C H A P T E R 41 Toxicity and Risk Assessment of Bisphenol A Anna M. Fan, Wei-Chun Chou, Pinpin Lin OUTLINE Introduction 765 Uses and Exposure 765 BPA Research Update 766 The Endocrine System 766 Endocrine Disruption 767 Endocrine Disruptors 767 Toxicology 768 Metabolism, Pharmacokinetics/Toxicokinetics 774 Animal Studies 774 Human Studies 776 Physiologically Based Pharmacokinetic Modeling 776 Major Evaluations and Assessments 778 Low-Dose Effects and Nonmonotonicity 784 Regulatory Aspects 789 Endocrine Disruptors 791 Concluding Remarks and Future Directions 793 References 793 INTRODUCTION Uses and Exposure BisphenolA(BPA)isanindustrialchemicalusedasa monomer in the manufacture of polycarbonate plastics and epoxy resins. This type of plastics is used in food contact materials such as reusable beverage bottles, infant feeding bottles, tableware (plates and mugs), and storage containers; compact discs; impact-resistant safety equipment; medical devices; automobile parts; andtoys.Epoxyresinsareusedaslacquerstocoatmetal products as protective linings for food and beverage cans, bottle tops, water supply pipes, dental sealants, and other products (US FDA, 2014a,b; CDC, 2016; NIEHS, 2016). The primary source of exposure to BPA for most peopleisthroughthedietwhereBPAinfoodandbever- agesaccountsforthemajorityofdailyhumanexposure. BPA can leach into food from the protective internal epoxy resin coatings of canned foods and from con- sumer products such as polycarbonate tableware, food storage containers, water bottles, and baby bottles. The degreetowhichBPAleachesfrompolycarbonatebottles intoliquidmaydependmoreonthetemperatureofthe liquid or bottle than the age of the container. BPA can also be found in breast milk. Air, dust, and water are other possible but minor sources of exposure (NIEHS, 2016). Other minor exposures may occur in small chil- drenviahand-to-mouthanddirectoral(mouth)contact with materials containing BPA, in cases of dental treat- ment with BPA-containing sealants, and in workers who manufacture products containing BPA (CDC, 2016).IntheNationalHealthandNutritionExamination Survey conducted during 2003e04, as shown in the FourthNationalReportonHumanExposuretoEnviron- mental Chemical, scientists found detectable levels of BPA in the urine of most of the 2517 participants aged 6 years and older in the US population (CDC, 2016). Finding a measurable amount of BPA in the urine does not imply that the levels cause an adverse health effect. The information provides physicians and public health officials with reference values for comparison with the general population, and helps scientists plan and conductresearchonexposureandhealtheffects.Various 765 Reproductive and Developmental Toxicology Copyright © 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/B978-0-12-804239-7.00041-X