♂Endocrine Disruptors♀ By Sandy Poulos. Endocrine Disruption ♠ Endocrine System-a complex network of glands that produce and secrete the hormones that

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  • Endocrine Disruptors By Sandy Poulos
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  • Endocrine Disruption Endocrine System-a complex network of glands that produce and secrete the hormones that regulate all the major body functions. Endocrine Disruptor-chemical that interferes with the endocrine system to produce an undesired response, which may affect health, growth, and reproduction.
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  • Mechanisms of Action Mimics Stimulators Blockers Endocrine flushers Enzyme flushers Destructors
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  • EDCs Estrogens: any family of steroid hormones that regulate and sustain female sexual development and reproductive function Androgen: a class of male sex hormones related to the steroid androstane and produced in the adrenal cortex and the testes Substances mimicking feminizing effects are estrogenic and those mimicking masculinizing effects are androgenic Also anti-estrogenic and anti-androgenic
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  • Classification Pesticides, herbicides, fungicides Polyaromatic compounds - PAHs Organic oxygen compounds (phthalates, bisphenol A) Surfactants Drugs Metals Phytoestrogens
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  • Pesticide-DDT 1950s to 1960s DDT Estogenic Affected reproduction system of birds Disrupted the eagle's endocrine system, interfering with calcium metabolism and produced weak egg shells, feminized frogs DDT metabolite (DDE) anti-androgens Atrazine & Endosulfan
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  • DDT
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  • Bisphenol A & Phthalates Bisphenol A Used in the manufacture of some clear plastics (e.g. baby feeding bottles), and used in the resin which lines most tin cans Potency 4 to 6 times less than 17 - estradiol Weakly estrogenic, anti-androgenic Phthalates Potency 6 to 7 times less than 17 - estradiol Weakly estrogenic
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  • Bisphenol A Cans 80 g/kg canned food EU limit 3 mg/kg Surface water: 0.0005-0.41 g/L Sewage effluent: 0.018-0.702 g/L Sediments: 0.01-0.19 mg/kg Sewage sludge: 0.004-1.363 mg/kg Mean conc. in landfill leachate: 269 g/L
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  • Bisphenol A Examined for effects on reproductive organs and daily sperm production in male offspring of mice fed BPA during pregnancy From gestation day 11-17 female mice were fed an average concentration (dissolved in oil) of bisphenol A of 2 ng/g body weight (2 ppb) and 20 ng/g (20 ppb). The 2 ppb dose of bisphenol A is lower than the amount reported to be swallowed during the first hour after application of a plastic dental sealant (up to 931 micrograms; 13.3 ppb in a 70 kg adult). They found that the 2 ng/g dose of bisphenol A permanently increased the size of the preputial glands, but reduced the size of the epididymides. At 20 ng/g, bisphenol A significantly decreased efficiency of sperm production by 20% relative to control males.
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  • Phthalates Another study in rats 0.75 g/kg (from gestational day 14 to postnatal day 3) Reduced pregancy weight gain (14-24g) Reduced pup weight (15%) Reduced testis weights (~35%) Males display female-like nipples (up to 87% compared to 0% in control group)
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  • Phthalates Exposure of patients to phthalates from polyvinyl chloride PVC tubes and bags during dialysis A group of patients not yet on dialysis treatment was used as control The DEHP concentration was 0.8-4.2 g/mL serum in the 17 hemodialysis patients after dialysis In all of the pre-dialysis patients, DEHP could not be detected (less than 0.1 g/mL).
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  • Phthalates DEHP Surface water: 0.33-97.8 g/L Sewage effluent: 1.74-182 g/L Sediments: 0.21-8.44 mg/kg Sewage sludge: 27.9-154 mg/kg
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  • Surfactants APEs: alkylphenol polyethoxylates Used in detergents, cleaning products, paints, and pesticides Degradation product 4-octylphenol Estrogenic Found in surface water Feminized male fish downstream from sewage treatment plants Impaired testicular development
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  • Surfactants
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  • Fish with both male and female sex tissue have been discovered near Colorado wastewater treatment plants on the South Platte River and Boulder Creek Newborn male fish become female fish after exposure to hormones There are many reports of alkylphenols causing production of a female associated liver protein, vitellogenin, in male fish -EPA
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  • Drug Example - DES DES Diethylstilbestrol Used from 1938 to 1971 Prescribed to 4.8 million women List - http://www.desaction.org/what.htmhttp://www.desaction.org/what.htm Marketed as a miscarriage preventative and a wonder drug that would make bigger and stronger babies
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  • Drug Example - DES Actually caused higher miscarriage rate In utero exposure (DES daughters) linked to: Malformations of reproductive organs Increased infertility 2-3 times risk for miscarriage, premature labor 2.5 times more likely to develop breast cancer DES mothers : 30-40% increased risk for breast cancer
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  • Sewage Treatment West Virginia HS student found three antibiotics in the river and tap water Sewage sludge/biosolids - run-off from agricultural fields Endogenous hormones, synthetic hormonally active compounds, antibiotics, blood lipid regulators, NSAIDs, beta-blockers, bronchodilators, antidepressants, obsessive-compulsive regulators, antiepileptics, antineoplastics (cancer drugs), impotence drugs, tranquilizers, retinoids, diagnostic contrast media, and numerous personal care products, including fragrances (synthetic musks), preservatives, disinfectants, antiseptics, sunscreen agents, and herbal remedies Tin, arsenic, selenium, tellurium, lead, gold, mercury, titanium, platinum, and palladium
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  • Metals TBT Tributyl Tin Component of antifouling paint for ships Leach 200g TBT/day into waters Androgenic properties Masculinization of female mollusks Arsenic inhibit the function of the receptor when normal glucocorticoid hormones bind Natl Academy of Sciences issued a report in 1999 Exposures at levels below EPA drinking water standard of 50 ppb caused problems with blood sugar regulation
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  • Organotins Used in plastics industry found in sponges cellophane wrap, baking parchments transferred to cookies on parchment
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  • EDCs in Cosmetics & Toiletries Alkylphenol Ethoxylates Benzophenone-3 (Bp-3) Butyl Benzyl Phthalate Butylated Hydroxyanisole (BHA) Butyl- methoxydibenzoylmethane (B-MDM) Dibutyl Phthalate Diethyl Phthalate Homosalate (HMS) Methyl-benzylidene Camphor (4-MBC) Nitro Musks Octyl-dimethyl-PABA (OD- PABA) Octyl-methoxycinnamate (OMC) Parabens Polycyclic Musks Resorcinol
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  • Parabens? Methyl, propyl, ethyl, and butylparaben Shampoos, conditioners, hair styling gels, nail creams, foundations, facial masks, skin creams, deodorants, etc. Suspected Endocrine Disruptor Parabens have been found to act like the hormone estrogen in laboratory experiments, although the activity was somewhat weak UK study has established the presence of intact parabens in human breast tumors
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  • Dioxin Viktor Yushchenko
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  • Dioxin Formed as an by-product of many industrial processes involving chlorine such as waste incineration, chemical and pesticide manufacturing and pulp and paper bleaching Anti-androgenic, anti-estrogenic Birds heart defects in chicks asymmetric brains in herons hatched from eggs containing 60 ppt
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  • Dioxin Rats Female rats 0.1 g/kg/day decrease fertility and litter size 1 g/kg give birth to females with delayed puberty and abnormal genitals 1 g/kg give birth to males with low sperm count and testosterone levels, delayed testicular descent, and altered sexual behavior Male rats - reduces testosterone levels, sperm counts, fertility, appetite, and body weight
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  • Dioxin Fish LD 50 for fertilized lake trout eggs is 65 pg/kg egg weight LD 50 for rainbow trout juveniles is 10 g/kg (ppb) body weight Monkeys 0, 5, and 25 parts per trillion diet 0 ppt 8/8 had live births, 17% endometriosis 5 ppt 6/8 had live births, 71% endometriosis 25 ppt 1/8 had live births, 86% endometriosis
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  • Dioxin Diesel oil releases dioxin when burned Rats exposed to diesel exhaust Lower sperm count, cells linked with an increased risk of testicular cancer Abnormal ovaries, delayed development of the thymus gland (immunological impairment) In pregnant rats levels of testosterone were significantly higher than normal
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  • Dioxin 1977 industrial accident released large amounts of dioxin in Seveso, Italy The most heavily exposed mothers gave birth to almost twice as many girls as boys Love Canal - tooth abnormalities such as double sets of teeth and teeth at birth Yusho, Japan contaminated rice oil high infant mortality almost all affected babies had chloracne
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  • Dioxin Vietnam Agent Orange CDC reports a higher incidence of spina bifida, cleft lip and cleft palate, hydrocephalus, and childhood cancers in children of American Vietnam veterans than in controls Higher incidence of miscarriages of fetuses fathered by Vietnam veterans 25 pg/g of blood fat compared to 3.9 pg/g

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