1. Phthalates
Edwin Chiang
May 18, 2005
Bio 2B

2. 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

3. Chemical Properties 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

4. 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

5. Other Uses Keep nail polish from chipping Hair sprays
Coatings on numerous pharmaceutical products
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.
Make tool handles strong and more resistant to breaking
Nail extenders
Bath soaps
Detergents
Aftershave lotions

6. Exposure 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

7. Exposures (DEHP) Air Water
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.

8. (continue…) Food Cosmetics
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.
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).

9. Harmful Effects
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

10. (continued…)
Carcinogenic
Damaged the liver of rats and mice at high doses
Relevant to humans: unknown

11. 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

12. 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

13. DEHP & Male Reproductive System
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
Purpose: See effects on sexual differentiation in male rats
Results: diverse profiles of reproductive malformations in the male rat.
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).
DEHP induced high levels of testicular and epididymal abnormalities
Atrophy and agenesis.

14. (continue…) 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

15. (continue…)
The study also determined the percentage of male pups born with areola. Males in the control group never had areolas.

16. 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

17. 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 weeks

18. 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

19. 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

20. (continued…)
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.

21. 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.

22. 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

23. Credits http://www.dcchem.co.kr