Atrazine (ATZ) is a widely used and environmentally persistent chlorinated herbicide that has been implicated in various adverse effects in mammals, including cellular toxicity in red blood cells (RBCs) from various species. Human RBCs in particular are a proxy for systemic toxicity whose susceptibility to ATZ remains largely unexplored. In this study, RBCs purified from whole blood were treated with 0.01–1.0 mM of ATZ, and several toxic endpoints were subsequently investigated using photometric, potentiometric, cytofluorimetric, and microscopic techniques. ATZ elicited concentration-dependent hemolysis that resulted in lactate dehydrogenase and K+ leakage due to membrane pore formation, which was resealed by polyethylene glycol 8,000 (PEG). Additionally, ATZ significantly increased phosphatidylserine translocation and free radicals and decreased forward scatter without an appreciable Ca2+ increase. The hemolytic activity of ATZ was ameliorated by urea and sucrose, whereas phosphatidylserine exposure was reversed by urea and extracellular Ca2+ deprivation. Moreover, co-treatment of cells with ATZ and ATP, SB203580, or L-NAME significantly inhibited ATZ-induced cell death. In conclusion, this study shows, for the first time, that ATZ elicits eryptosis and hemolysis in RBCs mediated by osmotic membrane rupture, PS translocation, loss of ionic regulation and cellular volume, oxidative stress, metabolic exhaustion, extracellular Ca2+ availability, and p38 MAPK/nitric oxide synthase stimulation. The insights presented herein highlight the potential systemic effects of ATZ, which inform toxicological assessments critical for refining human health regulations.
Sodium hypochlorite (NaOCl) is a biocidal substance widely used in household bleaching products and industrial applications. However, repeated, or long-term dermal exposure poses risks to human health. To address these concerns, the present study evaluated the potential dermal toxicity of sodium dodecanoyloxybenzenesulfonate (LOBS), which was developed as an alternative to NaOCl as a disinfectant and bleaching agent. This 13-week repeated dermal toxicity study was conducted in compliance with Organisation for Economic Co-operation and Development (OECD) Test Guideline 411. LOBS was administered dermally for 13 weeks and no treatment-related mortality or systemic toxicity was observed. No toxicologically meaningful changes were detected in body weight, food consumption, hematological or clinical chemistry parameters. Furthermore, no alterations were observed in organ weights, or gross and histopathological examinations of major organs. Local reactions observed at the injection site and on the skin were mild and reversible, and were not considered adverse effects related to the test substance. Based on these findings, the no observed adverse effect level for LOBS was determined to be 1000 mg/kg/day for both males and female SD rats. The results indicate that LOBS has an acceptable toxicological profile following repeated dermal exposure. Additionally, this study provides safety data supporting its use as a disinfectant and bleaching agent.
Ethyl hexyl salicylate (EHS) is a salicylate derivative commonly used as a UV filter in cosmetic products at concentrations up to 5
In recent years, New Approach Methodologies (NAMs) are rapidly emerging as a central paradigm for advancing human-relevant approaches in toxicology, biomedical research, and environmental health science. In respiratory toxicology, traditional two-dimensional cell cultures have limited capacity to reflect human physiological responses, structural complexity, and relevant inhalation exposure environments. Additionally, in vivo models not only present ethical challenges but also lack sufficient human relevance to reliably predict human responses. Recent advances in three-dimensional in vitro models, particularly organoids and microphysiological systems such as organ-on-chip platforms, offer promising alternatives that better recapitulate the structural, molecular, and functional features of the human respiratory system. Lung organoids derived from pluripotent or adult stem cells provide multicellular architecture, lineage diversity, and regenerative capacity suitable for evaluation of toxic mechanisms. Meanwhile, organ-on-chip systems enable dynamic exposure environments, including airflow, mechanical stretch, and air–liquid interface (ALI) conditions, improving the relevance of inhalation exposure modeling. This review summarizes current advances in lung organoid and organ-on-chip models as NAMs for respiratory toxicity testing, discusses their application potential and limitations, and outlines future directions to accelerate their translation into predictive, regulatory-relevant toxicology frameworks.
