Di(2-ethylhexyl)phthalate
Lynn Feutz
Erich Mack
Becky Mader
Background
• Di(2-ethylhexyl)phthalate other
names
– DEHP
– Bis(2-ethylhexyl)phthalate
• Cas Number: 117-81-7
• Chemical formula: C24H38O4
• Molecular model
DEHP
O
O
O
O
Properties of
DEHP
•
•
•
•
Colorless
Slight odor
Insoluble in water
Soluble with most organic
solvents
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
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
Hazardous??!!??!!
•
•
•
•
Health Care Without Harm
Greenpeace
Health Canada
FDA
Restrictions
• Sweden
– Children’s toys
under the age
of 3
• Brussels
– CAT 2
Carc
Cat 1
category 1
carcinogens
Carc
Cat 2
category 2
carcinogens
Carc
Cat 3
category 3
carcinogens
Chemicals
that may
cause
cancer or
increase
its
incidence.
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)
– >3% in pacifiers and teethers
• Safety regulations and effects
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
Hazardous Waste Sites in U.S.A
Industrial
Releases
• Air = 212,000
lbs.
• Soil = 24,000
lbs.
• Water = 669
lbs.
250000
200000
150000
100000
50000
0
Air
Soil
W ater
• Air =
280,000,000 lbs.
• Soil =
262,000,000 lbs.
• Water =
16,260,000 lbs.
Domestic
Releases
300000000
250000000
200000000
150000000
100000000
50000000
0
Air
Soil
Water
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
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
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
Washout rate
DEHP air release
Particulating rate
Particals
Graph 1
Rain
Air
half lif e water
half lif e soil
landf ill leaching rate
DEHP water realease
Leaching
Soil Deg
Water Deg
Soil
Water
Sedimentation
DEHP soil release
sedimentation rate
f ish uptake
Bioaccumulation f actor
Sediment sink
f ish half lif e
f ish dy ing
Fish Bioconcentration
f ish death rate
Fish elimination
Simulated Response of DEHP in the
Environment
2: Fish Bioconcent… 3: Sediment sink
1: Air
1:
2:
3:
4:
5:
1:
2:
3:
4:
5:
4
3
450950000
5
2
5
1
2
1
2
5
1
2
5
3
0
0.00
Page 1
5: Water
901900000
1
1:
2:
3:
4:
5:
4: Soil
3.75
7.50
Time
Untitled
11.25
15.00
3:35 PM Tue, Feb 26, 2002
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
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
Household Items Containing DEHP
Concentration of DEHP (mg/kg)
Household
Waste
Mean
Minimum
Maximum
64.3
4.8
334.7
Paper for recycling
29.7
10.0
60.3
Unusable paper
71.1
41.4
106.4
Cardboard
47.4
10.1
70.5
Plastic Films
444.9
169.0
907.9
Other plastics
1027.6
373.8
2035.3
Textiles
205.7
14.9
686.1
Compound waste
151.9
57.7
393.7
16820.6
7862.4
26352.0
74.1
14.2
322.2
Food waste
Compound materials
Disposable diapers
DEHP
di(2-ethylhexyl)phthalate
•
•
•
MW =
390.57g/mol
Colorless liquid
High log Kow
(7.50)
–
•
•
O
O
Sticks to fat
High log Koc (56)
–
O
Sticks to soils
Very low vapor
pressure
O
Important Metabolites of DEHP
MEHP
mono(2-ethylhexyl)phthalate
O
O
O
OH
• MW =
278.3474g/mol
• Colorless liquid
• Primary
breakdown
metabolite
• High affinity for
fat and soil
2-ethylhexanoic acid
• MW =
144.2132 g/mol
• Clear liquid
• Secondary
breakdown
metabolite
• Very low
solubility
(<0.01 g/L)
OH
O
2-ethyl-1hexanol
• MW =
130.2296
• Clear colorless
liquid
• Very low vapor
OH
pressure &
solubility
• Secondary
breakdown
metabolite
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
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
Medical Tubing: Who is at Risk?
•
•
•
•
Dialysis patients
Hemophiliacs
Neonatal infants
Respiratory
patients
• Patients in
general who need
extensive medical
care
Extraction from Blood Bags
• High affinity for components in
plasma
– Lipids
– Levels of cholesterol and
triglycerides
– Proteins
– Red Blood Cells
Why DEHP is used in
Blood Bags (PVC bags)?
- Makes bags
very flexible
- Can handle
extreme
temperatures
- Prolongs life of
blood
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)
Foods where DEHP can Accumulate
• Fatty foods
–
–
–
–
–
–
–
Milk
Cheese
Fish
Meat
Margarine
Eggs
Cereal
products
– Chocolate
How DEHP is Extracted from
Children’s toys
• Excessive
handling of the
toy
• Sucking and
chewing of the
toy by young
children.
– Plasticizer can
be edged
away from the
plastic
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
Children are at a Greater Risk
• Their bodies don’t
behave as ours
do
• The have a
different lifestyle
– Crawl on the floor
– Eat anything
– Don’t have
judgement to
avoid hazards
Children and Other
Routes of Exposure
• Inhalation
– Dust particles
• Medical tubing
– leaching of
DEHP
– Hemodialysis
– Transfusions
– Cardiopulmon
ary bypass
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
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
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
Breakdown of DEHP in the body
- Hydrolyzed by
the stomach
- Metabolites
accumulated in
fatty organs
- Metabolites
excreted
through bile
and urine
Fate of DEHP
in the Human Body
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
Effects of DEHP on the liver
Tumors found in rat and mice
livers
Peroxisome proliferation
Livers of dialysis patients
DEHP as an Allergen
• In the Lungs
– Response from prostaglandins
– Air passageways become
constricted
– Potentially dangerous for the
individual
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.
Allergen
• Each individual is different
• Age, sex, and genetic
disposition affect allergic
susceptibility
• DEHP affects everyone
differently
Reproductive Effects of DEHP
• FEMALES
– In Russia
• Decreased rates of pregnancy
• Increased rates of miscarriage
• Anovulation
– In rats
• Damage of Granulosa cells
Reproductive Effects on DEHP
• MALES
– Rats
• Testicular
toxicant
• Inhibitor of
FSH signals
– Affecting
Sertoli
Cells
– Increased
ability for
sperm
damage
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
Bibliography
1.
“Di(2-ethylhexyl)phthalate.” http://www.eco-usa.het/toxics/di2eph.shtml.
Accessed on 2/6/2002
2.
Cray, Charlie, “Experimenting on Children.” Environment and Healthy
Weekly: June 19, 1998, 603. http://www.monitor.net/rachel603.html.
Accessed on 2/6/2002
3.
“US Patent and Trademark.” http://patft.usptp.gov/netacgi/hph.html.
Accessed on 2/11/2002
4.
“Bis(2-ethylhexyl)phthalate.” http://www.epa.gov/ttn/uatw/hlthef/eth-phth.
Accessed on 2/6/2002
5.
“The Dose Makes a Difference.”
http://www.nepa.org/pl/environ/pd083/oog.html. Accessed on 2/6/2002
6.
“Classification and Labeling of DEHP.” http://www.eupc.org. Accessed on
2/8/02
7.
“ATSDR-ToxFAQs: DEHP.” http://www.atsdr.cdc.gov/tfacts9.htm. Accessed
on 2/6/2002
8.
U.S. Dept. of Health and Human Services, Draft Toxicological Profile for
DEHP. Syracuse Research Corporation., Sept. 2000 pg. 1-192
9.
Spectrum Laboratories, Chemical Fact Sheet; CAS#117817
10. Giam, C.S., The Handbook of Environmental Chemistry of Anthropogenic
Compounds, 67-141, 1994
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(2ethylhexyl)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/DEHPCarcinogen-EHIS.htm. Jan. 2001
16.
Dr. Kimberly Bates, Winona State University. Interview, 14 Feb. 2002.
Bibliography
17.
Haring, Hong, Liebich, Maier, Stube, and Wahl, Hans Gunther.
“Simultaneous analysis of the di(2-ethylhexyl)phthalate metabolites 2ethylhexanoic acid, 2-ethyl-3-hydroxyhexanoic acid and 2-ethyl-3oxohexanoic 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.
“H&S: Mono(2-ethylhexyl)phthalate.” http:/ntpsever.niehs.nih.gov/htdocs/CHEM_H&S/NTP_Chem4/Radian4376-209.html
19.
Hazardous Substance Data Bank. “Human Health Effects.”
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~BAAKQaamq:1
20.
Hoyer, Patricia. “Reproductive toxicology: current and future
directions” Biochemical Pharmacology. Vol. 62. 2001: pp. 1557-1564.
Thank you
Are there any questions?