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and including Persistent Organic Pollutants and Plastics
Kids with exposure to nature have less ADHD

EDCs = endocrine disrupting chemicals
MOA: agonist and antagonist of receptor, upreg or downreg production or metabolism via enzymes
PCBs, PBDEs, BPA Phthalates, DDT, Dixoins, PAHs, pesticides, fertilizers, heavy metals

DIETHYSTILBESTROL aka DES
first known endocrine disrupter
used 1938-1971 to reduce miscarriage and premies, as fertility drug
a synthetic estrogen "supplement"
increases clear cell adenocarcinoma (CCA) of the vagina to 1/1000 for women exposed to DES in utero
manifests in late 20's early 30's
also linked to cervical dysplasia, congenital anatomic abn, infertility (2.1x), spontanteous abortion (4x)
possible link to breast ca
no relation with other est-related ca sofar
not a pop or "environmental" toxic
http://www.cdc.gov/des

EDCs - endocrine disrupting chemicals
greatest concern in utero exposure
effects on procreative inside baby-->grandchildren can be affected
http://www.ncbi.nlm.nih.gov/pubmed/20609371
Epigenetic effects of endocrine-disrupting chemicals on female reproduction: an ovarian perspective.
Abstract
The link between in utero and neonatal exposure to environmental toxicants, such as endocrine-disrupting chemicals (EDCs) and adult female reproductive disorders is well established in both epidemiological and animal studies. Recent studies examining the epigenetic mechanisms involved in mediating the effects of EDCs on female reproduction are gathering momentum. In this review, we describe the developmental processes that are susceptible to EDC exposures in female reproductive system, with a special emphasis on the ovary. We discuss studies with select EDCs that have been shown to have physiological and correlated epigenetic effects in the ovary, neuroendocrine system, and uterus. Importantly, EDCs that can directly target the ovary can alter epigenetic mechanisms in the oocyte, leading to transgenerational epigenetic effects. The potential mechanisms involved in such effects are also discussed.

DOHaD
Developmental Origins of Health and Disease

Theo Colborn, PhD
first to ID environmental EDCs
book: Our Stolen Future
www.endocrinedisruption.com

Critical Windows of Development
www.criticalwindows.com
looks at fetal development, conception to end of gestation
can click on toxin and see what evidence is by organ system and fetal timing

OBESITY
prental exposure to xeno-estorgens and other EDCs now called "obesogens"
predispose for accumulation of adipose
systems involved: adispose tissue receptors, leptins, thyroid, HPA axis, IR
http://www.tandforline.com/doi/abs/10.1080/1093740 ...
www.cdc.gov/obesity/data/trends/html has map of % of pop that are obese, can see trend
1/4-1/3 of all healthcare costs nationally are obesity related

TOXIC LOAD
toxins settle in favorite tissues
many lipophilic, heavy metals in +2 state like bone
bio-accumulation
bio-magnification occurs across vertical trophic levels of food web, mercury concentrates in carnivorous fish (heavy metals, POPs)

POPs = PERSISTENT ORGANIC POLLUTANTS
they persist, bio-accumulate, cause adverse effects
2001 UN Stockholm convention on POPs
only 5 countries have not ratified elimination
http://chm.pops.int/
incl synthetics containing carbon are durable, last decades or longer
many highly lipid soluble
many are hallogenated: chlorine, bromine, fluorine on carbon aka organohalides, halocarbons
halogenation prevents chemical degratdation, strongest possible atomic bonds is C-Fl, very toxic
(list of hallogenated ones in notes)
PCBs, dioxins, furans, adlrin, diealdrin, DDT, endrin, chlordane, hexachlorobenzene, mrex, toxaphene, heptachlor
congener = related chms with sim chem stx and fx (like isomer but for chems)

PCBs
over 200 congeners
2 bonded benzene rings
variable # of chlorine atoms (C12H10-xClx)
thick, viscous liquid @STP, odorless, tasteless, clear to pale yellow
industrial, usu coolants and insulators in electrical equipment ie transofrmers, capacitors, also lubricants, sealants: caulk, adhesive, pain, surgical implants, microscopy fixatives, carbonless copy paper
Monsanto made it 1929-1977
toxicity known since 1937
banned in 1970's: open sources in 73, enclosed sources in 77
GE released 1.3 million lbs into Hudson river-->1984 superfund site, www.epa.gov/hudson/
Westinghouse electric Bloomington, IN, damaged capacitors in landfills, PCB oil in sewage tx, sewage sludge into compost
residents of area may have 100xnormal PCB levels
Great Lakes (IL, WI, MI, OH, IN) fish eaters have 2-4x higher level PCB in blood
www.great-lakes.net/humanhealth/fish/critical ...
MAIN EXPOSURES via food, fish esp, also from product grown in contaminated food
inhalation ncbi.nlm.niv.gov/pubmed/18939536 it's in arctic snow
breast milk: first toxic detected
HEALTH EFFECTS OF PCBS
liver damage, liver and gallbladder cancer "probable", damages tight junctions in gut
Chloracne = dense acne is first obvious sign of high dose exposure, is permanent, dense comedones & pustules
developmental disorders: delayed responsiveness, impaired visual recognition, poor short term memory, ADHD
non-hodgkin's lymphoma, hypothyroidism, anemia
premies, low birth wt, microcephaly
endometriosis, irreg menses, low sperm production
LABS: metametrix labs, serum, polychlorinated-biphenyl-testing

PBBS are POLYBROMINATED BIPHENYLES
Sx: N/v, abd pn, jt pn, fatigue, acne, hepatic and renal damage, endocrine disruption

PBDES are POLYBROMINATED DIPHENYL ETHERS
radical increase in last 20 years, starting to decrease in last few
oxygen mol connects 2 benzene rings, agonist for t4 receptors, inverse correlation with T4
if more then decr TSH in preg female
used as flame retardants, in mattresses/foam padding/upholstry, electronics/circuitboards
mixed into plastics, not bonded
97% of US pop have some
prevention: personal/food hygiene, HEPA filter, dust surfaces
EFFECTS: decr glutathione fx, decr antiox, incr ox stress
neuro development, thyroid disruption, poor activity initiation, learning and memory
attention, cognition, psychomotor, language, conceptual development
PCB exposure increases effect
correlate with longer time to preg (decr fertility)
travel in breast milk, high lipid content
advice: detox before attempting preg, reduce exposures, keep breast feeding!!!
mercola on PBDE's: http://articles.mercola.com/sites/articles/archive/2012/12/27/flame-retardant-chemicals.aspx?e_cid=20121227_DNL_art_1
posting about notes on above article on 12/27/28

PRECAUTIONARY PRINCIPLE
burden on proof is on showing that a chem is NOT harmful
better safe than sorry
false positive better than false negative
this policy adopted by EU re: envir threat
US not in there yet

OTHER PFCS
POLYFLUOROTETRAETHYLENE (PRTE) is TEFLON
massive exposure from use when headed
only known health effect: fluroropolymer fever ("Teflon Flu") is immune rxn
mostly inert
Advice: Do NOT use

PFCAS aka PFAAS
POLYFLUORINATED CARBOXYLIC ACIDS or PERFLUOROALKYL ACIDS
water and oil repellant
in scotchguard, goretex, teflon, waxy cardboard, fire extinguisher, dental floss, stain resistant carpet, microwave popcorn bags
found in soil, water, air, food, dust

PFOAS
PERFLUOROCTANOIC ACIDS
aka C8
most common PFAA, ubiquitous exposure, immune to degradation
health effects: thyroid, liver, kidney, cancer of Li, testes, panc, immunotox, infert, LBW, birth defects
no current standard for drinking water, Shrub's limit set in 2009 is 10X higher than MADL max allowable dose
Tx: cholestyramine (Questran) pubmet 20621793, is a bile chelator

DIOXINS
"no safe dose", active at concentrations in parts per trillion (pg/kg)
standard tolerable daily intake (TDI) is 1-4 pg/kg/day, average is 1-2, many exceed, known damage at 1
CARCINOGEN: main action on Aryl Hydrocarbon receptor (AhR) essential to all DNA/RNA transcription (imp in ONCOLOGY)
broad class of chems, 75 congeners
colorless, odorless, solid crystal at SPT, occurs naturally and synthetic
C4H4O2, highly toxic
subclasses: polychlorinated dibenzodioxins (PCDDs) are dioxins (6 sided)
polychlorinated dibenzofurans (PCDFs) aka Furans (5 sided)
present in combustion organics from forest fires, volcanoes, accidental by product of industry
90% of exposure through food (meat, dairy, seafood), exposure is ubiquitous
beef, dairy, milk, chicken, pork, freshwaster fish, butter, cheese, human milk, meats, ice cream, eggs (vegans have least)
one more reason not to eat a diet high in animal products
here's one: 2,3,7,8-TCCD is 2nd most toxic human-made chem known (after botox), LD50=100ug/kg
flat planar stucture allows penetration btw lipid membranes
TEF toxic equivalence factor in range of 0-1; 2,3,7,8 is set at upper end of range at 1
TEQ Total Dioxin Toxic Equivalence is total body burden of all dioxins combined
HX: in agent orange defoliant used in Vietnam war-->birth defects/deformities in 500,000 Vietnamese babies, also 400,000 deaths
Also in Bentonite clay used in chicken feed, ceramic clay, why is it in there? not known
2004 atempted assassination of Ukranian pres candidate Viktor Yushchenko
SX: food poisoning, acute pancreatitis, chloracne
LABS: TCDD levels
SX: CHLORACNE, Li, Cirr, endocrine, abort/miscarriage, birth defect, CA

PCDFs is furans
125 congeners
same as dixons for most concerns

PERCHLORATES/PERFLUORATES
anionic compounds, cLo4
USES: rocket fuel, fireworks, road flares
medical uses: to tx hyperthyroidism, inhibits iodine/sodium symporter-->decr T3 and T4 production
no longer used in US dt health concerns, now use methimazole
SX: aplastic anemia
ubiquitous, very water soluble
presence of perchlorate in urine inversely proportional to thyroid fx
major cause of subclinical hypothyroidism
Tx: Iodine! SSKI, Lugols, etc. (see radiation section for dosing)
study last year denying that it was causing thyroid dysfx, this year PEA is regulating it with safe drinking water act
drinking water equivalent level 24.5 ug/L (ppb)
current envir exposure is about 5ppb, thyroid effects occur at 3, EPA level ref dose (RfD) is 7pb
Iodine updtake inhibition resolves in 2-3 days
short half life
only thyroid affected

PLASTICS
revolutionary
malleable, durable, resists degradation, waterproof, inexpensive, easily available
scene from movie: The Graduate
synthetic polymers, very large molecules made of repeating monomers
polystyrene, PVC, polyethylene: named for monomer
production increased radically since invention in 1950's, much more in world than in Europe

COOL WEBSITE: THE TRUTH ABOUT PLASTIC
www.reusethisbag.com/reusable-bag-infographics/the-truth-about-plastic.asp

TYPES OF PLASTIC BY SPI NUMBER

#1 PETE
fairly safe
polyethylene terephthalate, aka polyester, mc type
soda bottles, plastic bags, pipes, clothing
suspected carcinogen but no definitive data: one of the safer kinds
biggest concern is environmental: trash, Great Pacific Garbage Patch is 2x side of Texas

#2
one of the two safest types
HDPE high density polyethylene
detergent bottles, playground equipment

#3
harmful
PVC polyvinyl

PHTHALATES
esterified bilaterally around central benzene ring, colorless liquid, slight odor, bitter taste
"plasticizers" added to plastics to soften plastic mostly in type 3, up to 60% of a plastic
spacer btw plastic mols, alows long chain polymers to slide past each other
not covalently bonded to PVC, leeches very easily into air and water on contact
does NOT bioaccumulate (NOT a persistent organic pollutant POP)
used in toys (child and adult), gels, enteric coatings, emulsifiers, nail polish, eye liner, perfume, mascara, ink, paint
detergent, soap, shampoo, pesticide, fertilizer
lots in adult toys, this was mentioned several times
exposure via air, dust, ingestion, skin, release rate determined by temp, moisture, contact
exposure risk highest in toddlers, then children, infants, adults last
endocrine disrupter: xenoestrogen
breast ca pubmed 20368132
endometriosis, adenomyosis, leiomyosis pubmed 20147336
thyroid pubmed 200621847
effects development: undescended testes, shortened anogenital distance, decreased genital size, low T
ncbi.nlm.nig.gov/pubmed/20002220
obesogen, incr IR-->incr adiposityt pubmed/17589594, Stahlhut et al
Banned in US Aug 2008, can't have over 0.1% in things that go in kids mouths
LABS: Metametrix : Pthalates and parabens panel, and US Biotek: Evironmental pollutants profile both in urine

BISPHENOL-A
hazardous
LABS: Metametrix panel and NMSlab.com/services-clinical-bisphenol-a-bpa
BPA is a single mol
used in hard plastics, polycarbonate #7 and PVC #3
refillable beverage containers, some plastic utensils, containers, sports equipment, epoxies, dental composites, sealants
corrosion-resistant lining of all food/beverage cans
very common in marketplace, #2 chemical produced in US, over 6 billion tons/year produced in US (wiki says 8 billion)
95% of pop has elevated levels
EPA safe level is 50 ug/kg-day is 25x levels known to have health effects
subtle biochemical changes detected at levels of 0.001ug/kg (ie 1ppt part per trillion)
most human exposure via food, hard plastic bottles (nalgene, baby bottle) and cans (soft drinks, beer, food, baby formula)
breast fed babies have 10x less BPA exposure, powdered formulas safer than liquid
polycarbonate bottle-->13ug/kg-day exposure
temperature affects BPA leaching, 55x more if boiling relative to room temp
no difference based on age of container, no data on freezing
strategy: limit canned food consumption
10% of all cans have enough BPA to expose person to 200x level of safe exposure for pregnant woman
http://www.ewg.org/reports/bisphenola
MOVIE scene: The Jerk
top 10 foods to avoid: coconut milk, soup, meat, veggies, meals, juice, fish, beans, meal-replacement drinks, fruit
(what about tomatoes? not on his list)

3 day dietary intervention-->66% less BPA and 56% less phthalates in urine
back on usu diet, 202% incr BPA, 20% incr phthalates
result: both are transient, exposure is ubiquitous but it is eliminated quickly

exposure source: thermal paper, 40% of receptis are 1-3% BPA y wieght, 250-10000x more than in a can
easily transferred by handling, more with wet fingers, cashiers get 30% more BPA than average up to 71ug/day

BPA effects
xenoestrogen, concern esp during preg
incr prost and braest ca after natal exposure to BPA (rats)
predisposes tissues to be highly sensitive to estrogens in adulthood
gametogenic exposure, decr sperm count
meiotic aneuploidy--uneqal distrib of chromosomes in daughter cells (trisomy, etc)
obesogen, IR: prenatal exposure of 1ppb-->incr weight gain at weaning
some say BPA affects hundreds of genes, probably contributor to most chronic dz
behavior: hyperactivity (30ppb), aggression (2-40ppb), lower fear/pain threshhold (40ppb), learning disability (100ppb), reversal of geneder typed sexual behavior (30ppb), altered socialization skills (40ppb), incr drug addiction (40-300), memory formation (10ppb)

Many attempts to control BPA
cities, counties, states, countries have banned in child products
Oregon failed to pass ban in 2010 and 2011, tied vote split repub/dem
a local vote is happening 10/27 on county ban, http://salsa.democracyinaction.org/o587/p/dia/action...more
FDA "some concern", 10/7/11 American Chemistry Council asked FDA to remove from baby stuff
NIEHS $40 million studies ongoing
Bangor Daily News politics/gov-lepage-dismisses-dangers-of-bpa

#4
one of the two safest types

#5 PP
fairly safe
POLYPROPYLENE
packaging, tupperware, thermal underwear
heat resistant, durable
no known health effects
does leach into food
plastic test tubes and wells used in all bio a nd med research release low levels of oleamdie, an endogenous neurotransmitter, induces sleep, health and liab validity impacts unkonwn. http://www.sciencedaily.com/releases/2008/11/081118173218.htm doesn't work

#6
harmful
POLYSTYRENE
CD cases, plastic jewelry, petri dishes, plastic models, disposable razors, packing peanuts, styrofoam,
inexpensive, not usu recycled
releases PAHs, CO and styrene monomers when burned: extremely toxic
"smell of burnt plastic"
styrene is a weak toxin, LD40: 500-1000mg/kg
acute exposure-->irrit of membranes, resp
chronic-->dizz, fagiue, N/V, neural toxicity, possibly renal/hepatic at very high doses, industrial exposure
potential human carcinogen

#7 other
some are harmful

RELATIVE SAFETY OF TYPES OF PLASTIC
***(presentation is incorrect, this will be on final)
Safest: #2, 4, inert
Safe: #1, 5
Harmful: #3, 6, some 7

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