In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5–100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as “Annexin A1” or “Lipocortin 1” and “Breast cancer” or “TNBC”. A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-β signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.

Health risks which result from exposure to pesticides have sparked awareness among researchers, triggering the idea of developing nanoencapsulation pesticides with the aim to enhance cytoprotection as well as genoprotection of the pesticides. In addition, nanocapsules of pesticides have slow release capability, high bioavailability, and site-specific delivery, which has attracted great interest from researchers. Hence, the objective of this work is to synthesize a nanoformulation of a fungicide of different sizes, namely, chitosan-hexaconazole nanoparticles (18 nm), chitosan-dazomet nanoparticles (7 nm), and chitosan-hexaconazole-dazomet nanoparticles (5 nm), which were then subjected to toxicological evaluations, including cytotoxicity, genotoxicity, cell death assay, and dermal irritation assays. Incubation of chitosan-based nanofungicides with V79-4 hamster lung cell did not reveal cytotoxicity or genotoxicity, potentially suggesting that encapsulation with chitosan reduces direct toxicity of the toxic fungicides. Meanwhile, pure fungicide revealed its high cytotoxic effect on V79-4 hamster lung cells. In addition, dermal exposure assessment on rabbits revealed that chitosan-hexaconazole nanoparticles are classified under corrosive subcategory 1C, while chitosan-dazomet nanoparticles are classified under corrosive subcategory 1B. Moreover, both chitosan-hexaconazole nanoparticles and chitosan-dazomet nanoparticles are classified as causing mild irritation.

Nanotechnology offers promising ecosustainable solutions for crop protection, but the use of nanopesticides, such as 2,4-dichlorophenoxyacetic acid-loaded polymeric nanopesticides (2,4D-NPs), presents significant human health risks, particularly via inhalation. This study was carried out to assess the cytotoxicity and underlying mechanisms of 2,4D-NPs on human lung epithelial A549 cells, which were selected as a representative model for the primary site of inhalation exposure. The synthesized 2,4D-NPs were well-defined spherical particles with an average size of approximately 49 nm, a negative ζ potential, and high encapsulation efficiency, confirming successful nanoformulation. Cytotoxicity assessments showed that the 2,4D-NPs had a significantly enhanced effect compared to raw 2,4D, with an IC₅₀ of 72.63 ± 1.23 μg/mL at 24 h. The increase in toxicity was primarily driven by robust oxidative stress, evidenced by elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, which led to severe mitochondrial dysfunction and depletion of adenosine triphosphate (ATP). The nanoparticles induced apoptosis, marked by increased cytochrome c release and caspase-3 activation, and exacerbated inflammation. Notably, no primary DNA damage was observed, underscoring that apoptosis and redox imbalance, not genotoxicity, were the main drivers of toxicity. Our findings provide a critical new blueprint for nanopesticide safety by demonstrating that the amplified cellular impact of 2,4D-NPs is mediated through specific pathways of redox imbalance and mitochondrial disruption. This moves the field forward by highlighting the need for a shift in safety assessments to include these mechanistic end points and by guiding the innovative engineering of safer agricultural nanomaterials.