower concentrations exhibited moderate reductions in chlorophyll (0.23-0.81 mg/L to 4.90-5.96 mg/L). The most remarkable results are the amplification of toxicity at combined low concentration (low-mix group caused 52% growth inhibition compared to only 14-24% of single pharmaceuticals at the same low doses). The high-dose mixture had the greatest effect on M. aeruginosa by 58.7% growth inhibition. Multi-biomarker analyses indicated significant changes in 1) esterase activity (60.7% decrease), 2) microcystin-LC production (fivefold increase from 0.55 to 2.90 µg/L), and 3) genotoxic effects (IF > 1.5), as evidenced by the SOS chromotest particularly in treatments containing CBZ. Overall, the multi-biomarker responses indicate that pharmaceutical mixtures overwhelm cellular defenses, inducing amplified stress responses even at environmentally realistic concentrations. These findings highlight the urgent need to incorporate mixture toxicity into risk assessment frameworks.

IntroductionRituximab, an anti-CD20 monoclonal antibody used in B-cell malignancies, is associated with infusion-related reactions (IRRs) during the initial infusion. Standard premedication includes acetaminophen, corticosteroids, and a histamine-1 (H1) antagonist, typically diphenhydramine. Second-generation H1 antagonists offer similar efficacy with less sedation. Some institutions also incorporate histamine-2 (H2) antagonists despite limited supporting evidence. This study evaluated whether dual H1/H2 antagonist premedication reduces IRRs compared with H1-antagonist monotherapy when given with standard premedication.MethodsThis retrospective study reviewed health records of adults with a hematologic malignancy who received their first rituximab infusion at Brown University Health system between January 1, 2022 and June 30, 2025. Patients received premedication with either an H1-antagonist alone or dual H1/H2 receptor-antagonists with acetaminophen and a corticosteroid. The primary endpoint was IRR incidence during or within 24 h of infusion initiation. Secondary endpoints included IRR severity, incidence of grade 3-4 IRRs across subgroups, and time to IRR onset.ResultsAmong 299 patients (mean age 65; 55% male), 62% had aggressive lymphoma, 28% indolent lymphoma, and 10% leukemia. Baseline features included bone marrow involvement (38%), bone disease (39%), advanced-stage nodal disease (54%), B symptoms (48%), and >2 extranodal sites (28%). IRRs occurred in 38% of patients receiving dual H1/H2 antagonist premedication versus 36.5% with H1-antagonist monotherapy, with no difference in grade 3-4 IRRs. Most IRRs occurred 30 to 60 min after infusion initiation.ConclusionDual H1/H2-antagonist premedication was not associated with differences in the incidence or severity of rituximab IRRs compared with H1-antagonist monotherapy in addition to standard premedication.

Spaceflight induces altered physiology that has the potential to alter medication pharmacokinetics due to factors including gastrointestinal motility, fluid balance, circulatory dynamics, hormonal changes, and metabolic alterations. Here, we report the first pharmacokinetic analysis using blood samples during spaceflight. The four SpaceX Polaris Dawn crewmembers ingested 500 mg of oral acetaminophen pre-flight, in-flight, and post-flight. Post-ingestion capillary blood samples were collected using volumetric absorptive microsampling (VAMS). Samples were analyzed using liquid chromatography-tandem mass spectrometry. All samples collected in microgravity were adequate for post-flight analysis. Compared to pre-flight baseline, in-flight increases were observed in the Cmax (mean [SD] ng/mL: pre-flight = 9110 [3290], in-flight = 43,300 [5700], P < .001), AUC0-last (mean [SD] h ng/mL: pre-flight = 26,100 [4520], in-flight = 109,000 [29,400]), and λz (mean [SD] 1/h: pre-flight = 0.227 [0.0688], in-flight = 0.336 [0.0209]). Compared to pre-flight baseline, in-flight decreases were observed in tmax (mean [SD] h: pre-flight = 1.06 [0.657], in-flight = 0.688 [0.239]), t1/2 (mean [SD] h: pre-flight = 3.27 [0.950], in-flight = 2.07 [0.130]), CL/F (mean [SD] mL/h: pre-flight = 16,200 [2990], in-flight = 3890 [559]), and Vz/F (mean [SD] mL: pre-flight = 74,700 [18,800], in-flight = 11,500 [1100]). Compared to pre-flight baseline, Cmax, AUC, and λz increased in-flight, while tmax, t1/2, Vz/F, and CL/F decreased in-flight. Cmax, AUC, Vz/F, and CL/F showed residual changes 3 days post-flight (R + 3). Supratherapeutic blood levels with standard terrestrial dosing raises concern for inadvertent toxicity in the spaceflight environment, and highlights the value of further pharmacokinetic study of medications commonly included within spaceflight medical systems. Overall, VAMS enabled pharmacokinetic study during spaceflight and could serve as a platform for future pharmacokinetic studies.

Phytoremediation of the emerging contaminant acetaminophen (ACT) by the robust Eichhornia crassipes (Mart.) Solms and recycling the ACT-laden biomass for biochar production to avoid secondary pollution risk has rarely been reported. Hence, E. crassipes was cultivated in an outdoor hydroponic system containing synthetic domestic wastewater with five ACT dosages of 0.5, 0.75, 1, 1.25, and 1.5 mg g[-1] FW. Interestingly, the phytoremediation system achieved removal efficiencies of 95.3 ± 4% for ACT and 92.41 ± 0.94% for COD. SEM and XRD analysis revealed ACT's successful uptake and accumulation within E. crassipes leaves. Up to 1 mg g[-1] FW, E. crassipes could sustain cellular steady-state ROS levels and mitigate ACT-induced oxidative damages by incrementing antioxidant activities such as SOD, APX, and POD, as well as phenolic and carotenoid contents. To further investigate the recyclability of E. crassipes's biomass, the depleted plant was pyrolyzed at 500°C for biochar production. The generated biochar showed porous structures with several functional groups and elements that could be applied in wastewater treatments and as a soil amendment. The economic feasibility of the phytoremediation/pyrolysis integrated system was achieved by recouping the initial investment within a payback period of 6.2 years (i.e., shorter than the project lifetime). This system fulfilled SDGs#3, 6, and 14 by pollution reduction, SDGs# 12 by storing C in biochar, and SDG# 8 by maintaining a positive net present value (NPV). This is the first study to point to E. crassipes as a resilient plant in remediating ACT-laden wastewater accompanied by the potential recyclability of the exhausted biomass for biochar production.

Drug-induced liver injury (DILI) is characterized by direct hepatocellular damage and liver dysfunction caused by pharmaceutical agents. However, effective diagnostic methods are currently lacking due to the absence of suitable biomarkers. Hypochlorous acid/hypochlorite (HOCl/ClO[-]) serves as a prodromal factor in DILI and holds promise as a novel biomarker for liver injury. Fluorescence imaging has made the real-time in vivo detection of HOCl possible. To achieve HOCl detection, we progressively designed three molecules: PTZ, DPTZ, and DPSZ, which successively realized fluorescence imaging of HOCl, extended the emission wavelength, and achieved reversible imaging. Ultimately, DPSZ was successfully applied to living cell imaging, demonstrating the capability for long-term reversible imaging of HOCl and an endoplasmic reticulum (ER) targeting tendency. Furthermore, it successfully monitored the progression of acetaminophen (APAP)-induced liver injury and the therapeutic process mediated by resveratrol. This chemosensor provides an effective tool for the early diagnosis and treatment of DILI, further highlighting the critical role of HOCl in liver injury.

[This retracts the article DOI: 10.1155/2016/9470954.].

Introduced in the 1950s, acetaminophen is one of the most widely used antipyretics and analgesics worldwide. In 1999, the International Agency for Research on Cancer (IARC) judged the available data inadequate to determine carcinogenicity, and in 2024 an IARC Advisory Group recommended high-priority re-evaluation. Given this context, we conducted a quantitative weight-of-evidence (QWoE) analysis of in vivo rodent carcinogenicity studies using a previously developed framework for biological relevance and methodological quality (Kougias et al., 2025a; Kougias et al., 2025b). A total of 192 QWoE entries were derived from 32 publications assessing two main carcinogenicity-related endpoints-tumorigenicity and tumor-promoting potential-with additional analyses of tissue-specific tumorigenicity. Mean outcome and methods scores (0-4 scale) were calculated overall and by sex for each endpoint. Across endpoints, mean methods scores ranged from 2.1 to 2.5, indicating moderate data quality, while mean outcome scores ranged from 0.0 to 0.4, indicating minimal evidence for biologically relevant carcinogenic responses. Isolated tumor findings were infrequent, inconsistent, not reproducible, and they generally occurred under conditions involving high toxicity and/or interpretive limitations. Accordingly, our quantitative synthesis concludes that there is inadequate evidence to support a carcinogenic effect of acetaminophen, as reflected by the lack of consistent, reproducible, or biologically relevant indications of carcinogenic or tumor-promoting activity in male or female rodents across tested exposure levels.