Transcript What are Phthalates?

Phthalates
Edwin Chiang
May 18, 2005
Bio 2B
What are Phthalates?
•Phthalates are a class of widely used industrial compounds used as
plasticizers especially in PVC (polyvinyl chloride)
•Various types of phthalates
–Range from one carbon to seventeen carbons
–PVC plasticizers generally range from 4-13 carbons
•Examples:
–DINP (di-isononyl phthalate)
–DIDP (di-isodecyl phthalate)
–DBP (di-butyl phthalate)-common ingredient in nail polish
–DEHP (di-2-ethylhexyl phthalate)-used to make PVC
Chemical Properties
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Insoluble in water
Soluble in most organic solvents
Colorless liquid with almost no odor
DINP: Superior anti-heat, anti-cold, and anti-volatile
properties
• DIDP: Low volatile properties, anti-heat and anti-aging
properties, and electricity insulation properties
Uses of Phthalates
• Accounts for 80–90 percent of the world plasticizer consumption
• Used primarily as plasticizers in polyvinyl chloride (PVC) products
• Child’s toys
• Kitchen floor
• Building materials
• Medical devices: Plastic in IV, blood bags, etc.
• Fixatives for perfume, slowing down evaporation and making the
scent linger longer
Other Uses
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Keep nail polish from chipping
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Hair sprays
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Coatings on numerous pharmaceutical products
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New car smell: Partly the pungent odor of phthalates volatilizing from a hot plastic
dashboard. In the evening's cool they then condense out of the inside air of the car to
form an oily coating on the inside of the windshield.
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Make tool handles strong and more resistant to breaking
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Nail extenders
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Bath soaps
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Detergents
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Aftershave lotions
Exposure
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Anything plastic
Fatty items like cheese and meat from food packages
Medical tubing/bags
New car smell
Toys
Cosmetics
Leather
Cables
Products with vinyl
Study on the Levels of Seven Urinary Phthalate Metabolites in a Human Reference
Population conducted by Blount, BC, MJ Silva, SP Caudill, LL Needham, JL Pirkle, EJ
Sampson, GW Lucier, RJ Jackson, JW Brock in 2000
Highest level of exposure was women of child-bearing age,
High levels of DEP, DBP, BBP
Likely sources of these exposures are through cosmetics, including hair sprays, nail
polishes and perfumes, which are common applications of DBP
DEHP & DINP were not found in high concentrations
Exposures
(DEHP)
• Air
– Diethyl phthalate has been measured in the indoor air of a telephone
switching office and in outdoor air in Newark, USA, at concentrations
ranging from 1.60 to 2.03 µg/m3 and from 0.40 to 0.52 µg/m3,
respectively, during a 43-day sampling period (Shields & Weschler,
1987).
• Water
– Concentrations range from 0.01 µg/litre (in 6 of 10 US cities) to 1.0
µg/litre (in Miami, Florida) found in drinking-water samples from water
treatment
– US EPA (1989) summarized various studies (originally reported in
1980–1982) in which diethyl phthalate was detected in the groundwater
of 33% of 39 public water wells in New York state; other phthalate
esters were also detected. Again, it is difficult to determine whether
these phthalates originated from the waterworks systems or from
sample contaminations.
(continue…)
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Food
– Baked foods in the United Kingdom packaged in cardboard boxes with cellulose
acetate windows (containing 16–17% w/w diethyl phthalate) had diethyl phthalate
concentrations of 1.7–4.5 mg/kg. It was suggested that diethyl phthalate may
volatilize from the plastic window to the food without direct contact or be
adsorbed in condensate on the window, which would then fall back onto the food
(Castle et al., 1988). Diethyl phthalate was quantified from retort food at
concentrations of 0–0.51 mg/kg (Giam & Wong, 1987). Based on the levels of
diethyl phthalate found in food by Castle et al. (1988), Kamrin & Mayor (1991)
estimated a total daily dietary exposure to diethyl phthalate of 4 mg, assuming
daily ingestion of 1 kg of cellulose acetate-wrapped food containing 4 mg diethyl
phthalate/kg. This represents a worst-case scenario, as it assumes that most
foods are packed in cardboard boxes with cellulose acetate windows containing
diethyl phthalate.
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Cosmetics
– A 2001 survey of fragrance manufacturers in the USA provided maximum
concentrations of 1–11% diethyl phthalate in perfume and up to 1.0% in
deodorants and other personal cleanliness products. The products may be
applied to skin, eyes, hair, and nails, and they may come in contact with mucous
membranes and the respiratory tract; contact may be frequent (several times a
day) and of prolonged duration (years). Diethyl phthalate is also approved for use
as a component of food manufacturing equipment and packaging at unlimited
concentrations (Anonymous, 1985) and in drug product containers (Kamrin &
Mayor, 1991).
Harmful Effects
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At high doses of phthalates do constitute risks in the sense of traditional
toxicology, these low doses change the stakes dramatically
Male reproductive development is acutely sensitive to some phthalates
DBP & DEHP produced dramatic changes in male sexual characteristics
when exposure took place in utero, at levels far beneath those of previous
toxicological concern
Males
– Hypospadias (anomaly of the urethra )
– Damage of Sertoli cells caused by a metabolite of DEHP,
monoethylhexyl phthalate (MEHP)
– Low sperm count
– Reductions in semen quality
– DNA damage to sperm
Females
– Premature breast development
Premature birth
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• Carcinogenic
• Damaged the liver of rats and mice at high doses
– Relevant to humans: unknown
Research
• Scientists have long known that relatively large doses of some
phthalates can lead to health problems, including cancer.
• Lower levels may also have negative effects.
• Lowest level that produced adverse effects in the rats was 100 mg a
day/kg body weight
• Animal studies have shown that phthalates can disrupt the
endocrine system, inhibiting male hormones and causing male
infertility and birth defects
• A study published in the Environmental Health Perspectives found
that a group of men with DNA-damaged sperm also had higher
levels of diethyl phthalate (DEP) - regarded as one of the less toxic
phthalates
• DINP causes liver damage in animals & constitutes 40% of plastic
toys
More Studies
• DINP can leach out at risky levels when kids suck on them
• Study by the Silent Spring Institute found "significant concentrations"
of phthalates including DEHP and DBP in air and house dust of 120
Massachusetts houses
DEHP & Male Reproductive
System
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In 1999 Gray, LE, C Wolf, C Lambright, P Mann, M Price, RL Cooper and J
Ostby studied effects of anti-androgenic pesticides and toxic substances on
male rats
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Purpose: See effects on sexual differentiation in male rats
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Results: diverse profiles of reproductive malformations in the male rat.
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DEHP proved to be highly toxic to the reproductive system of male offspring
in transgenerational studies (in which the pregnant female was exposed and
effects measured in her offspring).
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DEHP induced high levels of testicular and epididymal abnormalities
– Atrophy and agenesis.
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A striking effect of DEHP was noted in 8-day old pups
Several males from different litters displayed hemorrhagic testes that were
visible by gross examination of the inguinal region
Conclusion: the testis is a direct target of DEHP during prenatal life
One of the endpoints study.
measured was the percentage of
male pups born with hypospadias
(left). Males in the control group
never had hypospadias
(continue…)
The study also determined the
percentage of male pups born
with areola. Males in the control
group never had areolas.
Pre-mature Birth
• Research:
– Took cord blood from babies at birth in a hospital in Brindisi, Italy
– Analyzed the blood for DEHP and its metabolite MEHP
– Examined the relationships between several aspects of the
infants' health at birth and exposure to DEHP and MEHP
Pre-mature Birth
• Found:
– Of 84 babies born consecutively
– 11 were preterm
– 3 had low birth weight
– 4 considered small for gestational age
– DEHP and/or MEHP present in 88% of the cord
serum samples
– Both were present in 77% of samples
– Babies with MEHP had a significantly lower
gestational age than those without MEHP
exposures, averaging 38-39 weeks
Other Results from Research
• Lowest level that produced adverse effects in the rats
was 100 mg/day kg of body weight
• About 500 times more than what a 2001 study by CDC
found in the general human population
• Phthalates found in largest quantities were DBP and
DEP , which tend to be used in cosmetics and
perfumes
• Maximum exposure level w/o adverse affects: 0.1 mg /
kg body weight a day (DBP & DEP)
• Of 72 name-brand cosmetics - everything from
shampoo to perfume to deodorant – 52 had phthalates
• Word “phthalate” not on label b/c Federal laws don’t
require it
Should We Worry ?
• Issue since early 1980's
• Very controversial
• Some sources claim that they pose no risk to humans
or environments
– Carcinogenic and reproductive effects found in
rodents are species specific and of little relevance
to humans
– Environmental impact considered to be low due to
their ready biodegradability and low toxicity
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• European Union conducted a risk assessment on DINP, DIDP and
DBP and found no risk
• Assessments on DEHP and BBP by EU are still underway
• FDA says phthalate-containing beauty products are safe
• U.S. Consumer Product Safety Commission concluded after 4 yr
study of DINP: children sucked on toys an average of 1.9 minutes
per day, and would have to suck for 39 minutes to ingest risky levels
• Industry argues that years of phthalate use without visible harm
prove product safety.
But…
• Contrary to EU assessment, toxicologist Paul Foster of the National
Institute of Environmental Health Sciences DBP & DEHP is
considered to be the most toxic phthalate.
• Studies found that human health endpoints are consistent with
phthalate damage found in animal experiments.
What’s Being Done?
• In 1998, U.S. toy manufacturers voluntarily agreed to stop using
phthalates in pacifiers and rattlers
• The EU has banned DINP in toys for kids 3 and under, while Japan
has announced a plan to get rid of DEHP and DINP in toys for kids 6
and under
• Still more research
Credits
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http://www.dcchem.co.kr
http://www.epa.gov/safewater/dwh/c-soc/phthalat.html
http://www.nsc.org/library/chemical/di(2-eth.htm
http://www.atsdr.cdc.gov/tfacts9.html