Disrupting Defenses: Effects of Bisphenol A and Its Analogs on Human Antibody Production In Vitro.

Bisphenol A (BPA) is an endocrine-disrupting chemical with estrogen-like activity, known to impair immune function. BPA may act as a pro-inflammatory agent, reducing immune response efficacy, increasing bacterial load in E. coli infections, and altering immune responses in parasitic infections (Leishmania major, Nippostrongylus brasiliensis, Toxocara canis) through cytokine and regulatory T-cell modulation.

Assessing the sensitisation hazard of microbial pesticides: potential value of New Approach Methodologies (NAMs) to overcome current challenges.

Over the past years, the use of chemical pesticides has increased considerably worldwide, and concerns about human health and the environment have stimulated the development of safer alternatives. Biopesticides, including those with microorganisms as active substances, i.e.

Addressing Immune Response Dysfunction in an Integrated Approach for Testing and Assessment for Non-Genotoxic Carcinogens in Humans: A Targeted Analysis.

Most known chemical carcinogens induce the direct activation of DNA damage, either directly or following metabolic activation. However, carcinogens do not always operate directly through genotoxic mechanisms but can do so via non-genotoxic carcinogenic (NGTxC) mechanisms. Immune dysfunction is one of these key events that NGTxCs have been shown to modify.

Follow-up of the re-evaluation of silver (E 174) as a food additive (EFSA-Q-2023-00169).

Silver (E 174) is a food colour that was re-evaluated by the EFSA ANS Panel (2016). The ANS Panel concluded that the information available then, was insufficient to assess the safety of silver as food additive. The major issues included limited characterisation of silver E 174 (e.

In vitro approaches to investigate the effect of chemicals on antibody production: the case study of PFASs.

The increasing variety and quantity of new chemical substances have raised concerns about their potential immunotoxic effects, making it essential to assess their impact on human health. One key concern is the reduction of antibody production, as seen with per- and poly-fluoroalkyl substances (PFASs), commonly known as "forever chemicals." Both in vivo and epidemiological data show that PFASs have immunosuppressive effects, leading to reduced antibody responses, particularly following vaccination.

New approach methodologies to assess wanted and unwanted drugs-induced immunostimulation.

This review examines various classes of drugs, focusing on their therapeutic and adverse effects, particularly in relation to immunostimulation. We emphasize the potential of new approach methodologies (NAMs) to study both expected and unexpected immunostimulatory effects. By evaluating the modes of action of different immunostimulatory drugs, we aim to provide insights into effectively assessing unwanted immunostimulatory responses.

Imbalance of human CD4 T lymphocyte subsets following atrazine treatment.

While being banned in the European Union, the herbicide atrazine (ATR) is still one of the most used herbicides in the world. ATR is classified as an endocrine disruptor, but the immunotoxic effects of ATR may also be due to its direct impact on immune cells. To study the effects of ATR on human T cells, we activated T cells present in PBMCs of 8 healthy donors in the presence of ATR (0.

A Novel Approach for In Vitro Testing and Hazard Evaluation of Nanoformulated RyR2-Targeting siRNA Drugs Using Human PBMCs.

Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns-particularly those specific to this class of drugs-is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs.

Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation.

Re-evaluation of silicon dioxide (E 551) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups.

The present opinion is the follow-up of the conclusions and recommendations of the Scientific Opinion on the re-evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle-TR, the conventional safety assessment has been complemented with nano-specific considerations.

Pioneering bioinformatics with agent-based modelling: an innovative protocol to accurately forecast skin or respiratory allergic reactions to chemical sensitizers.

The assessment of the allergenic potential of chemicals, crucial for ensuring public health safety, faces challenges in accuracy and raises ethical concerns due to reliance on animal testing. This paper presents a novel bioinformatic protocol designed to address the critical challenge of predicting immune responses to chemical sensitizers without the use of animal testing. The core innovation lies in the integration of advanced bioinformatics tools, including the Universal Immune System Simulator (UISS), which models detailed immune system dynamics.

Short occupational exposure to glyphosate and its biomonitoring via urinary levels of glyphosate and metabolite AMPA (Amino-MethylPhosphonic acid), in Italian vineyard workers.

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted.

Advancing PFAS risk assessment: Integrative approaches using agent-based modelling and physiologically-based kinetic for environmental and health safety.

Per- and polyfluoroalkyl substances (PFAS), ubiquitous in a myriad of consumer and industrial products, and depending on the doses of exposure represent a hazard to both environmental and public health, owing to their persistent, mobile, and bio accumulative properties. These substances exhibit long half-lives in humans and can induce potential immunotoxic effects at low exposure levels, sparking growing concerns. While the European Food Safety Authority (EFSA) has assessed the risk to human health related to the presence of PFAS in food, in which a reduced antibody response to vaccination in infants was considered as the most critical human health effect, a comprehensive grasp of the molecular mechanisms spearheading PFAS-induced immunotoxicity is yet to be attained.

The evaluation of skin sensitization potential of the UVCB substance diisopentyl phthalate by in silico and in vitro methods.

Diisopentyl phthalate (DiPeP) is primarily used as a plasticizer or additive within the production of polyvinyl chloride (PVC), and has many additional industrial applications. Its metabolites were recently found in urinary samples of pregnant women; thus, this substance is of concern as relates to human exposure. Depending upon the nature of the alcohol used in its synthesis, DiPeP may exist either as a mixture consisting of several branched positional isomers, or as a single defined structure.

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project.

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.

Redox-activity and in vitro effects of regional atmospheric aerosol pollution: Seasonal differences and correlation between oxidative potential and in vitro toxicity of PM.

Particulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated.

Protecting Human and Animal Health: The Road from Animal Models to New Approach Methods.

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs).

In Vitro Effects of Cypermethrin and Glyphosate on LPS-Induced Immune Cell Activation.

(1) Background: The insecticide cypermethrin (Cypm) and the herbicide glyphosate (Glyp) are among the most widely used pesticides. While the two pesticides have been considered to have low toxicity in mammals, some indication of potential immunotoxicity has emerged. The aim of this work was to investigate in vitro the effects of Cypm and Glyp on bacteria lipopolysaccharide (LPS)-induced immune cell activation and of Cypm on 2-mercaptobenzothiazole (MBT)-induced maturation of dendritic cells (DCs).

Exposure to urban nanoparticles at low PM[Formula: see text] concentrations as a source of oxidative stress and inflammation.

Exposures to fine particulate matter (PM[Formula: see text]) have been associated with health impacts, but the understanding of the PM[Formula: see text] concentration-response (PM[Formula: see text]-CR) relationships, especially at low PM[Formula: see text], remains incomplete. Here, we present novel data using a methodology to mimic lung exposure to ambient air (2[Formula: see text] 60 [Formula: see text]g m[Formula: see text]), with minimized sampling artifacts for nanoparticles. A reference model (Air Liquid Interface cultures of human bronchial epithelial cells, BEAS-2B) was used for aerosol exposure.

Impact of chemical mixtures from wastewater treatment plant effluents on human immune cell activation: An effect-based analysis.

Background: Humans are exposed to many different chemicals on a daily basis, mostly as chemical mixtures, usually from food, consumer products and the environment. Wastewater treatment plant effluent contains mixtures of chemicals that have been discarded or excreted by humans and not removed by water treatment. These effluents contribute directly to water pollution, they are used in agriculture and may affect human health.

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender.

Humans can be exposed to endocrine disruptors (EDs) in numerous ways. EDs can interfere with endogenous hormones at different levels, resulting in numerous adverse human health outcomes, including immunotoxicity. In this regard, this study aimed to investigate in vitro the possible effects of EDs on immune cells and possible gender differences.