Emerging Pollutants: From source to health effects to policy Miriam Diamond University of Toronto 13/04/2011 1 Preamble • Extremely high production volume (HPV) chemicals (> 1 million tonnes/year) are inevitably in us • Some are known to disrupt endocrine function at low exposures • Are population-wide exposures putting some/all at risk? 13/04/2011 2 Per Capita Material Flows Input goods 6 Liquid waste 0.8 Stock ~0 Solid waste 0.1 Airborne waste 5.1 Input goods 89 Stock 266 Solid waste 3 Sewage 61 Airborne waste 19 Brunner & Rechberger 2001 Tons/capita/year 13/04/2011 3 Consumption Trends 13/04/2011 4 Matos & Wagner. 1998. Ammu. Rev. Energy Environ. 23:107-122.13/04/2011 5 Growth in Chemical Production Wilson & Scharzman 2009, Environ Health Perspectives13/04/2011 6 Cities as Resource Concentrators!! “Modern cities are material hotspots, containing more hazardous materials than most hazardous landfills.” Brunner & Rechberger 2001 13/04/2011 7 Chemical Production (g/c.d) Rate % Exp to Prod Ratio, ppm BPA 9.13 US 6-10%/y 0.23 (adult) DEHP 6.54 Germany ~1000X ‘77-’88 46 (adult) PBDEs 0.07 North America 33% (’91-’99) 2 (adult) 28 (infant) PCBs 0.06 Canada 57% (‘60-’64 vs ‘65-’69) 3 (adult) 13/04/2011 8 Correlation coefficient > 0.9, p<0.001 Helm D.2007 Correlation between production amounts of DEHP and daily intake. Sci Total Environ 388:398-391. Population Scale Correlation between Intake and Production 13/04/2011 9 Region Indoor Environment Terrestrial Food Web Aquatic Food Web Human Exposure City Air Dust Food Air & Soil Fish & seafood Fruits, Vegetables Animal Products SVOCs in Materials & Products If Persistent & not metabolised Diamond & Harrad. 2009. The chemicals that will not go away: implications for human exposure to reservoirs of POPs. Persistent Organic Pollutants: Current Issues and Future Challenges. S.J. Harrad Chichester, UK, Wiley. 13/04/2011 10 Region Indoor Environment Terrestrial Food Web Aquatic Food Web Human Exposure Policies & Regulations: Product and Material Management City Air & Dust Air & Soil Fish & seafood Fruits, Vegetables Animal Products Material & Product Stocks and Flows Diamond & Harrad. 2009. The chemicals that will not go away: implications for human exposure to reservoirs of POPs. Persistent Organic Pollutants: Current Issues and Future Challenges. S.J. Harrad Chichester, UK, Wiley. 13/04/2011 11 Contaminant Exposure Indoor Food Time Magnitudeof Exposure Start of production Harrad & Diamond 2006 Atmos Environ 40:1187-1188 PCBs PBDEs 13/04/2011 12 Region Indoor Environment Terrestrial Food Web Aquatic Food Web Human Exposure Policies & Regulations: Product and Material Management City Material & Product Stocks and Flows Material Flow Analysis Multimedia Indoor Model Multimedia Urban Model Multispecies Food Web Model 13/04/2011 13 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 • Policy 13/04/2011 14 Plastics • Manufactured as a material that could be molded to different shapes • Earliest mass produced plastic was Bakelite – Very hard, durable plastic – Black (could not take pigment) http://www.vam.ac.uk/vastatic/microsites/1331_mod ernism/files/97/1931_germany_chermayeff.jpg http://www.google.ca/imgres?imgurl=http://blog.blacknight.ie/imag es/black-phone.jpg&imgrefurl=http://blog.blacknight.com/updated-telephone- numbers.html&h=282&w=425&sz=90&tbnid=cNcr9CZrLrRS_M:&tbnh=84&tbnw=12 6&prev=/images%3Fq%3Dblack%2Btelephone&usg=__CfwZ0xqRE6Kpkn34FYk5fDLg T1Y=&ei=4gyyS7LPN8P58Aa845HJAQ&sa=X&oi=image_result&resnum=1&ct=image &ved=0CAsQ9QEwAA http://cgi.ebay.ca/VINTAGE-GYPSY-JAZZ- GUITAR-PICK-CATALIN- BAKELITE_W0QQitemZ310209646065QQcmdZV iewItemQQptZGuitar_Accessories?hash=item4 839ef8df1 13/04/2011 15 Flexible Plastic • Durable (won’t break, crack, yellow over time) • Take colours • Easily molded • Inexpensive • Light weight http://media.giantbomb.com/uploads/0/2750 /238166-beachball_large.jpeg http://www.vam.ac.uk/images/image/15519-large.jpg http://www.vestaldesign.com/blog/wp- content/uploads/plastic-bottle-blowing- hand.jpg 13/04/2011 16 Outline 1. What are phthalates, what are their uses, what products are they in? 2. How do phthalates move around the environment? (fate) 3. How are we exposed to phthalates? 4. What are some of the toxicological concerns about this exposure? 5. How do we minimize our exposure? • Individual action, • Policies & regulations 13/04/2011 17 What are phthalates? • Esters of phthalic acid • R can be short (C1-4) or long (C8-11) alkyl groups • Global production – ~3.5-4 billion kg/yr in 2003 (Lin et al. 2003) – ~ 6 billion kg/yr in 2004 (Rudel & Perovich 2009) http://en.wikipedia.org/wiki/Phthalate Di(2-ethylhexylphthalate) or DEHP 13/04/2011 18 Common Phthalates Wormuth et al. 2006 Risk Analysis 26(3): 803-824 13/04/2011 19 Phthalate Uses • Plasticizer – Increase flexibility & transparency • esp with polyvinyl chloride • Lubricant • Solvent • Emulsifier • Added 10-60% by wt http://www.americanchemistry.com/s_chlorine/docs/images/pvc_poly2.gif13/04/2011 20 Polyethylene Polyvinyl chlorinde Phthalate Uses • DEHP, BBZP Building materials vinyl tiles, vinyl wall paper, shower curtains, vinyl clothing • DnBP Consumer products – Cosmetics, fragrances, shampoos, moisturizers, hair spray • Medical equipment – IV & tubing • Food wrappers • Gloves used in food handling • Agricultural crop covers • “Inert” carrier in pesticide mixtures http://www.home-improvement- time.com/2008/09/06/sierra-plank-konecto- flooring-vinyl-tiles/ http://www.di rectwallpaper. co.uk/product s.html http://niceskin.org/index.php?pa geNum_product=11&case=search &ps=Colorescience-Lip-Polish- Wand-Softer-Shade-Of- Pale&pscat=Make+Up http://www.thecoolhunter.net /article/detail/1533 http://plasticulture.cas.psu.edu/IM AGES/field/imagepages/image4.ht m http://commons.wikimedia.org/wi ki/File:Regular_strength_enteric_c oated_aspirin_tablets.jpg 13/04/2011 21 Outline 1. What are phthalates, what are their uses, what products are they in? 2. How do phthalates move around the environment? (fate) 3. How are we exposed to phthalates? 4. What are some of the toxicological concerns about this exposure? 5. How do we minimize our exposure? • Individual action, • Policies & regulations 13/04/2011 22 Tangent http://oncampus.macleans.ca/education/2009/10/06/after-the-fork-in-the-road/ Introduction - Fugacity • Partitioning – Distribution of chemicals among environmental compartments • Chemicals do not partition in the environment to achieve equal concentrations, but to achieve chemical equilibrium • Fugacity – escaping tendency of a chemical – In units of pressure (Pa) – Comes from the Latin fugere, describing a “fleeing” or “escaping” tendency – Coined in 1901 by G.N. Lewis, a UC-Berkeley professor – Don Mackay, a former U of T engineering professor first applied it to modeling contaminants in the late 1970s – Commonly used in contaminant fate modelling Vinegar Lemon Juice Air Olive Oil 13/04/2011 24 At chemical equilbrium: fair = fwater = fsoil/sed = fbiota If: fair > fwater = fsoil/sed = fbiota How will chemical move? Equilibrium: • State at which there is no tendency to change • Fugacity in each compartment is equal • Regardless of where and how a chemical is discharged or found in the environment, all chemicals will strive to obtain a characteristic distribution or equilibrium among environmental compartments Fugacity capacity •capacity of an environmental compartment to hold a chemical •Function of the solubility of the chemical in a phase Vinegar Lemon Juice Air Olive Oil Air Soil Water Sediment13/04/2011 25 Chemical Transport • The case of the killer vinyl shower curtains http://www.environment aldefence.ca/pressroom/v iewnews.php?id=419 13/04/2011 26 http://cn1.kaboodle.com/hi/img/2/0/0 /34/e/AAAAArSBf8cAAAAAADTlqg.jpg Molecular Diffusion High Fugacity  Low Fugacity Rate • Fick’s 1st Law N ≈ Δ f (Pa) ▪ MTC (m/s) • Molecular weight • Temperature • Sorbents such as other plastics that don’t contain compound 13/04/2011 27 Phthalates & VP DEHP DBP DIBP DEP Mackay et al. 2006 0.22 1.15E-3 Pa 13/04/2011 28 103 KOA D(advection)/D(deposition) PBDE PCB BPA Phthalate Bisphenol A BBP DEHP PCB28 PCB 45 PCB 95 PCB 138 PCB 180 BDE 28 BDE 47BDE 99 BDE 153 BDE 183 Gas phase dominant Particle phase dominant BDE 100 BDE 154 105 107 109 1011 1013 1015 10-2 10-1 1 10 102 103 104 105 106 Outline 1. What are phthalates, what are their uses, what products are they in? 2. How do phthalates move around the environment? (fate) 3. How are we exposed to phthalates? 4. What are some of the toxicological concerns about this exposure? 5. How do we minimize our exposure? • Individual action, • Policies & regulations 13/04/2011 30 Wormuth et al. 2006 Risk Analysis 26(3): 803-824 Summary of Routes of Exposure 13/04/2011 31 How are we exposed? Food Medications Home – Air – Inhalation – Dermal – Saliva – Dust Hand-to-mouth Biomarker – Urine – Blood -How representative is the sample? -All metabolites? -Back-calculation to intake? - All intake routes? - Representative intake rates? - Reliable measured concentrations? 13/04/2011 32 Forward & Reverse Dosimetry Clewell et al. 2008. Quantitative interpretation of human biomonitoring data. Toxiol App Pharm 231:122-133.13/04/2011 33 Forward Dosimetry: Phthalate Exposure Assessment • Compilation of phthalates in foods, air, dust • Compilation of how much of each food is consumed, air inhaled, etc. • Example: – Wormuth et al. 2006 European exposure assessment 13/04/2011 34 Phthalates in our Foods Kankhauser et al. 2006. PVC plasticizers/additives migrating from the gaskets of metal closures into oily food: Swiss market survey June 2005. Eur Food Res Technol 223:447-453. 13/04/2011 35 Phthalates don’t bioaccumulate PCBs C8-10 Phthalates MacIntosh et al. 2004 Environ Sci Technol 38:2011-202013/04/2011 36 Phthalate Metabolism R Hauser and A M Calafat Phthalates and human health Occup Environ Med 2005 62: 806-81813/04/2011 37 Consumption Rates (European) Wormuth et al. 2006 What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Analysis 26(3): 803-824.13/04/2011 38 Phthalate Conc in Foods 13/04/2011 39 Wormuth et al. 2006 What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Analysis 26(3): 803- 824. BBzP Food Exposure Conc in food (mg/kg) X Intake Rate (kg/d) Dermal Exposure Conc in air/glove X skin permeability Inhalation Conc in air (ng/m3) X air inhalation rate (m3/d) 13/04/2011 40 Wormuth et al. 2006 What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Analysis 26(3): 803-824. 13/04/2011 41 Summary of Forward Dosimetry Calculation Reverse Dosimetry: Phthalate Exposure μg phthalate met/g creatinine BBzP DEHP 6-11 yrs 38.1 5.38 12-19 yrs 17.9 3.62 20+ yrs 12.7 3.81 Females 15.7 4.43 Males 12.7 3.32 Mexican Americans 12.4 4.16 Non-hispanic blacks 16.7 4.59 Non-hispanic whites 13.9 3.63 Geometric means of creatinine corrected urine, ug/g creatinine, 01-02 data, CDC 2005. Silva et al. 2004 Environ Health Perspectives 112:331-338; Mono-ester metabolite. 13/04/2011 42 Reverse: Exposure Reconstruction for NHANES III Data on Di-n-Butyl Phthalate (DnBP) *Assumed to be sum of three ingestion events per day NHANES III Predicted Percentile Concentration in Urine Intermittent Exposure* Continuous Exposure (µg/L) (µg/kg/day) (µg/kg/day) 10% - 0.30 25% - 0.45 0.25 50% 20.4 1.17 0.8 75% 40.4 3.78 1.4 90% 73.6 5.46 3.0 95% 108 7.74 4.2 Compares well with 24-hour urine data in German study (Wittassek et al., 2007): average = 1.9 µg/kg/day, 95% = 5.3 µg/kg/day Clewell 200913/04/2011 43 Correlation coefficient > 0.9, p<0.001 Helm D.2007 Correlation between production amounts of DEHP and daily intake. Sci Total Environ 388:398-391. Mean or Extreme of Exposure Distribution? 13/04/2011 44 Koch and Calafat 2009. Human body burdens of chemicals used in plastic manufacture. Phil. Trans. Royal Soc B 364:2063-2078. Mean or Extreme of Exposure Distribution? The Most Highly Exposed http://www.deathreference.com/images/medd_02_img0090.jp g 13/04/2011 46 Outline 1. What are phthalates, what are their uses, what products are they in? 2. How do phthalates move around the environment? (fate) 3. How are we exposed to phthalates? 4. What are some of the toxicological concerns about this exposure? 5. How do we minimize our exposure? • Individual action, • Policies & regulations 13/04/2011 47 Phthalate Toxicity – a moving target • Early studies – Hepatic cancer & teratogenesis at high doses – Cancer found to involve PPARα (peroxisome proliferator activated receptor) • therefore not relevant for humans • Newer studies have found liver tumors, pancreatic acinar adenomas • Factors other than PPARα • Some types of PPAR agonists involved in inflammatory response National Academies of Sciences 2008 13/04/2011 48 Toxicity – a moving target • Early studies – Did not find teratogenesis • Recent studies – Do find teratogenic effects on male reproductive system • Effects in offspring depend on timing of exposure • Effects more subtle (not included in early study protocols) National Academies of Sciences 2008 13/04/2011 49 Summary Risk Assessments NTP* Summary • DEHP, DBP & BBP hazardous to human reproduction & development • DiNP & DiDP hazardous to human development • DnHP & DnOP – insufficient data to determine risk REACH** • DEHP, DBP & BBP classified as human reproductive toxins (effects on fertility & development • DiNP & DiDP – no risk • DnOP yet to be assessed US Nation Toxicology Program European Registration, Evaluation, Authorization & Restriction of Chemicals National Academy of Science Phthalate Risk Assessment 2008 13/04/2011 51 Dose Additivity Sprague- Dawley rats exposed on gestational days 8- 18. Testicular testosterone production. Total 1300 mg phthalate/kg/d, DPP, BBP, DBP, DEHP and DiBP Howdeshell et al. 2008 Toxicol Sci 105:153-165 In Vivo Mode of Toxicological Action • Mono-ester metabolites appear to be toxic agent • Classified as peroxisome proliferators – Mediated by nuclear transcription of peroxisome proliferator-activated receptors (PPARs) • Some types of PPAR agonists involved in inflammatory response • Mechanism underlying association between asthma and rhinitis in kids & phthalate concentrations in dust? E.g., Bornehag et al. 2004 EHP Reproductive & Development Toxicity • BBzP, DiBP, DnBP, DPeP, DEHP, DiNP As an Endocrine Modulator* • Modulate endogenous production of fetal testicular testosterone • Influence insulin-like Factor 3 & folliclestimulating hormone production • Results in functional & structural impairment of male reproduction & development – Production of steroid hormones & spermatozoa, reduced fertility * A chemical that mimics or interferes with the biosynthesis, binding and/or action of natural hormones and thus disrupts physiological processes that are hormonally controlled (Jobling et al. 1995) Phthalate Syndrome National Academy of Science Phthalate Risk Assessment 2008 13/04/2011 55 Summary of Reproductive Effects National Academy of Science Phthalate Risk Assessment 200813/04/2011 56 Regression coefficients (95% confidence intervals) for a change in total T3 (ΔT3) associated with quintiles of MEP, MCiOP, MBP, MBzP, and sum of DEHP metabolite concentrations (∑DEHP) (adjusted for sex and age; n = 758). Relationship between Phthalate Metabolites & Thyroid Hormones in kids (4-9 yrs old) Boas et al. 2010 Environ Health Perspec 118:1458- 1464. “Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes.” Consistency between human & rat symptoms National Academy of Science Phthalate Risk Assessment 200813/04/2011 58 Swan et al. 2005 Environ Health Perspec 113(8):1056- 1061 Shorter than expected anogenital distance in boys 2-36 months old significantly related to urinary phthalate (metabolite) concentration 13/04/2011 59 Phthalate Syndrome National Academy of Science Phthalate Risk Assessment 2008 13/04/2011 60 Margin of Exposure The estimated 95th percentile of the population exposure distribution is 0.0077 mg/kg/day Margin of Exposure NOAEL = 30 mg/kg/day MOE = 30/0.0077 = 3896 Comparison with RfD Proposed RfD = 0.3 mg/kg/day (UF 100) MOE = 0.3/0.0077 = 38.96 Clewell 200913/04/2011 61 Outline 1. What are phthalates, what are their uses, what products are they in? 2. How do phthalates move around the environment? (fate) 3. How are we exposed to phthalates? 4. What are some of the toxicological concerns about this exposure? 5. How do we minimize our exposure? • Individual action, • Policies & regulations 13/04/2011 62 Regulation & Policy Individual Level • Minimize phthalates in dust? • Minimize phthalate products in home? Chemical Management • Risk management of particular phthalates? E.g., DEHP in kids toys Industry • What chemicals should be produced? Societal Level • Healthy kids living in healthy homes & playing outside • Chemical use13/04/2011 63 Canadian Environmental Protection Act • DEHP (1994) declared toxic • DBP (1994) OK • BBP (2000) OK • DnOP (1993, 2003) insufficient info • DiNP & DiDP – not assessed 13/04/2011 64 Regulations EU & USA • DEHP, BBP, DBP, DiNP, DiDP, DnOP banned from soft kids toys & childcare products EU • Banned DEHP & DBP in cosmetics, restrictions in products coming into contact with food Canada • Restrict use of DEHP & DiNP in products used by kids 0-4 yr intended to be mouthed • Imports?? • Hazardous Products Act, June 2009 proposal to harmonize with US & EU 13/04/2011 65 Consumer Action in Market Place Largely imported materials, goods & products 13/04/2011 66 Summary 1. What are phthalates, what are their uses, what products are they in? everywhere, in many products! 2. How do phthalates move around the environment? (fate) not persistent, relatively volatile 3. How are we exposed to phthalates? food (from packaging), consumer products, other?? 4. What are some of the toxicological concerns about this exposure? Endocrine disruptor, “phthalate syndrome” 5. How do we minimize our exposure? • Individual action • Policies & regulations13/04/2011 67