Array 11 – Chemical Immune Reactivity Screen

produced by a polyketide pathway by many strains of the mold, Aspergillus.

produced by a polyketide pathway by many strains of the mold, Aspergillus.

Classified as a hydrocarbon, Benzene [C6H6] is an organic chemical compound composed of 6 carbon atoms forming a hexagonal ring arrangement. Benzene is a solvent found in crude oil; because it has a high octane number, it is utilized in gasoline. Benzene is also used as a precursor to heavy chemicals (i.e. ethylbenzene, cumene from which acetone and phenols are derived). Most solvents are neurotoxic and many are carcinogenic. Acute inhalation exposure to high concentrations of benzene can cause drowsiness, fatigue, nausea, vertigo, narcosis, and other symptoms of central nervous system (CNS) depression; however, the most damaging health effects associated with benzene exposure are chronic effects due to repeated exposure to low concentrations over many years. Benzene causes bone marrow failure. Many epidemiologic, clinical, and laboratory data link benzene to aplastic anemia, acute leukemia, and bone marrow abnormalities. Specific hematologic malignancies directly related to benzene include: acute myeloid leukemia (AML), aplastic anemia, myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). The American Petroleum Institute (API) stated in 1948 that "it is generally considered that the only absolutely safe concentration for benzene is zero.” Due to their lipophilicity, most organic solvents, like benzene ring compounds, tend to accumulate in lipid-rich organs, such as nerve tissues in both the peripheral and the central nervous systems. Studies with adult populations exposed to occupational benzene ring compounds support the finding that changes in the visual function can serve as an early marker of neurotoxic damage, especially that resulting from chronic low-level exposure. Benzene is known to cross the placenta and has been found in cord blood at levels equal to or higher than maternal blood; furthermore, an association between maternal airborne benzene exposure and birth defects has been noted. Texas ranks number one in the United States for benzene levels in ambient air and accounts for 48% of all benzene emissions in the nation. In a study conducted in Texas, it was shown that the risk of having a spina bifida-affected infant more than doubled for mothers living in census tracts with estimated benzene levels of ≥ 3 μg/m3. Benzene can lead to genetic toxicity by covalently binding to DNA and forming DNA adducts, which, if not repaired, disrupt the microenvironment of the cell, leading to inhibition of important enzymes, cell death, and alteration of other cells. If this occurs during the critical window of fetal development, the complex cellular processes involved in neurulation (e.g., folate metabolism, cell proliferation, cellular adhesion, and vascular development) may be disturbed. The end result could be neural tube defects. The detection of antibodies to Benzene Ring Compounds bound to human protein in serum indicates a breakdown in immunological tolerance and induction of chemical intolerance. Benzene or its metabolites can bind to human tissue proteins and form neo-antigens. These new antigens are comprised of the haptenic chemical plus the tissue antigen. The formation of neo-antigens initiates an immune response, which may result in antibody production against the chemical and the human tissue. Continued exposure to the chemical and the subsequent production of antibodies against various tissue antigens, may result in autoimmune reactivity. Persons with antibodies to Benzene Ring Compounds bound to human protein in serum should avoid exposure to these substances, with special attention taken to clean up the home and work environments. Quick List Sources of Benzene Ring Compounds: - Tobacco Smoke - Industrial emissions - Auto exhaust - Glues - Paints - Furniture wax

Benzene, Pheno, Toluene, Xylene

exposure occurs in multiple home and work environments

exposure occurs in multiple home and work environments

a family of highly reactive, low molecular weight chemicals.

a family of highly reactive, low molecular weight chemicals.

Chemical Found In: Mercury (Hg) is a heavy chemical element that is emitted to the air by human activities, such as manufacturing or burning coal for fuel, and from natural sources, such as volcanoes. It is deposited, via ecosystem transport, into lakes and oceans, where it bioaccumulates in fish. According to the US EPA, "nearly all methylmercury exposures in the U.S. occur through eating fish and shellfish." In addition, mercury is used in thermometers, barometers, float valves, mercury switches, and other devices where exposure can occur with device breakage. It is also found in amalgam material for dental restorations, energyefficient light bulbs, and is used in scientific research applications. References: Dufault, et al. Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behavioral and Brain Functions, 2009, 5:44 doi:10.1186/1744-9081-5-44. Gallagher and Meliker. Mercury and thyroid autoantibodies in U.S. women, NHANES 2007–2008. Environ Internl, 2013; 40:39–43. Havarinasab and Hultman. Organic mercury compounds and autoimmunity. Autoimmun Rev, 2005; 4:270– 275. Heyer, et al. Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood. Toxicologic Sci, 2004; 81:354–363. Pigatto and Guzzi. Linking mercury amalgam to autoimmunity. Trends Immunol, 2009; 31(2):48-49. Referenced links: https://www.epa.gov/mercury

Parabens are a class of chemical used as preservatives and have bactericidal and fungicidal properties. Parabens are used in many personal care and beauty products, and pharmaceuticals. Parabens are man-made chemicals often used in small amounts as preservatives in cosmetics, pharmaceuticals, foods, and beverages. Common parabens are methylparaben, ethylparaben, propylparaben, and butylparaben. Often more than one paraben is used in a single product. How People Are Exposed to Parabens: People can be exposed to parabens through touching, swallowing, or eating products that contain parabens. Many products, such as makeup, moisturizers, hair-care products, and shaving creams, contain parabens. Parabens in these products are absorbed through the skin. Parabens also can enter the body when pharmaceuticals, foods, and drinks containing parabens are swallowed or eaten. Parabens that enter the body are quickly excreted. How Parabens Affect People’s Health: Human health effects from environmental exposure to low levels of parabens are unknown. In 2006, the industry-led Cosmetic Ingredient Review (CIR), in a partnership with the U.S. Food and Drug Administration (FDA), determined that there was no need to change CIR’s original conclusion from 1984 that parabens are safe for use in cosmetics. The FDA allows single or multiple parabens to be added to food or food packaging as antimicrobials to prevent food spoilage. Levels of Parabens in the U.S. Population: Centers for Disease Control and Prevention scientists measured parabens in the urine of more than 2,548 participants aged six years and older who took part in the National Health and Nutrition Examination Survey (NHANES) during 2005–2006. By measuring these chemicals in urine, scientists can estimate the amount of parabens that has entered people’s bodies. CDC scientists found Methylparaben and propylparaben in the urine of most of the people tested, indicating widespread exposure to these parabens in the U.S. population. In adults younger than age 60, non-Hispanic blacks had higher levels of methyl paraben than non-Hispanic whites. Females had several-fold higher concentrations of methylparaben and propylparabens than males, which likely reflect the greater use of products containing parabens. Finding a measurable amount of parabens in urine does not imply that they cause an adverse health effect. Biomonitoring studies on levels of parabens provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of parabens than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects. References: Chen J, et al. Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol Applied Pharmacol, 2007; 221:278–284. Oishi, S. Effects of propyl paraben on the male reproductive system. Food Chem Toxicol, 2002; 40:1807–1813. Referenced links: https://www.cdc.gov/biomonitoring/parabens_factsheet.html

Tetrachloroethylene (PCE) Overview Tetrachloroethylene (PCE) [Cl2C=CCl2] is a chemical widely used in the dry cleaning of clothes and fabrics and in metal degreasing. It is also a prevalent drinking water contaminant. Contamination and Exposure In 1980, New England government officials discovered that PCE was leaching into public drinking water supplies from the inner vinyl lining of asbestos cement water distribution pipes. A study conducted on Cape Cod involved 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. The results suggest that exposure to PCE around the time of conception increased the risk of certain congenital anomalies among the offspring of exposed women, including: → Gastrointestinal defects: Particularly oral clefts, with a 2.2 - 3.5 fold increase in risk. → Neural tube defects: Particularly anencephaly, with a 2.5 fold increase in risk. → Cardiac anomalies: Modest increases, with a risk three times higher. Furthermore, analysis of females from the Cape Cod study showed an increased risk of breast cancer after high exposure to PCE. Because PCE is lipid-soluble and women typically have a higher proportion of body fat than men, it is anticipated that women would retain PCE longer. A study by the EPA found that developmental exposure to PCE is common; 100% of samples of breast milk from four U.S. urban areas contained detectable levels of PCE. Health Effects of Tetrachloroethylene Immunotoxicity: Chronic exposure to PCE, both environmental and occupational, can lead to the development of autoimmunity. This includes conditions such as systemic lupus erythematosus, scleroderma, diabetes, and hepatitis. Acute Exposure: Effects of acute inhalation exposure to PCE in humans include: Irritation of the upper respiratory tract and eyes. Kidney dysfunction. Neurological effects such as reversible mood and behavioral changes, impairment of coordination, dizziness, headache, sleepiness, and unconsciousness. Chronic Exposure: Primary effects from chronic inhalation exposure are neurological, including: Impaired cognitive and motor neurobehavioral performance. Visual deficits, including deficits in color vision. The three primary neurological effects most consistently associated with subchronic or chronic PCE exposure in human studies are vision, visuospatial memory, and neuropsychological function (e.g., reaction time). Other Health Effects: PCE exposure may cause adverse effects on the kidney, liver, immune system, hematologic system, development, and reproduction. It is also considered a carcinogen. Immune Response and Chemical Intolerance The detection of antibodies to tetrachloroethylene bound to human protein in serum indicates a breakdown in immunological tolerance and induction of chemical intolerance. Tetrachloroethylene or its metabolites can bind to human tissue proteins and form neo-antigens. These neo-antigens consist of the haptenic chemical plus the tissue antigen, initiating an immune response that may result in antibody production against both the chemical and the human tissue. Continued exposure to the chemical, along with the subsequent production of antibodies against various tissue antigens, may result in autoimmune reactivity. Individuals with antibodies to tetrachloroethylene bound to human protein in serum should avoid exposure to the substance and ensure that their home and work environments are free from contamination. Common Sources of Tetrachloroethylene - Spot removers - Leather products - Paint removers - Adhesives - Water repellents - Paper coatings - Dry-cleaned clothes - Chlorinated water