Journal of Toxicology and Environmental Health Part B

Barbosa, Silvia Leticia Maciel; Porto, Jhonatas Cley Santos; Pereira, Joedna Cavalcante; Filho, José Ivo Araújo Beserra; da Silva, Felipe Carneiro Cavalcanti; de Castro e Sousa, João Marcelo; de Oliveira Ferreira, José Roberto; Militão, Gardenia Carmen Gadelha; Ferreira, Paulo Michel Pinheiro

doi: 10.1080/10937404.2026.2664722pmid: N/A

Approximately 75% of the ovarian cancer (OC) patients are diagnosed in advanced stages and platinum-based chemotherapy presents severe side effects and high recurrence rates. This narrative review consolidates current knowledge and describes the pathophysiological characteristics of OC and how molecular aspects influence clinical outcomes of traditional and antibody-drug chemotherapies. Subsequently, a comprehensive picture regarding the current benefits identifies gaps and potential adverse risks of ADCs to treat OC. High-grade serous carcinomas, the most frequently diagnosed OCs, present TP53 and BRCA1/2 mutations, hypermethylation, and deregulation of retinoblastoma 1 and phosphatidylinositol 3-kinase (PI3K)/Akt/Ras pathways. After conventional treatment (surgery with or without systemic chemotherapy) and follow-up by CA125 levels, poly(ADP-ribose) polymerase inhibitors and hormone therapies were included. Unfortunately, approximately half of advanced patients who achieved a complete response following chemotherapy exhibit residual tumor(s). In this context, ADCs displayed marked cytotoxicity and incorporated a hypothesis-driven target identification strategy to recognize specific/tumor overexpressing-proteins. Independent clinical studies bibliographic searches in the PubMed database conducted between January 2020 and May 2025 revealed some ADCs have expanded progression-free survival and displayed partial/complete remission in OC patients at small doses if compared to traditional chemotherapies, suggesting acceptable safety profiles and potential synergism among cisplatin/carboplatin/paclitaxel/doxorubicin and ADC-based immunotherapies. A total of 18 clinical trials selected indicate (i) mild-to-moderate severity of side/adverse effects up to grade 2, (ii) low intervention or drug discontinuation, (iii) few drug-related deaths, and/or (iv) reversible toxicity. Thus, therapeutic performance of ADCs demonstrated that personalized treatment maximizes clinical benefits and improves efficacy for heterogeneous populations and polyclonal tumors.

Spliethoff, Henry M.; Palmer, Mackenzie C.; Marquez-Bravo, Lydia G.; Marks, Tia; Ginsberg, Gary

doi: 10.1080/10937404.2026.2665431pmid: N/A

Perfluorooctane sulfonate (PFOS) is a persistent per-fluoroalkyl substance that bioaccumulates in freshwater fish and is increasingly driving new fish consumption advisories in the United States. Toxicity assessments have derived low PFOS reference doses that might be exceeded by fish consumption from many relatively uncontaminated waterbodies. Because PFOS cannot be readily removed from fish, and fish provide substantial nutritional health benefits, advisory programs need to consider health consequences of both PFOS-initiated toxicity and lost benefits of reduced fish intake. This narrative review synthesizes epidemiological and mechanistic evidence for benefits of fish consumption overlapping with four priority PFOS noncancer health endpoints (immune, hepatic, cardiovascular, developmental) identified by USEPA. For each endpoint, biological pathways were examined through which n-3 PUFAs may counterbalance/modulate PFOS-associated toxicity, including competitive binding at nuclear receptors, anti-inflammatory signaling, lipid regulation, and effects on fetal growth and immune function. Although quantitative data are lacking, evidence supports a risk-benefit framework for PFOS fish advisories that acknowledges potential offsets between PFOS risks and fish-consumption-associated health benefits. In addition, critical data gaps were identified, including the need for biomonitoring studies assessing PFOS and fish-derived nutrient co-exposures. Overall, this review provides scientific context for balanced public health decision-making for those individuals who rely on local fish as an accessible and health-promoting food.

Biamis, Christina; Kühn, Susanne; Payo-Payo, Ana; Dick, Jaimie; Bize, Pierre; van Franeker, Jan; Hardiman, Gary

doi: 10.1080/10937404.2026.2674012pmid: 42178492

The northern fulmar (Fulmarus glacialis) is well suited to contribute to a “One Health” approach for understanding plastic-associated toxicity. Plastics contain additives that act as endocrine-disrupting chemicals (EDCs), which leach into the environment, often disrupting hormonal signaling in wildlife. As an ecotoxicological model, the fulmar, a seabird, provides a unique opportunity to investigate these effects under real-world exposure conditions. Fulmars are currently utilized in The EU’s Marine Strategy Framework Directive as passive bioindicators of marine litter in the Northeast Atlantic, based upon the proportion of individuals with significant plastic burdens in their stomachs. The aim of this review is to advocate for elevating the fulmar’s role from a passive indicator to active sentinel species to better understand long-term environmental health impacts of chronic plastic exposure. The fulmar’s unique ecological niche, high trophic level, and wide-ranging foraging behavior make it particularly vulnerable to plastic ingestion, providing a relevant model for exposure assessment. The role of epigenetic mechanisms was examined in mediating gene–environment interactions, particularly how plastic exposure may influence gene expression and contribute to adverse health outcomes. Further, advances in genome sequencing and annotation enabled identification of molecular pathways affected by plastic-derived EDCs, contributing to the development of complex adverse outcomes that might be characterized through systems biology. Finally, practical benefits and methodological challenges of integrating molecular and genomic analyses into fulmar-based monitoring, focusing upon bycaught individuals and long-term study cohorts, was determined. This framework supports the fulmar’s potential as a sentinel species for monitoring plastic-related health risks in marine ecosystems.