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      Elevated levels of antibodies against xenobiotics in a subgroup of healthy subjects

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          Abstract

          In spite of numerous research efforts, the exact etiology of autoimmune diseases remains largely unknown. Genetics and environmental factors, including xenobiotics, are believed to be involved in the induction of autoimmune disease. Some environmental chemicals, acting as haptens, can bind to a high-molecular-weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self-tissue as an invader and launch an immune response against it, leading to autoimmunity. This study aimed to examine the percentage of blood samples from healthy donors in which chemical agents mounted immune challenges and produced antibodies against HSA-bound chemicals. The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors. We found that 10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin-HSA adduct. The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM). Performance of serial dilution and inhibition of the chemical–antibody reaction by specific antigens but not by non-specific antigens were indicative of the specificity of these antibodies. Although we lack information about chemical exposure in the tested individuals, detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals. Currently the pathological significance of these antibodies in human blood is still unclear, and this protein adduct formation could be one of the mechanisms by which environmental chemicals induce autoimmune reactivity in a significant percentage of the population.

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          Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

          The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.
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            Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved

            Background: Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in fetal and juvenile mammals. Objectives: We sought to determine whether commercially available plastic resins and products, including baby bottles and other products advertised as bisphenol A (BPA) free, release chemicals having EA. Methods: We used a roboticized MCF-7 cell proliferation assay, which is very sensitive, accurate, and repeatable, to quantify the EA of chemicals leached into saline or ethanol extracts of many types of commercially available plastic materials, some exposed to common-use stresses (microwaving, ultraviolet radiation, and/or autoclaving). Results: Almost all commercially available plastic products we sampled—independent of the type of resin, product, or retail source—leached chemicals having reliably detectable EA, including those advertised as BPA free. In some cases, BPA-free products released chemicals having more EA than did BPA-containing products. Conclusions: Many plastic products are mischaracterized as being EA free if extracted with only one solvent and not exposed to common-use stresses. However, we can identify existing compounds, or have developed, monomers, additives, or processing agents that have no detectable EA and have similar costs. Hence, our data suggest that EA-free plastic products exposed to common-use stresses and extracted by saline and ethanol solvents could be cost-effectively made on a commercial scale and thereby eliminate a potential health risk posed by most currently available plastic products that leach chemicals having EA into food products.
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              Pharmacological interaction of drugs with antigen-specific immune receptors: the p-i concept.

              W Pichler (2002)
              Drug allergies are examples of immune reactions to small molecular compounds. In many drug allergies drug specific CD4+ and CD8+ T-cells can be detected, which recognize small chemicals via their alphabeta-T-cell receptor in a major histocompatibility complex dependent way. In this review a new concept of drug presentation to T-cells is presented. Drugs were stimulatory for T-cells if they bound covalently to peptides or proteins, but also if the drug had structural features allowing it to bind in a labile way (noncovalently) to the major histocompatibility peptide complex. This latter binding method has some similarities to superantigen stimulations and can explain allergies to drugs that are not metabolized. It has been described in patients with maculopapular, bullous and neutrophilic drug eruption, as well as in contact dermatitis. Noncovalent drug presentation leads to the stimulation of immune cells, namely T-cells. The drug needs two surface molecules (one inert serving as a scaffold, major histocompatibility complex, and one reactive, T-cell receptor) to exert its function. Although two receptor structures are involved, the process is reminiscent of a pharmacological interaction between a drug and its receptors and, from the phrase pharmacological interaction with immune receptors, was thus termed the p-i concept.
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                Author and article information

                Journal
                J Appl Toxicol
                J Appl Toxicol
                jat
                Journal of Applied Toxicology
                BlackWell Publishing Ltd (Oxford, UK )
                0260-437X
                1099-1263
                April 2015
                18 July 2014
                : 35
                : 4
                : 383-397
                Affiliations
                [a ]Immunosciences Lab., Inc. 822 S. Robertson Blvd., Ste. 312, Los Angeles, CA, 90035, USA
                [b ]Department of Clinical Sciences, Bastyr University California 4106 Sorrento Valley Blvd, San Diego, CA, 92121, USA
                [c ]Department of Mathematics, Boise State University 1910 University Dr., Boise, ID, 83725, USA
                Author notes
                *Correspondence to: Aristo Vojdani, Immunosciences Lab., Inc., 822 S. Robertson Blvd., Ste. 312, Los Angeles, CA 90035, USA., Email: drari@ 123456msn.com
                Article
                10.1002/jat.3031
                4365752
                25042713
                f5e18b1a-2212-4ecb-bcee-d0b1dbbf1ecb
                Copyright © 2014. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 12 February 2014
                : 15 April 2014
                : 27 April 2014
                Categories
                Research Articles

                Toxicology
                haptens,autoimmunity,xenobiotics,chemicals,adducts
                Toxicology
                haptens, autoimmunity, xenobiotics, chemicals, adducts

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