Lecture 2: Introduction to Environmental Endocrine Disrupting Chemicals - PDF

VIBS 422/622: ENDOCRINE TOXICOLOGY Lecture 2: Introduction to Environmental Endocrine Disrupting Chemicals Sakhila K. Banu Professor  TEACHING PHILOSOPHY 1. LEARNING ENVIRONMENT: Create a stress-free learning environment for...

VIBS 422/622: ENDOCRINE TOXICOLOGY Lecture 2: Introduction to Environmental Endocrine Disrupting Chemicals Sakhila K. Banu Professor  TEACHING PHILOSOPHY 1. LEARNING ENVIRONMENT: Create a stress-free learning environment for students, where they learn without stress, feel comfortable, supported, and free to interact and learn with joy, curiosity, and passion. I firmly believe that a stress-free class-room environment dramatically impacts students' learning interests, performance, interaction, and the outcome of their learning. It is the teacher's responsibility to make the students love the subject, even if the course is challenging. Comment from one of the students from 2022 class: , “Dr. Banu really created such a comfortable and encouraging learning environment. She is passionate about her work and her students and it made me really want to learn the material”. Comment from one of the students from 2021 class: “very sweet and caring personality encouraged students to put effort into the class. Students were even telling each other to show up to class. Dr. Banu has been one of the most genuine, caring professors I have had the privilege of learning from - I am truly grateful for my time in her course!”  TEACHING PHILOSOPHY 2. SPECIFIC STRATEGIES OF MY TEACHING (i) Fostering students' self-esteem: My first approach is to help the students feel their own values, uniqueness, and talents. I try to break the stranger anxiety between the students and me (the teacher). (ii) Being available and approachable: I AM available for the students as long as they needed me, and I AM always available and approachable. Comment from one of the students from 2022 Endocrine Toxicology class, “I thoroughly enjoyed attending this class. Dr. Banu is an absolute angel and made me feel so welcome in her class. It's very clear that she loves her students and wants to see us all succeed. She was available almost 24/7 If we needed her. She's the best professor I have had at A&M!” (iii) Seeing the students as the future leaders: When I interact with the students, I view, address, approach, and interact with students as the future leaders, physicians, directors, presidents, and researchers, not mere students in the classroom. This approach is very potential to elevating students learning ability and raising the bar above the average learning curve. (iv) Fostering curiosity and enthusiasm in students for learning: I designed and taught this course in such a way that the students showed curiosity and enthusiasm in learning the materials and exploring related information and interacting with me and other students about the new information that they learn. It is a challenging course; however, students seem to appreciate learning about exposure to these harmful chemicals and how to avoid them in their daily lives, making healthy lifestyle choices. Many students shared what they learned with their family and friends. Prepare EDCs chart to help study for your exam. See the model below. EDCs – Names and Health effects NAMES OF EDCs MAJOR CATEGORY/USES Major Health effects DDT Pesticide Cancer, impairs egg shell thickness Atrazine Herbicide Feminization BPA Plasticizer Cancer, reduces sperm quantity and quality Phthalate Plasticizer Cancer, reduces sperm quantity and quality Endocrine Toxicology (2024) leadership team  Part -1 Endocrine System The Endocrine Organs THYROID THYROID PCB MIMICS GLAND HORMONE OVARIES ESTROGEN BPA MIMICS TESTIS TESTOSTERONE ATRAZINE ANTAGONIZE  Types of hormones Functional Endocrine Hormones – Travel through the blood to act at a site distant from the secreting cell or gland, E.g. Steroid and thyroid hormones. Paracrine Hormones – Act on cells near the secreting cell Autocrine Hormones – Act on the secreting cell Neurocrine Hormones – Secreted by neural cells neurotransmitters neurohormones Long Distance Communication: Endocrine Hormones EDC? Neurotransmitters: glutamate, aspartate, D-serine, γ- aminobutyric acid (GABA), glycine. Monoamines: dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SER, 5-HT). Neurohormones: oxytocin and the antidiuretic hormone (also referred to as vasopressin). Long distance cell-to-cell communication E.g.. Acetylcholine E.g.. Hypothalamic releasing hormones such as TRH, GnRH. Protein and Polypeptide Hormones: Synthesis and Release Peptide hormone action Peptide Peptide  Amine Hormones Derived from the amino acid tyrosine Includes thyroid hormones and catecholamines (chromaffin cells of the adrenal medulla) Stored until secreted Amine Hormone Structure PCB  Steroid Hormones: Characteristics Are made from cholesterol, are lipophilic & can enter target cells Are immediately released from the cells after synthesis Interact with cytoplasmic or nuclear receptors Activate DNA for protein synthesis Are slower acting and have longer half-life than peptide hormones Examples: cortisol, estrogen & testosterone Steroid Hormones: Structure Steroid Hormones: Action  Feedback Regulation Stimulatory pathways are in green; negative feedback pathways are in red. T3 and T4 feed back on the hypothalamus and the anterior pituitary, thereby limiting their own production.  Summary of the Endocrine System : Hypothalamus Hormone Secreted By Function Thyrotropin-releasing Parvocellular neurosecretory Stimulate thyroid-stimulating hormone (TSH) TRH hormone neurons release from anterior pituitary (primarily) Dopamine Dopamine neurons of the arcuate (Prolactin-inhibiting DA or PIH Inhibit prolactin released from anterior pituitary nucleus hormone) Growth hormone- Neuroendocrine neurons of the Stimulate Growth hormone (GH) release from GHRH releasing hormone Arcuate nucleus anterior pituitary Inhibit Growth hormone (GH) release from Somatostatin SS, GHIH, or Neuroendocrine cells of the anterior pituitary (growth hormone- SRIF Periventricular nucleus Inhibit thyroid-stimulating hormone (TSH) inhibiting hormone) release from anterior pituitary Stimulate follicle-stimulating hormone (FSH) Gonadotropin-releasing GnRH or Neuroendocrine cells of the Preoptic release from anterior pituitary hormone LHRH area Stimulate luteinizing hormone (LH) release from anterior pituitary Parvocellular neurosecretory Corticotropin-releasing Stimulate adrenocorticotropic hormone (ACTH) CRH or CRF neurons of the Paraventricular hormone release from anterior pituitary Nucleus Magnocellular neurosecretory Uterine contraction Oxytocin OT or OXT neurons of the Supraoptic nucleus Lactation (letdown reflex) and Paraventricular nucleus Parvocellular neurosecretory Increases water permeability in the distal neurons, Magnocellular Vasopressin ADH or AVP convoluted tubule and collecting duct of neurosecretory neurons of the (antidiuretic hormone) or VP nephrons, thus promoting water reabsorption Paraventricular nucleus and and increasing blood volume Supraoptic nucleus  Summary of the Endocrine System : Hormone Secreted By Function Pineal body Antioxidant Monitors the circadian rhythm Melatonin Pinealocytes including inducement of drowsiness and lowering of the core body temperature Posterior pituitary lobe (neurohypophysis) Magnocellular Uterine contraction Oxytocin neurosecretory cells Lactation (letdown reflex) Increases water permeability in the distal convoluted tubule Vasopressin ADH or Parvocellular and collecting duct of (antidiuretic AVP neurosecretory neurons nephrons, thus promoting hormone) water reabsorption and increasing blood volume  Anterior pituitary lobe (adenohypophysis) Hormone Secreted By Function Growth hormone Stimulates growth and cell reproduction GH Somatotrophs (somatotropin) Stimulates Insulin-like growth factor 1 release from liver Thyroid- Stimulates thyroxine (T4) and triiodothyronine (T3) synthesis and release stimulating TSH Thyrotrophs from thyroid gland hormone Stimulates iodine absorption by thyroid gland (thyrotropin) Adrenocorticotro Stimulates corticosteroid (glucocorticoid and mineralcorticoid) and pic hormone ACTH Corticotrophs androgen synthesis and release from adrenocortical cells (corticotropin) Beta-endorphin - Corticotrophs Inhibits perception of pain In females: Stimulates maturation of ovarian follicles in ovary Follicle- In males: Stimulates maturation of seminiferous tubules stimulating FSH Gonadotrophs In males: Stimulates spermatogenesis hormone In males: Stimulates production of androgen-binding protein from Sertoli cells of the testes In females: Stimulates ovulation Luteinizing In females: Stimulates formation of corpus luteum LH Gonadotrophs hormone In males: Stimulates testosterone synthesis from Leydig cells (interstitial cells) Stimulates milk synthesis and release from mammary glands Prolactin PRL Lactotrophs Mediates sexual gratification Melanocyte- Melanotropes in the stimulating MSH Pars intermedia of the Stimulates melanin synthesis and release from skin/hair melanocytes hormone Anterior Pituitary  Summary of the Endocrine System : Thyroid & Parathyroid Hormone Secreted By Function Stimulates body oxygen and energy consumption, thereby increasing Thyroid epithelial the basal metabolic rate Triiodothyronine T3 cell Stimulates RNA polymerase I and II, thereby promoting protein synthesis Stimulates body oxygen and energy consumption, thereby increasing Thyroxine Thyroid epithelial the basal metabolic rate (tetraiodothyroni T4 cells Stimulates RNA polymerase I and II, thereby promoting protein ne) synthesis Parafollicular Stimulates osteoblasts and thus bone construction Calcitonin cells Inhibits Ca2+ release from bone, thereby reducing blood Ca2+ Calcium: Stimulates Ca2+ release from bone, thereby increasing blood Ca2+ Stimulates osteoclasts, thus breaking down bone Stimulates Ca2+ reabsorption in kidney Parathyroid Parathyroid chief PTH Stimulates activated vitamin D production in kidney hormone cell Phosphate: Stimulates PO3-4 release from bones, thereby increasing blood PO3-4. Inhibits PO3-4 reabsorption in kidney, so more PO3-4 is excreted Overall, small net drop in serum PO3-4.  Summary of the Endocrine System : Pancreas Hormone Secreted By Function Intake of glucose, glycogenesis and glycolysis in liver and Insulin β Islet cells muscle from blood intake of lipids and synthesis of triglycerides in adipocytes Other anabolic effects glycogenolysis and gluconeogenesis in liver increases blood Glucagon α Islet cells glucose level Inhibit release of insulin Inhibit release of glucagon Suppress Somatostatin δ Islet cells the exocrine secretory action of pancreas. Pancreatic Self regulate the pancreas secretion activities and effect the PP cells polypeptide hepatic glycogen levels.  Summary of the Endocrine System : Adrenal – Adrenal Cortex Hormone Secreted By Function Stimulates gluconeogenesis zona Stimulates fat breakdown in adipose tissue Glucocorticoids fasciculata and Inhibits protein synthesis (chiefly cortisol) zona reticularis Inhibits glucose uptake in muscle and adipose tissue cells Inhibits immunological responses (immunosuppressive) Inhibits inflammatory responses (anti-inflammatory) Stimulates active sodium reabsorption in kidneys Mineralocorticoid Zona Stimulates passive water reabsorption in kidneys, thus increasing blood s (chiefly glomerulosa volume and blood pressure aldosterone) cells Stimulates potassium and H+ secretion into nephron of kidney and subsequent excretion Zona Androgens fasciculata and In males: Relatively small effect compared to androgens from testes (including DHEA Zona reticularis In females: masculinizing effects and testosterone) cells Stimulates gluconeogenesis zona Stimulates fat breakdown in adipose tissue Glucocorticoids fasciculata and Inhibits protein synthesis (chiefly cortisol) zona reticularis Inhibits glucose uptake in muscle and adipose tissue cells Inhibits immunological responses (immunosuppressive) Inhibits inflammatory responses (anti-inflammatory)  Summary of the Endocrine System : Adrenal – Adrenal Medulla Hormone Secreted By Function Fight-or-flight response: Boost the supply of oxygen and glucose to the brain and muscles (by increasing heart rate and stroke Adrenaline Chromaffin volume, vasodilation, increasing catalysis of glycogen in liver, (epinephrine) cells breakdown of lipids in fat cells) (Primarily) Dilate the pupils Suppress non-emergency bodily processes (e.g., digestion) Fight-or-flight response: Boost the supply of oxygen and glucose to the brain and muscles (by increasing heart rate and stroke Noradrenaline Chromaffin volume, vasoconstriction and increased blood pressure, (norepinephrine) cells breakdown of lipids in fat cells) Increase skeletal muscle readiness. Chromaffin Dopamine Increase heart rate and blood pressure cells Chromaffin Enkephalin Regulate pain cells  Summary of the Endocrine System : Testis Hormone Secreted By Function Anabolic: growth of muscle mass and strength, increased Androgens Leydig bone density, growth and strength, Virilizing: maturation of (chiefly cells sex organs, formation of scrotum, deepening of voice, testosterone) growth of beard and axillary hair. Sertoli Estradiol Prevent apoptosis of germ cells cells Sertoli Inhibin Inhibit production of FSH cells  Summary of the Endocrine System : Ovary Hormone Secreted By Function Support pregnancy: Convert endometrium to secretory stage; Make cervical mucus thick and impenetrable to sperm; Inhibit immune response, e.g., towards the human embryo; Decrease uterine smooth muscle contractility; Inhibit lactation; Inhibit onset of labor. Other: Raise epidermal growth factor-1 levels; Increase core temperature during ovulation; Granulosa Progesteron Reduce spasm and relax smooth muscle (widen bronchi and regulate mucus) cells, e Anti-inflammatory: Reduce gall-bladder activity; Normalize blood clotting and vascular tone, theca cells zinc and copper levels, cell oxygen levels, and use of fat stores for energy; Assist in thyroid function and bone growth by osteoblasts; Increase resilience in bone, teeth, gums, joint, tendon, ligament, and skin; Promote healing by regulating collagen; Provide nerve function and healing by regulating myelin; Prevent endometrial cancer by regulating effects of estrogen Androstened Theca Substrate for estrogen ione cells Structural: Promote formation of female secondary sex characteristics; Accelerate height growth; Accelerate metabolism (burn fat); Reduce muscle mass; Stimulate endometrial growth; Increase uterine growth; Maintain blood vessels and skin; Reduce bone resorption, increase bone formation Estrogens Granulosa Protein synthesis: Increase hepatic production of binding proteins (mainly cells Coagulation: Increase circulating level of factors antithrombin III, plasminogen; Increase platelet estradiol) adhesiveness; Increase HDL, triglyceride, height growth; Decrease LDL, fat deposition Fluid balance: Regulate salt (sodium) and water retention; Increase GH; Increase cortisol, SHBG Gastrointestinal tract: Reduce bowel motility; Increase cholesterol in bile Lung function: Promote lung function by supporting alveoli. Granulosa Inhibin Inhibit production of FSH from anterior pituitary cells  Part - 2 Endocrine Disruptors  The classic work that brought effects of chemical pollution in wildlife to our attention was Rachel Carson’s Silent Spring in 1962. The classic work that brought effects of EDCs in wildlife to our attention was Our Stolen Future in 1996. Editors: Dianne Dumanoski "A critically important book that forces us to John Peterson Myers ask new questions about the synthetic chemicals that we have spread across this Theo Colborn earth."—Al Gore.  What are Endocrine Disruptors? Endocrine disruptors are man-made synthetic chemicals and natural phytoestrogens (naturally occurring plant- or fungal metabolite-derived estrogen) that act on the endocrine systems of humans and animals by mimicking, blocking and/or interfering in some manner with the natural instructions of hormones to cells.  Classes of EDCs  Heavy Metals  Combustion by-products  Pharmaceuticals (DES, Birth control, Cancer drugs)  Pesticides (DDT, dieldrin, endosulfan)  Plasticizers (DEHP, DBP, BBP or phthalates)  Plastic monomers (Bisphenol-A)  Flame Retardants (PBDEs)  Detergents/surfactants (nonylphenol, octylphenol)  Persistent Organochlorines (PCBs, dioxins, furans) Polybrominated diphenyl ethers or PBDEs  Sources of environmental disruptors (EDCs)  Byproduct of industrial processes such as the paper bleaching  Emissions from steel foundries and motor vehicles  Incineration of chlorine containing products such as PVC incinerators  Building fires  Heavy metal pollutants from catalytic convertors, cigarette smoke, pesticides and fungicides etc.,.  Health and beauty aids (cosmetics, sunscreens, perfumes).  Sources of Environmental Disruptors (EDs) Day-to-day use….  Pharmaceuticals (birth control pills).  Dental sealants.  Solvents.  Surfactants.  Pesticides (Monsanto's Roundup®)  Plastics (PVC) polystyrene aka Styrofoam® EDCs have a wide range of molecular size, volume, and potency. The potency depends upon the target organ or cell and specific end point. Toxicants can accumulate and biomagnify DDT  Some toxicants can be excreted or metabolized.  Fat-soluble toxicants are stored in fatty tissues  Bioaccumulation = toxicants build up in animal tissues  Biomagnification=toxicants concentrate in top predators  The increased concentration of toxic chemicals in the tissues of organisms that are at higher levels in food webs. ppm – parts per million  Human (Highest accumulation) Mammals Birds Large fish Small fish Zoo-planktons Water Phytoplanktons  Being at the top of the food chain, humans have some of the highest EDCs concentrations.  EDCs can cross the placenta into the fetus.  EDCs are also fed to the suckling infants via the mother’s milk.  The combination of more than one chemical can have the synergistic effect of increasing the toxicity many times above that of each chemical separately; eg., Roundup®, the herbicide and glyphosate (herbicide that kills weeds). (additive effect vs. synergistic effect)  Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene (pesticides), are 1000 times as potent as each separately. EDCs mimic the chemical structure of steroid hormones, particularly estrogen, and binds with ERs.  Structural similarity in different estrogenic compounds. Raloxifene – estrogen receptor modulator EDCs- chemical structure  Endocrine disruptors can: 1. Mimic or partly mimic naturally occurring hormones in the body like estrogens, androgens, and thyroid hormones, potentially producing overstimulation. 2. Bind to a receptor within a cell and block the endogenous hormone from binding. The normal signal then fails to occur and the body fails to respond properly (eg: anti-estrogens, anti-androgens, and anti-thyroid drugs). 3. Interfere or block hormone metabolism in the liver. 1 2 3 EDC EDC  EDC effect on wildlife TCDD – Other name for Dioxin Planar Halogenated Aromatic Hydrocarbon (PHAH); Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) Chryptorchidism – undescended testicles Cryptorchidism  EDC effect on wild life Vitellogenin - a precursor protein of egg yolk normally in the blood or hemolymph only of females that is used as a biomarker in vertebrates of exposure to environmental estrogens which stimulate elevated levels in males as well as females.  Human exposure to major EDCs… Plastics: Poly Vinyl Chloride (PVC) contributes the greatest exposure to EDCs of all plastics. It is toxic during production, use, and when it is disposed of. PVC is used in residential and municipal water pipes, toys, food wrap, clothing, raincoats, shoes, building products such as windows, siding, roofing, flooring, and medical equipment such as hospital blood bags, I.V bags, tubing and many other devices. PVC contains phthalates, and dioxin is produced during PVC manufacturing. Dioxins :  Dioxins are produced when heating our food in the microwave using plastic containers.  High heat and plastics release dioxins into the food and ultimately into the cells of the body.  Dioxins are carcinogens and highly toxic to the cells of our bodies.  Half-life of Dioxin is 8.5 years in the human body PCB compounds are called – PCB Congeners. 209 congeners are available.  Beluga whales deposit most of their body fat into a thick layer of blubber - a thick layer of fat and fibrous connective tissue that lies just below the skin of most marine mammals. Blubber accounts for more than 40% of a beluga whale's weight. This blubber layer insulates the whale and streamlines the body. Blubber samples of Beluga Whales from Alaska's north coast contain organochlorines, including toxaphene, PCBs, DDTs and chlordane. Toxaphene was the organochlorine pesticide found in the highest concentration in all samples. Q: What are the major EDCs found in the blubber of beluga whales? PCBs were highest concentrations measured in Belugas.  Which PCB is more toxic? A B C D PCB (Polychlorinated biphenyl) :  PCBs are used as coolants and fluids for transformers and capacitors, stabilizing additives in flexible PVC coatings of electrical wiring.  Higher chlorinated PCBs are associated with the neurological damage.  Common symptoms included dermal and ocular lesions, irregular menstrual cycles and a decreased immune responses.  BPA (Bisphenol-A) is the most common plasticizer in PVC. BPA leaches into liquid and fatty products packaged in it.  Flexible PVC products can be more than half plasticizers by weight. About 95% of phthalates are used in PVC.  The incinerated PVC creates dioxin.  This causes cancers, endocrine system dysfunction, and environmental pollution. Name any two commonly used plasticizers:  BPA and phthalates.  BPA (Bisphenol A) : Plastic water and baby bottles, food and beverage can linings and dental sealants are the most commonly encountered uses of this chemical. BPA lowers sperm count and increases infertile sperm and promotes breast cancer. BPA binds with ER (Estrogen receptor) because it’s chemical structure is very similar to estrogen. MBP - MONOBUTYL PHTHALATE  Polystyrene food containers are used for packaging meats, fish, cheeses, yogurt, foam containers, foam and rigid plates, clear bakery containers, audiocassette CD cases, disposable cutlery.  Styrene monomer leaches in hot and cold water.  Many cities have banned the use of polystyrene by fast-food vendors. Polystyrene Pesticides: DDT (Dichlorodiphenyltrichloroethane) :  Americans use some 2 billion pounds of pesticides each year, and some pesticide residues stay in the food chain for decades.  Congenital malformations in wild animals.  Decline of sperm counts in men.  Increases breast cancer in women. Herbicide: Atrazine (ATZ) - widely-used agricultural herbicide for control of broadleaf and grassy weeds, predominantly for weed control in corn and soybean crops. One of the most commonly used herbicides in the US, with ~ 75 million pounds applied per year. Its widespread agricultural use allows atrazine to invade the environment repeatedly. Excess amounts of ATZ runs off into surface water such as lakes, streams, and rivers. Some amount migrates into groundwater - stay for a long time, because ATZ breaks down very slowly. Once it reaches water, it can contaminate wells that supply drinking water.  ATZ inhibits production of testosterone  Results in chemical castration (demasculinization) and feminization.  Decrease in testosterone - decreased sperm counts- impaired fertility - reduction in masculine features.  ATZ exposure is associated with decreased sperm and reduced fertility in humans.  Induces estrogen production upsetting the balance between estrogen and testosterone.  Reports published in fish, amphibians, reptiles, and mammals. Which chemical is known to cause chemical castration? ATRAZINE  The increase in estrogen by ATZ results in feminization of males in fish, amphibians, and reptiles.  “Feminized” male fish and amphibians produce eggs and egg yolk and some males even grow ovaries (become hermaphrodites).  ATZ induces gonadal malformations in males.  The testes in this Northern leopard frog have been feminized.  Not only have eggs developed, but they have accumulated yolk and are bursting through the surface of the testes. ATZ treated CONTROL  Health Effects of Endocrine Disruptors Birth defects: alterations in sexual and functional development; neurologic disorders, diabetes mellitus, immunologic disorders, early puberty in young girls. Ex. Feminization of males by ATZ, masculinization of females in PCOS Cancers: breast, colon, vaginal, endometriosis, cervix, testicular; sexual differentiation of the brain and other estrogen target tissues, structural abnormalities of the oviduct, uterus, cervix and vagina, a contributing factor to subfertility. Non-Hodgkin's lymphoma, genital birth defects, cryptorchidism, reduced sperm counts, and enlargement/reduction of prostate.  Health Effects of Endocrine Disruptors Developmental, behavioral and mental disorders, anger, inattention, decreased mental capacity, learning disabilities, dyslexia, attention deficit/hyperactivity disorder (ADHD), autism, propensity to violence, reduced motor skills, and gross and fine eye-hand coordination. The incidence of all cancers among infants less than one year old, both sexes, has risen 36% when comparing the years 1976-1994. Mention well known health effects in humans due to EDC exposure.  Health Effects of Endocrine Disruptors  Dioxin stored in the mother’s fat, is consumed by nursing infants at a rate of 35-100 pg/kg.  The WHO's acceptable daily intake of dioxin is 1-4 pg/kg. The EPA (environmental protection agency) "Risk List down Specific Dose" is 0.01 pg/kg, which is EDCs 10,000 times lower than that the nursing child receives.  Both the quantity and quality of sperm can be reduced, can cause damage to sperm DNA, the sperm can be coated in toxins.  Decreasing sperm counts in many industrialized nations are about 1.5% annually.  DES affects uterine development Normal Uterus Bicarnate Uterus synthetic estrogen, is a drug to prevent miscarriages. It was found to be a teratogen Double Uterus Septal Uterus when given to pregnant women. List of some important EDCs… Persistent Organohalogens: Dioxins and furans, PBBs, PCBs, Hexachlorobenzene, Octachlorostyrene, Pentachlorophenol Pesticides: 2,4,5-T, 2,4-D, alachlor, aldicarb, d-trans allethrin, amitrole, atrazine, benomyl, beta-HCH, carbaryl, chlordane, chlozolinate, -cyhalothrin, cis- nonachlor, cypermethrin, DBCP, DDT, DDT metabolites, dicofol, dieldrin, endosulfan, esfenvalerate, ethylparathion, fenvalerate, glyphosate (the active ingredient in Roundup), h-epoxide, heptachlor, iprodione, kelthane, kepone, ketoconazole, lindane, linurone, malathion, mancozeb, maneb, methomyl, methoxychlor, metiram, metribuzin, mirex, nitrofen, oxychlordane, permethrin, procymidone, sumithrin, synthetic pyrethroids, toxaphene, trans-nonachlor, tributyltin oxide, trifluralin, vinclozolin (fungicide), zineb, ziram  List of some important EDs… Phthalates: Di-ethylhexyl phthalate (DEHP), Butyl benzyl phthalate (BBP), Di- n-butyl phthalate (DBP), Di-n-pentyl phthalate (DPP), Di-hexyl phthalate (DHP), Di-propyl phthalate (DprP), Dicyclohexyl phthalate (DCHP), Diethyl phthalate (DEP) Others: Penta- to Nonyl-Phenols, Bisphenol A, Bisphenol F, Styrene dimers and trimers, Benzo(a)pyrene, ethane dimethane, sulphonate, tris-4-(chlorophenyl), methane, tris-4-(chlorophenyl), methanol, Benzophenone, N-butyl benzene, 4-nitrotoluene, 2,4-dichlorophenol, Cyanazine, Diethylhexyl adipate, DES (diethylstilbestrol)  List of some important EDs… Pharmaceuticals: drug estrogens - birth control pills, DES, cimetidine (Tagamet). Recent reports of cimetidine toxicity are summarized. Toxic to cardiovascular, central nervous system, dermatologic, endocrine, gastrointestinal, hematologic, or renal toxicity Common EDCs: heavy metals (arsenic), cadmium, lead, mercury, 209 PCBs, (polychlorinated biphenyl), 75 dioxins, and 135 furans, exhaust from all motor vehicles, cigarette smoke, ordinary household products (breakdowns products of detergents and associated surfactants, including nonylphenol and octylphenol.  Endocrine Disruption – Impact on children  Children are not little adults  Pound for pound, a child’s exposure is greater than an adults (dose-response)  Immature blood-brain barrier - allows more chemical passage  Detoxification systems may not be fully functional. Why children are more susceptible to EDCs?  Endocrine Disruption – Impact on children  Because children have more future years of life than most adults, they have more time to develop chronic diseases that may be triggered by early exposures. Landrigan et al. 2003. Assessing the effects of endocrine disruptors in the national children’s study. Environ. Health Perspectives 111(13): 1678-1682.  Dirty dozen endocrine disruptors # 1: BPA BPA has been linked to everything from breast cancer and other cancers to reproductive problems, obesity, early puberty and heart disease, and according to government tests, 93 percent of Americans have BPA in their bodies. How to avoid it? Go fresh instead of canned – many food cans are lined with BPA – or research which companies don’t use BPA or similar chemicals in their products. Avoid plastics marked with a “PC,” for polycarbonate, or recycling label #7. Not all of these plastics contain BPA, but many do. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 2: Dioxin  Dioxins can disrupt the pathways that both male and female sex hormone signaling occurs in the body.  Dioxins are very long-lived, build up both in the body and in the food chain, are powerful carcinogens and can also affect the immune and reproductive systems. Half life 8.5 years How to avoid it?  American food supply is widely contaminated. Products including meat, fish, milk, eggs and butter are most likely to be contaminated, but you can cut down on your exposure by eating fewer animal products.  Stop microwaving food in plastic containers. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors What Is Dioxin (TCDD)? Dioxin is a general name for a large group of chemical compounds with similar structure. These compounds are made up of carbon, oxygen, hydrogen and chlorine atoms. The number of the chlorine atoms and their positions in the dioxin molecule are what determines the toxicity of different dioxins. The most toxic dioxin has four chlorine atoms in positions 2, 3, 7 and 8. This dioxin ( 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) is often referred to as TCDD or “dioxin”. TCDD is the most studied and the most toxic of the dioxins.  Dirty dozen endocrine disruptors # 3: Atrazine  Atrazine is widely used on the majority of corn crops in the United States, and consequently it’s a pervasive drinking water contaminant.  Atrazine has been linked to breast tumors, delayed puberty and prostate inflammation in animals, and some research has linked it to prostate cancer in people. How to avoid it?  Buy organic produce and get a drinking water filter certified to remove atrazine. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 4: Phthalates  Phthalates linked to hormone changes, lower sperm count, less mobile sperm, birth defects in the male reproductive system, obesity, diabetes and thyroid irregularities. How to avoid it?  Avoid plastic food containers, children’s toys (some phthalates are already banned in kid’s products), and plastic wrap made from PVC, which has the recycling label #3.  Some personal care products also contain phthalates, so read the labels and avoid products that simply list added “fragrance,” since this catch-all term sometimes means hidden phthalates. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 5: Perchlorate  When perchlorate gets into your body it competes with the nutrient iodine, which the thyroid gland needs to make thyroid hormones. Basically, this means that if you ingest too much of it you can end up altering your thyroid hormone balance. How to avoid it?  You can reduce perchlorate in your drinking water by installing a reverse osmosis filter.  As for food, it’s pretty much impossible to avoid perchlorate, but you can reduce its potential effects on you by making sure you are getting enough iodine in your diet. Eating iodized salt is one good way. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 6: Fire retardants  These chemicals can imitate thyroid hormones in our bodies and disrupt their activity. That can lead to lower IQ, among other significant health effects.  These are incredibly persistent, so they’re going to be contaminating people and wildlife for decades to come. How to avoid it?  Use a vacuum cleaner with a HEPA filter, which can cut down on toxic-laden house dust  Avoid reupholstering foam furniture; take care when replacing old carpet (the padding underneath may contain PBDEs). http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 7: Lead  Lead harms almost every organ system in the body and has been linked to a staggering array of health effects, including permanent brain damage, lowered IQ, hearing loss, miscarriage, premature birth, increased blood pressure, kidney damage and nervous system problems. How to avoid it?  Crumbling old paint is a major source of lead exposure, so get rid of it carefully.  A good water filter can also reduce your exposure to lead in drinking water. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 8: Arsenic  If you eat enough of it, arsenic will kill you outright. In smaller amounts, arsenic can cause skin, bladder and lung cancer.  It can interfere with normal hormone functioning in the glucocorticoid system that regulates how our bodies process sugars and carbohydrates.  Arsenic linked to weight gain/loss, protein wasting, immunosuppression, insulin resistance, osteoporosis, growth retardation and high blood pressure. How to avoid it?  Reduce your exposure by using a water filter that lowers arsenic levels. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 9: Mercury  Mercury is more toxic to pregnant women, since the metal is known to concentrate in the fetal brain and can interfere with brain development.  Mercury can deregulate women’s menstrual cycle and ovulation, interfering with normal signaling pathways.  Sushi you are eating could be hazardous to your health; It could be a mercury-contaminated seafood. How to avoid it?  For people who still want to eat (sustainable) seafood with lots of healthy fats but without a side of toxic mercury, wild salmon and farmed trout are good choices. http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 10: Perfluorinated chemicals (PFCs)  Perfluorochemicals are so widespread and extraordinarily persistent that 99 percent of Americans have these chemicals in their bodies.  PFCs linked to decreased sperm quality, low birth weight, kidney disease, thyroid disease and high cholesterol, among other health issues. How to avoid it?  Skip non-stick pans as well as stain and water-resistant coatings on clothing, furniture and carpets http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 11: Organophosphate pesticides  Organophosphates can affect the human body include interfering with the way testosterone signaling in cells, lowering testosterone and altering thyroid hormone levels. How to avoid it?  Buy organic produce and use EWG’s Shopper’s Guide to Pesticides in Produce, which can help you find the fruits and vegetables that have the fewest pesticide residues. Check it out at: www.ewg.org/foodnews/ http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  Dirty dozen endocrine disruptors # 12: Glycol Ethers  These chemicals “may damage fertility or the unborn child.” Studies of painters have linked exposure to certain glycol ethers to blood abnormalities and lower sperm counts.  And children who were exposed to glycol ethers from paint in their bedrooms had substantially more asthma and allergies. How to avoid it?  Avoid products with ingredients such as 2- butoxyethanol (EGBE) and methoxydiglycol (DEGME).  Start by checking out EWG’s Guide to Healthy Cleaning (www.ewg.org/guides/cleaners/). http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors  In general: How to avoid exposure to EDCs.  Avoid using strong chemicals, glues, paints, nail polish and remover, floor & carpet cleaners.  Don’t heat food or eat hot food in plastic containers, even the ones frozen dinners now come in.  Purchase fresh organic produce, meats and milk free from rBGH.  Buy produce at your local Farmers' Market  Eat lower on the food chain.  Use fewer processed, prepackaged foods whenever possible.  Avoid canned goods unless absolutely a must.  Don’t stay in places that smell of chemicals.  In general, substitute natural products for synthetic products whenever possible.