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  • 1. Nov 3 – Endocrine Disruptors cont – Phthalates Dialkyl or alkyl/aryl esters of 1,2-benzenedicarboxylic acid (7 primary ones) – toxicity varies greatly across individual esters and mixtures Used in plastics and other consumer products Used in plastics to increase flexibility; also used as softeners in skin care products; used as medium to hold fragrances and colors in detergents and cosmetics Found in perfumes, hairsprays and cosmetics, construction materials, wood finishes, adhesives, floorings, and paints, PVC plastics. Also found in retainers used in orthodontic dentistry; certain dental composites; nipples on baby bottles; tubing used in medical “devices” – blood bags; liquid food bags; tubing for blood transfusions, ventilation air bags; timed released medications. Ingestion, inhalation, and dermal exposure throughout life.
  • 2. 7 Most Common Phthalates 1. Butyl benzyl phthalate: mostly in production of vinyl tiles. Also used in food conveyor belts, artificial leather, automotive trim, and traffic cones. BBzP – also known to be toxic 2. Di- n -butyl phthalate: a component of latex adhesives. Also used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. DNBP – also known to be toxic 3. Di(2-ethylhexyl) phthalate: Used in a wide variety of products, including flooring, wallpaper, vehicle upholstery, raincoats, toys, and food packaging. Currently the only phthalate plasticizer used in polyvinyl chloride medical devices such as blood bags and IV tubing. *most commonly used and studied – DEHP – known toxicant 4. Di- n -hexyl phthalate: Occurs in industrially important phthalates such as di-isohexyl phthalate (up to 25%) and C6-10 phthalate (up to 1%). May also occur in a variety of commercial products such as tool handles, dishwasher baskets, flooring, vinyl gloves, flea collars, and food conveyor belts.
  • 3. 7 Most Common Phthalates 5. Di-isodecyl phthalate: Used in a wide variety of products, including coverings on wires and cables, artificial leather, toys, carpet backing, and pool liners. Has only limited use in food packaging and handling. DIDP 6. Di-isononyl phthalate: Used in a wide variety of products, including garden hoses, pool liners, flooring tiles, tarps, and toys . Has only limited use in food packaging. DINP 7. Di- n -octyl phthalate: makes up approximately 20% of the industrially important C6-10 phthalate mixture, used to manufacture flooring, carpet tiles, tarps, pool liners, garden hoses, seam cements, bottle cap liners, and conveyor belts. Approved by the Food and Drug Administration as an indirect food additive.
  • 4. Widely found in environment – leach out of the plastics and other products 18 billion pounds used/year DEHP is the most common phthalate – 2 million tons/year EPA sets tolerable daily limit (TDL) for DEHP = 20 micrograms/kg body weight/day Avg US adult exposures = 3-30 micrograms/kg/day (avg is below TDL) More than 90% from food contamination (plastic packaging, use of PVC gloves in meal preparation) If receiving certain medical trts or working in certain occupations, may get 450+/kg/day Infants/toddlers get 50% from food and the rest from ingesting dust from toys, bottles, etc.
  • 5. Rest of lecture taken from: National Toxicology Program – Center for Health Effects Research, Center for the Evaluation of Risks to Human Reproduction August, 2005 – draft report open for public comment NTP-CERHR EXPERT PANEL UPDATE on the REPRODUCTIVE and DEVELOPMENTAL TOXICITY of DI(2-ETHYLHEXYL) PHTHALATE
  • 6. 2003
  • 7. Worst are oils and fats, cheeses, poultry products, processed meats.
  • 8. Effects in Adult Animals (most studies on DEHP): Carcinogens and liver toxicants Reproductive toxicants in male rats, mice, ferrets, and guinea pigs when administered orally – effects on sperm counts, motility, and morphology; effects on fertility; reduced testosterone production Data from female adult animal studies not conclusive – some studies indicate reduced fertility; reduced estrogenic activity; others do not.
  • 9. Effects in Adult Humans: Phthalates found in most adult urine samples and blood samples, as well as breast milk, and infant samples. Carcinogenic effects are controversial. Inadequate human data.
  • 10.
    • Animal Developmental Toxicity Findings (oral administration):
    • intrauterine death
    • malformations – skeletal (tail, limb, digits); eye abnormalities; neural tube defects (exencephaly)
    • abnormalities in male reproductive tract – anatomical, cellular, physiological
    • developmental delay
  • 11. Developmental Effects - Human 1. Levels found in umbilical cord blood have shown that higher levels  shorter pregnancy durations. 2. Urinary levels in pregnant women are associated with reduced anogenital distance in male infants (Swan et al, 2005). Problem levels found in 25% of American women. 3. Inadequate/absent data on other concerns.
  • 12. Lines represent the average anogenital distance at each age. Boys with higher collective exposures had shorter distances.