DAY 3: Source  Emission  Fate  Exposure  Toxicity Policy 1. Phthalates • Exposure • Toxicity 2. Polybrominated diphenyl ethers (PBDEs) & Polychlorinated biphenyls • Material Flow Analysis (MFA) • Indoor Environment • Urban Environment 3. PBDEs & Bisphenol A • Food web transfer • More controversy 13/04/2011 1 Region Indoor Environment Terrestrial Food Web Aquatic Food Web Human Exposure Policies & Regulations: Product and Material Management City Material & Product Stocks and Flows Multispecies Food Web Transfer 13/04/2011 2 Fig. 1. Concentrations (in ng/g wet weight, except dioxins) of 14 contaminants found in farmraised (red bars) and wild (green bars) salmon. R A Hites et al. Science 2004;303:226-229 Published by AAAS Hites et al. 2004. Global assessment of organic contaminants in farmed salmon. Science 303: 226- 229. PCBs Bioaccumulate but Phthalates don’t PCBs C8-10 Phthalates MacIntosh et al. 2004 Environ Sci Technol 38:2011-202013/04/2011 5 Some definitions Bioconcentration • Originally for trout muscle:water • The process leading to [organism] > [medium inhaled water or air] • Water or air borne exposure only • Therefore can only be determined in lab study where uptake from diet is minimal • BCF = CB/CW • Equilibrium process – i.e. fB = fW water BCF Kow Bioconcentration from water proportional to Kow Mackay 1982 Environ. Sci. Technol. BCF = 0.048 * Kow Where 0.048 approximates lipid content of fish Log BCF Loss of linear correlation for high Kow compounds •Low chemical bioavailability in water, partitions onto particulate mater in water •Insufficient exposure time to achieve equilibrium •Large size of molecules – too big to partition across gills •Growth of fish Gobas et al. 1989 – lab study for guppy Biomagnification • Process leading to [organism] > [organism diet] • Due to dietary absorption • Best determined in lab • BMF = CB/CD • Non-equilibrium process – i.e. fB > fdiet Fisk et al. 1998 Lab study of juvenile Rainbow trout Loss of linear correlation for high Kow •Insufficient time to obtain equilibrium •Size of molecule – too big to partition into the fish from gut Bioaccumulation • Process leading to [organism] > [surrounding medium] as a result of chemical uptake through all possible routes of exposure – For fish • Diet • Water • i.e. sum of biomagnification and bioconcentration • Can be assess under field conditions • BAF = CB/CW • Tends to increase with Kow water Voutsas et al. 2002 BAF Log Kow BAFs measured in the field Quantifying Chemical Uptake water Food water feces biodegradation growth Calculate concentration or fugacity = ? Gill Uptake/Elimination • Dissolved phase chemicals because must be small enough to diffuse across the gill surface • Major pathway in smaller organisms – Juvenile fish – Algae – Zooplankton • Smaller organisms have a greater respiratory surfaceto-body weight ratio – Increases their ability to accumulate and eliminate from/to water Metabolic Transformation • Negligible – E.g., PCBs, PCDD/F • Non-polar compounds metabolize to more polar excretion product – Phthalates, bisphenol A (glucoronidated) – Some metabolise to more toxic form • DDT to DDE • PAH to oxy-PAH (Cytochrome P450 oxidizing enzymes) • PBDEs debrominated to form lower bromine congeners Growth Dilution • When growth rate > chemical uptake • Important – young organisms who are growing at high rates – eutrophic conditions Dietary Uptake • Dominant pathway in adult, predatory fish – Log Kow 5 to ~7 • Contaminants are biomagnified through the food web Fecal Egestion • Dominates for contaminants with very low (>5) or very high (<~7.5) log Kow Bioaccumulation Phytoplankton Zooplankton Benthic Invertebrates Planktivorous fish Piscivorous fish Benthivorous fish Sediment/Detritus Food web structure • Longer the food web, more biomagnification • More benthic driven, higher conc in fish Food Web Biomangification & PhysicalChemical Properties Kelley BC et al. 2007 Science 317: 236-239 What About PBDEs? Kelley et al. 2008 Sci Total Environ 401: 60-72. (Stapleton et al 2004) BDE-99 debromination in Common Carp Food Body (Carp) After 5 days Stapleton et al. Environ. Sci. Technol., 40 (15): 4714 -4721, 2006 Debromination Paths BDE-153 BDE-100 BDE-99 BDE-47 74o N 19o E Bjørnøya met.-station N 0 1 2 km Contour interval 100 m Ellasjøen Bear Island Growth Dilution Debromination Ingestion/Egestion Bioformation Gill Ventilation0 0.26 21 0 92 18 323 21.5 5.4 12.4 96 8.5 124 1597 736 8996 2353 BDE – 47 000 41 0.13 0 0 0 Plankton Chironomid C obs = 37.8 C est = 34.3 Caddisfly C obs = NA C est = 45.9 Small Char C obs = 312.8 C est = 170.7 Large Char C obs = 392.9 C est = 290.2 3028 Bear Island: Transport Rates: BDE-47 Measured vs. Modelled – Arctic Char NM NM  Not measured 0 100 200 300 400 500 BDE-47 BDE-99 BDE-100 BDE-153 Concentration(ng/glipid) Measured Modeled, transformation  Modeled, debromination  Modeled, debromination  bioformation  Next step • congeners BUT apply to ONE FISH • Use experimental data rather than natural environment data – Better model parameterization • Run model for multiple scenarios with same basic fish energetic parameters – for multiple doses – for more than one time-point Debromination paths considered Nona-BDE BDE-209 Octa-BDE 1Octa-BDE 2 BDE-183 2,2’,3,4,4’,5’,6 BDE-190 2,3,3’,4,4’,5,6 BDE-138 2,2’,3,4,4’,5’ BDE-153 2,2’,4,4’,5,5’ BDE-154 2,2’,4,4’,5’,6 BDE-85 2,2’,3,4,4’ BDE-99 2,2’,4,4’,5 BDE-100 2,2’,4,4’,6 BDE-47 2,2’,4,4’ BDE-66 2,3’,4,4’ BDE-77 3,3’,4,4’ BDE-28 2,4,4’ Gandhi et al. 2011. Can biotransformation of BDE-209in lake trout cause bioaccumulation of more toxic lower-brominated PBDEs (BDE- 47, 99) over the long term? Environ Internat 37: 170-177. 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration Model Calibration: BDE-153AE(%) Half life (days) 1 70 10 365 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration Model Calibration: BDE-153AE(%) Half life (days) 1 70 10 365 0 20 40 60 80 100 120 140 160 180 200 220 0 20 40 60 80 100 120 140 160 180 Uptake Depuration Model vs Obs (multichem, BDE-99) 0 20 40 60 80 100 120 140 160 180 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 140 0 20 40 60 80 100 120 140 160 180 Uptake Depuration Without Debromination With Debromination Experimental Data Model Estimation …if the model did not account for the bioformation (i.e., single-chem model).. 0 20 40 60 80 100 0 20 40 60 80 100 120 140 160 180 Uptake Depuration 0 20 40 60 80 100 120 0 20 40 60 80 100 120 140 160 180 Uptake Depuration BDE-100 BDE-47 Take Home Messages • Chemicals vary in their tendency to bioaccumulate – Bioavailability – Tendency to biomagnify vs loss via metabolism – Uptake efficiency across the gut wall – Greatest bioaccumulation of higher chlorinated PCBs, polyunsaturated fatty acids (omega-3 fatty acids) • Multi-chemical, dynamic fish model using the fugacity approach • Applied to 13 PBDEs – 168-day Experimental data with juvenile lake trout  Tomy et al. 2004 • Model results suggest – Bioformation of lower brominated compounds – Debromination/metabolic half-lives: 20-150 days – ⇑ Br  ⇑ Half-lives – Assimilation efficiency  20-40% Environ Defense Bisphenol A Road Map • Why are we concerned? • Where is BPA? • What is BPA & why do we use so much? • Our exposure – Outdoor environment? – Exposure assessment • have we missed something? • Alternatives? http://www.bikertony.org/PicsChile/PicsChileTorres1-2/02road%20side%20pop%20bottle%20prayer%20thingy(not%20sure).jpg What’s the Controversy? Population Dose Tolerable Dose Age group? Highly exposed? Main exposure route? Exposure scenario? Endpoint? < > = Policy Decisions • EU – Food Safety Authority 2007, exposure << NOAEL of 5 mg/kg body wt/d – Voluntary industry phase out of BPA use in PVC polymerization or stabilizer of vinyl chloride • US – State- level initiatives – California (2007) AB 1108 restricts BPA & certain phthalates from kids (<3 yrs) toys • Japan 2005 – Exposure << effects level • Canada 2008 – Declared toxic, with removal of baby bottles Canadian Environmental Protection Act or CEPA April 14, 2008 – Notice to designate BPA “CEPA Toxic” (list on Schedule 1) Toxics Reduction Scientific Expert Panel Co-chairs M Diamond & L Collins April 14, 2008 – First meeting to hear evidence to adjudicate on BPA 1. What are the Health Concerns? • Harvard Center for Risk Analysis • Evidence for low dose effects of BPA is weak • Funded by American Plastics Council 2. What are the Health Concerns? Chapel Hill Expert Panel “…. Human exposure to BPA is within the range that is predicted to be biologically active in over 95% of people sampled.” “Recent trends in human diseases relate to adverse effects observed in experimental animals exposed to low doses of BPA. Specific examples include: the increase in prostate and breast cancer, uro-genital abnormalities in male babies, a decline in semen quality in men, early onset of puberty in girls…” Vom Saal et al. 2007 Reproductive Toxicology 24: 131-138. 3. What are the health concerns? NTP Nov 26, 2007 Some concern: neural & behavioural effects in pregnant women, fetuses, infants & children Minimal concern: prostate cancer, birth defects & abnormalities, accelerated puberty Negligible concern: adverse reproductive effects 4. What are the health concerns? NTP April 14, 2008 Some concern: neural & behavioural effects in fetuses, infants & children at current exposures; effects on prostate & mammary gland, earlier age for puberty in girls Negligible concern: birth defects, reduced birth weight & growth, reproductive effects (nonoccupationally exposed) 5. What are the health concerns? NTP June 11, 2008 Some concern: neural & behavioural effects in pregnant women,fetuses, infants & children; effects on prostate gland Minimal concern: effects on mammary gland, accelerated puberty Negligible concern: birth defects & abnormalities, adverse reproductive effects US FDA “Some Concern” Jan 1, 2010 Effects in Mice & Rats Human Health Trends Abnormal urethra Abnormal penis & urethra Prostate hyperplasia & cancer  Prostate cancer Mammary gland hyperplasia Breast cancer  Sperm count  Sperm count Early puberty in females Early sexual maturation Hyperactivity/Impaired learning ADHD Abnormal oocytes Miscarriage  Body weight  Obesity What’s the controversy? • Analytical methods – GC-MS or LC-MS LOWER – ELISA (enzyme linked immunosorbent assay) HIGHER • Vom Saal & Hughes (2005 EHP 113: 926-933) – Harvard meta-analysis, ANIMAL STRAIN & FUNDING significant predictors of positive (BPA is an EDC) vs negative (BPA is not an EDC) outcomes • Funding – Sample size, # generations What’s the controversy? Metabolism • ~2/3 BPA glucuronidated in adult • Minimal metabolism in fetus • Humans – Glucuronidated in gut wall & liver, then excretion in urine • Rodents – Glucuronidated in liver, excreted to bile where it is cleaved into BPA & glucuronidase, reabsorbed in blood, finally excreted in feces BPA’s Estrogenic Activity P. Harper, Sick Kids Hospital Road Map • Why are we concerned? • Where is BPA? • What is BPA & why do we use so much? • Our exposure – Outdoor environment? – Indoor environment? – Exposure assessment • have we missed something? • Alternatives? http://www.bikertony.org/PicsChile/PicsChileTorres1-2/02road%20side%20pop%20bottle%20prayer%20thingy(not%20sure).jpg Usage Rates • > 27 companies use/import BPA in Canada 2006 • Global production capacity < 3 billion kg/y in 2003 • World demand  6-10%/y • US demand – 7.3 million kg in 1991 – >1 billion kg in 2004 (~4.5 g/person each day) Where is my bisphenol A coming from? Where is BPA? • Food – Polycarbonate bottles – Can epoxy linings – Kettles – Food containers – Pipe surface coatings • Consumer Products – Adhesives – Eye glass coatings – Thermal paper – Crash helmets • Electronics – Cell phone & lap top casings – CDs & DVDs – Power plugs • Automotive – Bumpers – Safety glazing – Inside lights – Grills 54 •Polycarbonate polymer – bottles and other food containers •Single step combines BPA, second monomer and catalyst - “thermoplastic” polymer - “n” determines melting temperature - first heat, then mold, cool to fix form of final product - forms hard, clear, dent resistant polymer BPA Chemistry - background “carbonate” group S. Brown, Queen’s University 55 •Polycarbonate polymer – bottles and other food containers •Polycarbonate also potential source of BPA release - hydrolysis of carbonate group produces BPA - promoted by heat, alkaline conditions (also acid) - depends on time, nature of food or liquid contents - also affected by history – cleaning, heating, etc. BPA Chemistry - background Hydrolysis of these sites releases BPA S. Brown, Queen’s University 56 •Epoxy liners and coatings – “thermoset” polymer •Step one produces epoxy “pre-polymer” (or resin) - liquid easily blended with curing agents, other ingredients (e.g. titanium oxide for white liners) - liquid easily sprayed for coating surfaces BPA Chemistry - background “epoxy” group “BADGE” based resin S. Brown, Queen’s University 57 •Epoxy liners and coatings – “thermoset” polymer •Step two adds curing agent and heat to make “thermoset” - thermoset polymer cured in place, does not re-melt - high thermal and chemical stability, good surface adhesion - “hydrolysis” of ether oxygen can result in release of BPA (may be promoted by heat, acid or alkaline conditions) - long-term stability depends partly on contents BPA Chemistry - background “crosslink” group Hydrolysis of these sites releases BPA S. Brown, Queen’s University Road Map • Why are we concerned? • Where is BPA? • What is BPA & why do we use so much? • Our exposure – Outdoor environment? – Indoor environment? – Exposure assessment • have we missed something? • Alternatives? http://www.bikertony.org/PicsChile/PicsChileTorres1-2/02road%20side%20pop%20bottle%20prayer%20thingy(not%20sure).jpg Fate of BPA in the Environment Matrix Half Life Notes Air 0.2 days Unlikely to be transported Water 2.4-4 days Biodegradation most significant process Little volatilization, photo-degredation, or hydrolysis Soil 30 days (3 days) Low mobility Not expected to be stable, mobile or bioavailable Tissue Fish - Bioconcentration Factor =3.5-68 Clams - Bioconcentration Factor =134-144 Emissions: • sewage treatment plants (us) • industrial discharges (NPRI) Source: Kleywegt & Fletcher 2008 Fate: • Soil, sediment • Water Chemical Indoor Emission (ug/m2 d) Chemical Mass (mg) Residence Time (y) Annual Release (%) BPA 1.2-2.5 240 76 1.3 BBP 0.4-13.3 22 27 4 DEHP 4.3-7.7 17000 1175 0.1 PCB 0.8 600 800 0.1 PBDE 0.03-0.2 4.6 0.001 Road Map • Why are we concerned? • Where is BPA? • What is BPA & why do we use so much? • Our exposure – Outdoor environment? – Indoor environment? – Exposure assessment • have we missed something? • Alternatives? http://www.bikertony.org/PicsChile/PicsChileTorres1-2/02road%20side%20pop%20bottle%20prayer%20thingy(not%20sure).jpg Biomarker Exposure Assessment Calafat et al. 2008 Exposure of the U.S. Population to Bisphenol A and 4tertiary-Octylphenol: 2003–2004. Environ Health Perspec 116(1):39-44 0 0.1 0.2 0.3 0.4 0.5 Breast M ilk Form ula Food Soil/Dust Indoor Air 0-1 Month 12-18 Months 1-4 Years 5-11 Years 12-19 Years Adult Average Exposureµg/kgbodywt/day Average Exposure, Draft Screening Assessment for Phenol, 4,4’-(1-methylethylidene) bis- (80-05-7) April 2008 CEPA. Where does mom get BPA from? Mom’s transfer of BPA to infant Figure 1. Mean total exposure dose rates with source-related variability. Figure 2. Contribution of sources to the total dose rate for the mean exposure scenario. Von Goetz et al. 2010 Risk Analysis Infant – 1. PC baby bottle 2. Breast milk Adult – canned soup BPA on our hands group massbpa 5,1212,19>20<5 140 120 100 80 60 40 20 0 Boxplot of mass bpa vs group D. Berliner, M. Robson & M Diamond UofT, X-L Cao Health Canada 1469 people fasting* Stahlhut et al. 2009 EHP Exposure from Drinking Bottles Carwile et al. 2009 EHP 79 university students Exposure from Cash Register Receipts Biedermann et al. 2010 anal Biochem Chem Wash your hands! Road Map • Why are we concerned? • Where is BPA? • What is BPA & why do we use so much? • Our exposure – Outdoor environment? – Indoor environment? – Exposure assessment • have we missed something? • Alternatives? http://www.bikertony.org/PicsChile/PicsChileTorres1-2/02road%20side%20pop%20bottle%20prayer%20thingy(not%20sure).jpg Alternatives? BPA Epoxy Can Linings • BPA-based epoxy phenolic coatings • Polyester – Shorter shelf life – Less resistant to acidic foods • Cycloaliphatic epoxy resins • PVC vinyl-based Phenolic Gold linings from CDI SAKATA Source: S. Brown, Danish EPA 2004 Although several firms said they rely on their suppliers to make changes to food packaging, the report commends ConAgra and Campbell Soup for "extensive testing processes for BPA-free can linings." Yet the firms' efforts still lack transparency, says report author Emily Stone of Green Century. "The companies are tight-lipped about the substitutes they are testing," she says. Alternatives? Polycarbonate • Glass, stainless steel • HDPE, PP • Polyamide (nylon) • Polyethersulphone $9 each $8 each Source: S. Brown, Danish EPA 2004 Alternatives? Printing inks, toners, dental materials, plumbing coatings • Nitrocellulose, polyvinyl butyral, polyamide polyester • For food packaging: polypropylene, nylon Source: Danish EPA 2004 Conclusions • Why are we concerned? – Toxicity is controversial, regulatory action • Where is BPA? All over the place • What is BPA & why do we use so much? – Durable, excellent material properties • Our exposure – Outdoor environment? 70% Degrades – Indoor environment? Emissions 100’s ng/h – Exposure assessment • have we missed something? Where does mom get her BPA? • Alternatives? Not well tested! Reduce Use  Sustainability http://someonehadtosayit.files.wordpress.com/2008/04/elephant-in-the-room-harrison1.jpg Safe Products Less time indoors Increase ventilation Less is better Increase longevity of products Need multi-pronged to minimize exposure & promote health Less Time Indoors! • 22/24 hours spent indoors • Kids 6-11 yr old spend 53 hours/week with electronic devices • 6% of 9-13 yr olds in US play outside in a typical week (R. Louv) Sony plans lawsuit against government ad http://www.gossipjackal.com/entertainment/2010/0 7/24/premature-death-linked-to-sedentary-lifestyle/ Less Stuff “The average U.S. Person now consumes twice as much as they did 50 years ago.” Planned & Perceived Obsolescence Fig. 2. Emission of TCPP from two PIR insulating boards with different specific (ρ1=30 g l−1, ρ2=80 g l−1). Fig. 4. Emission of selected PBDE from a printed circuit board at simulated operating conditions (60°C) as a function of time Kemmlein et al. 2003 Atmos Environ 37: 5485-5493 Do we maximize SVOC releases as a consequence of continual replacement of “stuff” Acknowledgements Funding • NSERC • Great Lakes Commission • Ontario Min of Environment • Environment Canada Lisa Melymuk Matt Robson Xianming Zhang Amanda Giang Susie Csiszar Catherine Abreu Jennifer Sawyer Nilima Gandhi Cristian Mugnai Stuart Harrad, Univ of Birmingham Paul Helm, Ont Min of Environ Sean Backus, Environ Canada