{"Affiliation":[{"label":"Affiliation","value":"Medicine, Faculty of","attrs":{"lang":"en","ns":"http:\/\/vivoweb.org\/ontology\/core#departmentOrSchool","classmap":"vivo:EducationalProcess","property":"vivo:departmentOrSchool"},"iri":"http:\/\/vivoweb.org\/ontology\/core#departmentOrSchool","explain":"VIVO-ISF Ontology V1.6 Property; The department or school name within institution; Not intended to be an institution name."},{"label":"Affiliation","value":"Population and Public Health (SPPH), School of","attrs":{"lang":"en","ns":"http:\/\/vivoweb.org\/ontology\/core#departmentOrSchool","classmap":"vivo:EducationalProcess","property":"vivo:departmentOrSchool"},"iri":"http:\/\/vivoweb.org\/ontology\/core#departmentOrSchool","explain":"VIVO-ISF Ontology V1.6 Property; The department or school name within institution; Not intended to be an institution name."}],"AggregatedSourceRepository":[{"label":"AggregatedSourceRepository","value":"DSpace","attrs":{"lang":"en","ns":"http:\/\/www.europeana.eu\/schemas\/edm\/dataProvider","classmap":"ore:Aggregation","property":"edm:dataProvider"},"iri":"http:\/\/www.europeana.eu\/schemas\/edm\/dataProvider","explain":"A Europeana Data Model Property; The name or identifier of the organization who contributes data indirectly to an aggregation service (e.g. Europeana)"}],"Campus":[{"label":"Campus","value":"UBCV","attrs":{"lang":"en","ns":"https:\/\/open.library.ubc.ca\/terms#degreeCampus","classmap":"oc:ThesisDescription","property":"oc:degreeCampus"},"iri":"https:\/\/open.library.ubc.ca\/terms#degreeCampus","explain":"UBC Open Collections Metadata Components; Local Field; Identifies the name of the campus from which the graduate completed their degree."}],"Creator":[{"label":"Creator","value":"Webster, Glenys Muriel","attrs":{"lang":"en","ns":"http:\/\/purl.org\/dc\/terms\/creator","classmap":"dpla:SourceResource","property":"dcterms:creator"},"iri":"http:\/\/purl.org\/dc\/terms\/creator","explain":"A Dublin Core Terms Property; An entity primarily responsible for making the resource.; Examples of a Contributor include a person, an organization, or a service."}],"DateAvailable":[{"label":"DateAvailable","value":"2011-07-20T23:47:35Z","attrs":{"lang":"en","ns":"http:\/\/purl.org\/dc\/terms\/issued","classmap":"edm:WebResource","property":"dcterms:issued"},"iri":"http:\/\/purl.org\/dc\/terms\/issued","explain":"A Dublin Core Terms Property; Date of formal issuance (e.g., publication) of the resource."}],"DateIssued":[{"label":"DateIssued","value":"2011","attrs":{"lang":"en","ns":"http:\/\/purl.org\/dc\/terms\/issued","classmap":"oc:SourceResource","property":"dcterms:issued"},"iri":"http:\/\/purl.org\/dc\/terms\/issued","explain":"A Dublin Core Terms Property; Date of formal issuance (e.g., publication) of the resource."}],"Degree":[{"label":"Degree","value":"Doctor of Philosophy - PhD","attrs":{"lang":"en","ns":"http:\/\/vivoweb.org\/ontology\/core#relatedDegree","classmap":"vivo:ThesisDegree","property":"vivo:relatedDegree"},"iri":"http:\/\/vivoweb.org\/ontology\/core#relatedDegree","explain":"VIVO-ISF Ontology V1.6 Property; The thesis degree; Extended Property specified by UBC, as per https:\/\/wiki.duraspace.org\/display\/VIVO\/Ontology+Editor%27s+Guide"}],"DegreeGrantor":[{"label":"DegreeGrantor","value":"University of British Columbia","attrs":{"lang":"en","ns":"https:\/\/open.library.ubc.ca\/terms#degreeGrantor","classmap":"oc:ThesisDescription","property":"oc:degreeGrantor"},"iri":"https:\/\/open.library.ubc.ca\/terms#degreeGrantor","explain":"UBC Open Collections Metadata Components; Local Field; Indicates the institution where thesis was granted."}],"Description":[{"label":"Description","value":"Perfluorinated compounds (PFCs) are used as stain, grease and water repellents in a wide range of consumer products. Despite their widespread use and known thyroid disrupting potential in animal studies, uncertainties remain about sources of exposure and thyroid effects in humans. Thyroid effects are of particular concern during early pregnancy, when thyroid hormones play a critical role in fetal brain development. \n\nThe Chemicals, Health and Pregnancy study (CHirP) was designed to address these knowledge gaps. The main goals of this dissertation were 1) to describe and evaluate a wide range of recruitment techniques used to enroll women in early pregnancy into the study, 2) to identify the main determinants of PFC levels in maternal serum, and 3) to examine the relationships between PFCs and thyroid hormones in maternal serum during a critical window of thyroid-mediated fetal brain development. \n\nOne hundred and fifty two women from Metro Vancouver were recruited into the study. Posters, flyers, and a booth at pregnancy trade shows were among the most effective recruitment methods. The recruited population was older, less ethnically diverse, more educated and more affluent than the population of pregnant women in Vancouver (Chapter 2). \n\nSignificant determinants of PFCs in maternal serum included pork-based foods, raw fish and shellfish, microwave and movie theatre popcorn, ethnicity, time spent in cars and airplanes, mattress age, stain repellent use on carpets, spot remover use on carpets, rugs and furniture, and levels of certain PFCs or their precursors in dust. Maternal PFC levels also declined strongly with parity, highlighting concerns about fetal or infant exposures to PFCs across the placenta or via breast milk (Chapter 3).\n\nWe found significant negative relationships between several PFCs in maternal serum and maternal free thyroxine (fT4), and positive relationships with maternal thyroid stimulating hormone (TSH), but only in women with markers of autoimmune hypothyroidism. These results suggest that PFCs may exacerbate low fT4 and high TSH levels in up to 45,000 pregnancies per year in Canada (i.e. in the 10% of women with these markers), with unknown effects on fetal brain development (Chapter 4). These results await replication in larger, population-based studies.","attrs":{"lang":"en","ns":"http:\/\/purl.org\/dc\/terms\/description","classmap":"dpla:SourceResource","property":"dcterms:description"},"iri":"http:\/\/purl.org\/dc\/terms\/description","explain":"A Dublin Core Terms Property; An account of the resource.; Description may include but is not limited to: an abstract, a table of contents, a graphical representation, or a free-text account of the resource."}],"DigitalResourceOriginalRecord":[{"label":"DigitalResourceOriginalRecord","value":"https:\/\/circle.library.ubc.ca\/rest\/handle\/2429\/36225?expand=metadata","attrs":{"lang":"en","ns":"http:\/\/www.europeana.eu\/schemas\/edm\/aggregatedCHO","classmap":"ore:Aggregation","property":"edm:aggregatedCHO"},"iri":"http:\/\/www.europeana.eu\/schemas\/edm\/aggregatedCHO","explain":"A Europeana Data Model Property; The identifier of the source object, e.g. the Mona Lisa itself. This could be a full linked open date URI or an internal identifier"}],"FullText":[{"label":"FullText","value":"EXPOSURE SOURCES AND THYROID EFFECTS OF PERFLUORINATED COMPOUNDS (PFCs) DURING PREGNANCY: RESULTS FROM THE CHEMICALS, HEALTH AND PREGNANCY STUDY (CHirP) by Glenys Muriel Webster M.R.M., Simon Fraser University, 2003 B.Sc., The University of British Columbia, 2000 B.Mus., The University of British Columbia, 1995 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Occupational and Environmental Hygiene) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2011 \u00a9 Glenys Muriel Webster, 2011 ii ABSTRACT Perfluorinated compounds (PFCs) are used as stain, grease and water repellents in a wide range of consumer products. Despite their widespread use and known thyroid disrupting potential in animal studies, uncertainties remain about sources of exposure and thyroid effects in humans. Thyroid effects are of particular concern during early pregnancy, when thyroid hormones play a critical role in fetal brain development. The Chemicals, Health and Pregnancy study (CHirP) was designed to address these knowledge gaps. The main goals of this dissertation were 1) to describe and evaluate a wide range of recruitment techniques used to enroll women in early pregnancy into the study, 2) to identify the main determinants of PFC levels in maternal serum, and 3) to examine the relationships between PFCs and thyroid hormones in maternal serum during a critical window of thyroid-mediated fetal brain development. One hundred and fifty two women from Metro Vancouver were recruited into the study. Posters, flyers, and a booth at pregnancy trade shows were among the most effective recruitment methods. The recruited population was older, less ethnically diverse, more educated and more affluent than the population of pregnant women in Vancouver (Chapter 2). Significant determinants of PFCs in maternal serum included pork-based foods, raw fish and shellfish, microwave and movie theatre popcorn, ethnicity, time spent in cars and airplanes, mattress age, stain repellent use on carpets, spot remover use on carpets, rugs and furniture, and levels of certain PFCs or their precursors in dust. Maternal PFC levels also declined strongly with parity, highlighting concerns about fetal or infant exposures to PFCs across the placenta or via breast milk (Chapter 3). We found significant negative relationships between several PFCs in maternal serum and maternal free thyroxine (fT4), and positive relationships with maternal thyroid stimulating hormone (TSH), but only in women with markers of autoimmune hypothyroidism. These results suggest that PFCs may exacerbate low fT4 and high TSH levels in up to 45,000 pregnancies per year in Canada (i.e. in the 10% of women with these markers), with unknown effects on fetal brain development (Chapter 4). These results await replication in larger, population-based studies. iii PREFACE Chapters 2-4 of this dissertation have been written as stand-alone manuscripts for publication in the peer-reviewed literature. Chapter 2 has already been published, and Chapter 4 will be submitted in the next few months. Chapter 3 will be revised and condensed before being submitted for publication. As primary author, I led each of these chapters, and was also the creator and director of the larger Chemicals, Health and Pregnancy study (CHirP) from which the data used in this dissertation are drawn. In this section, I provide details of my role in creating the CHirP study, as well as my contributions and those of my co-authors to each of the dissertation chapters. Recruitment procedures and data collection for the Chemicals, Health and Pregnancy study were approved by the University of British Columbia\u2019s Clinical Research Ethics Board (CREB certificate H06-70292), as well as by the ethics boards of other participating research centres. Overview: Creation of the Chemicals, Health and Pregnancy study (CHirP) I created the CHirP study in 2005 as the foundation for my PhD research. I led all aspects of this work, including designing the study, building a new team of interdisciplinary researchers from across the US and Canada, obtaining research funds totaling $370,000 from 4 different grants, hiring and training 7 research assistants, developing and pilot-testing two new exposure assessment questionnaires, recruiting study participants, overseeing all sample collection, conducting all interviews, and undertaking all data analysis and writing for the work presented in this dissertation. Other projects using CHirP samples have been conducted at Environment Canada and the University of Alberta, and have resulted in two other co-authored publications that are not included in this dissertation [1, 2]. Shoeib M, Harner TM, Webster GM, Lee SC. Indoor Sources of Poly- and Perfluorinated Compounds (PFCS) in Vancouver, Canada: Implications for Human Exposure. DOI: 10.1021\/es103562v. Environ Sci Technol. 2011 02\/18. Beesoon S, Webster GM, Shoeib M, Harner T, Benskin JP, Martin JW. Isomer Profiles of Perfluorinated Compounds in Matched Maternal, Cord and House Dust Samples; Manufacturing Sources and Transplacental Transfer (final revisions submitted May 2011). iv Chapter 2: Recruitment of Healthy First-Trimester Pregnant Women: lessons from the Chemicals, Health and Pregnancy Study (CHirP). Several research assistants helped with the recruitment of study participants. Cristina Cotea helped to design the recruitment poster, flyer, study magnet, baby T-shirts and other recruitment materials. Sara Leckie coordinated much of study advertising campaign. Cristina Cotea, Sara Leckie, Sarah Hilbert-West and No\u00ebl Patten helped to design and present the CHirP study booth at various events around Vancouver. I oversaw all aspects of the recruitment phase, attended all tradeshows and other events, gave 12 presentations to the clinical staff at the three participating hospitals, and was the primary contact for prospective and enrolled participants throughout the study. I conducted all data analysis and wrote the manuscript. Kay Teschke and Patricia Janssen provided feedback on the paper. My overall contribution: 90%. A version of Chapter 2 has been published: Webster, G.M., Teschke, K. and Janssen, P.A. (2011). Recruitment of Healthy First-Trimester Pregnant Women: Lessons From the Chemicals, Health & Pregnancy Study (CHirP). Maternal and Child Health Journal. 2011 Jan 6. DOI 10.1007\/s10995-010-0739-8. Copyright permission has been obtained to include this paper in this dissertation. Chapter 3: Determinants of Perfluorinated Compounds (PFCs) in Maternal Serum. Research assistants Robin Simms and Cristina Cotea helped with the design and pilot testing of the two exposure assessment questionnaires. Materials required for the collection of indoor dust as well as air, lint and water samples (data not included in this dissertation) were provided by Tom Harner, Mahiba Shoeib and Derek Muir (Environmental Canada, Toronto and Burlington). Sara Leckie, Sarah Hillbert-West, No\u00ebl Patten, Cristina Cotea and Linda Dix-Cooper helped with the assembly and mailing of the serum collection kits. Cristina Cotea and Linda Dix-Cooper assisted with the collection, management and shipping of home samples, as well as with data collection during the home walk-throughs. I administered all in-person questionnaires (n=152), sent all reminder emails about consent forms, serum sampling, home visits, questionnaires and cord blood collections (not included in this dissertation) to all participants, and coordinated all serum sampling at the hospitals. PFC levels in serum were analyzed at ALS lab in Edmonton. PFC levels in home samples were analyzed by Mahiba Shoeib and Sum Chi Lee at Environment Canada in Toronto (dust, air, lint), and in water by Derek Muir at Environment Canada in v Burlington (only dust data are included in this dissertation). No\u00ebl Patten and I picked up cord blood samples collected during home births and delivered them to the hospital labs (data not included in this dissertation). Data entry was performed by a local data entry company. Rebecca Love assisted with data cleaning. I conducted all statistical analyses and wrote most of the chapter. Dr Jon Martin (University of Alberta) wrote the section describing the analytical methods used to analyze PFCs in maternal serum. Dr Martin also provided guidance about the identity and potential degradation routes of many different PFCs. Dr Kay Teschke provided guidance through the development of the questionnaire and during data analysis, and provided the majority of feedback about the chapter. My contribution: 90%. Chapter 3 will be condensed and submitted for publication in the next few months. Chapter 4: Effect of Perfluorinated Compounds (PFCs) on Maternal Thyroid Hormones during Early Pregnancy. Thyroid hormone levels in maternal and cord serum were analyzed by Alison Young at BC Women\u2019s Hospital. Guidance on data analysis was provided by Dr Scott Venners and Dr Karen Grace Martin (statistical consultant, Analysis Factor, www.analysisfactor.com). Dr Andre Mattman provided guidance on thyroid hormone assays and physiology, and helped to interpret our thyroid hormone results. Scott Venners conducted the influential points analyses in SAS, as I did not have easy access to this software. I conducted all other statistical analyses, and wrote the chapter. My contribution: 95%. A version of this chapter will be submitted for publication in the next few months. vi TABLE OF CONTENTS ABSTRACT................................................................................................................................................. ii PREFACE.................................................................................................................................................. iii TABLE OF CONTENTS....................................................................................................................... vi LIST OF TABLES.................................................................................................................................... xi LIST OF FIGURES................................................................................................................................ xiii LIST OF ABBREVIATIONS................................................................................................................ xv ACKNOWLEGEMENTS .................................................................................................................... xvi DEDICATION..................................................................................................................................... xviii CHAPTER 1: INTRODUCTION..................................................................................................... 1 1.1 Overview................................................................................................................................... 1 1.2 Literature Review..................................................................................................................... 2 1.2.1 What are perfluorinated compounds (PFCs)? ............................................................. 2 1.2.2 PFC levels in human tissues ........................................................................................... 2 1.2.3 Sources of PFC exposure................................................................................................ 3 1.2.4 Health effects of PFCs.................................................................................................... 4 1.2.5 Research questions........................................................................................................... 6 1.2.6 Specific objectives ............................................................................................................ 7 1.3 Overall Design of the CHirP Study ...................................................................................... 7 1.3.1 Justification of study setting \u2013 why Vancouver? ......................................................... 8 1.4 Dissertation Structure ............................................................................................................. 9 1.4.1 Chapter 2: Recruitment of healthy first-trimester pregnant women ........................ 9 1.4.2 Chapter 3: Determinants of perfluorinated compounds (PFCs) in maternal serum 9 1.4.3 Chapter 4: Effect of perfluorinated compounds (PFCs) on maternal thyroid hormones during early pregnancy ............................................................................................ 10 CHAPTER 2: RECRUITMENT OF HEALTHY FIRST-TRIMESTER PREGNANT WOMEN: LESSONS FROM THE CHEMICALS, HEALTH & PREGNANCY STUDY (CHIRP) ................................................................................................................................................ 13 vii 2.1 Summary ................................................................................................................................. 13 2.2 Introduction............................................................................................................................ 14 2.3 Methods................................................................................................................................... 14 2.3.1 Eligibility and study design ........................................................................................... 15 2.3.2 Recruitment methods .................................................................................................... 16 2.3.3 Enrollment and consent procedures........................................................................... 17 2.4 Results ..................................................................................................................................... 18 2.4.1 Enrollment and retention.............................................................................................. 18 2.4.2 Time and cost-effectiveness of different recruitment methods.............................. 18 2.4.3 Participant demographics.............................................................................................. 20 2.5 Discussion............................................................................................................................... 21 2.5.1 Recruitment strategies - comparisons with prior studies ......................................... 22 2.5.2 Non-representative study population.......................................................................... 23 2.6 Conclusion .............................................................................................................................. 24 CHAPTER 3: DETERMINANTS OF PERFLUORINATED COMPOUNDS (PFCS) IN MATERNAL SERUM........................................................................................................................ 31 3.1 Summary ................................................................................................................................. 31 3.2 Introduction............................................................................................................................ 32 3.3 Materials and Methods.......................................................................................................... 35 3.3.1 Study population and protocol..................................................................................... 35 3.3.2 Data collection and chemical analysis ......................................................................... 35 3.3.3 Statistical analyses........................................................................................................... 39 3.4 Results ..................................................................................................................................... 42 3.4.1 Quality assurance \/ quality control.............................................................................. 42 3.4.2 Descriptive statistics ...................................................................................................... 43 3.4.3 Modeling results: univariate screening models (step 1) ............................................ 45 3.4.4 Modeling results: multivariate models (steps 2-4) ..................................................... 49 3.4.5 Multivariate model diagnostics & influential points ................................................. 52 3.4.6 Summary of multivariate models ................................................................................. 52 3.5 Discussion............................................................................................................................... 53 3.5.1 PFC levels in serum ....................................................................................................... 53 3.5.2 PFC levels in dust........................................................................................................... 53 viii 3.5.3 Determinants of PFCs in serum.................................................................................. 54 3.5.4 Study strengths and limitations .................................................................................... 63 3.6 Conclusions ............................................................................................................................ 65 CHAPTER 4: EFFECT OF PERFLUORINATED COMPOUNDS (PFCS) ON MATERNAL THYROID HORMONES DURING EARLY PREGNANCY....................... 92 4.1 Summary ................................................................................................................................. 92 4.2 Introduction............................................................................................................................ 93 4.3 Methods................................................................................................................................... 95 4.3.1 Data collection................................................................................................................ 95 4.3.2 Statistical analysis............................................................................................................ 98 4.4 Results ................................................................................................................................... 101 4.4.1 Population characteristics ........................................................................................... 101 4.4.2 PFC concentrations in serum..................................................................................... 101 4.4.3 Thyroid hormone concentrations in serum ............................................................. 101 4.4.4 Relationships between serum PFCs and thyroid hormones.................................. 102 4.5 Discussion............................................................................................................................. 104 4.5.1 Modes of action............................................................................................................ 104 4.5.2 Previous studies in humans ........................................................................................ 106 4.5.3 Unexpected findings.................................................................................................... 108 4.5.4 Clinical significance...................................................................................................... 109 4.5.5 Strengths and limitations............................................................................................. 110 4.6 Conclusion ............................................................................................................................ 112 CHAPTER 5: CONTRIBUTIONS, IMPACTS AND FUTURE DIRECTIONS................ 125 5.1 Overview............................................................................................................................... 125 5.2 Objectives ............................................................................................................................. 125 5.3 Key Findings......................................................................................................................... 125 5.3.1 Chapter 2: Recruitment of healthy first-trimester pregnant women .................... 125 5.3.2 Chapter 3: Determinants of perfluorinated compounds (PFCs) in maternal serum 126 5.3.3 Chapter 4: Effect of perfluorinated compounds (PFCs) on maternal thyroid hormones during early pregnancy .......................................................................................... 128 5.3.4 Synthesis ........................................................................................................................ 129 ix 5.4 Other Unique Contributions.............................................................................................. 129 5.4.1 Interdisciplinarity and team building......................................................................... 129 5.4.2 New tools ...................................................................................................................... 130 5.4.3 Comprehensive data-set available for future research............................................ 130 5.5 Initial Challenges.................................................................................................................. 131 5.6 Implications of this Work................................................................................................... 133 5.6.1 Risk assessments and regulations: PFOA................................................................. 134 5.6.2 Risk assessments and regulations: PFOS.................................................................. 135 5.6.3 Implications for human risk assessment................................................................... 136 5.6.4 Implications for PFC regulations............................................................................... 136 5.6.5 Recommendations for reducing personal exposures to PFCs .............................. 138 5.7 Knowledge Translation....................................................................................................... 139 5.8 Strengths and Limitations................................................................................................... 139 5.9 Future Directions................................................................................................................. 142 5.9.1 PFCs in pork................................................................................................................. 142 5.9.2 PFCs in food packaging .............................................................................................. 143 5.9.3 PFCs in the transportation industry.......................................................................... 143 5.9.4 Thyroid hormone studies............................................................................................ 144 5.9.5 Analyses using existing data or archived samples.................................................... 144 References................................................................................................................................................ 146 Appendices .............................................................................................................................................. 167 Appendix 1: Consent form, part 1 (main study)\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.. 168 Appendix 2: Consent form, part 2 (optional tissue banking)\u2026.\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026...174 Appendix 3: Recruitment poster\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.......178 Appendix 4: Recruitment flyer\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.179 Appendix 5: CHirP study recruitment booth on display at a local baby trade show\u2026\u2026\u2026......181 Appendix 6: Blood collection protocol, BC Children\u2019s and Women\u2019s Hospital, Vancouver Canada\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026182 Appendix 7: Dust collection and foil cleaning protocols\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.......186 x Appendix 8: Online questionnaire\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026...190 Appendix 9: In-person questionnaire\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026...249 Appendix 10: Diagnostic plots for the Step 3a PFHxS (left) and Step 3b LnPFHxS (right) models. Natural log transformation of PFHxS improved model assumptions (normality and homoscedasticity of the residuals), as well as model fit (adjusted R2 = 0.19 versus 0.31 for PFHxS and LnPFHxS respectively)\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026......297 Appendix 11: Untransformed (left) and natural log transformed (right) distributions of PFHxS, PFNA, PFOS and PFOS in maternal serum at 15 weeks gestation. Values less that the detection limit (