Presentation on theme: "International Academy of Oral Medicine & Toxicology Conference, San Antonio, 2009 Carl E. Heltzel, Ph.D. Executive Director Global Environmental Awareness."— Presentation transcript:
International Academy of Oral Medicine & Toxicology Conference, San Antonio, 2009 Carl E. Heltzel, Ph.D. Executive Director Global Environmental Awareness & Resources (GEAR) Bisphenol A Leaching from Dental Composites Project: Phase I
Bisphenol A CA Global production at 4 billion kg in 2006, and a U.S. production of 1 billion kg in 2007 Has not been found to occur naturally Found in drinking water, surface waters, sediment, groundwater and soil, as well as in municipal and industrial waste treatment products, and YOU
Contact with drinking water may occur through the use of polycarbonate for water pipes and epoxy-phenolic resins in surface coatings of drinking water storage tanks. Polycarbonate plastics and blends may be used in the manufacture of compact discs, glazing applications and films, food containers (e.g., milk, water, and infant bottles), medical devices including dental sealants, flowables, and composites, injected molded parts used in alarms, mobile phone housings, coil cores, displays, computer parts, household electrical equipment, lamp fittings, power plugs, light reflectors and coverings, bumpers, radiator and ventilation grills, safety glazing, inside lights, motorcycle shields and helmets; epoxy resins are used in protective coatings, structural composites, electrical laminates, electrical applications, and adhesives, can coatings, polyvinylchloride (PVC) plastic, thermal paper, polyurethane, protective window glazing, building materials, optical lenses, dyes, coatings, adhesives, and putties available to the general pubic for use in automobiles, home maintenance and repair, and hobbies.
Bisphenol A Average daily exposure levels in the U.S. and Japan population, based on urine analysis indicated a mean daily intake of bpa of 3.75–5 μg/day for adults
Why do this study? So far, few human studies have been performed, but a study conducted by the Centers For Disease Control (CDC) found that in a sample population of 2,517 people ages 6 and over, Dental composite manufacturers claim that there is no free, unreacted BPA in bis-GMA or bis-DMA resins, and that it would take heating to a temperature of several hundred degrees to liberate the BPA from these resins. 93% were found to have traces of BPA in their urine. Welshons WV, Nagel SC, vom Saal FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology. 2006, 147(6 Suppl): S56-69.
Formation of polymer containing bpa monomer
Composite resins are formulated from a mixture of monomers and are most commonly based on bisphenol A glycidyl methacrylate, usually abbreviated as bis-GMA In addition to bis-GMA, composite resins generally include other monomers to modify the properties of the resin, for example bisphenol A dimethacrylate (bis-DMA) Although several key components of composite resins are derived from BPA, there is no known use of free BPA itself in composite resins. Resin Dental Sealants and Bisphenol A Oral Exposure Steven G. Hentges, Ph.D., Director, Polycarbonate Business Unit American Plastics Council In addition to monomers and fillers, composites also may contain initiators, to promote polymerization from light treatment, and stabilizers, to maximize storage of the uncured resin and stability of the cured resin. O O
Several researchers have studied whether BPA leaches from cured dental composites or sealants. In 1996, Nicolas Olea and coworkers at the University of Granada (Spain) and Tufts University in Boston, MA applied a commercially available sealant to twelve molars each of eighteen men and women, using about 50 mg of sealant per person. Saliva samples were collected one hour prior to and one hour after application. After treatment, all saliva samples were reported to contain BPA in amounts ranging from 90 to 931 µg (3.3 to 30 ppm). (Olea et al, 1996) Olea N., R. Pulgar., P. Perez, F. Olean-Serrano, A. Rivas, A. Novillo-Fertell, V. Pedraza, A. M. Soto and C. Sonnenschein, Estrogenicity of resin-based composites and sealants used in dentistry, Environmental Health Perspectives, vol. 104, The source of BPA that leaches from dental sealants is likely to be from hydrolysis of bis-DMA, a common monomer used in dental resin formulations.
Hydrolysis of Bis-DMA Ester link is subject to hydrolysis, releasing free bpa and other molecules O Acid or base catalyzed, add H 2 O +
Quinlan CA, Zisterer DM, Tipton KF, O’Sullivan MI. In vitro cytotoxicity of a composite resin and compomer. Int Endod J 2002; 35(1):47– : Pulgar and others studied biphenolic components eluted from 7 composites: Charisma, Pekalux, Voco, Silux-Plus, Z-100 (3M), Tetric, Brillant, and 1 sealant (Delton, Dentsply), before and after in vitro polymerization. They found BPA, bis-DMA, bisphenol A diglycidylether, bis-GMA, and ethoxylate and propoxylate [esters] of bisphenol A in the media in which samples of different commercial products were maintained under controlled pH and temperature conditions. They confirmed the leaching of estrogenic monomers into the environment by bis-GMA based composites and sealants at concentrations similar tothose that have produced biologic effects in in vivo experimental models.
By the end of 2004, a PubMed (National Library of Medicine, Bethesda, MD) search identified 115 published studies concerning effects of low doses of BPA in experimental animals. Bis-GMA O
September 3, 2008: National Toxicology Program (NTP) Finalizes Report on bisphenol A: Current human exposure to bisphenol A (BPA), is of “some concern” for effects on development of the prostate gland and brain and for behavioral effects in fetuses, infants and children.
Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption Laura N. Vandenberg, Maricel V. Maffini, Carlos Sonnenschein, Beverly S. Rubin and Ana M. Soto Tufts University School of Medicine, Department of Anatomy and Cellular Biology, Boston, Massachusetts 02111, Endocrine Reviews 30 (1): 75-95, 2008 The controversy continues…
MS of bpa derivative
50 ppb BPA spike in matrix 99.4% recovery
pH buffer (5.81) showing zero bpa
Sample ID INITIAL DATA Sample run; composites Derivatized BPA 1 hr, (ppb); pH Derivatized BPA 24 hr, (ppb); pH a 3b Diamond Lite Diamond Lite (polished) Diamond Lite (polished duplicate) (1.63) (1.67) (1.86) (1.99) 28Plastic from glass pipette box—2.67— Polymer known to contain zero bpa0000
Sample ID Composite Sample Derivatized BPA 24 hr, 5.81 pH (ppb) Derivatized BPA 24 hr, 7.00 pH, (ppb) 1 1b Virtuoso (duplicate) a 2b Renamel (duplicate) a 3b Diamond Lite (duplicate) a 4b Grandio (duplicate) a 5b Tetric Evo-Ceram (duplicate) a 6b Filtek Supreme Universal (duplicate) a 7b Estelite Sigma (duplicate) a 8b Vit-L-Essence (duplicate) a 9b TPH 3 (duplicate) a 10b Venus (duplicate) a 11b Heliomolar (duplicate) a 12b N’Durance (duplicate)
Using N 2 gas to evap samples Curing composite samples Composite samples were prepared in glass sleeves; 1 cm 2 of surface area each plug Into the lab
Placing samples in sonicating water bath at 37 o C GC-MS instrument GrandioVirtuoso
What’s an endocrine disruptor or xenoestrogen? Xenoestrogens: A group of chemicals that exert a biological reaction comparable to that of estrogens, bind to the estrogen receptors of relevant cells at subtoxic concentrations, impairing the development, health and reproductive systems of life. McLachlan JA, Arnolds SF. Environmental estrogens. Am Scientist 1996; 84: 452–61.
Estrogenic chemicals –wide range of structures
Sample IDComposite Sample Derivatized BPA 24 hr, 5.81 pH (ppb) Derivatized BPA 24 hr, 7.00 pH, (ppb) 1 1b Virtuoso (duplicate) a 3b Diamond Lite (duplicate) a 4b Grandio (duplicate) a 5b Tetric Evo-Ceram (duplicate) a 7b Estelite Sigma (duplicate) a 9b TPH 3 (duplicate) a 10b Venus (duplicate) a 12b N’Durance (duplicate)
What’s the bottom line? The precautionary principle — the idea that government should ban products believed to cause harm despite the absence of scientific certainty. This is a concept that’s big in Europe and gaining ground in North America. Lexan polycarbonate water bottle leached > 70 ppb over a 3-day period (Alliance Technologies, Inc.)
Future work Test the composites at 30 days. Test sealants, bonds, and cements. Endocrine Disruptor Bio-Assay. Disseminate results.
SOURCES: IAOMT Web site Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption Laura N. Vandenberg, Maricel V. Maffini, Carlos Sonnenschein, Beverly S. Rubin and Ana M. Soto Endocrine Reviews, 30 (1): (2009) ADA Positions & Statements Bisphenol A and Dental Sealants, Composite Dental Fillings, December, 2007 Environment California: health/stop-toxic-toys/bisphenol-a-overviewhttp://www.environmentcalifornia.org/environmental- health/stop-toxic-toys/bisphenol-a-overview Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to 2,2-BIS(4-HYDROXYPHENYL)PROPANE (Bisphenol A) Summary of Opinion The EFSA Journal, 428 (2006) An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment Frederick S. vom Saal and Claude Hughes, Environ Health Perspect 113: 926–933 (2005)
Acknowledgements 1.IAOMT 2.University of KY ERTL Lab Mr. John May Ms. Trisha Coakley Dr. Folami Ladipo 3. Ms. Audrey Keown 4. Dr. Greg Buerschen 5. Dr. N. Parinandi