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As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC). [ABSTRACT FROM AUTHOR]

Background: Bisphenol (BP‐)A is a chemical used in Europe to produce polycarbonate plastics and epoxy resin or as colour developer in thermal paper. Due to its toxicity, BPA presence was restricted by European regulations. Therefore, substitute chemicals are replacing BPA. Objective: To assess the allergenic sensitizing potential of 27 substitutes to BPA used in the industry. Methods: The expression of two costimulatory molecules and six cytokines were analysed by flow cytometry in mouse bone marrow‐derived dendritic cells (BMDCs) exposed to the chemicals. Results: All substances except one induced overexpression of at least one receptor and were thus identified as having allergenic sensitizing potential. Based on the BMDC model, they were classified as extreme (1 out of 27), strong (20 out of 27) and moderate (5 out of 27) sensitizers. BPA was classified as a moderate sensitizer and BPF was the only substitute classified as a non‐sensitizer. The more potent substitutes induced more than 2‐fold secretion of CCL3, CCL4 and/or CCL5 by dendritic cells. Conclusion: Most of the BPA substitutes tested in this study have an allergenic sensitizing potential; 24 of them being more potent than BPA itself. Only BPE, BPF and 2,4‐BPS appeared to be weaker sensitizers than BPA. [ABSTRACT FROM AUTHOR]

Plastic waste degrades slowly in aquatic environments, transforming into microplastics (MPs) and nanoplastics (NPs), which are subsequently ingested by fish and other aquatic organisms, causing both physical blockages and chemical toxicity. The fish immune system serves as a crucial defense against viruses and pollutants present in water. It is imperative to comprehend the detrimental effects of MPs on the fish immune system and conduct further research on immunological assessments. In this paper, the immune response and immunotoxicity of MPs and its combination with environmental pollutants on fish were reviewed. MPs not only inflict physical harm on the natural defense barriers like fish gills and vital immune organs such as the liver and intestinal tract but also penetrate cells, disrupting intracellular signaling pathways, altering the levels of immune cytokines and gene expression, perturbing immune homeostasis, and ultimately compromising specific immunity. Initially, fish exposed to MPs recruit a significant number of macrophages and T cells while activating lysosomes. Over time, this exposure leads to apoptosis of immune cells, a decline in lysosomal degradation capacity, lysosomal activity, and complement levels. MPs possess a small specific surface area and can efficiently bind with heavy metals, organic pollutants, and viruses, enhancing immune responses. Hence, there is a need for comprehensive studies on the shape, size, additives released from MPs, along with their immunotoxic effects and mechanisms in conjunction with other pollutants and viruses. These studies aim to solidify existing knowledge and delineate future research directions concerning the immunotoxicity of MPs on fish, which has implications for human health. [Display omitted] [ABSTRACT FROM AUTHOR]

2,2′,4,4′-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans and other organisms. Prior research has confirmed that BDE-47 can induce oxidative damage in RAW264.7 cells, resulting in apoptosis and impaired immune function. The current study mainly focused on how Isoliquiritigenin (ISL) and Licochalcone B (LCB) might protect against BDE-47's immunotoxic effects on RAW264.7 cells. The results show that ISL and LCB could increase phagocytosis, increase the production of MHC-II, and decrease the production of inflammatory factors (TNF-α, IL-6, and IL-1β) and co-stimulatory factors (CD40, CD80, and CD86), alleviating the immune function impairment caused by BDE-47. Secondly, both ISL and LCB could reduce the expressions of the proteins Bax and Caspase-3, promote the expression of the protein Bcl-2, and reduce the apoptotic rate, alleviating the apoptosis initiated by BDE-47. Additionally, ISL and LCB could increase the levels of antioxidant substances (SOD, CAT, and GSH) and decrease the production of reactive oxygen species (ROS), thereby counteracting the oxidative stress induced by BDE-47. Ultimately, ISL and LCB suppress the NF-κB pathway by down-regulating IKBKB and up-regulating IκB-Alpha in addition to activating the Nrf2 pathway and promoting the production of HO-1 and NQO1. To summarize, BDE-47 causes oxidative damage that can be mitigated by ISL and LCB through the activation of the Nrf2 pathway and inhibition of the NF-κB pathway, which in turn prevents immune function impairment and apoptosis. These findings enrich the current understanding of the toxicological molecular mechanism of BDE-47 and the detoxification mechanism of licorice. [ABSTRACT FROM AUTHOR]

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).