Di(2-ethylhexyl)phthalate

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Di(2-ethylhexyl)phthalate

• Lynn Feutz
• Erich Mack
• Becky Mader

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Background

• Di(2-ethylhexyl)phthalate other names
• DEHP
• Bis(2-ethylhexyl)phthalate
• Cas Number 117-81-7
• Chemical formula C24H38O4
• Molecular model

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DEHP
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Properties of DEHP

• Colorless
• Slight odor
• Insoluble in water
• Soluble with most organic solvents

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Use of DEHP

• Primary, plasticizers in polyvinyl chloride (PVC)
• pacifiers - soft squeeze toys
• balls
• vinyl upholstery - tablecloths
• shower curtains -raincoats -adhesives
• polymeric coating -defoaming agents
• food containers - animal glue
• OTHER ARE MANY OTHERS

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Other Industrial Products

• Blood Bags-
• Multiple bag system
• Method and system for collecting, processing, and
  storing blood components
• Flexible surgical/medial products
• Process for the distillation of alcohol
• There are 112 patens for DEHP presently

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Hazardous??!!??!!

• Health Care Without Harm
• Greenpeace
• Health Canada
• FDA

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Restrictions

• Sweden
• Childrens toys under the age of 3
• Brussels
• CAT 2

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US and their Regulations

• Reference dose 0.02 mg/kg/d
• EPA, OSHA, ACGIH limitations
• 6 ppb and 5 mg/m3 over 8 hour work day
• 10 mg/m3 for a 15-minute exposure
• Toy Manufacturers of America (TMA)
• gt3 in pacifiers and teethers
• Safety regulations and effects

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Release of DEHP into the Environment

• Industrial and domestic
• Found in 710 of the 1598 hazardous waste sites
  (NPL)
• 704 in the U.S.A
• States w/ highest release rates
• Michigan, Maryland, New York, Pennsylvania,
  Tennessee

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Hazardous Waste Sites in U.S.A
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Industrial Releases

• Air 212,000 lbs.
• Soil 24,000 lbs.
• Water 669 lbs.

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Domestic Releases

• Air 280,000,000 lbs.
• Soil 262,000,000 lbs.
• Water 16,260,000 lbs.

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Fate of DEHP in Soil

• Rain particles / More DEHP
• High KOC ratio
• Half-life 120-550 hours
• Depends on soil conditions
• Evaporation Hydrolysis have little effect

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Fate of DEHP in Air

• High KOC
• Absorbs to particulates
• Rain washes out DEHP over land/water
• Half-life very long, washes out
• Limited travel
• Due to KOC / fast washout rate
• Concentrated to region of release

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Fate of DEHP in Water

• Half-life varies
• Aerobic
• Fast/slow moving currents
• High/Low salinity
• High KOC ratio
• Adheres to particle in water column
• Falls to sediment bed
• Leachate from landfills (slight)
• Fish ingest and bioaccumulate DEHP

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Simulated Response of DEHP in the Environment
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Effect of DEHP in Seafood

• Fish excretion half-life
• Minnow 168 hours
• Bluegill 72 hours
• Fish bioaccumulate DEHP
• Minnow BCF 851
• Bluegill BCF 115
• Major sink for DEHP
• Direct source for human exposure

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Household DEHP exposure routes

• Food wraps and seals
• Leaches DEHP into food
• Contaminated food stuffs
• Milk
• Cheese
• meat

• Plastic toys
• Dolls
• pacifiers
• Household
• Shower curtains
• tile

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Household Items Containing DEHP
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DEHP
di(2-ethylhexyl)phthalate

• MW 390.57g/mol
• Colorless liquid
• High log Kow (7.50)
• Sticks to fat
• High log Koc (5-6)
• Sticks to soils
• Very low vapor pressure

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Important Metabolites of DEHP
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MEHP mono(2-ethylhexyl)pht
halate

• MW 278.3474g/mol
• Colorless liquid
• Primary breakdown metabolite
• High affinity for fat and soil

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2-ethylhexanoic acid

• MW 144.2132 g/mol
• Clear liquid
• Secondary breakdown metabolite
• Very low solubility (lt0.01 g/L)

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2-ethyl-1hexanol

• MW 130.2296
• Clear colorless liquid
• Very low vapor pressure solubility
• Secondary breakdown metabolite

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Why DEHP is used in Medical Tubing

• Create more flexible less brittle tubes
• Increase strength, safety and comfort for patient
• Catheters, oxygen masks, intravenous tubing
• Prevent clotting of blood
• Materials can easily move through soft tubes

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Medical Tubing

• DEHP leaching from medical tubes
• DEHP not covalently bonded to tubes
• Extracted easily if DEHP has a high affinity for
  substance being passed through
• Excessive flexing and handling of tubes help
  extraction
• Entering into the body

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Medical Tubing Who is at Risk?

• Dialysis patients
• Hemophiliacs
• Neonatal infants
• Respiratory patients
• Patients in general who need extensive medical
  care

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Extraction from Blood Bags

• High affinity for components in plasma
• Lipids
• Levels of cholesterol and triglycerides
• Proteins
• Red Blood Cells

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Why DEHP is used inBlood Bags (PVC bags)?

• Makes bags very flexible
• Can handle extreme temperatures
• Prolongs life of blood

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Why is DEHP used in Food Packaging?

• Preservation of food
• Ability to handle extreme temperatures
• (Used in plastic food wraps, heat seal coatings
  for foil, closure seals for containers, and food
  printing inks)

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Foods where DEHP can Accumulate

• Fatty foods
• Milk
• Cheese
• Fish
• Meat
• Margarine
• Eggs
• Cereal products
• Chocolate

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How DEHP is Extracted from Childrens toys

• Excessive handling of the toy
• Sucking and chewing of the toy by young
  children.
• Plasticizer can be edged away from the plastic

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Exposure Route from Toys into the Body

• Saliva
• Main exposure route
• DEHP may be attracted to organic salts or various
  enzymes found in saliva
• Blood vessels in mouth
• Underneath tongue
• Easy access to the bloodstream

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Children are at a Greater Risk

• Their bodies dont behave as ours do
• The have a different lifestyle
• Crawl on the floor
• Eat anything
• Dont have judgement to avoid hazards

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Children and Other Routes of Exposure

• Inhalation
• Dust particles
• Medical tubing leaching of DEHP
• Hemodialysis
• Transfusions
• Cardiopulmonary bypass

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Occupational Exposure

• Inhalation
• DEHP binds to particles in air
• Threshold limit in the workplace is 5.0
  micrograms/L
• Workers exposed to 1.1 micrograms/L
• Very little risk if exposed to DEHP via skin

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Is DEHP Harmful to the Human Body

• Thought to be a human carcinogen (EPA)
• Not enough proof to verify this
• Animal testing
• DEHP affects all species differently
• Few human observations

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Adverse Health Effects from DEHP Metabolites

• Peroxisome proliferation
• Cells that accumulate when there is a foreign
  substance in the body and the body is trying to
  get rid of it
• Stimulation of the initial responses of
  peroxisome sites to produce more cells
• Nephrotoxicity
• Toxic agents found in the liver

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Breakdown of DEHP in the body

• Hydrolyzed by the stomach
• Metabolites accumulated in fatty organs
• Metabolites excreted through bile and urine

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Fate of DEHP in the Human Body
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Effects of Human Ingestion of DEHP

• First study
• 10 g DEHP ingested
• Mild abdominal pain
• diarrhea
• Second study
• One dose 71.4 mg/kg/day NOAEL
• Another dose 142.9 mg/kg/day
• Gastrointestinal distress

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Effects of DEHP on the liver

• Tumors found in rat and mice livers
• Peroxisome proliferation
• Livers of dialysis patients

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DEHP as an Allergen

• In the Lungs
• Response from prostaglandins
• Air passageways become constricted
• Potentially dangerous for the individual

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Allergen

• Medical tubing used for hemodialysis patients
• 27 patients
• 3 cases of non-specific hepatitis
• Hepatitis disappears after use of tubing
  containing DEHP is stopped.
• Hepatitis was thought to be allergic reaction to
  DEHP.

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Allergen

• Each individual is different
• Age, sex, and genetic disposition affect allergic
  susceptibility
• DEHP affects everyone differently

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Reproductive Effects of DEHP

• FEMALES
• In Russia
• Decreased rates of pregnancy
• Increased rates of miscarriage
• Anovulation
• In rats
• Damage of Granulosa cells

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Reproductive Effects on DEHP

• MALES
• Rats
• Testicular toxicant
• Inhibitor of FSH signals
• Affecting Sertoli Cells
• Increased ability for sperm damage

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Recommendation from Risk

• Clear risk to human health
• Eliminate food packing w/ DEHP
• Alternate plasticizers
• Regulate certain toys DEHP concentrations
• Especially baby toys
• Eliminate DEHP use in the medical sector
• Use alternate/safer plasticizers
• Learn from the EU actions
• Set precedents
• Government
• Corporation

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Bibliography

• Di(2-ethylhexyl)phthalate. http//www.eco-usa.h
  et/toxics/di2eph.shtml. Accessed on 2/6/2002
• Cray, Charlie, Experimenting on Children.
  Environment and Healthy Weekly June 19, 1998,
  603. http//www.monitor.net/rachel603.html.
  Accessed on 2/6/2002
• US Patent and Trademark. http//patft.usptp.gov
  /netacgi/hph.html. Accessed on 2/11/2002
• Bis(2-ethylhexyl)phthalate. http//www.epa.gov/
  ttn/uatw/hlthef/eth-phth. Accessed on 2/6/2002
• The Dose Makes a Difference. http//www.nepa.org
  /pl/environ/pd083/oog.html. Accessed on 2/6/2002
  
• Classification and Labeling of DEHP.
  http//www.eupc.org. Accessed on 2/8/02
• ATSDR-ToxFAQs DEHP. http//www.atsdr.cdc.gov/t
  facts9.htm. Accessed on 2/6/2002
• U.S. Dept. of Health and Human Services, Draft
  Toxicological Profile for DEHP. Syracuse Research
  Corporation., Sept. 2000 pg. 1-192
• Spectrum Laboratories, Chemical Fact Sheet
  CAS117817
• Giam, C.S., The Handbook of Environmental
  Chemistry of Anthropogenic Compounds, 67-141,
  1994

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Bibliography

• 11. Turner, A. Rawling, M.C., The
  Behavior of DEHP in Estuaries, Marine Chemistry.
  2000
•  
• 12. European Council for Plasticisers and
  Intermediates (ECPI). Phthalates in Medical
  Applications Proven Life Savers.
  http//medicalplast.ecpi.org/ 9 Feb. 2002.
•  
• 13. Hill, Shaw, and Wu, Alan H.B. The
  clinical effects of plasticizers, antioxidants,
  and other contaminants in medical
  polyvinylchloride tubing during respiratory and
  non-respiratory exposure Clinica Chimica Acta.
  Vol. 304, Issues 1-2. Feb, 2001 pp. 1-8.
•  
• 14. Azar, Brunet, Dine, Gressier,
  Kambia, Luyckx. Comparative study of the
  leachability of di(2-ethylhexyl)phthalate and
  tri(2-ethylhexyl)trimelliate from haemodialysis
  tubing International Journal of Pharmaceutics.
  Vol 229, 31 Jul 2001 pp. 139-146.
•  
• 15. EHIS 9th Report on Carcinogens.
  Di-2-ethylhexyl phthalate (DOP, DEHP) Cas No.
  117-81-7. http//www.mindfully.org/Plastic/DEHP-
  Carcinogen-EHIS.htm. Jan. 2001
•  
• Dr. Kimberly Bates, Winona State University.
  Interview, 14 Feb. 2002.

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Bibliography

• Haring, Hong, Liebich, Maier, Stube, and Wahl,
  Hans Gunther. Simultaneous analysis of the
  di(2-ethylhexyl)phthalate metabolites
  2-ethylhexanoic acid, 2-ethyl-3-hydroxyhexanoic
  acid and 2-ethyl-3-oxohexanoic acid in urine by
  gas chromatography-mass spectrometry Journal of
  Chromatography B Biomedical Sciences and
  Applications. Vol 758, Issue 2. 15 Jul 2001
  pp. 213-219.
• 18. HS Mono(2-ethylhexyl)phthalate.
  http/ntp-sever.niehs.nih.gov/htdocs/CHEM_HS/NTP_
  Chem4/Radian4376-20-9.html
•  
• 19. Hazardous Substance Data Bank. Human
  Health Effects. http//toxnet.nlm.nih.gov/cgi-bin
  /sis/search/f?./temp/BAAKQaamq1
•  
• 20. Hoyer, Patricia. Reproductive
  toxicology current and future directions
  Biochemical Pharmacology. Vol. 62. 2001 pp.
  1557-1564.

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Thank you

• Are there any questions?