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Estrogenic Project BI 242 Environmental Science. Rachel Coughlin Sarah Laudenslager Meghan Maginnis Michael Southerton. The Endocrine System. Controls biological processes Consists of Glands (Pituitary, Adrenal, Thyroid, Pineal) Hormones are produced by the Glands - PowerPoint PPT Presentation
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Estrogenic ProjectBI 242 Environmental Science
Rachel CoughlinSarah Laudenslager
Meghan MaginnisMichael Southerton
The Endocrine System
Controls biological processesConsists of Glands (Pituitary, Adrenal,
Thyroid, Pineal)Hormones are produced by the Glands When the Hormones are released they
bind with receptors (plasma membrane or intracellular) located in certain organs and tissues.
This binding equals biological activity
Effects of Endocrine Disrupters
Endocrine Disrupters are chemicals that interfere with the natural Endocrine System
They “trick” the body into believing they are natural hormones Mimic Trigger Block
What is the Government Doing?
In 2003, 2004, 2005, the Bush administration tried to cut all EPA funding for independent scientists who do Endocrine-Disrupting research.
Total Budget for those three years was a combined 15 million dollars.
By comparison, Japan recently spent 135 million dollars on a research program.
http://bb.desales.edu/@@6212558F3460BDB0A498840036A3CF7C/courses/1/BI242-
What We Did
Testing of Lehigh Valley Wastewater Treatment Plants
We looked for the concentration of the EDC Estradiol in the influent (pre-treatment water) and the effluent (post-treatment water) over the course of three years. Upper Saucon Easton Philipsburg Nazareth Bath Allentown
Insecticides
Pesticides are intentionally released Operate by killing the insect or otherwise preventing it from engaging
in behaviors deemed destructive Little is known about the extent of environmental transport and fate of
these compounds. Many believed to be Endocrine Disrupting Compounds
Interfere with endocrine systems of humans and wildlife DES and methoxychlor – delay ovulation in adult rats Dicofol- retards reproductive development in alligators
• Alters concentrations of sex steroid hormones PCB- alter sexual determination in turtles Vinclozolin- delay puberty in rats
(Crews 2000)
(Lyons 1999)
Chlordane
C10H6Cl8First used in the 1940s as an insecticide
Usage was restricted to termite killing in 1978
Banned in 1988
Garages and soil still have remnants of previous chlordane usage
Not flammable, but may decompose in flammable solvents
Chlordane decomposes to produce toxic fumes that include chlorine, phosgene
(mustard gas), and hydrogen chloride.
(Stuart 2001)
IUPAC Name: 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene
Transported
Major sources of transport are through the air and water Enters atmosphere by: soil erosion by wind, dust and sprays Enters aquatic systems by: surface runoff and rainfall Absorbed into the bottom sediments
Can last from 3-15 years Highest samples are found closest to where it was sprayed
Convulsions, seizures, coma, respiratory depression It is considered a toxic systemic poison that is absorbed well by
inhalation, and through the skin On occasion, has been found in breast milk, as has oxychlordane
the stable metabolite. (Eisler 1990)
Effects on Humans
To determine the combined affect of environmental chemicals on hormonal activity estrogen receptors from either an Alligator (aER) or Human (hER) were incubated with one
of three chemicals: Chlordane, dieldrin, and toxaphene. Chlordane, dieldrin, and toxaphene individually demonstrated no significant
displacement of 17ß-estradiol from aER and hER at the concentration tested. A combination of these chemicals; however, inhibited the binding of 17ß-estradiol by
20 to 40% (Arnold 1997).
Toxicologist John A. McLachlan did a similar study involving a combination of these three compounds.
Inserted human estrogen receptors into yeast cells and a chemical response system that turned yellow when activated
Chlordane and the compounds, taken individually, are weak when mimicking estrogen
When chlordane was combined with another compound they acted synergistically and created an effect almost as toxic as dieldrin (insecticide endocrine disrupting compound). (Raloff 1996).
Studies Exhibiting Endocrine Effects
Effect of endocrine-disrupting chemicals on sex determination in the red eared slider turtle
•Analysis of yolk from alligator eggs identified different compounds in different amounts
•Same concentrations were applied to red-eared slider turtle eggs
•Significant number reversed sexes
•Influenced steroid hormone levels after hatching (low compared to the amount of natural estrogen)
•Data suggests that even at very low concentrations, endocrine disruptors found in the environment carry risk (Crews 2000).
Air Concentrations (ng/m3)
Between Bermuda and Rhode Island
(1973)
<0.005-0.9
Southern Hemisphere
(various locations- 1980-1984)
0.005-0.19
Northern Hemisphere
(Atlantic Ocean-1973-1978)
0.009-0.084
Pacific Ocean (1979-1981)
0.013Iraq, Tigris-Euphrates-Delta (1986)
57
Urban runoff 100
Lower Mississippi River
1.2-4
Fresh Water Concentrations (ng/L)
(Eisler 1990)
Seawater Concentrations (ng/L)
Sargasso Sea <10
Northern Pacific Ocean and Bering
Sea
40-50
Tokyo Bay, Japan 2
United States - Croplands
1970-80,000
1971-60,000
1972-50,000
Residential Areas- 1975
(upper 7.6 cm)
5.4*10^6
National Parks 5.0*10^6
Soil Concentrations (ng/kg)
Stream beds, drainage ditches (Nova Scotia)
0-6.64*10^5
Bottom muds (Ontario, Canada)
<100-3100
Streams, Tributaries to San Francisco Bay
4000-8000
Sediment Concentrations (ng/kg)
(Eisler 1990)
•Crews, David. (2000, September). Endocrine Disruptors: Present Issues, Future Directions. The Quarterly Review of Biology. 75, 243-260. Retrieved March 19, 2006 from EBSCO.Stuart, Bennent M. (2001). Chlordane. Retrieved March 20, 2006 : http://www.the-piedpiper.co.uk/th13(k).htm•Eisler, Ronald. (1990, July). Chlordane Hazards to Fish, Wildlife and Invertebrates: A Synoptic Review. Contaminant Hazard Reviews. 85, 1-62. Retrieved March 20, 2006: http://www.pwrc.usgs.gov/infobase/eisler/CHR_21_Chlordane.pdf•Arnold, Steven F. (1997, March). in vitro Synergistic Interaction of Alligator and Human Estrogen Receptors with Combinations of Environmental Chemicals. Environmental Health Perspectives. 103, 1. Retrieved March 20, 2006: http://www.ehponline.org/docs/1997/Suppl-3/arnold.html•Lyons, Gwynne. (1999, December). Endocrine Disrupting Pesticides. Pesticides News. 46, 16-19. Retrieved March 19, 2006. http://www.pan-uk.org/pestnews/actives/endocrin.htm•Raloff, J. (1996, June). `Estrogen' pairings can increase potency. Science News. 149, 356. Retrieved March 20, 2006 from EBSCO. •Gordon, John D. Detection of Estrogen Receptor Endocrine Potency of Commonly Used Organochlorine Pesticides Using the LUMI-CELL Bioassay. Organohalogen Compounds. 66, 196-174. Retrieved March 20, 2006: http://www.dioxins.com/pdfdocs/LUMI-CELL%20ER%20Pesticides%20Dioxin%202004.pdf
Works Cited
Plasticizers
Plasticizers:Small, often volatile molecules that are added to hard, stiff plastics to make them softer and more flexible.
From http://www.epa.gov/envirohealth/children/background/glossary.htm
Types of Plasticizers
Pthalate-based Plasticizers Bis(2-ethylhexyl)phalate (DEHP) Diisononyl phthalate (DINP) Butyl benzyl phthalate (BBzP) Bis(n-butyl)phthalate (DnBP, DBP) Diisodecyl phthalate (DIDP),
From http://www.answers.com/topic/plasticizer
More Types of Plasticizers
Adipate-based plasticizers Used for low-temperature or resistance to
ultraviolet light Bis(2-ethylhexyl)adipate (DOA) Dimethyl adipate (DMAD) Monomethyl adipate (MMAD) Dioctyl adipate (DOA)
From http://www.answers.com/topic/plasticizer
Still More Types of Plasticizers
Trimellitates used in automobile interiors and other
applications where resistance to high temperature is required
Trimethyl trimellitate (TMTM) Tri-(2-ethylhexyl) trimellitate (TEHTM-MG) Tri-(n-octyl,n-decyl) trimellitate (ATM)
From http://www.answers.com/topic/plasticizer
Other Plasticizers
MaleatesBenzoatesEpoxidized Vegetable OilsSulfonamidesPhosphatesGlycols / Polyethers From http://www.answers.com/topic/plasticizer
Phthalates
Most Common type of Plasticizer
“Phthalates migrate to the surface of plastics, and can then evaporate or leach into the surrounding environment. This limits the usefulness of phthalate plasticizers, as they eventually migrate out of plastics entirely, and as a result the plastics become brittle 2. The release of phthalates into the environment represents an environmental hazard as well. Because of the widespread use of phthalates, they have become one of the most abundant industrial pollutants in the environment.”
From http://www.carbohydrateeconomy.org/library/admin/uploadedfiles/Biochemical_Plasticizers.html
Photo from http://www.answers.com/topic/phthalates
Where are Phthalates Found?
Food Packaging Children’s Toys Medical Devices Cling Wrap Vinyl Tiles Traffic Cones Food Conveyer Belts Artificial Leather Plastic Foams
From http://www.answers.com/topic/plasticizer
Shoes Garden Hoses Building Materials Cellulose Plastics Food Wraps Adhesives Perfumes Cosmetics
Health Concerns
Health Care Without Harm“Aggregate Exposures to Phthalates in
Humans” – July 2002Analyzed and exposed many concerns
regarding human contact with phthalateshttp://www.noharm.org/details.cfm?type=d
ocument&id=796
Health Care Without Harm FindingsWho is exposed? Young, developing organisms are more vulnerable to
exposure to phthalates than adults In particular, the developing male reproductive tract
appears to be the most sensitive to exposure to several phthalates.
Effects on the liver, kidneys, lungs, and blood clotting are also of concern.
Women of reproductive age experience some of the highest exposure levels to phthalates - a special concern because phthalates can interfere with normal reproductive tract development of developing boys during pregnancy.
Children also have elevated levels of some phthalates.
Health Care Without Harm FindingsHow are people exposed?
Direct Exposure Direct use of cosmetics or exposure to medical
devices containing Phthalates
Indirect Exposure Puts general population at risk Exposure through discarded products, causing
“Worldwide Ecosystem Contamination.”
Phthalate Exposure and EarlyThelarche
In 2000, Colon, I, D Caro, CJ Bourdony, and O. Rosario. Released their findings that that since 1969 4,674 cases of Thelarche (the premature growth of breasts in girls) in Puerto Rico. This included the development of breast in a 23 month old child.
They documented the Thelarche as being a result of Phthalates present in the water supply.
http://bb.desales.edu/webapps/portal/frameset.jsp?tab=courses&url=/bin/common/course.pl?course_id=_3897_1
Dangerous Levels
The June 1998 edition of Consumer Reports sought to find the migration of phthalates from plastic wrappers to cheese slices.
The study provides an indication of the danger of Phthalates.
They identified three levels of contamination: Very High (50 to 160 parts per million) Moderate (1 to 4 parts per million) Little to No Contamination
From www.mindfully.org/Pesticide/Hormone-Mimics-In-Food.htm
Avoiding Phthalates
http://www.charityadvantage.com/mhop/whatyoucandotoreduce.asp
HAIRSPRAY-Phthalate Free DEODORANTS-Phthalate Free
Aussie Mega Styling SprayHelene Curtis Finesse Touchables Silk
Protein EnrichedHelene Curtis Thermasilk Heat Activated
Firm HairspraySuave Naturals Aloe Vera Extra Hold Hairspray
Certain Dri Anti-Perspirant Roll-OnDove Powder Anti-Perspirant DeodorantLady Speed Stick Soft Solid Anti-PerspirantSecret Anti-Perspirant & Deodorant Platinum Protection Ambition ScentSoft & Dri Anti-Perspirant Deodorant Clear Gel
FRAGRANCES-Phthalate Free HAIR GEL Phthalate Free
All of the fragrances we tested contained phthalates.
Physique Extra Control Structuring Gel
HAIR MOUSSE-Phthalate Free NAIL POLISH-Phthalate Free
Finesse Touchables Silk Protein Enriched Mousse
Helene Curtis Thermasilk Heat Activated Mousse for Fine/Thin HairL'Oreal Paris Studio Line: Springing Curls Mousse
Kiss Colors Nail PolishL'Oreal Jet Set Nail EnamelL'Oreal Jet-Set Quick Dry Nail EnamelMaybelline Shades of Your Nail ColorNaturistics 90 Second Dry! Super Fast Nail
ColorRevlon Nail EnamelRevlon Super Top SpeedUrban Decay
Personal Care Products: phthalates
DEHPdi(2-ethylhexyl)
Homer doesn’t allow cosmetics underhis roof…should you?
Chemicals
DEHP is a plastcizer in chemical form: di(2-ethylhexyl Phthalic Acid, Di(2-ethylhexyl) Ester
Molecular Formula: C24H38O4Abbreviations: DEHP, MEHP [mono(2-ethylhexyl) phthalate], PVC (polyvinyl chloride), PP (peroxisome proliferation).Synonyms and Trade Names: 1,2-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester; Bis(2-ethylhexyl) phthalate; Compound 889; Di(2-ethylhexyl) orthophthalate; Di(2-ethylhexyl) phthalate; Ergoplast FDO; 2-Ethylhexyl phthalate; Vestinol AH; Vinicizer 80; Witcizer 312
Physical and Chemical Properties of DEHP
DEHP is a colorless liquid with almost no odor Solubility: insoluble in water Water 41 μg/L at 25 ECa Organic solvent(s) Miscible in mineral oil and
hexane Soluble in most organic solvents
Potency (cont.)
Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity within in vitro
phthalate plasticiser DEHP (di-2-ethylhexyl phthalate) measured estrogenic potency is very weak
Sources
DEHP is widely used in medical devices, flooring, auto parts, and many other products.
DEHP is a phthalate ester widely used as a plasticizer to make polyvinyl chloride (PVC or vinyl) medical products soft and flexible and to increase moisturizing properties of some personal care products
It is used to detect leaks in protective face gear, and as a test material for filtration systems. It has also been used as a replacement for polychlorinated biphenyls (PCBs) in dielectric fluids for electric capacitors and in vacuum pumps.
According to EPA’s Toxics Release Inventory for 2000, reporting industries released nearly 250,000 pounds of DEHP into the environment.
Sources (cont.)
Point sources-from emissions or spills from sites that use DEHP in their manufacturing processes.Diffuse sources, and point sources included in aggregated emissions data-its wide use, volatility, & persistence mean that DEHP is widely distributed in the environment.Natural sources-DEHP has been suggested as a possible natural product in some animals and plants.Mobile sourcesNone Consumer products which may contain Di-(2-Ethylhexyl) phthalate (DEHP)-DEHP is in polyvinyl chloride (PVC) plastic products like toys, vinyl upholstery, shower curtains, adhesives, and coatings. It is used in some food packaging, and medical product containers (including those for blood) and equipment. It is also used in some inks, pesticides, cosmetics, and vacuum pump oil
Effects; why are they hard to determine?
Humans are exposed to substantial levels of DEHP through medical devices. Hemophiliacs, kidney dialysis patients, and high risk newborns are particularly heavily exposed.
The few studies of exposed human populations means that conclusions about DEHP risks must be based on laboratory animal studies.
Studies of laboratory animals, supported by very limited human data, suggest that a wide range of toxic effects occur in exposed mammals. Insufficient evidence exists to conclude that the toxic mechanisms found in laboratory animals do not occur in humans.
Uncertainty about the potential health hazards of DEHP remains. Quantitative estimates of risk to humans at various stages of life or health, or of safe levels of exposure, cannot be validated at this time.
Materials exist which do not contain DEHP or similar plasticizers, and are currently being used in medical devices. These materials are potentially safer alternatives to DEHP-containing medical devices.
Effects on Humans Health effects
Exposure: from use of medical products packaged in plastic such as blood products (particularly when used extensively, such as for kidney dialysis), eating some foods packaged in certain types of plastics or coated papers (ex. fatty foods, milk products, fish and seafood), soils, drinking contaminated water or breathing air containing DEHP where it is used or spilled. Di-(2-Ethylhexyl) phthalate (DEHP) enters the body:DEHP enters the body by breathing the vapors or ingesting it directly or through contaminated products. Absorption through skin contact is also possible but slow.Relative health hazardOn a health hazard spectrum of 0 - 3 Di-(2-Ethylhexyl) phthalate (DEHP) is a 1.3. A 3 represents a very high hazard, 2 represents a medium hazard and 1 is harmful to health. Factors for this ranking are; the extent of the material's toxic or poisonous nature and/or its lack of toxicity, and the evaluation of its tendency to cause, or not cause cancer and/or birth defects. It does not take into account exposure to the substance.
There is no evidence that DEHP causes serious health effects in humans. Most of what we know about the health effects of DEHP comes from high exposures to rats and mice which may not be representative of the effects on humans. Effects observed in animals were from very high and prolonged doses. Exposure to DEHP in air did not result in any observed effects. Exposure in food and water resulted in effects on sperm production, the ability to reproduce and birth defects. Kidney damage similar to the damage seen in the kidneys of long-term dialysis patients has also observed.DEHP is one of a range of phthalates which have been suggested as being able to be effect human and animal endocrine systems (endocrine disruptors)
Effects of Wildlife, Environment, & Water and Soil Environmental effects
DEHP in the atmosphere is present either as a gas or attached to solid particles. It breaks down quickly ( 1-2 days) due to the action of other chemicals in the atmosphere. The solid particles are removed from the atmosphere in 2-3 weeks by precipitation, wash out by rain, and reaction with other chemicals. DEHP is slightly prevalent in the environment. Small organisms in surface water or soil break it down into harmless compounds. It doesn't break down easily in deep soil, or in lake or river bottoms. It is in plants, fish, and other animals, but animals high on the food chain are able to breakdown DEHP, so tissue levels are usually low.Phthalate is slightly present in water but will break down in a few months.Environmental TransportDEHP from plastic materials, coatings, and flooring can increase indoor air levels. It dissolves faster in water if gas, oil, or paint removers are present. DEHP in the particle-phase is subject to wet and dry deposition. It will be transported in food chain & broken down and does not usually bioaccumulate. Concentration of DEHP in fish is expected to be much higher then the concentration in water in which the fish live.About 42.8% of DEHP will eventually end up in terrestrial soil; about 40% will end up in aquatic sediments; and about 17% will end up in air.Relative hazard to the environmentOn an environmental spectrum of 0 - 3 Di-(2-Ethylhexyl) phthalate (DEHP) is 1.2. A 3 represents very high hazard to the environment and 0 a negligible hazard. Factors include the extent of the material's toxic or poisonous nature and/or its lack of toxicity, and the measure of its ability to remain active in the environment and whether it accumulates in living organisms. It does not take into exposure to the substance.
Phthalates as Endocrine Disruptor Compounds: a very significant relationship between a mother's exposure during
pregnancy to phthalates changes in the ways that baby boy's genitals develop.
Baby boys with greater phthalate exposure had smaller AGI (anogenital index). measurements than normal.
Boys exposed to multiple phthalates simultaneously were also more likely to have smaller AGI scores.
Boys with lower AGIs had smaller penis volumes and were more likely to experience incomplete testicular descent.
The FDA warns anyone who is exposed to PVC (polyvinyl chloride) in a medical setting. DEHP is released from medical devices into solutions that come in contact with this plasticizer. Alternative methods are suggested when high exposure must take place; Especially for male neonates, pregnant women carrying male fetuses and peripubertal males (all having the greatest risk of negative effects).
EDC’s (cont.)
A valid human study linked prenatal phthalate exposure to adverse effects on the male reproductive system.
The associations between prenatal phthalate exposure and decreased AGI were very large and highly statistically significant.
In rodents, fetal exposure to phthalates causes a “phthalate syndrome.” It includes decreases in AGD, increased frequency of incomplete testicular descent and a birth defect of the penis called 'hypospadias,' increased risk of testicular cancer in adulthood, impaired sperm quality and more.
Scientists studying people found a pattern of male abnormalities called testicular dysgensis syndrome.' It includes hypospadias, cryptorchidism, impaired sperm quality and testicular cancer. One potential cause of TDS has been exposure to endocrine disrupting chemicals like phthalates.
The changes in AGI were observed at phthalate levels below those found in one-quarter of women in the United States, based on CDC’s nationwide sample.
Women are also denying products with any chemical link to defects (ex. Phthalates) One of the key points is DEHP's impact on developing Sertoli cells, cells in the male
reproductive tract that are central to sperm formation. Damaged Sertoli cells during development lead to sperm maladies in adulthood, including low sperm count. DEHP does not cause Sertoli damage directly; damage is caused by a metabolite of DEHP, monoethylhexyl phthalate (MEHP).
Sources Used:
www.epa.govwww.fda.govhttp://www.atsdr.cdc.gov/toxprofiles/tp9-c4.pdfhttp://www.mindfully.orghttp://www.noharm.orghttp://www.envirohealthaction.orghttp://www.npi.govhttp://lb.chemie.unihamburg.de/static/
data2/92_1upvg4mr.html
Detergents
Essential to personal and public healthContribute to good personal hygieneReduce germs that cause infectious
diseasesFour categories of detergents
Personal cleansing Laundry Dishwashing Household cleaning
Chemicals found in Detergents
There are many different chemicals that are found in cleaning detergents Acetone Benzaldehyde Benzyl Acetate Linalool Nonylphenol Ethylene Oxide
Nonylphenol
Part of the alkylphenol family Used as a surfactant in cleaning and cosmetic products and as a spermicide
in contraceptives C15H240 Properties
Thick, light yellow, color liquid with slight characteristic phenolic odor Poorly soluble in water, soluble in alcohols
Effects Shown to have estrogenic properties Poisoning decreased weight gain, caused changes in the liver,
hemorrhages Stimulates breast tumor cells in vitro Increase uterine weight Allergenic effect-skin sensitization reaction Safe level in drinking water– 0.001mg/l
Nonylphenol (cont.)
Gets into water through everyday actions Washing hands Doing the laundry Taking showers and baths
Have been shown to have effects on many aquatic organisms (bound estrogen receptors)
Non-occupational exposure does not pose any risk for humans To get the same effect with 17B estrodial you need 11,000 times higher
concentration of nonylphenol Other effects
Human males over the past 2 generations have 50% lower sperm counts Rising rates of testicular cancer and birth defects (undescended testicles) Change of genitals in animals
Estradiol
Sex hormone labeled as the female hormone but also found in men because it represents the major estrogen in humans
Critical for sexual functioning Supports bone growth Derived from cholesterol Androstendione – key intermediary; is converted to testosterone which
undergoes aromatization and then turns into estradiol
Chemical Formula – C18H24O2
Estradiol (cont.)
Most is produced in women by the granolusa cells of the ovaries Fat cells are active to convert precursors to estradiol, and will
continue to do so even after the menopause Effects
Breast development Adding fat to hips, thighs and breasts during puberty Improving bone strength and density Growth in the uterus Participating in triggering ovulation Preservation of egg cells
Three Year Totals
Influent and efffluent values of estrogenic compounts in Lehigh Valley wastewater treatment plants
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
Pberg Easton Usaucon Nazareth Bath Allentown
wastewater treatment plant
Pa
rts
pe
r T
rill
ion
of
es
tro
ge
nic
n
eq
uiv
ale
nt
7/20/04 Influent
7/20/04 Influent
10/8/04 Influent
10/8/04 Effluent
3/14/05 Influent
3/14/05 Effluent
6/28/05 Influent
6/28/05 Effluent
3/13/06 Influent
3/13/06 Effluent
Total Average Part Per Trillion over Three Year Period = 16.3