Österreichisches Forschungsinstitut www.ofi.at für Chemie und Technik Austrian Research Institute for Chemistry & Technology CONSTRUCTION PLASTIC PRODUCTS PHARMA BIOENERGY SURFACE TECHNOLOGY CERTIFICATION Locations & Scope of Work www.ofi.at Location 1030 Vienna, Arsenal Location 1110 Vienna, Brehmstraße Applied Polymer Technology Surface Technology Building & Construction Sports technology starting summer 2010: Packaging Pharma & Medical Devices Bio energy Food & Feed analysis New location at TFZ Wr. Neustadt Member of Our Focus www.ofi.at Polymer Technology Processing & application of polymers, elastomers, paints, coatings and adhesives Building & Construction Building materials, structural monitoring, dehumidification of masonry, sports technology Pharma & Packaging Trace analysis, stability studies, packaging development; food & feed analysis Biomass fuels Manufacturing method, quality assurance, plant design Member of Agenda www.ofi.at What can you expect? Current discussion Definition – what are EDCs? Assay methods and first results What can we do? Member of Studies on BPA www.ofi.at NTP (NIH) USA 09/2008: At current exposure of the U.S. population: Developmental toxicity to fetuses / infants : „some concern for adverse effects (brain, behavior, prostate)“ Federal Office of Public Health (Switzerland) (2009): „No risk to consumers“ Problem of evasion to other / worse characterized ingredients Statement of the Endocrine Society 06/2009: „EDCs are a significant concern to public health“ Statement of the BfR 10/2009: „No health risk. No risk to infants and young children.“ Member of Actual situation www.ofi.at EDCs in contact with food – plastic, paper, laminates, coated metal cans... Effects of EDCs in packaging : • Potential danger (but not proven) • Currently concentration on a few substances • Large number of potential EDCs in packaging Need for action: • Analysis (Bioanalytsis; chemical analysis) • Toxicological studies • There are no comprehensive studies on EDCs in packaging • Reduction of the EDC burden of packaging Member of Definition ED www.ofi.at Member of Endocrine Disruptors (EDCs) www.ofi.at Definition: EPA Exogenous substances that act like hormones and disrupt the physiologic function of the endocrine system European comission Exogenous substances that act like hormones, disrupt the physiologic function of the endocrine system and cause adverse health effects. Member of www.ofi.at Effects on the environment Change of sex organs Purple snail (TBT) Alligators (DDT, Dicofol) Accumulation during food chain Example. PCB: Polar bear: 3 billion times the concentration originally found in water Member of www.ofi.at EDCs in plastic Monomers, stabilizers, plasticizers, antioxidants, contaminants ... Bisphenol A Alkylphenols (Nonylphenol) Phthalates Problem: migration out of the plastic into the food Member of www.ofi.at Why estrogens? Member of www.ofi.at Xenoestrogens Act like the primary female sex hormone estrogen Estrogen is involved in the regulation of many sensitive developing steps and metabolism functions in both men and women A disfunction of these mechanisms can cause reproductive problems, developmental disorders or cancer Member of German study: high estrogenic activity in mineral water www.ofi.at Authors assume that plastic bottles are the source BUT: other reasons possible Highly contraversal study Direct analysis of the plastic bottles necessary (PET-Bottle, screw cap) Member of Selection of bioassays www.ofi.at • Yeast-Bioassays (YES / YAS) • Aspergillus Screen (highly sensitive reportersystem) • Cell cultures (breast cancer-, prostate cancer celllines) – E-Screen • Reproductiontests with Potamopyrgus antipodarum • ... Member of Bioassays www.ofi.at Reporter gene assays: • YES – Yeast Estrogen Screen (2 different strains) • Aspergillus nidulans - Bioassay Principle • Cloned gene for human estrogen receptor • Binding of estrogen or endocrine disruptor (e.g. plastic additive) activates receptor • Expression of ß-Galaktosidase • Conversion of CPRG (yellow) => CPR (red) • Photometric measurement Member of Effects of estrogens www.ofi.at Member of www.ofi.at Reportergen-Assay Member of Extraction vs. migration www.ofi.at Total extraction • ASE – Accelerated Solvent Extraction Food simulants • Water • 3% Acetic acid • 50% Ethanol • Isooctane Member of www.ofi.at 17ß-Estradiol standard curve Limit of detection: 10 pM Limit of quantification: 20 pM Member of First results www.ofi.at Materials total negative positive (pg EEQ* / g sample) Limit of detection [pg EEQ/g sample] PP Yeast strain 1 23 22 1 Yeast strain 2 23 23 0 400 120 HDPE Yeast strain 1 13 12 1 2000 Yeast strain 2 13 12 1 1000 PET 6 Yeast strain 1 19 17 2 10 / 50 Yeast strain 2 19 14 5 50 - 80 *EEQ… 17ß-estradiolequivalent Member of Plasticadditives www.ofi.at Positive HDPE-sample: Bisphenol A: ca. 20 - 40 µg / g sample Benzylbutylphthalat: ca. 200 - 400 µg / g sample Member of www.ofi.at Plasticsamples 12 PET-bottles and PET-bottles preforms 4 PET-foils 13 screw caps 3 recycling flakes 6 positive samples, relatively low activities Member of www.ofi.at Results Member of www.ofi.at Interpretation Estrogen active substances can be found in plastics Low activity, but synthetical estrogens have a higher risk potential than natural estrogens Experiments with food simulants: no activity found In vitro - studies give no information on actual effects in humans Member of Why bioassays ? www.ofi.at Advantages Measurement of known and unknown substances Integration of synergistic effects (mixing effects) Evaluation of the complete package Simple screening tool Evaluation of toxicological effects possible No direct hints on in vivo effects Member of Bioassays www.ofi.at Disadvantages False negative results possible No conclusion about possible in vivo effects • only show: hormone binding to receptor Technical problems (solubilities / extracting agents / food simulants ...) No information of which substances are causing the hormone activity Combination with chemical analytic Member of Chemical Analysis www.ofi.at Chemical analysis • Development of testing methods for endocrine disruptors in packaging / food • Goal: Development of a multimethode for the 50 most frequent EDCs • GC/MS • LC/MSn Member of Next step: E-screen www.ofi.at In-vitro bioassay Human breast cancer cells (MCF 7 cells) No genetical modification Reproduction of the cancer cell line dependents on estrogens Reproduction of the cells (proliferation) is determined in comparison to a negative control and to estrogen standards high sensitivity (ca. 1 pmol/l) Member of www.ofi.at Member of COIN www.ofi.at COIN program line „structure" Funding authority: FFG on behalf of bmvit and BMWFJ Dimension: national Goals of the program • Development and improvement of key competences and functions • for providers of application-oriented F&E&I-expertise • particularly towards the KMU Runtime: 01.09.2010 until 30.08.2014 (48 months) Volume of the project: 1,8 Mio.€ Member of Goal: www.ofi.at Establishment of new bioanalytical methods Characterization of the total hormone burden of food contact materials (plastics, coated metal packaging, paper) Bio-Assay-Battery Sensitivity, standardization and high-throughput-analytic Chemical detection for the 50 most important EDCs in the ppb-range (preferable GC/MS) Member of Advisory board www.ofi.at International Scientific Advisory Board • Toxicologists • Food / Packaging analysts • Reference laboratory • Authorities Project Advisory Committee • Project partners (institutions) • Participating companies Member of Partners / Participating Companies www.ofi.at The following companies already joined the project : Plastics Europe Deutschland Tetra Holdings GmbH NÖM MAM Babyartikel GmbH Verein für Konsumenteninformation (VKI) REWE Teich AG ALPLA SIG Combibloc The following companies have expressed their interest: Greiner Packaging EREMA Miraplast MM Karton Member of - Hotline www.ofi.at For any questions please contact: DI Dr. Johannes Bergmair (DW 976, E-Mail: johannes.bergmair@ofi.at) ofi Research Institute Brehmstraße 14A 1110 Vienna +43-(0)1-798 16 01 -DW +43-(0)1-798 16 01- 480 Member of